Characteristics and course of chronic hepatitis B e antigen-negative infection | Gastroenterología y Hepatología (English Edition)

array:23 ["pii" => "S2444382417300275" "issn" => "24443824" "doi" => "10.1016/j.gastre.2016.11.009" "estado" => "S300" "fechaPublicacion" => "2017-02-01" "aid" => "1085" "copyright" => "Elsevier España, S.L.U., AEEH and AEG" "copyrightAnyo" => "2016" "documento" => "article" "crossmark" => 1 "subdocumento" => "fla" "cita" => "Gastroenterol Hepatol. 2017;40:59-69" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 570 "formatos" => array:2 [ "HTML" => 437 "PDF" => 133 ] ] "Traduccion" => array:1 [ "es" => array:19 [ "pii" => "S0210570516301637" "issn" => "02105705" "doi" => "10.1016/j.gastrohep.2016.11.002" "estado" => "S300" "fechaPublicacion" => "2017-02-01" "aid" => "1085" "copyright" => "Elsevier España, S.L.U., AEEH y AEG" "documento" => "article" "crossmark" => 1 "subdocumento" => "fla" "cita" => "Gastroenterol Hepatol. 2017;40:59-69" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 1996 "formatos" => array:2 [ "HTML" => 1591 "PDF" => 405 ] ] "es" => array:13 [ "idiomaDefecto" => true "cabecera" => "Original" "titulo" => "Características y evolución de la infección crónica por virus de la hepatitis B antígeno e negativo" "tienePdf" => "es" "tieneTextoCompleto" => "es" "tieneResumen" => array:2 [ 0 => "es" 1 => "en" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "59" "paginaFinal" => "69" ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "Characteristics and course of chronic hepatitis B e antigen-negative infection" ] ] "contieneResumen" => array:2 [ "es" => true "en" => true ] "contieneTextoCompleto" => array:1 [ "es" => true ] "contienePdf" => array:1 [ "es" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figura 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1813 "Ancho" => 2396 "Tamanyo" => 221828 ] ] "descripcion" => array:1 [ "es" => "Motivo del diagnóstico de la infección por el VHB. AP: atención primaria." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Antonio Guardiola Arévalo, Rafael Gómez Rodríguez, Marta Romero Gutiérrez, Ana Zaida Gómez Moreno, Almudena García Vela, Raquel Sánchez Simón, Cesar Gómez Hernando, Eva María Andrés Esteban" "autores" => array:8 [ 0 => array:2 [ "nombre" => "Antonio" "apellidos" => "Guardiola Arévalo" ] 1 => array:2 [ "nombre" => "Rafael" "apellidos" => "Gómez Rodríguez" ] 2 => array:2 [ "nombre" => "Marta" "apellidos" => "Romero Gutiérrez" ] 3 => array:2 [ "nombre" => "Ana Zaida" "apellidos" => "Gómez Moreno" ] 4 => array:2 [ "nombre" => "Almudena" "apellidos" => "García Vela" ] 5 => array:2 [ "nombre" => "Raquel" "apellidos" => "Sánchez Simón" ] 6 => array:2 [ "nombre" => "Cesar" "apellidos" => "Gómez Hernando" ] 7 => array:2 [ "nombre" => "Eva María" "apellidos" => "Andrés Esteban" ] ] ] ] ] "idiomaDefecto" => "es" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S2444382417300275" "doi" => "10.1016/j.gastre.2016.11.009" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2444382417300275?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0210570516301637?idApp=UINPBA00004N" "url" => "/02105705/0000004000000002/v1_201702050027/S0210570516301637/v1_201702050027/es/main.assets" ] ] "itemSiguiente" => array:19 [ "pii" => "S2444382417300251" "issn" => "24443824" "doi" => "10.1016/j.gastre.2016.04.012" "estado" => "S300" "fechaPublicacion" => "2017-02-01" "aid" => "1034" "copyright" => "Elsevier España, S.L.U., AEEH and AEG" "documento" => "article" "crossmark" => 1 "subdocumento" => "fla" "cita" => "Gastroenterol Hepatol. 2017;40:70-9" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 376 "formatos" => array:2 [ "HTML" => 298 "PDF" => 78 ] ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "Original article" "titulo" => "Historical analysis of experience with small bowel capsule endoscopy in a Spanish tertiary hospital" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "70" "paginaFinal" => "79" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Análisis histórico de la experiencia en cápsula endoscópica de intestino delgado en un hospital terciario español" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 991 "Ancho" => 990 "Tamanyo" => 110000 ] ] "descripcion" => array:1 [ "en" => "Inflammatory lesions in patients small bowel Crohn's disease." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Juan Egea Valenzuela, Gabriel Carrilero Zaragoza, Elena Iglesias Jorquera, Paula Tomás Pujante, Fernando Alberca de las Parras, Fernando Carballo Álvarez" "autores" => array:6 [ 0 => array:2 [ "nombre" => "Juan" "apellidos" => "Egea Valenzuela" ] 1 => array:2 [ "nombre" => "Gabriel" "apellidos" => "Carrilero Zaragoza" ] 2 => array:2 [ "nombre" => "Elena" "apellidos" => "Iglesias Jorquera" ] 3 => array:2 [ "nombre" => "Paula" "apellidos" => "Tomás Pujante" ] 4 => array:2 [ "nombre" => "Fernando" "apellidos" => "Alberca de las Parras" ] 5 => array:2 [ "nombre" => "Fernando" "apellidos" => "Carballo Álvarez" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0210570516300449" "doi" => "10.1016/j.gastrohep.2016.04.005" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0210570516300449?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2444382417300251?idApp=UINPBA00004N" "url" => "/24443824/0000004000000002/v1_201703060044/S2444382417300251/v1_201703060044/en/main.assets" ] "en" => array:21 [ "idiomaDefecto" => true "cabecera" => "Original article" "titulo" => "Characteristics and course of chronic hepatitis B e antigen-negative infection" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "59" "paginaFinal" => "69" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Antonio Guardiola Arévalo, Rafael Gómez Rodríguez, Marta Romero Gutiérrez, Ana Zaida Gómez Moreno, Almudena García Vela, Raquel Sánchez Simón, Cesar Gómez Hernando, Eva María Andrés Esteban" "autores" => array:8 [ 0 => array:4 [ "nombre" => "Antonio" "apellidos" => "Guardiola Arévalo" "email" => array:1 [ 0 => "antonio.guardiola@salud.madrid.com" ] "referencia" => array:3 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "Rafael" "apellidos" => "Gómez Rodríguez" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 2 => array:3 [ "nombre" => "Marta" "apellidos" => "Romero Gutiérrez" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 3 => array:3 [ "nombre" => "Ana Zaida" "apellidos" => "Gómez Moreno" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 4 => array:3 [ "nombre" => "Almudena" "apellidos" => "García Vela" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 5 => array:3 [ "nombre" => "Raquel" "apellidos" => "Sánchez Simón" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "c" "identificador" => "aff0015" ] ] ] 6 => array:3 [ "nombre" => "Cesar" "apellidos" => "Gómez Hernando" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "d" "identificador" => "aff0020" ] ] ] 7 => array:3 [ "nombre" => "Eva María" "apellidos" => "Andrés Esteban" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "e" "identificador" => "aff0025" ] ] ] ] "afiliaciones" => array:5 [ 0 => array:3 [ "entidad" => "Servicio de Aparato Digestivo, Hospital Virgen de la Salud, Toledo, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Servicio de Aparato Digestivo, Hospital Universitario de Fuenlabrada, Fuenlabrada, Madrid, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Anatomía Patológica, Hospital Virgen de la Salud, Toledo, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Microbiología, Hospital Virgen de la Salud, Toledo, Spain" "etiqueta" => "d" "identificador" => "aff0020" ] 4 => array:3 [ "entidad" => "Universidad Autónoma de Madrid, Madrid, Spain" "etiqueta" => "e" "identificador" => "aff0025" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Características y evolución de la infección crónica por virus de la hepatitis B antígeno e negativo" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1803 "Ancho" => 2413 "Tamanyo" => 215108 ] ] "descripcion" => array:1 [ "en" => "Reason for HBV infection diagnosis. PC, primary care." ] ] ] "textoCompleto" => "IntroductionChronic hepatitis B virus (HBV) infection is a global public health problem. An estimated 350–400million people worldwide have chronic HBV infection,<a class="elsevierStyleCrossRef" href="#bib0280">1</a> and around 620,000 people die annually from HBV-related causes.<a class="elsevierStyleCrossRef" href="#bib0285">2</a>Chronic HBV infection can present as hepatitis B e antigen (HBeAg) positive (+) or negative (−). HBeAg(−) chronic infection occurs after HBeAg seroconversion. In 75% of cases, the patient seroconverts from an HBeAg(+) chronic hepatitis state to an inactive HBV carrier (IC) state, characterised by persistently normal transaminases and low HBV deoxyribonucleic acid (DNA) (generally <2000IU/mL), with little histological damage. In the remaining 25%, HBeAg seroconversion gives rise to HBeAg(−) chronic hepatitis, either directly, mostly as a result of mutations that occur in the precore and/or core promoter region, or secondary to reactivation from the IC state, in which there are periods of reactivation with a pattern of fluctuating HBV DNA (HBV-DNA) and aminotransferase levels, and active hepatitis.<a class="elsevierStyleCrossRef" href="#bib0290">3</a>The HBeAg(−) chronic infection phase was first described in Mediterranean countries,<a class="elsevierStyleCrossRef" href="#bib0295">4</a> but has now been reported worldwide.<a class="elsevierStyleCrossRef" href="#bib0300">5</a> Studies from Europe, Asia and the United States describe an increase in the prevalence of these types of patients,<a class="elsevierStyleCrossRef" href="#bib0305">6</a> mainly due to ageing of the infected population, and it is the most common form of chronic hepatitis B not only in Europe, but worldwide,<a class="elsevierStyleCrossRef" href="#bib0310">7</a> currently affecting 85–90% of patients. In our published series of patients with chronic HBV infection,<a class="elsevierStyleCrossRef" href="#bib0315">8</a> those with HBeAg(−) chronic infection represented the largest group (87.61%), similar to other studies recently published in Spain,<a class="elsevierStyleCrossRefs" href="#bib0320">9,10</a> other Mediterranean countries,<a class="elsevierStyleCrossRef" href="#bib0330">11</a> and more remote regions, such as Asia<a class="elsevierStyleCrossRef" href="#bib0335">12</a> and South America.<a class="elsevierStyleCrossRef" href="#bib0340">13</a> Since HBeAg(−) patients are the largest HBV infection group, we set out to study the characteristics and clinical course of this patient group in our healthcare area.Materials and methodsObservational, retrospective cohort study of patients diagnosed with HBeAg(−) chronic HBV infection at the time of diagnosis in our healthcare area from June 2005 to July 2011, with follow-up through December 2012.All patients over the age of 13 years, HBsAg(+) for more than 6 months, with HBeAg(−) and Anti-HBeAg(+) were included. Exclusion criteria were: Patients coinfected with human immunodeficiency virus (HIV), hepatitis C virus (HCV) and/or hepatitis D virus (HDV); presence of advanced renal failure (creatinine clearance <30mL/min and/or dialysis) (since they are monitored by the nephrology department), other associated liver diseases (study of thyroid hormones, autoimmunity, iron profile [haemochromatosis gene if transferrin saturation was greater than 45% in 2 tests], urinary porphyrins, alpha-1 antitrypsin, blood copper, urinary copper and ceruloplasmin; also excluded were patients with obesity (body mass index [BMI]≥35kg/m2), steatohepatitis findings on liver biopsy, no definitive diagnosis of cirrhosis-induced chronic HBV infection and alcohol consumption ≥40g/day, as well as patients who had received previous treatment for HBV infection.Sociodemographic characteristics, epidemiological and clinical data at diagnosis and the reason chronic HBV infection was diagnosed were recorded. During the course of the study, analytical and serological variables, HBV-DNA measured by polymerase chain reaction (PCR), as well as hospital admissions and their reasons, were recorded every 6±2 months. Cirrhotic patients had ultrasound follow-up every 6 months and non-cirrhotic patients every 1 or 2 years.A liver fibrosis study was performed by liver biopsy (according to the METAVIR classification<a class="elsevierStyleCrossRef" href="#bib0345">14</a>), as per the indications of the current clinical guidelines. The following categories were established for this study: normal or minimal changes (A0-F0), different grades of fibrosis, and cirrhosis (F4). If there was no liver biopsy, but FibroScan® had been carried out, fibrosis was based the results of the scan, using the system presented by Viganò et al.<a class="elsevierStyleCrossRef" href="#bib0350">15</a> as a reference, where: F0-1 (from 2.5 to 6.2kPa), normal; F2-3 (from 6.2 to 13.1kPa), different grades of inflammation-fibrosis; and F4 (>13.1kPa), cirrhosis; which correspond to the fibrosis values in the METAVIR system used for the liver biopsies. Patients diagnosed with liver cirrhosis using clinical-analytical data or imaging tests, in whom liver biopsy or FibroScan® were not required to reach the diagnosis, were also categorised as F4 for the purposes of the study.Clinical follow-up of patients continued until the last check-up at the hepatology clinic. The analytical study included all tests up to the last follow-up laboratory test with HBV serology ordered by the hepatology unit. Only patients with 3 or more tests during follow-up were included in the analysis. In patients who required medical treatment for chronic HBV infection, the clinical follow-up was evaluated until the date of the visit at which treatment was started, and the analytical follow-up until the last test prior to this.ICs were defined as all patients with persistently normal alanine transaminase (ALT) (<40mU/mL, and low HBV-DNA, discriminating among those with persistent HBV-DNA <2000IU/mL (pure ICs), and those with occasional HBV-DNA between 2000 and 20,000IU/mL. Indeterminate state was defined as a patient presenting persistently normal or fluctuating ALT with slight elevations (generally <2 upper limit of normal [ULN]) and occasionally peak HBV-DNA >20,000IU/mL. Reactivation of an IC to HBeAg(−) chronic hepatitis B (CHB) was defined as any patient in whom the first 3 ALT results were normal (<40mU/mL) and HBV-DNA was low (<20,000IU/mL) but subsequently presented elevated ALT values above 40mU/mL together with HBV-DNA >20,000IU/mL. HBeAg(−) CHB phase at diagnosis was defined as any patient who, from the first laboratory tests, persistently presented ALT >40mU/mL and HBV-DNA >20,000IU/mL.Data from patients who presented cirrhosis during the clinical course, together with associated complications (hepatic encephalopathy [HE]), variceal gastrointestinal bleeding (VGIB), oedematous ascitic decompensation (OAD) or hepatocellular carcinoma (HCC) were recorded. HCC was diagnosed as space-occupying lesions >1cm in patients with liver cirrhosis, where at least one imaging test (tomography and/or contrast magnetic resonance imaging) showed a typical HCC pattern (enhancement in the arterial phase and washout in the portal or late phase). A histological study was performed in patients with atypical or suspicious radiological patterns, and in those with no liver cirrhosis. Adverse events during the study were defined as: presentation of cirrhosis, any of its complications, HCC in a non-cirrhotic liver, and/or need for treatment during the clinical course.The study was approved by the hospital ethics committee.Statistical analysisStatistical analysis was performed using SPSS software, v. 20.0 (IBM Corporation, 2011). Categorical variables are described as using the count (percentage). Quantitative variables are described using the mean±standard deviation if distribution is normal, and using the median (interquartile range [IQR]) if this hypothesis is not met.The distribution between dichotomous and categorical variables was compared using contingency tables with the Chi-square or Fisher's test, as applicable. Comparison of means between qualitative variables was performed using Student's t-test when 2 means were compared, or one-factor analysis of variance (ANOVA) when more than 2 means were compared, if normality criteria were met. If the variable of interest did not meet the assumption of normality, we used the non-parametric Mann–Whitney U test or the Kruskal–Wallis H test to compare the equality of the distribution of the quantitative variable in 2 groups, or in more than 2 groups, respectively.Patient evolution was studied using tests for dependent samples, such as the Student's t-test for related variables or ANOVA for repeated measures, if the variable had a normal distribution, or the Wilcoxon or Friedman test if not. A p value<0.05 was considered significant.Results<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a> shows the selection flow chart for HBsAg(+) patients during the study period who met all the inclusion and none of the exclusion criteria; 138 patients were included, 126 of whom had analytical follow-up.<elsevierMultimedia ident="fig0005"></elsevierMultimedia>The mean age at diagnosis was 40.5±12.2 years (56.5% of patients diagnosed before age 40). Fifty-four percent were women and 38% were of foreign origin. Diagnosis in Spanish natives and immigrants varied over time, with immigrant patients having increased significantly in recent years (p<0.001). Immigrants were predominantly from Eastern Europe (46%), mainly Romania (87.5% of those from this area), followed by Africa (31%), mainly Morocco (43% of Africans), Asia (10%), Central America (9%) and the Middle East (4%).In terms of epidemiology, 34 patients had a family history of HBV infection (24.6%), none were intravenous drug users or former users, 5.8% had previous transfusions, 5.1% had tattoos, and 1.45% had piercings.Chronic HBV infection had been diagnosed for various reasons (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>). The most common was hypertransaminasaemia (20.29%); however, grouping all the reasons for HBV screening together (pregnancy, fertility, family history, blood donors, or at the various clinics prior to immunosuppressant treatments) showed that hypertransaminasaemia was the reason for diagnosis in 55.07% of patients.<elsevierMultimedia ident="fig0010"></elsevierMultimedia>Twelve of the 138 patients (8.69%) presented signs or symptoms at diagnosis. These were clearly related with chronic HBV infection in only 1 patient (0.72%), as he presented OAD at diagnosis. Some patients presented symptoms that could be disease-related (3 patients with asthenia, 2 with arthralgia-arthritis and 1 with haematuria), while others presented more non-specific or unrelated symptoms (2 with dyspepsia, 1 with erythema nodosum, 1 with uveitis, and another with non-specific abdominal pain). On examination, only 1 patient presented stigmata of chronic liver disease at diagnosis (the same patient who had been diagnosed with OAD).<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> shows the biochemistry results at the time of diagnosis. ALT at diagnosis was normal in 103 patients (74.6%). Of these, 95 (91.26%) presented HBV-DNA <20,000IU/mL and 67 (64.08%) <2000IU/mL at diagnosis. Patients with normal ALT at diagnosis vs abnormal ALT values had a statistically significant lower viral load (916 [IQR: 110–3830]IU/mL vs 6840 [IQR: 479–38,000]IU/mL; p=0.003). The mean quantitative viral load at diagnosis was 43,726±238,701IU/mL, with a median of 6230IU/mL. We defined 4 groups based on HBV-DNA at diagnosis: undetectable (14%); 0–2000IU/mL (42%); 2000–20,000IU/mL (27%), and >20,000IU/mL (17%); with patients with HBV-DNA <2000IU/mL accounting for 56%.<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>Information on hepatic fibrosis was obtained during follow-up by histology in 36 cases and by FibroScan® in 28. No fibrosis was detected in 36 patients (55.4%), 25 presented different grades of inflammation-fibrosis (38.5%), and 4 presented cirrhosis (6.1%), one of whom was diagnosed by clinical-analytical and ultrasound findings at diagnosis, having commenced the study with OAD. The 4 patients with cirrhosis (3.1%) were men (p=0.024), with mean age greater than that of patients without cirrhosis (61.7±8.6 years vs 39.8±11.7 years; p=0.003), and classified as Child–Turcotte–Pugh stage A at diagnosis.Analytical follow-up was performed in 126 patients, with a mean follow-up time of 33.6±22.1 months, and an average of 6.5 laboratory tests per patient. Mean clinical follow-up time was 42.14±21.50 months. Median peak ALT was 32 (IQR: 23.5–65)mU/mL, and the median time to reach this peak was 10.4 (IQR: 4.4–25) months. The maximum median viral load value was 3620 (IQR: 531–13,900)IU/mL, and the minimum 216 (IQR: 30–1095)IU/mL Time to reach the HBV-DNA peak was a median of 11.2 (IQR: 3.5–23.6) months. Of the 108 patients who presented a detectable viral load at diagnosis, this remained detectable in 81 (75%), became undetectable in 18 (16.67%) and fluctuated between detectable and undetectable in 9 (8.33%). Of the 18 patients with an undetectable viral load, the viral load remained undetectable in 11 (61.11%%), became detectable in 6 (33.33%) and fluctuated in 1 (5.56%).If we analyse the trend in the percentage of patients with HBV-DNA <2000IU/mL and <20,000IU/mL at each point in the study, we can see in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>A how the percentage of patients with lower HBV-DNA tends to increase over the study follow-up, although significant differences were only observed in 2 of the study periods. Excluding patients who started treatment from the study may cause bias, as these generally had a higher viral load, although as can be observed in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>B, this trend continues, but with no significant differences in any period.<elsevierMultimedia ident="tbl0010"></elsevierMultimedia>Just over three quarters of patients (77.77%) were in an IC state (56.1% with persistent HBV-DNA <2000IU/mL and 44.9% with occasional HBV-DNA between 2000 and 20,000IU/mL). Of the patients in this group, 27.5% presented elevated ALT <2ULN at diagnosis or occasionally during follow-up, associated with steatohepatitis and/or sporadic alcohol consumption, not related to the disease activity.There were 8 patients (6.34%) in an indeterminate state (ALT normal or slightly fluctuating, with occasional HBV-DNA peak >20,000IU/mL). Of these, 5 presented persistently normal ALT, and 3 presented slight fluctuations in ALT, with peak ALT during the clinical course no higher than 97mU/mL (mean ALT of 64.25mU/mL), with no findings of liver disease in the ultrasound imaging; the highest ALT peak (97mU/mL) was observed in a patient with steatosis on the ultrasound and dyslipidaemia. These 8 patients underwent a liver fibrosis study, by FibroScan® and/or liver biopsy, all with normal results.A total of 15.87% of patients were in an HBeAg(−) CHB state since diagnosis. No reactivations from IC to HBeAg(−) CHB were observed, although we received 1 patient who had been referred for treatment due to reactivation secondary to lymphoma treatment. <a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a> shows the evolution of the patients, as well as complications; <a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a> presents the characteristics of patients in an indeterminate state, and <a class="elsevierStyleCrossRef" href="#tbl0025">Table 5</a> compares ICs and patients in an indeterminate state.<elsevierMultimedia ident="tbl0015"></elsevierMultimedia><elsevierMultimedia ident="tbl0020"></elsevierMultimedia><elsevierMultimedia ident="tbl0025"></elsevierMultimedia>Twenty patients received pharmacological treatment, according to the indications of the current clinical guidelines,<a class="elsevierStyleCrossRefs" href="#bib0355">16,17</a> accounting for 15.5% of the series. Treatment indications were: 4 for liver cirrhosis (20% of those treated) – 3 on detection of viral load and 1 who started the study with OAD –; 1 on presentation of an HBV-DNA peak >2000IU/mL and F2 on liver biopsy; and 16 patients for presenting an HBeAg(−) CHB phase (80% of those treated), one of whom did not start treatment as he abandoned follow-up. Of the 16 patients in an HBeAg(−) CHB state, 13 had presented abnormal ALT levels since diagnosis, and 3 during the course of the study.Five patients lost HBsAg (4%). Median time to HBsAg clearance was 26.47 (IQR: 8.64–43.94) months. Mean annual rate of HBsAg loss was 0.94%, and the cumulative rate at 3 years was 2.83%. Mean age of patients with HBsAg loss was 54.7±7.1years, while the mean age of those with no HBsAg loss was 38.7±10.9years (p=0.004). None of the patients with HBsAg loss presented complications over their clinical course; 3 of the 5 patients with HBsAg loss presented seroconversion to Anti-HBs (60% of those who cleared HBsAg). Median time from HBsAg loss to seroconversion was 10.5 (IQR: 0–22.7) months. Eighty percent of patients who cleared HBsAg presented ALT levels <40mU/mL and HBV-DNA <2000IU/mL (80% HBV-DNA undetectable) at diagnosis. <a class="elsevierStyleCrossRef" href="#tbl0030">Table 6</a> shows the comparative study of the ALT and HBV-DNA (baseline and peak) between patients with and without HBsAg loss.<elsevierMultimedia ident="tbl0030"></elsevierMultimedia>Five patients developed complications (3.6%). One had OAD and 4 HCC. Mean time to the complication was 3.5 years; 4 patients developed HCC (2.9%), 2 of whom presented cirrhosis and 2 did not (50% of those who developed HCC). All were Spanish and over 40 years of age (mean age 61.75±11.9), and 3 of the 4 were men. In two of these patients, cirrhosis was not identified by symptoms, laboratory tests, ultrasound or liver biopsy (both A1F0). The annual rate of development of HCC in patients with cirrhosis was 17.85%. Patients with complications were significantly older than those with no complications: 62.5±10.3 years vs 39.63±11.5 years (p=0.001).During follow-up, 5 patients were admitted for causes related to the HBV infection (3.87%), 80% in relation to the HCC diagnosis, treatment or surgery, and 20% for OAD.Two patients died (1.4%), one due to pulmonary squamous cell carcinoma and another to cholangiocarcinoma; the latter is the only death that might be related to the HBV infection (0.72%). The patient was a Romanian man who had been diagnosed at age 42 as a result of a study for dissociated cholestasis. At diagnosis he had ALT <40mU/mL and undetectable HBV-DNA; the HBV-DNA remained undetectable during follow-up, with no HBsAg loss. Gastroscopy did not show portal hypertension, abdominal ultrasound found no signs of chronic liver disease, and the patient presented no clinical, analytical or supplementary tests suggestive of cirrhosis.DiscussionFew recent studies have focussed on chronic HBV infection in Spain, and even fewer focused only on HBeAg(−) patients, although these make up the largest group in our clinics. Patients with HBeAg(−) CHB in older studies were between 40 and 55 years of age,<a class="elsevierStyleCrossRefs" href="#bib0365">18,19</a> older than patients with HBeAg(+) CHB.<a class="elsevierStyleCrossRef" href="#bib0375">20</a> In a more recent French series, the mean age of HBeAg(−) patients was 46.4±14.4 years, although a sub-analysis of naive patients in the same study found that the mean age was 40.9±14.8 years,<a class="elsevierStyleCrossRef" href="#bib0310">7</a> which is consistent with our findings, and with other studies similar to ours.<a class="elsevierStyleCrossRef" href="#bib0320">9</a>Older series noted a predominance of men (male/female ratio of 4.6/1.7),<a class="elsevierStyleCrossRef" href="#bib0375">20</a> and this continues to be the case in recent series (75–88%).<a class="elsevierStyleCrossRefs" href="#bib0380">21,22</a> Although in recent studies with well-selected, treatment-naive patients the male/female ratio remains predominantly male (2.3/1.5),<a class="elsevierStyleCrossRefs" href="#bib0310">7,13,23</a> the difference is smaller, and some even show a slight predominance of women.<a class="elsevierStyleCrossRef" href="#bib0395">24</a> Our findings show a predominance of women (54%). This could be due to the strict selection criteria used to avoid bias in the natural course of the disease, such as excluding patients with alcohol consumption—which is usually more common in men—or to the high percentage of patients diagnosed during antenatal screening (16.6%).Immigration has significantly affected the epidemiology of this infection. The last 2–3 decades have seen an increase in immigration from regions with high or intermediate prevalence of chronic HBV infection to industrialised countries,<a class="elsevierStyleCrossRefs" href="#bib0310">7,25</a> including Spain.<a class="elsevierStyleCrossRefs" href="#bib0315">8,9</a> In our series, the immigrant population accounts for 38% on average, with the ratio of immigrants to Spanish nationals increasing in the last few years of the study, a finding comparable to that described in a recent study conducted in Greece over a similar period.<a class="elsevierStyleCrossRef" href="#bib0405">26</a> Hence, screening is important in this population group, especially in pregnant women. Thus, in our study, 16% of patients were diagnosed during pregnancy, but there was a significant difference between Spanish and immigrant women (22.2% vs 44.8%; p=0.04).Twenty-four percent of patients in our series had a family history of HBV infection; other studies have reported percentages ranging from 13 to 63%.<a class="elsevierStyleCrossRefs" href="#bib0390">23,27</a> A recent Brazilian study<a class="elsevierStyleCrossRef" href="#bib0340">13</a> described possible vertical or intrafamilial transmission in 43% of patients. None of our patients had been infected by vertical transmission, no doubt because this is rarely seen in countries with developed healthcare systems, where antenatal screening programmes (16% of patients in our series were identified for this reason, accounting for 38% of women), vaccination, and primary prophylaxis in childbirth and the post-partum period are well-established. Vertical transmission is highly unlikely in this setting. Ten percent of patients in our series were diagnosed by screening prompted by family history, possibly because this testing is not done in the large foreign population. Saliva has been suggested as a possible mechanism of HBV transmission,<a class="elsevierStyleCrossRef" href="#bib0415">28</a> and could explain the percentage of patients with no obvious risk factors for acquiring the infection.At present, based on the accumulated evidence,<a class="elsevierStyleCrossRef" href="#bib0420">29</a> serological screening for hepatitis B has been established in patients scheduled for immunosuppressant treatments or chemotherapy. Thus, up to 8% of patients in our series (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>) were diagnosed with chronic HBV infection as a result of screening performed in rheumatology, haematology and dermatology clinics. Nevertheless, we must continue to raise awareness of the need for screening, since reactivations continue to occur in this patient group. An example of this is the reactivation to HBeAg(−) CHB presented by 1 patient treated for lymphoma in our series.Most patients with HBeAg(−) chronic HBV infection in our series were asymptomatic when they came to the clinic, and of the patients with symptoms (fewer than 9%), these were clearly related to the underlying liver disease in only one patient, who already had OAD. The other symptoms were non-specific. During follow-up, only one patient death was HBV-related, and 5 patients required admission for infection-related causes (3.87%); 80% were admitted in relation to HCC diagnosis, treatment and surgery. Thus, the quality of life of patients with HBeAg(−) chronic HBV infection can be considered to be good or acceptable in most cases.Since chronic HBV infection is usually a silent disease, the absence of symptoms is not sufficient to distinguish patients with significant progressive liver disease from ICs.<a class="elsevierStyleCrossRef" href="#bib0425">30</a> Therefore, a patient with HBsAg(+), HBeAg(−), Anti-HBe(+), normal ALT and undetectable HBV-DNA in a single test should not be classified as an IC without appropriate follow-up. In our study, we observed how the median peak ALT value was not obtained until 10.4 months, and the peak HBV-DNA until 11.2 months. Studies have reported that the risk of normal ALT at diagnosis changing during follow-up is greater during the first year (15–20%),<a class="elsevierStyleCrossRefs" href="#bib0430">31,32</a> and decreases after 3 years of follow-up,<a class="elsevierStyleCrossRefs" href="#bib0435">32–34</a> which is consistent with our findings. In the early years of follow-up, therefore, ALT monitoring is indicated in order to establish the disease state in these patients.<a class="elsevierStyleCrossRef" href="#bib0425">30</a>In line with other studies,<a class="elsevierStyleCrossRefs" href="#bib0450">35,36</a> HBV-DNA levels in HBeAg(−) patients decreased in the first year of follow-up due to the transformation of most of these types of patients to ICs, where the viral load becomes low or undetectable. Thus, in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>, we can see how the percentage of patients with low viral load gradually increases over time, suggesting a decrease in the viral load in ICs.HBsAg clearance is a rare event in the clinical course of patients with chronic HBV infection; thus, it has an estimated incidence of approximately 0.1–0.8% in patients who acquire the infection in childhood, and 0.4–2% in those who acquire it in adolescence or adulthood,<a class="elsevierStyleCrossRefs" href="#bib0460">37–40</a> as could be the case in our population. More recent studies with 25–30-year follow-up estimate an annual HBsAg clearance rate of between 1%<a class="elsevierStyleCrossRef" href="#bib0480">41</a> and 1.8%,<a class="elsevierStyleCrossRef" href="#bib0485">42</a> similar to our findings (0.94%). Of these patients, approximately half develop Anti-HBs, sometimes several months later.<a class="elsevierStyleCrossRef" href="#bib0490">43</a> Eighty percent of patients who cleared HBsAg presented ALT <40mU/mL and viral load <2000IU/mL at diagnosis in all cases, being undetectable in 80% of them. This is consistent with the literature,<a class="elsevierStyleCrossRef" href="#bib0495">44</a> which suggests that patients who clear HBsAg present low or persistently undetectable HBV-DNA years before seroconversion. Although these patients did not present complications over the course of this study, it should be taken into account that patients aged over 50 who clear HBsAg, as in our case, have an increased risk of developing HCC.<a class="elsevierStyleCrossRef" href="#bib0490">43</a> Therefore, even though at present the accumulated evidence is insufficient to recommend including them in an HCC screening programme, it would be prudent to schedule them for annual or bi-annual follow-up. In fact, some studies suggest that the risk of HCC is not reduced in patients who clear HBsAg compared to those who do not,<a class="elsevierStyleCrossRefs" href="#bib0500">45,46</a> and that clearing HBsAg does not necessarily imply good prognosis.The annual rate of progression to cirrhosis in patients with chronic HBV infection is between 1% and 7%,<a class="elsevierStyleCrossRefs" href="#bib0480">41,47</a> and higher (closer to 7%) in HBeAg(−) patients. The percentage of cirrhotic patients in our series was 6%, with an annual rate of 1.03% (data not shown, as the study was not conducted specifically with this aim); these low rates have been reported in other studies.<a class="elsevierStyleCrossRef" href="#bib0510">47</a> This low percentage could be explained by the large number of patients in the IC state. Age is a factor that is clearly related to the development of cirrhosis<a class="elsevierStyleCrossRefs" href="#bib0515">48,49</a>; thus, in our study, the mean age of patients with cirrhosis was clearly greater than those without. Most studies indicate that the possibility of significant histological damage should be considered in patients over the age of 40.<a class="elsevierStyleCrossRef" href="#bib0525">50</a> Some studies in developing countries suggest younger ages (around 30 years old<a class="elsevierStyleCrossRef" href="#bib0530">51</a>), taking into account that these are countries where the infection is mainly transmitted in pregnancy, childbirth and infancy. Thus, the disease has a longer course, which could explain the greater histological damage at an early stage. Another factor clearly related with the development of cirrhosis is being male.<a class="elsevierStyleCrossRef" href="#bib0520">49</a> This was corroborated in our study, where all patients with cirrhosis were men.There is a clear association between HCC and liver disease due to HBV,<a class="elsevierStyleCrossRef" href="#bib0535">52</a> but up to 30–50% of HBV-associated HCC cases occur in the absence of cirrhosis; in fact, only 50% of our patients who developed HCC presented cirrhosis. In our study, 75% of patients who presented HCC were men, which is consistent with other studies.<a class="elsevierStyleCrossRef" href="#bib0540">53</a>The mortality described in these types of patients varies from a low rate (1%),<a class="elsevierStyleCrossRef" href="#bib0480">41</a> to other studies where higher mortality rates are found (15%).<a class="elsevierStyleCrossRef" href="#bib0545">54</a> We only had 2 deaths; both patients were men over 40 years old at diagnosis. One of the 2 deaths was probably related to HBV infection (0.72% of the series), as the patient developed cholangiocarcinoma.<a class="elsevierStyleCrossRef" href="#bib0550">55</a>In our study, as in others in the literature, the largest patient group with HBeAg(−) CHB were the ICs. The latest European guidelines refer to IC in patients with persistently normal ALT and HBV-DNA <2000IU/mL (pure ICs).<a class="elsevierStyleCrossRef" href="#bib0360">17</a> However, as explained, this infection is dynamic, and some patients with normal ALT present HBV-DNA peaks between 2000 and 20,000IU/mL over the course of the disease (almost 45% of the ICs in our series). This patient group did not present greater histological damage or more complications during the study follow-up than the pure ICs (<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>). Furthermore, 6% of patients presented an indeterminate state, with HBV-DNA peaks sometimes higher than 20,000IU/mL, but with no significant histological damage or greater incidence of complications compared to ICs (<a class="elsevierStyleCrossRefs" href="#tbl0015">Tables 3–5</a>). Thus, we propose the term semi-inactive carrier for this group of indeterminate state patients. This group requires closer follow-up until their prognosis can be determined, but it is unclear whether their clinical course is poorer than that of ICs.Twenty patients (15.5%) were treated during follow-up, 80% in the HBeAg(−) CHB state. Of these, 81.25% had abnormal ALT at diagnosis, so in the vast majority of cases, patients who required treatment had abnormal ALT levels since the start of follow-up. A recent Spanish study obtained very similar findings to ours in this respect.<a class="elsevierStyleCrossRef" href="#bib0320">9</a>In summary, patients with HBeAg(−) chronic HBV infection are generally asymptomatic at diagnosis and during the course of the disease. The occurrence of cirrhosis is rare. It must be remembered that up to half of cases of HCC, which is the main complication, develop in patients without cirrhosis. The percentage of patients who require treatment must also be taken into account.Conflicts of interestThe authors declare that they have no conflicts of interests." "textoCompletoSecciones" => array:1 [ "secciones" => array:11 [ 0 => array:3 [ "identificador" => "xres810089" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Objective" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Materials and methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusion" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec807521" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres810090" "titulo" => "Resumen" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Objetivo" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Material y métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusión" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec807522" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Materials and methods" "secciones" => array:1 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Statistical analysis" ] ] ] 6 => array:2 [ "identificador" => "sec0020" "titulo" => "Results" ] 7 => array:2 [ "identificador" => "sec0025" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0030" "titulo" => "Conflicts of interest" ] 9 => array:2 [ "identificador" => "xack271487" "titulo" => "Acknowledgements" ] 10 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2016-02-06" "fechaAceptado" => "2016-11-04" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec807521" "palabras" => array:5 [ 0 => "Hepatitis B virus" 1 => "Negative HBe antigen" 2 => "HBe antigen-negative chronic hepatitis" 3 => "Glutamic pyruvic transaminase" 4 => "DNA" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec807522" "palabras" => array:5 [ 0 => "Virus de la hepatitis B" 1 => "Antígeno HBe(−)" 2 => "Hepatitis crónica antígeno HBe(−)" 3 => "Glutámico pirúvico transaminasa" 4 => "ADN" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "ObjectiveTo describe the epidemiological, analytical and histological characteristics and clinical course of hepatitis B virus (HBV) carriers with negative HBe antigen. Materials and methodsObservational, retrospective cohort study of HBV carriers with negative HBe antigen (2005–2012), with no other causes of liver disease. ResultsOne hundred and thirty-eight patients were included, with mean age 40.5±12.2 years; 54% were women, and 38% were of foreign origin; the number of foreign patients significantly increased (p<.001) over the years. Transaminases were normal in nearly 75% and HBV-DNA was <2000IU/mL in 56% of patients at diagnosis. There was a gradual decrease in HBV-DNA levels in inactive carriers over the study period. Fibrosis study was performed in 47% of patients by Fibroscan® or liver biopsy: 55.4% normal histology and 6.1% cirrhosis. Just over three quarters of patients (77.77%) were inactive carriers. Treatment was required in 15.5% of patients (20% because of cirrhosis and 80% HBeAg-negative chronic hepatitis B). Five patients cleared HBsAg (annual rate .94%), all of whom presented HBV-DNA <2000IU/mL at diagnosis. Five patients developed complications (3.6%), 4 of them hepatocellular carcinoma (HCC), of which only 2 had cirrhosis. There was 1 HBV-related death (.72%). ConclusionAmong HBV carriers with negative HBe antigen, inactive HBs-Ag carriers are predominant. HBV-DNA gradually decreases in the first few years after diagnosis. Morbidity and mortality are low, especially if glutamic pyruvic transaminase (GPT) is normal and HBV-DNA levels are low at diagnosis. Treatment is needed in a considerable number of patients. HCC is the most frequent complication, even in the absence of cirrhosis." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Objective" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Materials and methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusion" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "ObjetivoDescribir las características epidemiológicas, analíticas, histológicas y evolutivas de pacientes con infección crónica por VHB AgHBe-negativo. Material y métodosEstudio observacional de cohorte retrospectivo de pacientes diagnosticados de infección crónica VHB AgHBe-negativo (2005-2012) sin otras hepatopatías. ResultadosSe incluyeron 138 pacientes con edad media de 40,5±12,2 años, de los cuales el 54% eran mujeres. El 38% eran extranjeros, con incremento de estos en los últimos años (p<0,001). Las transaminasas en el momento del diagnóstico eran normales en casi el 75% y el ADN-VHB <2.000UI/ml en el 56%. En los portadores inactivos existe una disminución progresiva de los niveles de ADN-VHB en el periodo de estudio. En el 47% se evaluó la fibrosis hepática por Fibroscan® o biopsia hepática: el 55,4% resultó normal y el 6,1% reportó cirrosis. El 77,77% eran portadores inactivos. Precisaron tratamiento el 15,5% (20% por cirrosis y 80% por HBC AgHBe-negativo). Aclararon el AgHBs 5 pacientes (tasa anual 0,94%), presentando todos al diagnóstico ADN-VHB <2.000UI/ml. Cinco pacientes desarrollaron alguna complicación (3,6%), 4 de ellos carcinoma hepatocelular (CHC) (solo 2 presentaban cirrosis). Hubo un fallecimiento relacionado con el VHB (0,72%). ConclusiónEntre los enfermos con infección crónica por VHB AgHBe-negativo predominan los portadores inactivos. Se produce un progresivo descenso de ADN-VHB en los primeros años tras el diagnóstico. Desarrollan poca morbimortalidad, especialmente si existe GPT normal y ADN-VHB bajo al diagnóstico. Un número no despreciable de pacientes precisa tratamiento. El CHC es la complicación más frecuente, incluso en pacientes sin cirrosis." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Objetivo" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Material y métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusión" ] ] ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: Guardiola Arévalo A, Gómez Rodríguez R, Romero Gutiérrez M, Gómez Moreno AZ, García Vela A, Sánchez Simón R, et al. Características y evolución de la infección crónica por virus de la hepatitis B antígeno e negativo. Gastroenterol Hepatol. 2017;40:59–69." ] ] "multimedia" => array:8 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2790 "Ancho" => 1589 "Tamanyo" => 174829 ] ] "descripcion" => array:1 [ "en" => "Patient exclusion flow chart." ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1803 "Ancho" => 2413 "Tamanyo" => 215108 ] ] "descripcion" => array:1 [ "en" => "Reason for HBV infection diagnosis. PC, primary care." ] ] 2 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Analyte \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">n \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Median (IQR)<a class="elsevierStyleCrossRef" href="#tblfn0005">a</a> \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Haemoglobin (g/dL) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">137 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">14.7 (13.4–15.5) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">White blood cells (×109/L) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">137 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">6.3 (5300–7800) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Platelets (×109/L) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">137 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">211 (177,500–247,500) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">INR \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">121 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.97 (0.97–1.0) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Fibrinogen (mg/dL) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">121 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">320 (276–381) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Albumin (g/dL) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">128 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">4.7 (4.4–4.9) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Total bilirubin (mg/dL) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">137 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.57 (0.43–0.82) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">AST (mU/mL) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">136 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">23 (19–30.7) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">ALT (mU/mL) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">138 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">26 (19–40.2) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">GGT (mU/mL) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">137 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">16 (11.5–27) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">ALP (mU/mL) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">137 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">67 (55–80) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Blood glucose (mg/dL) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">138 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">92.5 (86.7–99.0) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Total cholesterol (mg/dL) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">138 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">190.5 (168.0–221.2) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Triglycerides (mg/dL) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">138 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">76.5 (53.7–109.2) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Alpha-fetoprotein (ng/mL) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">113 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2.5 (1.65–4.2) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1359757.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "a" "nota" => "Data are expressed as median (interquartile range [IQR]: p25–p75)." ] ] ] "descripcion" => array:1 [ "en" => "General laboratory results at diagnosis." ] ] 3 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at2" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">HBV-DNA \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Baseline \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">6 months \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">12 months \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">18 months \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">24 months \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">30 months \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">36 months \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">(A) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">n=126 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">n=126 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">n=126 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">n=99 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">n=90 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">n=84 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">n=72 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><2000IU/mL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">56.52% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">58.16% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">66.67% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">67.01% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">71.59% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">72.84% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">83.82% \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">p-value<a class="elsevierStyleCrossRef" href="#tblfn0010">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.398 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.094 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.479 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.247 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.427 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.045 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="8" align="left" valign="top"></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><20,000IU/mL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">83.33% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">81.63% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">91.89% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">93.81% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">92.05% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">95.06% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">97.06% \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">p-value<a class="elsevierStyleCrossRef" href="#tblfn0010">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.363 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.011 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.293 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.319 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.208 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.257 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="8" align="left" valign="top"></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">(B) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">n=106 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">n=106 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">n=106 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">n=77 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">n=70 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">n=64 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">n=52 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><2000IU/mL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">62.71% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">70% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">68.48% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">66.67% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">71.01% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">68.75% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">81.13% \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">p-value<a class="elsevierStyleCrossRef" href="#tblfn0010">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.141 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.415 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.401 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.285 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.388 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.059 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="8" align="left" valign="top"></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><20,000IU/mL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">92.37% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">95% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">94.57% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">94.87% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">95.65% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">95.31% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">98.11% \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">p-value<a class="elsevierStyleCrossRef" href="#tblfn0010">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.223 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.45 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.966 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.412 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.962 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.194 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1359759.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0010" "etiqueta" => "a" "nota" => "Statistical significance with respect to the preceding period." ] ] ] "descripcion" => array:1 [ "en" => "Percentage of patients with HBV-DNA <2000IU/mL and <20,000IU/mL at each point in the study. (A) In the general series, and (B) excluding patients who were treated." ] ] 4 => array:8 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at3" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "HCC, hepatocellular carcinoma; OAD, oedematous ascitic decompensation; IC, inactive carrier." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">n=126 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " colspan="2" align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Inactive carriers n=98 (77.77%)</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Indeterminate state n=8 (6.34%) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">HBeAg(−) CHB n=20 (15.87%) \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Follow-up time \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " colspan="2" align="left" valign="top">39.82±19.91 months</td><td class="td" title="table-entry " align="left" valign="top">45.25±16 months \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">14.18±11.15 months \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Peak HBV-DNA (IU/mL), n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Pure ICs <2000 54 (56.1%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2000–20,000 44 (44.9%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">>20,000 occasionally \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">>20,000 persistently (except 1 patient with cirrhosis with HBV-DNA between 2000 and 20,000) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Mean peak ALT±SD (mIU/mL) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">44.44±49.56 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">38.30±34.20 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">44.63±23.42 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">123.7±61.56 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Reactivation, n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1 (0.79%) (after lymphoma treatment) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Need for treatment, n (%) and reason \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1 (0.79%) Cirrhosis with OAD; HBV-DNA− \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1 (0.79%) F2 on biopsy \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0 (0%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">20 (100%) • 3 Cirrhosis with HBV-DNA+ • 16 HBeAg(−) (1 did not come to receive treatment) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Complication, n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2 (1.58%) • 1 OAD • 1 HCC (44 years) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0 (0%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0 (0%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3 HCC (15.78%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Adverse events, n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2 (1.58%) • 1 Cirrhosis+OAD+treatment • 1 HCC \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0 (0%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0 (0%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">4 (21.05%) • 2 HCC+cirrhosis • 1 Cirrhosis • 1 HCC \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1359755.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Evolution of patients with 3 or more ALT tests in follow-up." ] ] 5 => array:8 [ "identificador" => "tbl0020" "etiqueta" => "Table 4" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at4" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:3 [ "leyenda" => "ALT, alanine transaminase; BMI, body mass index." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Age (years) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Gender \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Peak ALT<a class="elsevierStyleCrossRef" href="#tblfn0015">a</a> (mU/mL) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Peak HBV-DNA<a class="elsevierStyleCrossRef" href="#tblfn0015">a</a> (IU/mL) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Dyslipidaemia \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">BMI 25–30kg/m2 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Abdominal ultrasound \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">FibroScan® \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Liver biopsy \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">53 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Male \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">97 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">24,200 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Steatosis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">F1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">22 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Female \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">45 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">31,000 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Steatosis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">A0F0 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">38 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Male \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">36 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">38,700 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Normal \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">A0F0 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">48 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Female \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">31 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">41,700 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Normal \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">F0-1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">18 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Female \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">32 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">48,200 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Normal \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">A0F0 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">37 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Female \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">31 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">468,000 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Normal \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">A0F0 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">33 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Male \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">58 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">999,000 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Normal \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">A0F0 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">40 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Female \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">27 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1,120,000 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Normal \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">F0-1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">A0F0 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1359758.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0015" "etiqueta" => "a" "nota" => "Peak values, but which did not meet criteria for chronic hepatitis in follow-up (ALT and HBV-DNA generally low and/or below the upper limit of normal)." ] ] ] "descripcion" => array:1 [ "en" => "Patients in indeterminate state in follow-up." ] ] 6 => array:8 [ "identificador" => "tbl0025" "etiqueta" => "Table 5" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at5" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "ALT, alanine transaminase; HBsAg, hepatitis B surface antigen; HCC, hepatocellular carcinoma; HE, hepatic encephalopathy; NA, not analysable; OAD, oedematous ascitic decompensation; VGIB, variceal gastrointestinal bleeding." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Inactive carriers (n=98) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Indeterminate (n=8) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">p \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Age (years) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">39.80±11.37 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">36.09±11.90 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.378 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Sex (men) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">42.27% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">37.50% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.395 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Foreign patients \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">38.78% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">25% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.196 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Follow-up time (months) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">39.82±19.91 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">45.25±16 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.454 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Mean peak ALT (mIU/mL) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">41.68±43.24 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">44.63±23.42 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.851 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Mean peak HBV-DNA (IU/mL) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3482.16±4255.23 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">346,350.00±465,811.87 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">HBsAg clearance \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5 (5.10%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.011 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Cirrhosis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.157 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Disease-related complications (OAD, HCC, VGIB, HE) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2 (both HCC) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.077 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Reactivations \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">N/A \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Need for treatment \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.039 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">HBV-related death \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.157 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1359760.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Comparison of inactive carriers vs patients in indeterminate state." ] ] 7 => array:8 [ "identificador" => "tbl0030" "etiqueta" => "Table 6" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at6" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "ALT, alanine transaminase; HBsAg, hepatitis B surface antigen." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="char" valign="top" scope="col" style="border-bottom: 2px solid black">n=126 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="char" valign="top" scope="col" style="border-bottom: 2px solid black">HBsAg clearance n=5 (3.97%) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="char" valign="top" scope="col" style="border-bottom: 2px solid black">No HBsAg clearance n=121 (96.03%) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="char" valign="top" scope="col" style="border-bottom: 2px solid black">p \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">ALT at diagnosis (mU/mL) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">25.80±17.81 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">31.97±28.72 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.421 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Peak ALT (mU/mL) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">34.00±22.53 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">43.74±44.94 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.566 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">HBV-DNA at diagnosis (IU/mL) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">21.60±48.30 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5214.70±16,074 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.002 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Peak HBV-DNA (IU/mL) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1089.60±1869.56 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">31,100.22±154,440.70 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.053 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1359756.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Comparison of ALT and HBV-DNA between patients with and without HBsAg loss." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:55 [ 0 => array:3 [ "identificador" => "bib0280" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The natural history and treatment of chronic hepatitis B: a critical evaluation of standard treatment criteria and end points" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "C.L. Lai" 1 => "M.F. Yeun" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Ann Intern Med" "fecha" => "2007" "volumen" => "147" "paginaInicial" => "58" "paginaFinal" => "61" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17606962" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0285" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A mathematical model to estimate global hepatitis B disease burden and vaccination impact" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "S.T. Goldstein" 1 => "F. Zhou" 2 => "S.C. Hadler" 3 => "B.P. Bell" 4 => "E.E. Mast" 5 => "H.S. Margolis" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1093/ije/dyi206" "Revista" => array:6 [ "tituloSerie" => "Int J Epidemiol" "fecha" => "2005" "volumen" => "34" "paginaInicial" => "1329" "paginaFinal" => "1339" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16249217" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0290" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hepatitis B e antigen-negative chronic hepatitis B" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "S.J. Hadziyannis" 1 => "D. Vassilopoulos" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1053/jhep.2001.27834" "Revista" => array:6 [ "tituloSerie" => "Hepatology" "fecha" => "2001" "volumen" => "34" "paginaInicial" => "617" "paginaFinal" => "624" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11584355" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0295" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Identification of HBV variants which cannot produce precore derived HBeAg and may be responsible for severe hepatitis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M.R. Brunetto" 1 => "M. Stemler" 2 => "F. Schodel" 3 => "H. Will" 4 => "A. Ottobrelli" 5 => "M. Rizzetto" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Ital J Gastroenterol" "fecha" => "1989" "volumen" => "21" "paginaInicial" => "151" "paginaFinal" => "154" ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0300" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "World-wide epidemiology of HBeAg negative chronic hepatitis B and associated precore and core promoter variants" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "M.L. Funk" 1 => "D.M. Rosenberg" 2 => "A.S. Lok" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "J Viral Hepatol" "fecha" => "2002" "volumen" => "9" "paginaInicial" => "52" "paginaFinal" => "61" ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0305" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Prevalence of HBV precore/core promoter variants in the United States" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "C.J. Chu" 1 => "E.B. Keeffe" 2 => "S.H. Han" 3 => "R.P. Perrillo" 4 => "A.D. Min" 5 => "C. Soldevila-Pico" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1053/jhep.2003.50352" "Revista" => array:6 [ "tituloSerie" => "Hepatology" "fecha" => "2003" "volumen" => "38" "paginaInicial" => "619" "paginaFinal" => "628" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12939588" "web" => "Medline" ] ] ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0310" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Characteristics of patients with chronic hepatitis B in France: Predominant frequency of HBe antigen negative cases" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J.P. Zarski" 1 => "P. Marcellin" 2 => "V. Leroy" 3 => "C. Trepo" 4 => "D. Samuel" 5 => "N. Ganne-Carrie" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jhep.2006.03.007" "Revista" => array:6 [ "tituloSerie" => "J Hepatol" "fecha" => "2006" "volumen" => "45" "paginaInicial" => "355" "paginaFinal" => "360" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16750585" "web" => "Medline" ] ] ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0315" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Characteristics of patients with chronic hepatitis B virus infection. Analysis of a series of 474 patients" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "R. Gómez Rodríguez" 1 => "A. Guardiola Arévalo" 2 => "A.Z. Gómez Moreno" 3 => "A. García Vela" 4 => "C. Gómez Hernando" 5 => "R. Rodríguez Merlo" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.gastrohep.2012.10.006" "Revista" => array:6 [ "tituloSerie" => "Gastroenterol Hepatol" "fecha" => "2013" "volumen" => "36" "paginaInicial" => "243" "paginaFinal" => "253" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23414836" "web" => "Medline" ] ] ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib0320" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Incidencia diagnóstica de AgH Bs positivo. Características epidemiológicas, clínicas y virológicas" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "E. Poves Martínez" 1 => "D. Del Pozo Prieto" 2 => "B. Costero Pastor" 3 => "G. Borrego Rodríguez" 4 => "I. Beceiro Pedroño" 5 => "C. Sanz García" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Rev Esp Enferm Dig" "fecha" => "2012" "volumen" => "104" "paginaInicial" => "10" "paginaFinal" => "15" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22300111" "web" => "Medline" ] ] ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib0325" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "HBeAg-positive chronic hepatitis B treatment with oral antiviral agents: Experience and results in clinical practice" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "R.M. Martín-Mateos" 1 => "V.F. Moreira Vicente" 2 => "L. Téllez-Villajos" 3 => "C. García-Sánchez" 4 => "M.T. Maroto-Castellanos" 5 => "F.J. García-Alonso" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.gastrohep.2013.11.011" "Revista" => array:6 [ "tituloSerie" => "Gastroenterol Hepatol" "fecha" => "2014" "volumen" => "37" "paginaInicial" => "280" "paginaFinal" => "288" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24462611" "web" => "Medline" ] ] ] ] ] ] ] ] 10 => array:3 [ "identificador" => "bib0330" "etiqueta" => "11" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The long-term outcome of interferon-treated and untreated patients with HBeAg-negative chronic hepatitis B" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "G.V. Papatheodoridis" 1 => "E. Manesis" 2 => "J.J. Hadziyannis" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "J Hepatol" "fecha" => "2001" "volumen" => "34" "paginaInicial" => "306" "paginaFinal" => "313" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11281561" "web" => "Medline" ] ] ] ] ] ] ] ] 11 => array:3 [ "identificador" => "bib0335" "etiqueta" => "12" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Precore and core promoter mutations of hepatitis B virus and hepatitis B e antigen-negative chronic hepatitis B in Korea" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "B.C. Yoo" 1 => "J.W. Park" 2 => "H.J. Kim" 3 => "D.H. Lee" 4 => "Y.J. Cha" 5 => "S.M. Park" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:7 [ "tituloSerie" => "J Hepatol" "fecha" => "2003" "volumen" => "38" "paginaInicial" => "98" "paginaFinal" => "103" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12480566" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0735109705029219" "estado" => "S300" "issn" => "07351097" ] ] ] ] ] ] ] 12 => array:3 [ "identificador" => "bib0340" "etiqueta" => "13" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Clinical, demographic and epidemiological characteristics of patients with hepatitis B followed at a university hospital in Southeastern Brazil: predominance of HBeAg negative cases" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "S.G. Chachá" 1 => "C. Ferreira Sda" 2 => "T.V. Costa" 3 => "L.C. Almeida Filho" 4 => "M.G. Villanova" 5 => "F.F. Souza" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Rev Soc Bras Med Trop" "fecha" => "2011" "volumen" => "44" "paginaInicial" => "13" "paginaFinal" => "17" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21340400" "web" => "Medline" ] ] ] ] ] ] ] ] 13 => array:3 [ "identificador" => "bib0345" "etiqueta" => "14" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Intraobserver and interobserver variations in liver biopsy interpretation in patients with chronic hepatitis C" "autores" => array:1 [ 0 => array:2 [ "colaboracion" => "The METAVIR Cooperative Study Group" "etal" => false ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Hepatology" "fecha" => "1994" "volumen" => "1" "paginaInicial" => "15" "paginaFinal" => "20" ] ] ] ] ] ] 14 => array:3 [ "identificador" => "bib0350" "etiqueta" => "15" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Dual cut-off transient elastography to assess liver fibrosis in chronic hepatitis B: A cohort study with internal validation" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M. Viganò" 1 => "S. Paggi" 2 => "P. Lampertico" 3 => "M. Fraquelli" 4 => "S. Massironi" 5 => "G. Ronchi" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1365-2036.2011.04722.x" "Revista" => array:6 [ "tituloSerie" => "Aliment Pharmacol Ther" "fecha" => "2011" "volumen" => "34" "paginaInicial" => "353" "paginaFinal" => "362" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21631559" "web" => "Medline" ] ] ] ] ] ] ] ] 15 => array:3 [ "identificador" => "bib0355" "etiqueta" => "16" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Chronic hepatitis B: update 2009. AASLD practical guidelines" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "A. Lok" 1 => "B.J. McMahon" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/hep.23190" "Revista" => array:6 [ "tituloSerie" => "Hepatology" "fecha" => "2009" "volumen" => "50" "paginaInicial" => "661" "paginaFinal" => "662" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19714720" "web" => "Medline" ] ] ] ] ] ] ] ] 16 => array:3 [ "identificador" => "bib0360" "etiqueta" => "17" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "EASL clinical practice guidelines: Management of chronic hepatitis B virus infection" "autores" => array:1 [ 0 => array:2 [ "colaboracion" => "European Association for the Study of the Liver" "etal" => false ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jhep.2012.02.010" "Revista" => array:7 [ "tituloSerie" => "J Hepatol" "fecha" => "2012" "volumen" => "57" "paginaInicial" => "167" "paginaFinal" => "185" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22436845" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0735109711028397" "estado" => "S300" "issn" => "07351097" ] ] ] ] ] ] ] 17 => array:3 [ "identificador" => "bib0365" "etiqueta" => "18" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hepatitis B e antigen negative chronic hepatitis B: from clinical recognition to pathogenesis and treatment" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "S.J. Hadziyannis" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Viral Hepat Rev" "fecha" => "1995" "volumen" => "1" "paginaInicial" => "7" "paginaFinal" => "36" ] ] ] ] ] ] 18 => array:3 [ "identificador" => "bib0370" "etiqueta" => "19" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Efficacy of long-term lamivudine monotherapy in patients with hepatitis B e antigen-negative chronic hepatitis B" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "S.J. Hadziyannis" 1 => "G.V. Papatheodoridis" 2 => "E. Dimou" 3 => "A. Laras" 4 => "C. Papaioannou" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1053/jhep.2000.17915" "Revista" => array:6 [ "tituloSerie" => "Hepatology" "fecha" => "2000" "volumen" => "32" "paginaInicial" => "847" "paginaFinal" => "851" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11003633" "web" => "Medline" ] ] ] ] ] ] ] ] 19 => array:3 [ "identificador" => "bib0375" "etiqueta" => "20" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Analysis of liver disease, nuclear HBcAg, viral replication, and hepatitis B virus DNA in liver and serum of HBeAg vs. anti-HBe positive carriers of hepatitis B virus" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "S.J. Hadziyannis" 1 => "H.M. Lieberman" 2 => "G.G. Karvountzis" 3 => "D.A. Shafritz" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Hepatology" "fecha" => "1983" "volumen" => "3" "paginaInicial" => "656" "paginaFinal" => "662" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/6618432" "web" => "Medline" ] ] ] ] ] ] ] ] 20 => array:3 [ "identificador" => "bib0380" "etiqueta" => "21" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Evaluation of liver biopsy in Egyptian HBeAg-negative chronic hepatitis B patients at initial presentation: Implications for therapy" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "A.R. El-Zayadi" 1 => "H.M. Badran" 2 => "A. Saied" 3 => "S. Shawky" 4 => "Attia Mel-D" 5 => "K. Zalata" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/ajg.2009.30" "Revista" => array:6 [ "tituloSerie" => "Am J Gastroenterol" "fecha" => "2009" "volumen" => "104" "paginaInicial" => "906" "paginaFinal" => "911" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19293791" "web" => "Medline" ] ] ] ] ] ] ] ] 21 => array:3 [ "identificador" => "bib0385" "etiqueta" => "22" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Virologic and histologic features of chronic hepatitis B virus-infected asymptomatic patients with persistently normal ALT" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M. Kumar" 1 => "S.K. Sarin" 2 => "S. Hissar" 3 => "C. Pande" 4 => "P. Sakhuja" 5 => "B.C. Sharma" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1053/j.gastro.2008.02.075" "Revista" => array:7 [ "tituloSerie" => "Gastroenterology" "fecha" => "2008" "volumen" => "134" "paginaInicial" => "1376" "paginaFinal" => "1384" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18471514" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0735109797883350" "estado" => "S300" "issn" => "07351097" ] ] ] ] ] ] ] 22 => array:3 [ "identificador" => "bib0390" "etiqueta" => "23" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The role of serial measurement of serum HBV DNA levels in patients with chronic HBeAg(−) hepatitis B infection: association with liver disease progression. A prospective cohort study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "G. Zacharakis" 1 => "J. Koskinas" 2 => "S. Kotsiou" 3 => "F. Tzara" 4 => "N. Vafeiadis" 5 => "M. Papoutselis" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jhep.2008.06.009" "Revista" => array:6 [ "tituloSerie" => "J Hepatol" "fecha" => "2008" "volumen" => "49" "paginaInicial" => "884" "paginaFinal" => "891" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18674840" "web" => "Medline" ] ] ] ] ] ] ] ] 23 => array:3 [ "identificador" => "bib0395" "etiqueta" => "24" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Liver fibrosis progression is uncommon in patients with inactive chronic hepatitis B: a prospective cohort study with paired transient elastography examination" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "G.L. Wong" 1 => "H.L. Chan" 2 => "Z. Yu" 3 => "H.Y. Chan" 4 => "C.H. Tse" 5 => "V.W. Wong" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:4 [ "tituloSerie" => "J Gastroenterol Hepatol" "fecha" => "2013" "paginaInicial" => "1842" "paginaFinal" => "1848" ] ] ] ] ] ] 24 => array:3 [ "identificador" => "bib0400" "etiqueta" => "25" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Changing epidemiology of HCV and HBV infections in Northern Italy: a survey in the general population" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "P. Fabris" 1 => "V. Baldo" 2 => "T. Baldovin" 3 => "E. Bellotto" 4 => "M. Rassu" 5 => "R. Trivello" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/MCG.0b013e318030e3ab" "Revista" => array:6 [ "tituloSerie" => "J Clin Gastroenterol" "fecha" => "2008" "volumen" => "42" "paginaInicial" => "527" "paginaFinal" => "532" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18277889" "web" => "Medline" ] ] ] ] ] ] ] ] 25 => array:3 [ "identificador" => "bib0405" "etiqueta" => "26" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The burden and recent epidemiological changes of the main chronic liver diseases in a Greek referral tertiary centre" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "I.P. Giannousis" 1 => "G.V. Papatheodoridis" 2 => "M.J. Deutsch" 3 => "S.G. Manolakopoulos" 4 => "E.K. Manesis" 5 => "J.S. Koskinas" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/MEG.0b013e328331115b" "Revista" => array:6 [ "tituloSerie" => "Eur J Gastroenterol Hepatol" "fecha" => "2010" "volumen" => "22" "paginaInicial" => "172" "paginaFinal" => "179" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19738477" "web" => "Medline" ] ] ] ] ] ] ] ] 26 => array:3 [ "identificador" => "bib0410" "etiqueta" => "27" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Histological changes in Chinese chronic hepatitis B patients with ALT lower than two times upper limits of normal" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "E.-Q. Chen" 1 => "F.-J. Huang" 2 => "L.-L. He" 3 => "L. Bai" 4 => "L.-C. Wang" 5 => "T.-Y. Zhou" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s10620-009-0724-5" "Revista" => array:6 [ "tituloSerie" => "Dig Dis Sci" "fecha" => "2010" "volumen" => "55" "paginaInicial" => "432" "paginaFinal" => "437" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19241166" "web" => "Medline" ] ] ] ] ] ] ] ] 27 => array:3 [ "identificador" => "bib0415" "etiqueta" => "28" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hepatitis B virus DNA in saliva from children with chronic hepatitis B infection: implications for saliva as a potential mode of horizontal transmission" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "I.L. Heiberg" 1 => "M. Hoegh" 2 => "S. Ladelund" 3 => "H.G. Niesters" 4 => "B. Hogh" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/INF.0b013e3181d8e009" "Revista" => array:6 [ "tituloSerie" => "Pediatr Infect Dis J" "fecha" => "2010" "volumen" => "29" "paginaInicial" => "465" "paginaFinal" => "467" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20335824" "web" => "Medline" ] ] ] ] ] ] ] ] 28 => array:3 [ "identificador" => "bib0420" "etiqueta" => "29" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Reactivation of hepatitis B virus infection after cytotoxic chemotherapy or immunosuppressive therapy" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "M.L. Manzano" 1 => "G. Castellano" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3748/wjg.v17.i12. 1531" "Revista" => array:6 [ "tituloSerie" => "World J Gastroenterol" "fecha" => "2011" "volumen" => "17" "paginaInicial" => "1531" "paginaFinal" => "1537" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21472116" "web" => "Medline" ] ] ] ] ] ] ] ] 29 => array:3 [ "identificador" => "bib0425" "etiqueta" => "30" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Follow-up and indications for liver biopsy in HBeAg-negative chronic hepatitis B virus infection with persistently normal ALT: a systematic review" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "G.V. Papatheodoridis" 1 => "S. Manolakopoulos" 2 => "Y.F. Liaw" 3 => "A. Lok" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jhep.2011.11.030" "Revista" => array:6 [ "tituloSerie" => "J Hepatol" "fecha" => "2012" "volumen" => "57" "paginaInicial" => "196" "paginaFinal" => "202" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22450396" "web" => "Medline" ] ] ] ] ] ] ] ] 30 => array:3 [ "identificador" => "bib0430" "etiqueta" => "31" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Is there a meaningful serum HBV DNA cut-off level for therapeutic decisions in HBeAg-negative chronic hepatitis B virus infection?" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "G.V. Papatheodoridis" 1 => "E.K. Manesis" 2 => "S. Manolakopoulos" 3 => "I.S. Elefsiniotis" 4 => "J. Goulis" 5 => "J. Giannousis" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/hep.22518" "Revista" => array:6 [ "tituloSerie" => "Hepatology" "fecha" => "2008" "volumen" => "48" "paginaInicial" => "1451" "paginaFinal" => "1459" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18924246" "web" => "Medline" ] ] ] ] ] ] ] ] 31 => array:3 [ "identificador" => "bib0435" "etiqueta" => "32" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Longitudinal changes in serum HBV DNA levels and predictors of progression during the natural course of HBeAg-negative chronic hepatitis B virus infection" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "G.V. Papatheodoridis" 1 => "N. Chrysanthos" 2 => "E. Hadziyannis" 3 => "E. Cholongitas" 4 => "E.K. Manesis" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1365-2893.2007.00957.x" "Revista" => array:6 [ "tituloSerie" => "J Viral Hepat" "fecha" => "2008" "volumen" => "15" "paginaInicial" => "434" "paginaFinal" => "441" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18194171" "web" => "Medline" ] ] ] ] ] ] ] ] 32 => array:3 [ "identificador" => "bib0440" "etiqueta" => "33" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Long-term outcome of hepatitis B e antigen-negative hepatitis B surface antigen carriers in relation to changes of alanine aminotransferase levels over time" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "D.I. Tai" 1 => "S.M. Lin" 2 => "I.S. Sheen" 3 => "C.M. Chu" 4 => "D.Y. Lin" 5 => "Y.F. Liaw" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/hep.22878" "Revista" => array:6 [ "tituloSerie" => "Hepatology" "fecha" => "2009" "volumen" => "49" "paginaInicial" => "1859" "paginaFinal" => "1867" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19378345" "web" => "Medline" ] ] ] ] ] ] ] ] 33 => array:3 [ "identificador" => "bib0445" "etiqueta" => "34" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Long-term outcome of HBV carriers with negative HBe antigen and normal aminotransferase" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "K. Ikeda" 1 => "Y. Arase" 2 => "S. Saitoh" 3 => "M. Kobayashi" 4 => "T. Someya" 5 => "T. Hosaka" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.amjmed.2006.04.036" "Revista" => array:6 [ "tituloSerie" => "Am J Med" "fecha" => "2006" "volumen" => "119" "paginaInicial" => "977" "paginaFinal" => "985" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17071167" "web" => "Medline" ] ] ] ] ] ] ] ] 34 => array:3 [ "identificador" => "bib0450" "etiqueta" => "35" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Quantitative serum HBV DNA levels during different stages of chronic hepatitis B infection" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "C.J. Chu" 1 => "M. Hussain" 2 => "A.S.F. Lok" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1053/jhep.2002.36949" "Revista" => array:6 [ "tituloSerie" => "Hepatology" "fecha" => "2002" "volumen" => "36" "paginaInicial" => "1408" "paginaFinal" => "1415" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12447866" "web" => "Medline" ] ] ] ] ] ] ] ] 35 => array:3 [ "identificador" => "bib0455" "etiqueta" => "36" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Serial HBV DNA levels in patients with persistently normal transaminase over 10 years following spontaneous HBeAg seroconversion" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "Y.-C. Chen" 1 => "S.-F. Huang" 2 => "C.-M. Chu" 3 => "Y.-F. Liaw" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1365-2893.2011.01450.x" "Revista" => array:6 [ "tituloSerie" => "J Viral Hepat" "fecha" => "2012" "volumen" => "19" "paginaInicial" => "138" "paginaFinal" => "146" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22239503" "web" => "Medline" ] ] ] ] ] ] ] ] 36 => array:3 [ "identificador" => "bib0460" "etiqueta" => "37" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The liver histology and frequency and clearance of the hepatitis B surface antigen (HBsAg) in chronic carriers" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "R.E. Sampliner" 1 => "F.A. Hamilton" 2 => "O.A. Iseri" 3 => "E. Tabor" 4 => "J. Boitnott" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Am J Med Sci" "fecha" => "1979" "volumen" => "277" "paginaInicial" => "17" "paginaFinal" => "22" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/425995" "web" => "Medline" ] ] ] ] ] ] ] ] 37 => array:3 [ "identificador" => "bib0465" "etiqueta" => "38" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The long-term serological course of asymptomatic hepatitis B virus carriers and the development of primary hepatocellular carcinoma" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "W.L.M. Alward" 1 => "B.J. McMahon" 2 => "D.B. Hall" 3 => "W.L. Heyward" 4 => "D.P. Francis" 5 => "T.R. Bender" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "J Infect Dis" "fecha" => "1985" "volumen" => "151" "paginaInicial" => "604" "paginaFinal" => "609" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/2982971" "web" => "Medline" ] ] ] ] ] ] ] ] 38 => array:3 [ "identificador" => "bib0470" "etiqueta" => "39" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Incidence, determinants and significance of delayed clearance of serum HBsAg in chronic hepatitis B virus infection: a prospective study" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "Y.F. Liaw" 1 => "I.S. Sheen" 2 => "T.J. Chen" 3 => "C.M. Chu" 4 => "C.C. Pao" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Hepatology" "fecha" => "1991" "volumen" => "13" "paginaInicial" => "627" "paginaFinal" => "631" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/2010157" "web" => "Medline" ] ] ] ] ] ] ] ] 39 => array:3 [ "identificador" => "bib0475" "etiqueta" => "40" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Spontaneous loss of HBsAg in children with chronic hepatitis B virus infection" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "H.Y. Hsu" 1 => "M.H. Chang" 2 => "C.Y. Lee" 3 => "J.S. Chen" 4 => "H.C. Hsu" 5 => "D.S. Chen" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Hepatology" "fecha" => "1992" "volumen" => "15" "paginaInicial" => "382" "paginaFinal" => "386" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/1544619" "web" => "Medline" ] ] ] ] ] ] ] ] 40 => array:3 [ "identificador" => "bib0480" "etiqueta" => "41" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Natural history of chronic HBV carriers in northern Italy: morbidity and mortality after 30 years" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M. Manno" 1 => "C. Cammà" 2 => "F. Schepis" 3 => "F. Bassi" 4 => "R. Gelmini" 5 => "F. Giannini" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Gastroenterology" "fecha" => "2004" "volumen" => "127" "paginaInicial" => "756" "paginaFinal" => "763" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15362032" "web" => "Medline" ] ] ] ] ] ] ] ] 41 => array:3 [ "identificador" => "bib0485" "etiqueta" => "42" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "HBsAg seroclearance in asymptomatic carriers of high endemic areas: Appreciably high rates during a long-term follow-up" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "C.M. Chu" 1 => "Y.F. Liaw" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/hep.21612" "Revista" => array:6 [ "tituloSerie" => "Hepatology" "fecha" => "2007" "volumen" => "45" "paginaInicial" => "1187" "paginaFinal" => "1192" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17465003" "web" => "Medline" ] ] ] ] ] ] ] ] 42 => array:3 [ "identificador" => "bib0490" "etiqueta" => "43" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "HBsAg seroclearance in chronic hepatitis B in Asian patients: replicative level and risk of hepatocellular carcinoma" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M.F. Yuen" 1 => "D.K. Wong" 2 => "J. Fung" 3 => "P. Ip" 4 => "D. But" 5 => "I. Hung" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1053/j.gastro.2008.07.008" "Revista" => array:6 [ "tituloSerie" => "Gastroenterology" "fecha" => "2008" "volumen" => "135" "paginaInicial" => "1192" "paginaFinal" => "1199" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18722377" "web" => "Medline" ] ] ] ] ] ] ] ] 43 => array:3 [ "identificador" => "bib0495" "etiqueta" => "44" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Serum hepatitis B DNA levels and liver histology in inactive HBsAg carriers" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M. Martinot-Peignoux" 1 => "N. Boyer" 2 => "M. Colombat" 3 => "R. Akremi" 4 => "B.-N. Pham" 5 => "S. Ollivier" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "J Hepatol" "fecha" => "2002" "volumen" => "36" "paginaInicial" => "543" "paginaFinal" => "548" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11943427" "web" => "Medline" ] ] ] ] ] ] ] ] 44 => array:3 [ "identificador" => "bib0500" "etiqueta" => "45" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "HBsAg seroclearance in chronic hepatitis B in the Chinese: virological, histological, and clinical aspects" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M.F. Yuen" 1 => "D.K. Wong" 2 => "E. Sablon" 3 => "E. Tse" 4 => "I.O. Ng" 5 => "H.J. Yuan" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/hep.20240" "Revista" => array:6 [ "tituloSerie" => "Hepatology" "fecha" => "2004" "volumen" => "39" "paginaInicial" => "1694" "paginaFinal" => "1701" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15185311" "web" => "Medline" ] ] ] ] ] ] ] ] 45 => array:3 [ "identificador" => "bib0505" "etiqueta" => "46" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Sero-clearance of hepatitis B surface antigen in chronic carriers does not necessarily imply a good prognosis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "T.I. Huo" 1 => "J.C. Wu" 2 => "P.C. Lee" 3 => "G.Y. Chau" 4 => "W.Y. Lui" 5 => "S.H. Tsay" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/hep.510280130" "Revista" => array:6 [ "tituloSerie" => "Hepatology" "fecha" => "1998" "volumen" => "28" "paginaInicial" => "231" "paginaFinal" => "236" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9657117" "web" => "Medline" ] ] ] ] ] ] ] ] 46 => array:3 [ "identificador" => "bib0510" "etiqueta" => "47" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The development of cirrhosis in patients with chronic type B hepatitis: a prospective study" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "Y.F. Liaw" 1 => "D.I. Tai" 2 => "C.M. Chu" 3 => "T.J. Chen" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Hepatology" "fecha" => "1988" "volumen" => "8" "paginaInicial" => "493" "paginaFinal" => "496" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/3371868" "web" => "Medline" ] ] ] ] ] ] ] ] 47 => array:3 [ "identificador" => "bib0515" "etiqueta" => "48" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Development of cirrhosis after chronic type B hepatitis: a clinicopathologic and follow-up study of HBeAg-positive asymptomatic patients" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "R. Moreno-Otero" 1 => "C. García-Monzón" 2 => "A. García-Sánchez" 3 => "L. García Buey" 4 => "J.M. Pajares" 5 => "A.M. di Bisceglie" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Am J Gastroenterol" "fecha" => "1991" "volumen" => "86" "paginaInicial" => "560" "paginaFinal" => "564" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/2028945" "web" => "Medline" ] ] ] ] ] ] ] ] 48 => array:3 [ "identificador" => "bib0520" "etiqueta" => "49" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Factors predictive of liver cirrhosis in patients with chronic hepatitis B: a multivariate analysis in longitudinal study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "T. Huo" 1 => "J. Wu" 2 => "S. Hwang" 3 => "C.R. Lai" 4 => "P.C. Lee" 5 => "S.H. Tsay" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Eur J Gastroenterol Hepatol" "fecha" => "2000" "volumen" => "12" "paginaInicial" => "687" "paginaFinal" => "693" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10912490" "web" => "Medline" ] ] ] ] ] ] ] ] 49 => array:3 [ "identificador" => "bib0525" "etiqueta" => "50" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "High prevalence of significant liver fibrosis and cirrhosis in chronic hepatitis B patients with normal ALT in central Europe" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "T. Göbel" 1 => "A. Erhardt" 2 => "M. Herwig" 3 => "C. Poremba" 4 => "S.E. Bald us" 5 => "A. Sagir" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/jmv.22048" "Revista" => array:6 [ "tituloSerie" => "J Med Virol" "fecha" => "2011" "volumen" => "83" "paginaInicial" => "968" "paginaFinal" => "973" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21503908" "web" => "Medline" ] ] ] ] ] ] ] ] 50 => array:3 [ "identificador" => "bib0530" "etiqueta" => "51" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Evaluation of normal or minimally elevated alanine transaminase, age and DNA level in predicting liver histological changes in chronic hepatitis B" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "S. Alam" 1 => "N. Ahmad" 2 => "G. Mustafa" 3 => "A. Shrestha" 4 => "A.K. Alam" 5 => "M. Khan" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1478-3231.2011.02491.x" "Revista" => array:6 [ "tituloSerie" => "Liver Int" "fecha" => "2011" "volumen" => "31" "paginaInicial" => "824" "paginaFinal" => "830" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21645213" "web" => "Medline" ] ] ] ] ] ] ] ] 51 => array:3 [ "identificador" => "bib0535" "etiqueta" => "52" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Natural history of chronic hepatitis B: special emphasis on disease progression and prognostic factors" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "G. Fattovich" 1 => "F. Bortolotti" 2 => "F. Donato" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jhep.2007.11.011" "Revista" => array:6 [ "tituloSerie" => "J Hepatol" "fecha" => "2008" "volumen" => "48" "paginaInicial" => "335" "paginaFinal" => "352" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18096267" "web" => "Medline" ] ] ] ] ] ] ] ] 52 => array:3 [ "identificador" => "bib0540" "etiqueta" => "53" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "C.J. Chen" 1 => "H.I. Yang" 2 => "J. Su" 3 => "C.L. Jen" 4 => "S.L. You" 5 => "S.N. Lu" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "J Am Med Assoc" "fecha" => "2006" "volumen" => "295" "paginaInicial" => "65" "paginaFinal" => "73" ] ] ] ] ] ] 53 => array:3 [ "identificador" => "bib0545" "etiqueta" => "54" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Long-term outcome of chronic hepatitis B in Caucasian patients: mortality after 25 years" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "G. Fattovich" 1 => "N. Olivari" 2 => "M. Pasino" 3 => "M. d’Onofrio" 4 => "E. Martone" 5 => "F. Donato" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/gut.2007.128496" "Revista" => array:6 [ "tituloSerie" => "Gut" "fecha" => "2008" "volumen" => "57" "paginaInicial" => "84" "paginaFinal" => "90" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17715267" "web" => "Medline" ] ] ] ] ] ] ] ] 54 => array:3 [ "identificador" => "bib0550" "etiqueta" => "55" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hepatitis B virus infection increases the risk of cholangiocarcinoma: a meta-analysis and systematic review" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M. Li" 1 => "J. Li" 2 => "P. Li" 3 => "H. Li" 4 => "T. Su" 5 => "R. Zhu" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1440-1746.2012.07207.x" "Revista" => array:6 [ "tituloSerie" => "J Gastroenterol Hepatol" "fecha" => "2012" "volumen" => "27" "paginaInicial" => "1561" "paginaFinal" => "1568" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22694354" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] "agradecimientos" => array:1 [ 0 => array:4 [ "identificador" => "xack271487" "titulo" => "Acknowledgements" "texto" => "We would like to thank Dr. Marcelino Sánchez Casado, ICU staff physician in Hospital Virgen de la Salud de Toledo, for his assistance in both the methodology and statistics." "vista" => "all" ] ] ] "idiomaDefecto" => "en" "url" => "/24443824/0000004000000002/v1_201703060044/S2444382417300275/v1_201703060044/en/main.assets" "Apartado" => array:4 [ "identificador" => "48441" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Original articles" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/24443824/0000004000000002/v1_201703060044/S2444382417300275/v1_201703060044/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2444382417300275?idApp=UINPBA00004N"]

Statistics

Original article

Characteristics and course of chronic hepatitis B e antigen-negative infection

Características y evolución de la infección crónica por virus de la hepatitis B antígeno e negativo

Antonio Guardiola Arévaloa,b,

Corresponding author

antonio.guardiola@salud.madrid.com

Corresponding author.

, Rafael Gómez Rodrígueza, Marta Romero Gutiérreza, Ana Zaida Gómez Morenoa, Almudena García Velaa, Raquel Sánchez Simónc, Cesar Gómez Hernandod, Eva María Andrés Estebane

a Servicio de Aparato Digestivo, Hospital Virgen de la Salud, Toledo, Spain

b Servicio de Aparato Digestivo, Hospital Universitario de Fuenlabrada, Fuenlabrada, Madrid, Spain

c Anatomía Patológica, Hospital Virgen de la Salud, Toledo, Spain

d Microbiología, Hospital Virgen de la Salud, Toledo, Spain

e Universidad Autónoma de Madrid, Madrid, Spain

Read

6073

Times
was read the article

739

Total PDF

5334

Total HTML

Share statistics

 array:23 [
  "pii" => "S2444382417300275"
  "issn" => "24443824"
  "doi" => "10.1016/j.gastre.2016.11.009"
  "estado" => "S300"
  "fechaPublicacion" => "2017-02-01"
  "aid" => "1085"
  "copyright" => "Elsevier Espa&#241;a&#44; S&#46;L&#46;U&#46;&#44; AEEH and AEG"
  "copyrightAnyo" => "2016"
  "documento" => "article"
  "crossmark" => 1
  "subdocumento" => "fla"
  "cita" => "Gastroenterol Hepatol. 2017;40:59-69"
  "abierto" => array:3 [
    "ES" => false
    "ES2" => false
    "LATM" => false
  ]
  "gratuito" => false
  "lecturas" => array:2 [
    "total" => 570
    "formatos" => array:2 [
      "HTML" => 437
      "PDF" => 133
    ]
  ]
  "Traduccion" => array:1 [
    "es" => array:19 [
      "pii" => "S0210570516301637"
      "issn" => "02105705"
      "doi" => "10.1016/j.gastrohep.2016.11.002"
      "estado" => "S300"
      "fechaPublicacion" => "2017-02-01"
      "aid" => "1085"
      "copyright" => "Elsevier Espa&#241;a&#44; S&#46;L&#46;U&#46;&#44; AEEH y AEG"
      "documento" => "article"
      "crossmark" => 1
      "subdocumento" => "fla"
      "cita" => "Gastroenterol Hepatol. 2017;40:59-69"
      "abierto" => array:3 [
        "ES" => false
        "ES2" => false
        "LATM" => false
      ]
      "gratuito" => false
      "lecturas" => array:2 [
        "total" => 1996
        "formatos" => array:2 [
          "HTML" => 1591
          "PDF" => 405
        ]
      ]
      "es" => array:13 [
        "idiomaDefecto" => true
        "cabecera" => "<span class="elsevierStyleTextfn">Original</span>"
        "titulo" => "Caracter&#237;sticas y evoluci&#243;n de la infecci&#243;n cr&#243;nica por virus de la hepatitis B ant&#237;geno e negativo"
        "tienePdf" => "es"
        "tieneTextoCompleto" => "es"
        "tieneResumen" => array:2 [
          0 => "es"
          1 => "en"
        ]
        "paginas" => array:1 [
          0 => array:2 [
            "paginaInicial" => "59"
            "paginaFinal" => "69"
          ]
        ]
        "titulosAlternativos" => array:1 [
          "en" => array:1 [
            "titulo" => "Characteristics and course of chronic hepatitis B e antigen-negative infection"
          ]
        ]
        "contieneResumen" => array:2 [
          "es" => true
          "en" => true
        ]
        "contieneTextoCompleto" => array:1 [
          "es" => true
        ]
        "contienePdf" => array:1 [
          "es" => true
        ]
        "resumenGrafico" => array:2 [
          "original" => 0
          "multimedia" => array:7 [
            "identificador" => "fig0010"
            "etiqueta" => "Figura 2"
            "tipo" => "MULTIMEDIAFIGURA"
            "mostrarFloat" => true
            "mostrarDisplay" => false
            "figura" => array:1 [
              0 => array:4 [
                "imagen" => "gr2.jpeg"
                "Alto" => 1813
                "Ancho" => 2396
                "Tamanyo" => 221828
              ]
            ]
            "descripcion" => array:1 [
              "es" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Motivo del diagn&#243;stico de la infecci&#243;n por el VHB&#46;</p> <p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">AP&#58; atenci&#243;n primaria&#46;</p>"
            ]
          ]
        ]
        "autores" => array:1 [
          0 => array:2 [
            "autoresLista" => "Antonio Guardiola Ar&#233;valo, Rafael G&#243;mez Rodr&#237;guez, Marta Romero Guti&#233;rrez, Ana Zaida G&#243;mez Moreno, Almudena Garc&#237;a Vela, Raquel S&#225;nchez Sim&#243;n, Cesar G&#243;mez Hernando, Eva Mar&#237;a Andr&#233;s Esteban"
            "autores" => array:8 [
              0 => array:2 [
                "nombre" => "Antonio"
                "apellidos" => "Guardiola Ar&#233;valo"
              ]
              1 => array:2 [
                "nombre" => "Rafael"
                "apellidos" => "G&#243;mez Rodr&#237;guez"
              ]
              2 => array:2 [
                "nombre" => "Marta"
                "apellidos" => "Romero Guti&#233;rrez"
              ]
              3 => array:2 [
                "nombre" => "Ana Zaida"
                "apellidos" => "G&#243;mez Moreno"
              ]
              4 => array:2 [
                "nombre" => "Almudena"
                "apellidos" => "Garc&#237;a Vela"
              ]
              5 => array:2 [
                "nombre" => "Raquel"
                "apellidos" => "S&#225;nchez Sim&#243;n"
              ]
              6 => array:2 [
                "nombre" => "Cesar"
                "apellidos" => "G&#243;mez Hernando"
              ]
              7 => array:2 [
                "nombre" => "Eva Mar&#237;a"
                "apellidos" => "Andr&#233;s Esteban"
              ]
            ]
          ]
        ]
      ]
      "idiomaDefecto" => "es"
      "Traduccion" => array:1 [
        "en" => array:9 [
          "pii" => "S2444382417300275"
          "doi" => "10.1016/j.gastre.2016.11.009"
          "estado" => "S300"
          "subdocumento" => ""
          "abierto" => array:3 [
            "ES" => false
            "ES2" => false
            "LATM" => false
          ]
          "gratuito" => false
          "lecturas" => array:1 [
            "total" => 0
          ]
          "idiomaDefecto" => "en"
          "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2444382417300275?idApp=UINPBA00004N"
        ]
      ]
      "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0210570516301637?idApp=UINPBA00004N"
      "url" => "/02105705/0000004000000002/v1_201702050027/S0210570516301637/v1_201702050027/es/main.assets"
    ]
  ]
  "itemSiguiente" => array:19 [
    "pii" => "S2444382417300251"
    "issn" => "24443824"
    "doi" => "10.1016/j.gastre.2016.04.012"
    "estado" => "S300"
    "fechaPublicacion" => "2017-02-01"
    "aid" => "1034"
    "copyright" => "Elsevier Espa&#241;a&#44; S&#46;L&#46;U&#46;&#44; AEEH and AEG"
    "documento" => "article"
    "crossmark" => 1
    "subdocumento" => "fla"
    "cita" => "Gastroenterol Hepatol. 2017;40:70-9"
    "abierto" => array:3 [
      "ES" => false
      "ES2" => false
      "LATM" => false
    ]
    "gratuito" => false
    "lecturas" => array:2 [
      "total" => 376
      "formatos" => array:2 [
        "HTML" => 298
        "PDF" => 78
      ]
    ]
    "en" => array:13 [
      "idiomaDefecto" => true
      "cabecera" => "<span class="elsevierStyleTextfn">Original article</span>"
      "titulo" => "Historical analysis of experience with small bowel capsule endoscopy in a Spanish tertiary hospital"
      "tienePdf" => "en"
      "tieneTextoCompleto" => "en"
      "tieneResumen" => array:2 [
        0 => "en"
        1 => "es"
      ]
      "paginas" => array:1 [
        0 => array:2 [
          "paginaInicial" => "70"
          "paginaFinal" => "79"
        ]
      ]
      "titulosAlternativos" => array:1 [
        "es" => array:1 [
          "titulo" => "Análisis histórico de la experiencia en cápsula endoscópica de intestino delgado en un hospital terciario español"
        ]
      ]
      "contieneResumen" => array:2 [
        "en" => true
        "es" => true
      ]
      "contieneTextoCompleto" => array:1 [
        "en" => true
      ]
      "contienePdf" => array:1 [
        "en" => true
      ]
      "resumenGrafico" => array:2 [
        "original" => 0
        "multimedia" => array:7 [
          "identificador" => "fig0015"
          "etiqueta" => "Figure 3"
          "tipo" => "MULTIMEDIAFIGURA"
          "mostrarFloat" => true
          "mostrarDisplay" => false
          "figura" => array:1 [
            0 => array:4 [
              "imagen" => "gr3.jpeg"
              "Alto" => 991
              "Ancho" => 990
              "Tamanyo" => 110000
            ]
          ]
          "descripcion" => array:1 [
            "en" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Inflammatory lesions in patients small bowel Crohn&#39;s disease.</p>"
          ]
        ]
      ]
      "autores" => array:1 [
        0 => array:2 [
          "autoresLista" => "Juan Egea Valenzuela, Gabriel Carrilero Zaragoza, Elena Iglesias Jorquera, Paula Tomás Pujante, Fernando Alberca de las Parras, Fernando Carballo Álvarez"
          "autores" => array:6 [
            0 => array:2 [
              "nombre" => "Juan"
              "apellidos" => "Egea Valenzuela"
            ]
            1 => array:2 [
              "nombre" => "Gabriel"
              "apellidos" => "Carrilero Zaragoza"
            ]
            2 => array:2 [
              "nombre" => "Elena"
              "apellidos" => "Iglesias Jorquera"
            ]
            3 => array:2 [
              "nombre" => "Paula"
              "apellidos" => "Tomás Pujante"
            ]
            4 => array:2 [
              "nombre" => "Fernando"
              "apellidos" => "Alberca de las Parras"
            ]
            5 => array:2 [
              "nombre" => "Fernando"
              "apellidos" => "Carballo Álvarez"
            ]
          ]
        ]
      ]
    ]
    "idiomaDefecto" => "en"
    "Traduccion" => array:1 [
      "es" => array:9 [
        "pii" => "S0210570516300449"
        "doi" => "10.1016/j.gastrohep.2016.04.005"
        "estado" => "S300"
        "subdocumento" => ""
        "abierto" => array:3 [
          "ES" => false
          "ES2" => false
          "LATM" => false
        ]
        "gratuito" => false
        "lecturas" => array:1 [
          "total" => 0
        ]
        "idiomaDefecto" => "es"
        "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0210570516300449?idApp=UINPBA00004N"
      ]
    ]
    "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2444382417300251?idApp=UINPBA00004N"
    "url" => "/24443824/0000004000000002/v1_201703060044/S2444382417300251/v1_201703060044/en/main.assets"
  ]
  "en" => array:21 [
    "idiomaDefecto" => true
    "cabecera" => "<span class="elsevierStyleTextfn">Original article</span>"
    "titulo" => "Characteristics and course of chronic hepatitis B e antigen-negative infection"
    "tieneTextoCompleto" => true
    "paginas" => array:1 [
      0 => array:2 [
        "paginaInicial" => "59"
        "paginaFinal" => "69"
      ]
    ]
    "autores" => array:1 [
      0 => array:4 [
        "autoresLista" => "Antonio Guardiola Arévalo, Rafael Gómez Rodríguez, Marta Romero Gutiérrez, Ana Zaida Gómez Moreno, Almudena García Vela, Raquel Sánchez Simón, Cesar Gómez Hernando, Eva María Andrés Esteban"
        "autores" => array:8 [
          0 => array:4 [
            "nombre" => "Antonio"
            "apellidos" => "Guardiola Arévalo"
            "email" => array:1 [
              0 => "antonio.guardiola@salud.madrid.com"
            ]
            "referencia" => array:3 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">a</span>"
                "identificador" => "aff0005"
              ]
              1 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">b</span>"
                "identificador" => "aff0010"
              ]
              2 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">&#42;</span>"
                "identificador" => "cor0005"
              ]
            ]
          ]
          1 => array:3 [
            "nombre" => "Rafael"
            "apellidos" => "Gómez Rodríguez"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">a</span>"
                "identificador" => "aff0005"
              ]
            ]
          ]
          2 => array:3 [
            "nombre" => "Marta"
            "apellidos" => "Romero Gutiérrez"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">a</span>"
                "identificador" => "aff0005"
              ]
            ]
          ]
          3 => array:3 [
            "nombre" => "Ana Zaida"
            "apellidos" => "Gómez Moreno"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">a</span>"
                "identificador" => "aff0005"
              ]
            ]
          ]
          4 => array:3 [
            "nombre" => "Almudena"
            "apellidos" => "García Vela"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">a</span>"
                "identificador" => "aff0005"
              ]
            ]
          ]
          5 => array:3 [
            "nombre" => "Raquel"
            "apellidos" => "Sánchez Simón"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">c</span>"
                "identificador" => "aff0015"
              ]
            ]
          ]
          6 => array:3 [
            "nombre" => "Cesar"
            "apellidos" => "Gómez Hernando"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">d</span>"
                "identificador" => "aff0020"
              ]
            ]
          ]
          7 => array:3 [
            "nombre" => "Eva María"
            "apellidos" => "Andrés Esteban"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">e</span>"
                "identificador" => "aff0025"
              ]
            ]
          ]
        ]
        "afiliaciones" => array:5 [
          0 => array:3 [
            "entidad" => "Servicio de Aparato Digestivo, Hospital Virgen de la Salud, Toledo, Spain"
            "etiqueta" => "a"
            "identificador" => "aff0005"
          ]
          1 => array:3 [
            "entidad" => "Servicio de Aparato Digestivo, Hospital Universitario de Fuenlabrada, Fuenlabrada, Madrid, Spain"
            "etiqueta" => "b"
            "identificador" => "aff0010"
          ]
          2 => array:3 [
            "entidad" => "Anatomía Patológica, Hospital Virgen de la Salud, Toledo, Spain"
            "etiqueta" => "c"
            "identificador" => "aff0015"
          ]
          3 => array:3 [
            "entidad" => "Microbiología, Hospital Virgen de la Salud, Toledo, Spain"
            "etiqueta" => "d"
            "identificador" => "aff0020"
          ]
          4 => array:3 [
            "entidad" => "Universidad Autónoma de Madrid, Madrid, Spain"
            "etiqueta" => "e"
            "identificador" => "aff0025"
          ]
        ]
        "correspondencia" => array:1 [
          0 => array:3 [
            "identificador" => "cor0005"
            "etiqueta" => "&#8270;"
            "correspondencia" => "Corresponding author."
          ]
        ]
      ]
    ]
    "titulosAlternativos" => array:1 [
      "es" => array:1 [
        "titulo" => "Características y evolución de la infección crónica por virus de la hepatitis B antígeno e negativo"
      ]
    ]
    "resumenGrafico" => array:2 [
      "original" => 0
      "multimedia" => array:7 [
        "identificador" => "fig0010"
        "etiqueta" => "Figure 2"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr2.jpeg"
            "Alto" => 1803
            "Ancho" => 2413
            "Tamanyo" => 215108
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Reason for HBV infection diagnosis. PC, primary care.</p>"
        ]
      ]
    ]
    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Chronic hepatitis B virus (HBV) infection is a global public health problem. An estimated 350&#8211;400<span class="elsevierStyleHsp" style=""></span>million people worldwide have chronic HBV infection,<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">1</span></a> and around 620,000 people die annually from HBV-related causes.<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">2</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Chronic HBV infection can present as hepatitis B e antigen (HBeAg) positive (+) or negative (&#8722;). HBeAg(&#8722;) chronic infection occurs after HBeAg seroconversion. In 75% of cases, the patient seroconverts from an HBeAg(+) chronic hepatitis state to an inactive HBV carrier (IC) state, characterised by persistently normal transaminases and low HBV deoxyribonucleic acid (DNA) (generally &#60;2000<span class="elsevierStyleHsp" style=""></span>IU/mL), with little histological damage. In the remaining 25%, HBeAg seroconversion gives rise to HBeAg(&#8722;) chronic hepatitis, either directly, mostly as a result of mutations that occur in the precore and/or core promoter region, or secondary to reactivation from the IC state, in which there are periods of reactivation with a pattern of fluctuating HBV DNA (HBV-DNA) and aminotransferase levels, and active hepatitis.<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">3</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">The HBeAg(&#8722;) chronic infection phase was first described in Mediterranean countries,<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">4</span></a> but has now been reported worldwide.<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">5</span></a> Studies from Europe, Asia and the United States describe an increase in the prevalence of these types of patients,<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">6</span></a> mainly due to ageing of the infected population, and it is the most common form of chronic hepatitis B not only in Europe, but worldwide,<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">7</span></a> currently affecting 85&#8211;90% of patients. In our published series of patients with chronic HBV infection,<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">8</span></a> those with HBeAg(&#8722;) chronic infection represented the largest group (87.61%), similar to other studies recently published in Spain,<a class="elsevierStyleCrossRefs" href="#bib0320"><span class="elsevierStyleSup">9,10</span></a> other Mediterranean countries,<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">11</span></a> and more remote regions, such as Asia<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">12</span></a> and South America.<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">13</span></a> Since HBeAg(&#8722;) patients are the largest HBV infection group, we set out to study the characteristics and clinical course of this patient group in our healthcare area.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Materials and methods</span><p id="par0020" class="elsevierStylePara elsevierViewall">Observational, retrospective cohort study of patients diagnosed with HBeAg(&#8722;) chronic HBV infection at the time of diagnosis in our healthcare area from June 2005 to July 2011, with follow-up through December 2012.</p><p id="par0025" class="elsevierStylePara elsevierViewall">All patients over the age of 13 years, HBsAg(+) for more than 6 months, with HBeAg(&#8722;) and Anti-HBeAg(+) were included. Exclusion criteria were: Patients coinfected with human immunodeficiency virus (HIV), hepatitis C virus (HCV) and/or hepatitis D virus (HDV); presence of advanced renal failure (creatinine clearance &#60;30<span class="elsevierStyleHsp" style=""></span>mL/min and/or dialysis) (since they are monitored by the nephrology department), other associated liver diseases (study of thyroid hormones, autoimmunity, iron profile [haemochromatosis gene if transferrin saturation was greater than 45% in 2 tests], urinary porphyrins, alpha-1 antitrypsin, blood copper, urinary copper and ceruloplasmin; also excluded were patients with obesity (body mass index [BMI]<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>35<span class="elsevierStyleHsp" style=""></span>kg/m<span class="elsevierStyleSup">2</span>), steatohepatitis findings on liver biopsy, no definitive diagnosis of cirrhosis-induced chronic HBV infection and alcohol consumption &#8805;40<span class="elsevierStyleHsp" style=""></span>g/day, as well as patients who had received previous treatment for HBV infection.</p><p id="par0030" class="elsevierStylePara elsevierViewall">Sociodemographic characteristics, epidemiological and clinical data at diagnosis and the reason chronic HBV infection was diagnosed were recorded. During the course of the study, analytical and serological variables, HBV-DNA measured by polymerase chain reaction (PCR), as well as hospital admissions and their reasons, were recorded every 6<span class="elsevierStyleHsp" style=""></span>&plusmn;<span class="elsevierStyleHsp" style=""></span>2 months. Cirrhotic patients had ultrasound follow-up every 6 months and non-cirrhotic patients every 1 or 2 years.</p><p id="par0035" class="elsevierStylePara elsevierViewall">A liver fibrosis study was performed by liver biopsy (according to the METAVIR classification<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">14</span></a>), as per the indications of the current clinical guidelines. The following categories were established for this study: normal or minimal changes (A0-F0), different grades of fibrosis, and cirrhosis (F4). If there was no liver biopsy, but FibroScan<span class="elsevierStyleSup">&reg;</span> had been carried out, fibrosis was based the results of the scan, using the system presented by Vigan&ograve; et al.<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">15</span></a> as a reference, where: F0-1 (from 2.5 to 6.2<span class="elsevierStyleHsp" style=""></span>kPa), normal; F2-3 (from 6.2 to 13.1<span class="elsevierStyleHsp" style=""></span>kPa), different grades of inflammation-fibrosis; and F4 (&#62;13.1<span class="elsevierStyleHsp" style=""></span>kPa), cirrhosis; which correspond to the fibrosis values in the METAVIR system used for the liver biopsies. Patients diagnosed with liver cirrhosis using clinical-analytical data or imaging tests, in whom liver biopsy or FibroScan<span class="elsevierStyleSup">&reg;</span> were not required to reach the diagnosis, were also categorised as F4 for the purposes of the study.</p><p id="par0040" class="elsevierStylePara elsevierViewall">Clinical follow-up of patients continued until the last check-up at the hepatology clinic. The analytical study included all tests up to the last follow-up laboratory test with HBV serology ordered by the hepatology unit. Only patients with 3 or more tests during follow-up were included in the analysis. In patients who required medical treatment for chronic HBV infection, the clinical follow-up was evaluated until the date of the visit at which treatment was started, and the analytical follow-up until the last test prior to this.</p><p id="par0045" class="elsevierStylePara elsevierViewall">ICs were defined as all patients with persistently normal alanine transaminase (ALT) (&#60;40<span class="elsevierStyleHsp" style=""></span>mU/mL, and low HBV-DNA, discriminating among those with persistent HBV-DNA &#60;2000<span class="elsevierStyleHsp" style=""></span>IU/mL (pure ICs), and those with occasional HBV-DNA between 2000 and 20,000<span class="elsevierStyleHsp" style=""></span>IU/mL. Indeterminate state was defined as a patient presenting persistently normal or fluctuating ALT with slight elevations (generally &#60;2 upper limit of normal [ULN]) and occasionally peak HBV-DNA &#62;20,000<span class="elsevierStyleHsp" style=""></span>IU/mL. Reactivation of an IC to HBeAg(&#8722;) chronic hepatitis B (CHB) was defined as any patient in whom the first 3 ALT results were normal (&#60;40<span class="elsevierStyleHsp" style=""></span>mU/mL) and HBV-DNA was low (&#60;20,000<span class="elsevierStyleHsp" style=""></span>IU/mL) but subsequently presented elevated ALT values above 40<span class="elsevierStyleHsp" style=""></span>mU/mL together with HBV-DNA &#62;20,000<span class="elsevierStyleHsp" style=""></span>IU/mL. HBeAg(&#8722;) CHB phase at diagnosis was defined as any patient who, from the first laboratory tests, persistently presented ALT &#62;40<span class="elsevierStyleHsp" style=""></span>mU/mL and HBV-DNA &#62;20,000<span class="elsevierStyleHsp" style=""></span>IU/mL.</p><p id="par0050" class="elsevierStylePara elsevierViewall">Data from patients who presented cirrhosis during the clinical course, together with associated complications (hepatic encephalopathy [HE]), variceal gastrointestinal bleeding (VGIB), oedematous ascitic decompensation (OAD) or hepatocellular carcinoma (HCC) were recorded. HCC was diagnosed as space-occupying lesions &#62;1<span class="elsevierStyleHsp" style=""></span>cm in patients with liver cirrhosis, where at least one imaging test (tomography and/or contrast magnetic resonance imaging) showed a typical HCC pattern (enhancement in the arterial phase and washout in the portal or late phase). A histological study was performed in patients with atypical or suspicious radiological patterns, and in those with no liver cirrhosis. Adverse events during the study were defined as: presentation of cirrhosis, any of its complications, HCC in a non-cirrhotic liver, and/or need for treatment during the clinical course.</p><p id="par0055" class="elsevierStylePara elsevierViewall">The study was approved by the hospital ethics committee.</p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Statistical analysis</span><p id="par0060" class="elsevierStylePara elsevierViewall">Statistical analysis was performed using SPSS software, v. 20.0 (IBM Corporation, 2011). Categorical variables are described as using the count (percentage). Quantitative variables are described using the mean<span class="elsevierStyleHsp" style=""></span>&plusmn;<span class="elsevierStyleHsp" style=""></span>standard deviation if distribution is normal, and using the median (interquartile range [IQR]) if this hypothesis is not met.</p><p id="par0065" class="elsevierStylePara elsevierViewall">The distribution between dichotomous and categorical variables was compared using contingency tables with the Chi-square or Fisher&#39;s test, as applicable. Comparison of means between qualitative variables was performed using Student&#39;s <span class="elsevierStyleItalic">t</span>-test when 2 means were compared, or one-factor analysis of variance (ANOVA) when more than 2 means were compared, if normality criteria were met. If the variable of interest did not meet the assumption of normality, we used the non-parametric Mann&#8211;Whitney <span class="elsevierStyleItalic">U</span> test or the Kruskal&#8211;Wallis <span class="elsevierStyleItalic">H</span> test to compare the equality of the distribution of the quantitative variable in 2 groups, or in more than 2 groups, respectively.</p><p id="par0070" class="elsevierStylePara elsevierViewall">Patient evolution was studied using tests for dependent samples, such as the Student&#39;s <span class="elsevierStyleItalic">t</span>-test for related variables or ANOVA for repeated measures, if the variable had a normal distribution, or the Wilcoxon or Friedman test if not. A <span class="elsevierStyleItalic">p</span> value<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0.05 was considered significant.</p></span></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Results</span><p id="par0075" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a> shows the selection flow chart for HBsAg(+) patients during the study period who met all the inclusion and none of the exclusion criteria; 138 patients were included, 126 of whom had analytical follow-up.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0080" class="elsevierStylePara elsevierViewall">The mean age at diagnosis was 40.5<span class="elsevierStyleHsp" style=""></span>&plusmn;<span class="elsevierStyleHsp" style=""></span>12.2 years (56.5% of patients diagnosed before age 40). Fifty-four percent were women and 38% were of foreign origin. Diagnosis in Spanish natives and immigrants varied over time, with immigrant patients having increased significantly in recent years (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0.001). Immigrants were predominantly from Eastern Europe (46%), mainly Romania (87.5% of those from this area), followed by Africa (31%), mainly Morocco (43% of Africans), Asia (10%), Central America (9%) and the Middle East (4%).</p><p id="par0085" class="elsevierStylePara elsevierViewall">In terms of epidemiology, 34 patients had a family history of HBV infection (24.6%), none were intravenous drug users or former users, 5.8% had previous transfusions, 5.1% had tattoos, and 1.45% had piercings.</p><p id="par0090" class="elsevierStylePara elsevierViewall">Chronic HBV infection had been diagnosed for various reasons (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>). The most common was hypertransaminasaemia (20.29%); however, grouping all the reasons for HBV screening together (pregnancy, fertility, family history, blood donors, or at the various clinics prior to immunosuppressant treatments) showed that hypertransaminasaemia was the reason for diagnosis in 55.07% of patients.</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0095" class="elsevierStylePara elsevierViewall">Twelve of the 138 patients (8.69%) presented signs or symptoms at diagnosis. These were clearly related with chronic HBV infection in only 1 patient (0.72%), as he presented OAD at diagnosis. Some patients presented symptoms that could be disease-related (3 patients with asthenia, 2 with arthralgia-arthritis and 1 with haematuria), while others presented more non-specific or unrelated symptoms (2 with dyspepsia, 1 with erythema nodosum, 1 with uveitis, and another with non-specific abdominal pain). On examination, only 1 patient presented stigmata of chronic liver disease at diagnosis (the same patient who had been diagnosed with OAD).</p><p id="par0100" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> shows the biochemistry results at the time of diagnosis. ALT at diagnosis was normal in 103 patients (74.6%). Of these, 95 (91.26%) presented HBV-DNA &#60;20,000<span class="elsevierStyleHsp" style=""></span>IU/mL and 67 (64.08%) &#60;2000<span class="elsevierStyleHsp" style=""></span>IU/mL at diagnosis. Patients with normal ALT at diagnosis vs abnormal ALT values had a statistically significant lower viral load (916 [IQR: 110&#8211;3830]<span class="elsevierStyleHsp" style=""></span>IU/mL vs 6840 [IQR: 479&#8211;38,000]<span class="elsevierStyleHsp" style=""></span>IU/mL; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.003). The mean quantitative viral load at diagnosis was 43,726<span class="elsevierStyleHsp" style=""></span>&plusmn;<span class="elsevierStyleHsp" style=""></span>238,701<span class="elsevierStyleHsp" style=""></span>IU/mL, with a median of 6230<span class="elsevierStyleHsp" style=""></span>IU/mL. We defined 4 groups based on HBV-DNA at diagnosis: undetectable (14%); 0&#8211;2000<span class="elsevierStyleHsp" style=""></span>IU/mL (42%); 2000&#8211;20,000<span class="elsevierStyleHsp" style=""></span>IU/mL (27%), and &#62;20,000<span class="elsevierStyleHsp" style=""></span>IU/mL (17%); with patients with HBV-DNA &#60;2000<span class="elsevierStyleHsp" style=""></span>IU/mL accounting for 56%.</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0105" class="elsevierStylePara elsevierViewall">Information on hepatic fibrosis was obtained during follow-up by histology in 36 cases and by FibroScan<span class="elsevierStyleSup">&reg;</span> in 28. No fibrosis was detected in 36 patients (55.4%), 25 presented different grades of inflammation-fibrosis (38.5%), and 4 presented cirrhosis (6.1%), one of whom was diagnosed by clinical-analytical and ultrasound findings at diagnosis, having commenced the study with OAD. The 4 patients with cirrhosis (3.1%) were men (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.024), with mean age greater than that of patients without cirrhosis (61.7<span class="elsevierStyleHsp" style=""></span>&plusmn;<span class="elsevierStyleHsp" style=""></span>8.6 years vs 39.8<span class="elsevierStyleHsp" style=""></span>&plusmn;<span class="elsevierStyleHsp" style=""></span>11.7 years; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.003), and classified as Child&#8211;Turcotte&#8211;Pugh stage A at diagnosis.</p><p id="par0110" class="elsevierStylePara elsevierViewall">Analytical follow-up was performed in 126 patients, with a mean follow-up time of 33.6<span class="elsevierStyleHsp" style=""></span>&plusmn;<span class="elsevierStyleHsp" style=""></span>22.1 months, and an average of 6.5 laboratory tests per patient. Mean clinical follow-up time was 42.14<span class="elsevierStyleHsp" style=""></span>&plusmn;<span class="elsevierStyleHsp" style=""></span>21.50 months. Median peak ALT was 32 (IQR: 23.5&#8211;65)<span class="elsevierStyleHsp" style=""></span>mU/mL, and the median time to reach this peak was 10.4 (IQR: 4.4&#8211;25) months. The maximum median viral load value was 3620 (IQR: 531&#8211;13,900)<span class="elsevierStyleHsp" style=""></span>IU/mL, and the minimum 216 (IQR: 30&#8211;1095)<span class="elsevierStyleHsp" style=""></span>IU/mL Time to reach the HBV-DNA peak was a median of 11.2 (IQR: 3.5&#8211;23.6) months. Of the 108 patients who presented a detectable viral load at diagnosis, this remained detectable in 81 (75%), became undetectable in 18 (16.67%) and fluctuated between detectable and undetectable in 9 (8.33%). Of the 18 patients with an undetectable viral load, the viral load remained undetectable in 11 (61.11%%), became detectable in 6 (33.33%) and fluctuated in 1 (5.56%).</p><p id="par0115" class="elsevierStylePara elsevierViewall">If we analyse the trend in the percentage of patients with HBV-DNA &#60;2000<span class="elsevierStyleHsp" style=""></span>IU/mL and &#60;20,000<span class="elsevierStyleHsp" style=""></span>IU/mL at each point in the study, we can see in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>A how the percentage of patients with lower HBV-DNA tends to increase over the study follow-up, although significant differences were only observed in 2 of the study periods. Excluding patients who started treatment from the study may cause bias, as these generally had a higher viral load, although as can be observed in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>B, this trend continues, but with no significant differences in any period.</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0120" class="elsevierStylePara elsevierViewall">Just over three quarters of patients (77.77%) were in an IC state (56.1% with persistent HBV-DNA &#60;2000<span class="elsevierStyleHsp" style=""></span>IU/mL and 44.9% with occasional HBV-DNA between 2000 and 20,000<span class="elsevierStyleHsp" style=""></span>IU/mL). Of the patients in this group, 27.5% presented elevated ALT &#60;2<span class="elsevierStyleHsp" style=""></span>ULN at diagnosis or occasionally during follow-up, associated with steatohepatitis and/or sporadic alcohol consumption, not related to the disease activity.</p><p id="par0125" class="elsevierStylePara elsevierViewall">There were 8 patients (6.34%) in an indeterminate state (ALT normal or slightly fluctuating, with occasional HBV-DNA peak &#62;20,000<span class="elsevierStyleHsp" style=""></span>IU/mL). Of these, 5 presented persistently normal ALT, and 3 presented slight fluctuations in ALT, with peak ALT during the clinical course no higher than 97<span class="elsevierStyleHsp" style=""></span>mU/mL (mean ALT of 64.25<span class="elsevierStyleHsp" style=""></span>mU/mL), with no findings of liver disease in the ultrasound imaging; the highest ALT peak (97<span class="elsevierStyleHsp" style=""></span>mU/mL) was observed in a patient with steatosis on the ultrasound and dyslipidaemia. These 8 patients underwent a liver fibrosis study, by FibroScan<span class="elsevierStyleSup">&reg;</span> and/or liver biopsy, all with normal results.</p><p id="par0130" class="elsevierStylePara elsevierViewall">A total of 15.87% of patients were in an HBeAg(&#8722;) CHB state since diagnosis. No reactivations from IC to HBeAg(&#8722;) CHB were observed, although we received 1 patient who had been referred for treatment due to reactivation secondary to lymphoma treatment. <a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a> shows the evolution of the patients, as well as complications; <a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a> presents the characteristics of patients in an indeterminate state, and <a class="elsevierStyleCrossRef" href="#tbl0025">Table 5</a> compares ICs and patients in an indeterminate state.</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><elsevierMultimedia ident="tbl0020"></elsevierMultimedia><elsevierMultimedia ident="tbl0025"></elsevierMultimedia><p id="par0135" class="elsevierStylePara elsevierViewall">Twenty patients received pharmacological treatment, according to the indications of the current clinical guidelines,<a class="elsevierStyleCrossRefs" href="#bib0355"><span class="elsevierStyleSup">16,17</span></a> accounting for 15.5% of the series. Treatment indications were: 4 for liver cirrhosis (20% of those treated) &#8211; 3 on detection of viral load and 1 who started the study with OAD &#8211;; 1 on presentation of an HBV-DNA peak &#62;2000<span class="elsevierStyleHsp" style=""></span>IU/mL and F2 on liver biopsy; and 16 patients for presenting an HBeAg(&#8722;) CHB phase (80% of those treated), one of whom did not start treatment as he abandoned follow-up. Of the 16 patients in an HBeAg(&#8722;) CHB state, 13 had presented abnormal ALT levels since diagnosis, and 3 during the course of the study.</p><p id="par0140" class="elsevierStylePara elsevierViewall">Five patients lost HBsAg (4%). Median time to HBsAg clearance was 26.47 (IQR: 8.64&#8211;43.94) months. Mean annual rate of HBsAg loss was 0.94%, and the cumulative rate at 3 years was 2.83%. Mean age of patients with HBsAg loss was 54.7<span class="elsevierStyleHsp" style=""></span>&plusmn;<span class="elsevierStyleHsp" style=""></span>7.1<span class="elsevierStyleHsp" style=""></span>years, while the mean age of those with no HBsAg loss was 38.7<span class="elsevierStyleHsp" style=""></span>&plusmn;<span class="elsevierStyleHsp" style=""></span>10.9<span class="elsevierStyleHsp" style=""></span>years (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.004). None of the patients with HBsAg loss presented complications over their clinical course; 3 of the 5 patients with HBsAg loss presented seroconversion to Anti-HBs (60% of those who cleared HBsAg). Median time from HBsAg loss to seroconversion was 10.5 (IQR: 0&#8211;22.7) months. Eighty percent of patients who cleared HBsAg presented ALT levels &#60;40<span class="elsevierStyleHsp" style=""></span>mU/mL and HBV-DNA &#60;2000<span class="elsevierStyleHsp" style=""></span>IU/mL (80% HBV-DNA undetectable) at diagnosis. <a class="elsevierStyleCrossRef" href="#tbl0030">Table 6</a> shows the comparative study of the ALT and HBV-DNA (baseline and peak) between patients with and without HBsAg loss.</p><elsevierMultimedia ident="tbl0030"></elsevierMultimedia><p id="par0145" class="elsevierStylePara elsevierViewall">Five patients developed complications (3.6%). One had OAD and 4 HCC. Mean time to the complication was 3.5 years; 4 patients developed HCC (2.9%), 2 of whom presented cirrhosis and 2 did not (50% of those who developed HCC). All were Spanish and over 40 years of age (mean age 61.75<span class="elsevierStyleHsp" style=""></span>&plusmn;<span class="elsevierStyleHsp" style=""></span>11.9), and 3 of the 4 were men. In two of these patients, cirrhosis was not identified by symptoms, laboratory tests, ultrasound or liver biopsy (both A1F0). The annual rate of development of HCC in patients with cirrhosis was 17.85%. Patients with complications were significantly older than those with no complications: 62.5<span class="elsevierStyleHsp" style=""></span>&plusmn;<span class="elsevierStyleHsp" style=""></span>10.3 years vs 39.63<span class="elsevierStyleHsp" style=""></span>&plusmn;<span class="elsevierStyleHsp" style=""></span>11.5 years (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.001).</p><p id="par0150" class="elsevierStylePara elsevierViewall">During follow-up, 5 patients were admitted for causes related to the HBV infection (3.87%), 80% in relation to the HCC diagnosis, treatment or surgery, and 20% for OAD.</p><p id="par0155" class="elsevierStylePara elsevierViewall">Two patients died (1.4%), one due to pulmonary squamous cell carcinoma and another to cholangiocarcinoma; the latter is the only death that might be related to the HBV infection (0.72%). The patient was a Romanian man who had been diagnosed at age 42 as a result of a study for dissociated cholestasis. At diagnosis he had ALT &#60;40<span class="elsevierStyleHsp" style=""></span>mU/mL and undetectable HBV-DNA; the HBV-DNA remained undetectable during follow-up, with no HBsAg loss. Gastroscopy did not show portal hypertension, abdominal ultrasound found no signs of chronic liver disease, and the patient presented no clinical, analytical or supplementary tests suggestive of cirrhosis.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Discussion</span><p id="par0160" class="elsevierStylePara elsevierViewall">Few recent studies have focussed on chronic HBV infection in Spain, and even fewer focused only on HBeAg(&#8722;) patients, although these make up the largest group in our clinics. Patients with HBeAg(&#8722;) CHB in older studies were between 40 and 55 years of age,<a class="elsevierStyleCrossRefs" href="#bib0365"><span class="elsevierStyleSup">18,19</span></a> older than patients with HBeAg(+) CHB.<a class="elsevierStyleCrossRef" href="#bib0375"><span class="elsevierStyleSup">20</span></a> In a more recent French series, the mean age of HBeAg(&#8722;) patients was 46.4<span class="elsevierStyleHsp" style=""></span>&plusmn;<span class="elsevierStyleHsp" style=""></span>14.4 years, although a sub-analysis of naive patients in the same study found that the mean age was 40.9<span class="elsevierStyleHsp" style=""></span>&plusmn;<span class="elsevierStyleHsp" style=""></span>14.8 years,<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">7</span></a> which is consistent with our findings, and with other studies similar to ours.<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">9</span></a></p><p id="par0165" class="elsevierStylePara elsevierViewall">Older series noted a predominance of men (male/female ratio of 4.6/1.7),<a class="elsevierStyleCrossRef" href="#bib0375"><span class="elsevierStyleSup">20</span></a> and this continues to be the case in recent series (75&#8211;88%).<a class="elsevierStyleCrossRefs" href="#bib0380"><span class="elsevierStyleSup">21,22</span></a> Although in recent studies with well-selected, treatment-naive patients the male/female ratio remains predominantly male (2.3/1.5),<a class="elsevierStyleCrossRefs" href="#bib0310"><span class="elsevierStyleSup">7,13,23</span></a> the difference is smaller, and some even show a slight predominance of women.<a class="elsevierStyleCrossRef" href="#bib0395"><span class="elsevierStyleSup">24</span></a> Our findings show a predominance of women (54%). This could be due to the strict selection criteria used to avoid bias in the natural course of the disease, such as excluding patients with alcohol consumption&#8212;which is usually more common in men&#8212;or to the high percentage of patients diagnosed during antenatal screening (16.6%).</p><p id="par0170" class="elsevierStylePara elsevierViewall">Immigration has significantly affected the epidemiology of this infection. The last 2&#8211;3 decades have seen an increase in immigration from regions with high or intermediate prevalence of chronic HBV infection to industrialised countries,<a class="elsevierStyleCrossRefs" href="#bib0310"><span class="elsevierStyleSup">7,25</span></a> including Spain.<a class="elsevierStyleCrossRefs" href="#bib0315"><span class="elsevierStyleSup">8,9</span></a> In our series, the immigrant population accounts for 38% on average, with the ratio of immigrants to Spanish nationals increasing in the last few years of the study, a finding comparable to that described in a recent study conducted in Greece over a similar period.<a class="elsevierStyleCrossRef" href="#bib0405"><span class="elsevierStyleSup">26</span></a> Hence, screening is important in this population group, especially in pregnant women. Thus, in our study, 16% of patients were diagnosed during pregnancy, but there was a significant difference between Spanish and immigrant women (22.2% vs 44.8%; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.04).</p><p id="par0175" class="elsevierStylePara elsevierViewall">Twenty-four percent of patients in our series had a family history of HBV infection; other studies have reported percentages ranging from 13 to 63%.<a class="elsevierStyleCrossRefs" href="#bib0390"><span class="elsevierStyleSup">23,27</span></a> A recent Brazilian study<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">13</span></a> described possible vertical or intrafamilial transmission in 43% of patients. None of our patients had been infected by vertical transmission, no doubt because this is rarely seen in countries with developed healthcare systems, where antenatal screening programmes (16% of patients in our series were identified for this reason, accounting for 38% of women), vaccination, and primary prophylaxis in childbirth and the post-partum period are well-established. Vertical transmission is highly unlikely in this setting. Ten percent of patients in our series were diagnosed by screening prompted by family history, possibly because this testing is not done in the large foreign population. Saliva has been suggested as a possible mechanism of HBV transmission,<a class="elsevierStyleCrossRef" href="#bib0415"><span class="elsevierStyleSup">28</span></a> and could explain the percentage of patients with no obvious risk factors for acquiring the infection.</p><p id="par0180" class="elsevierStylePara elsevierViewall">At present, based on the accumulated evidence,<a class="elsevierStyleCrossRef" href="#bib0420"><span class="elsevierStyleSup">29</span></a> serological screening for hepatitis B has been established in patients scheduled for immunosuppressant treatments or chemotherapy. Thus, up to 8% of patients in our series (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>) were diagnosed with chronic HBV infection as a result of screening performed in rheumatology, haematology and dermatology clinics. Nevertheless, we must continue to raise awareness of the need for screening, since reactivations continue to occur in this patient group. An example of this is the reactivation to HBeAg(&#8722;) CHB presented by 1 patient treated for lymphoma in our series.</p><p id="par0185" class="elsevierStylePara elsevierViewall">Most patients with HBeAg(&#8722;) chronic HBV infection in our series were asymptomatic when they came to the clinic, and of the patients with symptoms (fewer than 9%), these were clearly related to the underlying liver disease in only one patient, who already had OAD. The other symptoms were non-specific. During follow-up, only one patient death was HBV-related, and 5 patients required admission for infection-related causes (3.87%); 80% were admitted in relation to HCC diagnosis, treatment and surgery. Thus, the quality of life of patients with HBeAg(&#8722;) chronic HBV infection can be considered to be good or acceptable in most cases.</p><p id="par0190" class="elsevierStylePara elsevierViewall">Since chronic HBV infection is usually a silent disease, the absence of symptoms is not sufficient to distinguish patients with significant progressive liver disease from ICs.<a class="elsevierStyleCrossRef" href="#bib0425"><span class="elsevierStyleSup">30</span></a> Therefore, a patient with HBsAg(+), HBeAg(&#8722;), Anti-HBe(+), normal ALT and undetectable HBV-DNA in a single test should not be classified as an IC without appropriate follow-up. In our study, we observed how the median peak ALT value was not obtained until 10.4 months, and the peak HBV-DNA until 11.2 months. Studies have reported that the risk of normal ALT at diagnosis changing during follow-up is greater during the first year (15&#8211;20%),<a class="elsevierStyleCrossRefs" href="#bib0430"><span class="elsevierStyleSup">31,32</span></a> and decreases after 3 years of follow-up,<a class="elsevierStyleCrossRefs" href="#bib0435"><span class="elsevierStyleSup">32&#8211;34</span></a> which is consistent with our findings. In the early years of follow-up, therefore, ALT monitoring is indicated in order to establish the disease state in these patients.<a class="elsevierStyleCrossRef" href="#bib0425"><span class="elsevierStyleSup">30</span></a></p><p id="par0195" class="elsevierStylePara elsevierViewall">In line with other studies,<a class="elsevierStyleCrossRefs" href="#bib0450"><span class="elsevierStyleSup">35,36</span></a> HBV-DNA levels in HBeAg(&#8722;) patients decreased in the first year of follow-up due to the transformation of most of these types of patients to ICs, where the viral load becomes low or undetectable. Thus, in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>, we can see how the percentage of patients with low viral load gradually increases over time, suggesting a decrease in the viral load in ICs.</p><p id="par0200" class="elsevierStylePara elsevierViewall">HBsAg clearance is a rare event in the clinical course of patients with chronic HBV infection; thus, it has an estimated incidence of approximately 0.1&#8211;0.8% in patients who acquire the infection in childhood, and 0.4&#8211;2% in those who acquire it in adolescence or adulthood,<a class="elsevierStyleCrossRefs" href="#bib0460"><span class="elsevierStyleSup">37&#8211;40</span></a> as could be the case in our population. More recent studies with 25&#8211;30-year follow-up estimate an annual HBsAg clearance rate of between 1%<a class="elsevierStyleCrossRef" href="#bib0480"><span class="elsevierStyleSup">41</span></a> and 1.8%,<a class="elsevierStyleCrossRef" href="#bib0485"><span class="elsevierStyleSup">42</span></a> similar to our findings (0.94%). Of these patients, approximately half develop Anti-HBs, sometimes several months later.<a class="elsevierStyleCrossRef" href="#bib0490"><span class="elsevierStyleSup">43</span></a> Eighty percent of patients who cleared HBsAg presented ALT &#60;40<span class="elsevierStyleHsp" style=""></span>mU/mL and viral load &#60;2000<span class="elsevierStyleHsp" style=""></span>IU/mL at diagnosis in all cases, being undetectable in 80% of them. This is consistent with the literature,<a class="elsevierStyleCrossRef" href="#bib0495"><span class="elsevierStyleSup">44</span></a> which suggests that patients who clear HBsAg present low or persistently undetectable HBV-DNA years before seroconversion. Although these patients did not present complications over the course of this study, it should be taken into account that patients aged over 50 who clear HBsAg, as in our case, have an increased risk of developing HCC.<a class="elsevierStyleCrossRef" href="#bib0490"><span class="elsevierStyleSup">43</span></a> Therefore, even though at present the accumulated evidence is insufficient to recommend including them in an HCC screening programme, it would be prudent to schedule them for annual or bi-annual follow-up. In fact, some studies suggest that the risk of HCC is not reduced in patients who clear HBsAg compared to those who do not,<a class="elsevierStyleCrossRefs" href="#bib0500"><span class="elsevierStyleSup">45,46</span></a> and that clearing HBsAg does not necessarily imply good prognosis.</p><p id="par0205" class="elsevierStylePara elsevierViewall">The annual rate of progression to cirrhosis in patients with chronic HBV infection is between 1% and 7%,<a class="elsevierStyleCrossRefs" href="#bib0480"><span class="elsevierStyleSup">41,47</span></a> and higher (closer to 7%) in HBeAg(&#8722;) patients. The percentage of cirrhotic patients in our series was 6%, with an annual rate of 1.03% (data not shown, as the study was not conducted specifically with this aim); these low rates have been reported in other studies.<a class="elsevierStyleCrossRef" href="#bib0510"><span class="elsevierStyleSup">47</span></a> This low percentage could be explained by the large number of patients in the IC state. Age is a factor that is clearly related to the development of cirrhosis<a class="elsevierStyleCrossRefs" href="#bib0515"><span class="elsevierStyleSup">48,49</span></a>; thus, in our study, the mean age of patients with cirrhosis was clearly greater than those without. Most studies indicate that the possibility of significant histological damage should be considered in patients over the age of 40.<a class="elsevierStyleCrossRef" href="#bib0525"><span class="elsevierStyleSup">50</span></a> Some studies in developing countries suggest younger ages (around 30 years old<a class="elsevierStyleCrossRef" href="#bib0530"><span class="elsevierStyleSup">51</span></a>), taking into account that these are countries where the infection is mainly transmitted in pregnancy, childbirth and infancy. Thus, the disease has a longer course, which could explain the greater histological damage at an early stage. Another factor clearly related with the development of cirrhosis is being male.<a class="elsevierStyleCrossRef" href="#bib0520"><span class="elsevierStyleSup">49</span></a> This was corroborated in our study, where all patients with cirrhosis were men.</p><p id="par0210" class="elsevierStylePara elsevierViewall">There is a clear association between HCC and liver disease due to HBV,<a class="elsevierStyleCrossRef" href="#bib0535"><span class="elsevierStyleSup">52</span></a> but up to 30&#8211;50% of HBV-associated HCC cases occur in the absence of cirrhosis; in fact, only 50% of our patients who developed HCC presented cirrhosis. In our study, 75% of patients who presented HCC were men, which is consistent with other studies.<a class="elsevierStyleCrossRef" href="#bib0540"><span class="elsevierStyleSup">53</span></a></p><p id="par0215" class="elsevierStylePara elsevierViewall">The mortality described in these types of patients varies from a low rate (1%),<a class="elsevierStyleCrossRef" href="#bib0480"><span class="elsevierStyleSup">41</span></a> to other studies where higher mortality rates are found (15%).<a class="elsevierStyleCrossRef" href="#bib0545"><span class="elsevierStyleSup">54</span></a> We only had 2 deaths; both patients were men over 40 years old at diagnosis. One of the 2 deaths was probably related to HBV infection (0.72% of the series), as the patient developed cholangiocarcinoma.<a class="elsevierStyleCrossRef" href="#bib0550"><span class="elsevierStyleSup">55</span></a></p><p id="par0220" class="elsevierStylePara elsevierViewall">In our study, as in others in the literature, the largest patient group with HBeAg(&#8722;) CHB were the ICs. The latest European guidelines refer to IC in patients with persistently normal ALT and HBV-DNA &#60;2000<span class="elsevierStyleHsp" style=""></span>IU/mL (pure ICs).<a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">17</span></a> However, as explained, this infection is dynamic, and some patients with normal ALT present HBV-DNA peaks between 2000 and 20,000<span class="elsevierStyleHsp" style=""></span>IU/mL over the course of the disease (almost 45% of the ICs in our series). This patient group did not present greater histological damage or more complications during the study follow-up than the pure ICs (<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>). Furthermore, 6% of patients presented an indeterminate state, with HBV-DNA peaks sometimes higher than 20,000<span class="elsevierStyleHsp" style=""></span>IU/mL, but with no significant histological damage or greater incidence of complications compared to ICs (<a class="elsevierStyleCrossRefs" href="#tbl0015">Tables 3&#8211;5</a>). Thus, we propose the term <span class="elsevierStyleItalic">semi-inactive carrier</span> for this group of indeterminate state patients. This group requires closer follow-up until their prognosis can be determined, but it is unclear whether their clinical course is poorer than that of ICs.</p><p id="par0225" class="elsevierStylePara elsevierViewall">Twenty patients (15.5%) were treated during follow-up, 80% in the HBeAg(&#8722;) CHB state. Of these, 81.25% had abnormal ALT at diagnosis, so in the vast majority of cases, patients who required treatment had abnormal ALT levels since the start of follow-up. A recent Spanish study obtained very similar findings to ours in this respect.<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">9</span></a></p><p id="par0230" class="elsevierStylePara elsevierViewall">In summary, patients with HBeAg(&#8722;) chronic HBV infection are generally asymptomatic at diagnosis and during the course of the disease. The occurrence of cirrhosis is rare. It must be remembered that up to half of cases of HCC, which is the main complication, develop in patients without cirrhosis. The percentage of patients who require treatment must also be taken into account.</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Conflicts of interest</span><p id="par0235" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interests.</p></span></span>"
    "textoCompletoSecciones" => array:1 [
      "secciones" => array:11 [
        0 => array:3 [
          "identificador" => "xres810089"
          "titulo" => "Abstract"
          "secciones" => array:4 [
            0 => array:2 [
              "identificador" => "abst0005"
              "titulo" => "Objective"
            ]
            1 => array:2 [
              "identificador" => "abst0010"
              "titulo" => "Materials and methods"
            ]
            2 => array:2 [
              "identificador" => "abst0015"
              "titulo" => "Results"
            ]
            3 => array:2 [
              "identificador" => "abst0020"
              "titulo" => "Conclusion"
            ]
          ]
        ]
        1 => array:2 [
          "identificador" => "xpalclavsec807521"
          "titulo" => "Keywords"
        ]
        2 => array:3 [
          "identificador" => "xres810090"
          "titulo" => "Resumen"
          "secciones" => array:4 [
            0 => array:2 [
              "identificador" => "abst0025"
              "titulo" => "Objetivo"
            ]
            1 => array:2 [
              "identificador" => "abst0030"
              "titulo" => "Material y m&eacute;todos"
            ]
            2 => array:2 [
              "identificador" => "abst0035"
              "titulo" => "Resultados"
            ]
            3 => array:2 [
              "identificador" => "abst0040"
              "titulo" => "Conclusi&oacute;n"
            ]
          ]
        ]
        3 => array:2 [
          "identificador" => "xpalclavsec807522"
          "titulo" => "Palabras clave"
        ]
        4 => array:2 [
          "identificador" => "sec0005"
          "titulo" => "Introduction"
        ]
        5 => array:3 [
          "identificador" => "sec0010"
          "titulo" => "Materials and methods"
          "secciones" => array:1 [
            0 => array:2 [
              "identificador" => "sec0015"
              "titulo" => "Statistical analysis"
            ]
          ]
        ]
        6 => array:2 [
          "identificador" => "sec0020"
          "titulo" => "Results"
        ]
        7 => array:2 [
          "identificador" => "sec0025"
          "titulo" => "Discussion"
        ]
        8 => array:2 [
          "identificador" => "sec0030"
          "titulo" => "Conflicts of interest"
        ]
        9 => array:2 [
          "identificador" => "xack271487"
          "titulo" => "Acknowledgements"
        ]
        10 => array:1 [
          "titulo" => "References"
        ]
      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2016-02-06"
    "fechaAceptado" => "2016-11-04"
    "PalabrasClave" => array:2 [
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec807521"
          "palabras" => array:5 [
            0 => "Hepatitis B virus"
            1 => "Negative HBe antigen"
            2 => "HBe antigen-negative chronic hepatitis"
            3 => "Glutamic pyruvic transaminase"
            4 => "DNA"
          ]
        ]
      ]
      "es" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec807522"
          "palabras" => array:5 [
            0 => "Virus de la hepatitis B"
            1 => "Antígeno HBe(&#8722;)"
            2 => "Hepatitis crónica antígeno HBe(&#8722;)"
            3 => "Glutámico pirúvico transaminasa"
            4 => "ADN"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:2 [
      "en" => array:3 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Objective</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">To describe the epidemiological, analytical and histological characteristics and clinical course of hepatitis B virus (HBV) carriers with negative HBe antigen.</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Materials and methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Observational, retrospective cohort study of HBV carriers with negative HBe antigen (2005&#8211;2012), with no other causes of liver disease.</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">One hundred and thirty-eight patients were included, with mean age 40.5<span class="elsevierStyleHsp" style=""></span>&plusmn;<span class="elsevierStyleHsp" style=""></span>12.2 years; 54% were women, and 38% were of foreign origin; the number of foreign patients significantly increased (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>.001) over the years. Transaminases were normal in nearly 75% and HBV-DNA was &#60;2000<span class="elsevierStyleHsp" style=""></span>IU/mL in 56% of patients at diagnosis. There was a gradual decrease in HBV-DNA levels in inactive carriers over the study period. Fibrosis study was performed in 47% of patients by Fibroscan<span class="elsevierStyleSup">&reg;</span> or liver biopsy: 55.4% normal histology and 6.1% cirrhosis. Just over three quarters of patients (77.77%) were inactive carriers. Treatment was required in 15.5% of patients (20% because of cirrhosis and 80% HBeAg-negative chronic hepatitis B). Five patients cleared HBsAg (annual rate .94%), all of whom presented HBV-DNA &#60;2000<span class="elsevierStyleHsp" style=""></span>IU/mL at diagnosis. Five patients developed complications (3.6%), 4 of them hepatocellular carcinoma (HCC), of which only 2 had cirrhosis. There was 1 HBV-related death (.72%).</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusion</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Among HBV carriers with negative HBe antigen, inactive HBs-Ag carriers are predominant. HBV-DNA gradually decreases in the first few years after diagnosis. Morbidity and mortality are low, especially if glutamic pyruvic transaminase (GPT) is normal and HBV-DNA levels are low at diagnosis. Treatment is needed in a considerable number of patients. HCC is the most frequent complication, even in the absence of cirrhosis.</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0005"
            "titulo" => "Objective"
          ]
          1 => array:2 [
            "identificador" => "abst0010"
            "titulo" => "Materials and methods"
          ]
          2 => array:2 [
            "identificador" => "abst0015"
            "titulo" => "Results"
          ]
          3 => array:2 [
            "identificador" => "abst0020"
            "titulo" => "Conclusion"
          ]
        ]
      ]
      "es" => array:3 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Objetivo</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Describir las caracter&iacute;sticas epidemiol&oacute;gicas, anal&iacute;ticas, histol&oacute;gicas y evolutivas de pacientes con infecci&oacute;n cr&oacute;nica por VHB AgHBe-negativo.</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Material y m&eacute;todos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Estudio observacional de cohorte retrospectivo de pacientes diagnosticados de infecci&oacute;n cr&oacute;nica VHB AgHBe-negativo (2005-2012) sin otras hepatopat&iacute;as.</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Se incluyeron 138 pacientes con edad media de 40,5<span class="elsevierStyleHsp" style=""></span>&plusmn;<span class="elsevierStyleHsp" style=""></span>12,2 a&ntilde;os, de los cuales el 54% eran mujeres. El 38% eran extranjeros, con incremento de estos en los &uacute;ltimos a&ntilde;os (p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0,001). Las transaminasas en el momento del diagn&oacute;stico eran normales en casi el 75% y el ADN-VHB &#60;<span class="elsevierStyleHsp" style=""></span>2.000<span class="elsevierStyleHsp" style=""></span>UI/ml en el 56%. En los portadores inactivos existe una disminuci&oacute;n progresiva de los niveles de ADN-VHB en el periodo de estudio. En el 47% se evalu&oacute; la fibrosis hep&aacute;tica por Fibroscan<span class="elsevierStyleSup">&reg;</span> o biopsia hep&aacute;tica: el 55,4% result&oacute; normal y el 6,1% report&oacute; cirrosis. El 77,77% eran portadores inactivos. Precisaron tratamiento el 15,5% (20% por cirrosis y 80% por HBC AgHBe-negativo). Aclararon el AgHBs 5 pacientes (tasa anual 0,94%), presentando todos al diagn&oacute;stico ADN-VHB &#60;<span class="elsevierStyleHsp" style=""></span>2.000<span class="elsevierStyleHsp" style=""></span>UI/ml. Cinco pacientes desarrollaron alguna complicaci&oacute;n (3,6%), 4 de ellos carcinoma hepatocelular (CHC) (solo 2 presentaban cirrosis). Hubo un fallecimiento relacionado con el VHB (0,72%).</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusi&oacute;n</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Entre los enfermos con infecci&oacute;n cr&oacute;nica por VHB AgHBe-negativo predominan los portadores inactivos. Se produce un progresivo descenso de ADN-VHB en los primeros a&ntilde;os tras el diagn&oacute;stico. Desarrollan poca morbimortalidad, especialmente si existe GPT normal y ADN-VHB bajo al diagn&oacute;stico. Un n&uacute;mero no despreciable de pacientes precisa tratamiento. El CHC es la complicaci&oacute;n m&aacute;s frecuente, incluso en pacientes sin cirrosis.</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0025"
            "titulo" => "Objetivo"
          ]
          1 => array:2 [
            "identificador" => "abst0030"
            "titulo" => "Material y m&eacute;todos"
          ]
          2 => array:2 [
            "identificador" => "abst0035"
            "titulo" => "Resultados"
          ]
          3 => array:2 [
            "identificador" => "abst0040"
            "titulo" => "Conclusi&oacute;n"
          ]
        ]
      ]
    ]
    "NotaPie" => array:1 [
      0 => array:2 [
        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0020">Please cite this article as: Guardiola Ar&eacute;valo A, G&oacute;mez Rodr&iacute;guez R, Romero Guti&eacute;rrez M, G&oacute;mez Moreno AZ, Garc&iacute;a Vela A, S&aacute;nchez Sim&oacute;n R, et al. Caracter&iacute;sticas y evoluci&oacute;n de la infecci&oacute;n cr&oacute;nica por virus de la hepatitis B ant&iacute;geno e negativo. Gastroenterol Hepatol. 2017;40:59&#8211;69.</p>"
      ]
    ]
    "multimedia" => array:8 [
      0 => array:7 [
        "identificador" => "fig0005"
        "etiqueta" => "Figure 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
            "Alto" => 2790
            "Ancho" => 1589
            "Tamanyo" => 174829
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Patient exclusion flow chart.</p>"
        ]
      ]
      1 => array:7 [
        "identificador" => "fig0010"
        "etiqueta" => "Figure 2"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr2.jpeg"
            "Alto" => 1803
            "Ancho" => 2413
            "Tamanyo" => 215108
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Reason for HBV infection diagnosis. PC, primary care.</p>"
        ]
      ]
      2 => array:8 [
        "identificador" => "tbl0005"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at1"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:2 [
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Analyte&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">n&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Median (IQR)<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Haemoglobin (g/dL)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">137&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">14.7 (13.4&#8211;15.5)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">White blood cells (&times;10<span class="elsevierStyleSup">9</span>/L)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">137&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">6.3 (5300&#8211;7800)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Platelets (&times;10<span class="elsevierStyleSup">9</span>/L)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">137&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">211 (177,500&#8211;247,500)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">INR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">121&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0.97 (0.97&#8211;1.0)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Fibrinogen (mg/dL)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">121&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">320 (276&#8211;381)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Albumin (g/dL)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">128&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4.7 (4.4&#8211;4.9)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Total bilirubin (mg/dL)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">137&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0.57 (0.43&#8211;0.82)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">AST (mU/mL)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">136&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">23 (19&#8211;30.7)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">ALT (mU/mL)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">138&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">26 (19&#8211;40.2)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">GGT (mU/mL)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">137&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">16 (11.5&#8211;27)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">ALP (mU/mL)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">137&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">67 (55&#8211;80)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Blood glucose (mg/dL)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">138&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">92.5 (86.7&#8211;99.0)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Total cholesterol (mg/dL)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">138&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">190.5 (168.0&#8211;221.2)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Triglycerides (mg/dL)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">138&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">76.5 (53.7&#8211;109.2)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Alpha-fetoprotein (ng/mL)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">113&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2.5 (1.65&#8211;4.2)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab1359757.png"
              ]
            ]
          ]
          "notaPie" => array:1 [
            0 => array:3 [
              "identificador" => "tblfn0005"
              "etiqueta" => "a"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Data are expressed as median (interquartile range [IQR]: p25&#8211;p75).</p>"
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">General laboratory results at diagnosis.</p>"
        ]
      ]
      3 => array:8 [
        "identificador" => "tbl0010"
        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at2"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:2 [
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">HBV-DNA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Baseline&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">6 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">12 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">18 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">24 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">30 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">36 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">(A)</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>126&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>126&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>126&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>99&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>90&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>84&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>72&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">&#60;2000<span class="elsevierStyleHsp" style=""></span>IU/mL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">56.52%&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">58.16%&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">66.67%&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">67.01%&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">71.59%&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">72.84%&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">83.82%&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">p</span>-value<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0.398&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0.094&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0.479&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0.247&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0.427&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0.045&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="8" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">&#60;<span class="elsevierStyleHsp" style=""></span>20,000<span class="elsevierStyleHsp" style=""></span>IU/mL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">83.33%&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">81.63%&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">91.89%&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">93.81%&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">92.05%&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">95.06%&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">97.06%&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">p</span>-value<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0.363&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0.011&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0.293&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0.319&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0.208&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0.257&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="8" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">(B)</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>106&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>106&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>106&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>77&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>70&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>64&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>52&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">&#60;2000<span class="elsevierStyleHsp" style=""></span>IU/mL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">62.71%&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">70%&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">68.48%&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">66.67%&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">71.01%&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">68.75%&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">81.13%&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">p</span>-value<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0.141&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0.415&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0.401&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0.285&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0.388&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0.059&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="8" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">&#60;<span class="elsevierStyleHsp" style=""></span>20,000<span class="elsevierStyleHsp" style=""></span>IU/mL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">92.37%&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">95%&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">94.57%&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">94.87%&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">95.65%&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">95.31%&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">98.11%&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">p</span>-value<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0.223&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0.45&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0.966&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0.412&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0.962&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0.194&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab1359759.png"
              ]
            ]
          ]
          "notaPie" => array:1 [
            0 => array:3 [
              "identificador" => "tblfn0010"
              "etiqueta" => "a"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Statistical significance with respect to the preceding period.</p>"
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Percentage of patients with HBV-DNA &#60;2000<span class="elsevierStyleHsp" style=""></span>IU/mL and &#60;20,000<span class="elsevierStyleHsp" style=""></span>IU/mL at each point in the study. (A) In the general series, and (B) excluding patients who were treated.</p>"
        ]
      ]
      4 => array:8 [
        "identificador" => "tbl0015"
        "etiqueta" => "Table 3"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at3"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">HCC, hepatocellular carcinoma; OAD, oedematous ascitic decompensation; IC, inactive carrier.</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>126&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " colspan="2" align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Inactive carriers n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>98 (77.77%)</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Indeterminate state n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>8 (6.34%)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">HBeAg(&#8722;) CHB n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>20 (15.87%)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Follow-up time&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " colspan="2" align="left" valign="top">39.82<span class="elsevierStyleHsp" style=""></span>&plusmn;<span class="elsevierStyleHsp" style=""></span>19.91 months</td><td class="td" title="table-entry  " align="left" valign="top">45.25<span class="elsevierStyleHsp" style=""></span>&plusmn;<span class="elsevierStyleHsp" style=""></span>16 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">14.18<span class="elsevierStyleHsp" style=""></span>&plusmn;<span class="elsevierStyleHsp" style=""></span>11.15 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Peak HBV-DNA (IU/mL), n (%)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Pure ICs<br>&#60;2000<br>54 (56.1%)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2000&#8211;20,000<br>44 (44.9%)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#62;20,000 occasionally&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#62;20,000 persistently (except 1 patient with cirrhosis with HBV-DNA between 2000 and 20,000)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Mean peak ALT<span class="elsevierStyleHsp" style=""></span>&plusmn;<span class="elsevierStyleHsp" style=""></span>SD (mIU/mL)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">44.44<span class="elsevierStyleHsp" style=""></span>&plusmn;<span class="elsevierStyleHsp" style=""></span>49.56&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">38.30<span class="elsevierStyleHsp" style=""></span>&plusmn;<span class="elsevierStyleHsp" style=""></span>34.20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">44.63<span class="elsevierStyleHsp" style=""></span>&plusmn;<span class="elsevierStyleHsp" style=""></span>23.42&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">123.7<span class="elsevierStyleHsp" style=""></span>&plusmn;<span class="elsevierStyleHsp" style=""></span>61.56&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Reactivation, n (%)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1 (0.79%) (after lymphoma treatment)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Need for treatment, n (%) and reason&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1 (0.79%)<br>Cirrhosis with OAD; HBV-DNA&#8722;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1 (0.79%)<br>F2 on biopsy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0 (0%)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">20 (100%)<br>&#8226; 3 Cirrhosis with HBV-DNA+<br>&#8226; 16 HBeAg(&#8722;) (1 did not come to receive treatment)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Complication, n (%)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2 (1.58%)<br>&#8226; 1 OAD<br>&#8226; 1 HCC (44 years)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0 (0%)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0 (0%)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3 HCC (15.78%)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Adverse events, n (%)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2 (1.58%)<br>&#8226; 1 Cirrhosis<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>OAD<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>treatment<br>&#8226; 1 HCC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0 (0%)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0 (0%)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4 (21.05%)<br>&#8226; 2 HCC<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>cirrhosis<br>&#8226; 1 Cirrhosis<br>&#8226; 1 HCC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab1359755.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Evolution of patients with 3 or more ALT tests in follow-up.</p>"
        ]
      ]
      5 => array:8 [
        "identificador" => "tbl0020"
        "etiqueta" => "Table 4"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at4"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:3 [
          "leyenda" => "<p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">ALT, alanine transaminase; BMI, body mass index.</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Age (years)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Gender&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Peak ALT<a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">a</span></a> (mU/mL)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Peak HBV-DNA<a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">a</span></a> (IU/mL)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Dyslipidaemia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">BMI 25&#8211;30<span class="elsevierStyleHsp" style=""></span>kg/m<span class="elsevierStyleSup">2</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Abdominal ultrasound&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">FibroScan<span class="elsevierStyleSup">&reg;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Liver biopsy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">53&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Male&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">97&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">24,200&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Steatosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">F1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">22&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Female&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">45&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">31,000&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Steatosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">A0F0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">38&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Male&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">36&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">38,700&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Normal&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">A0F0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">48&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Female&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">31&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">41,700&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Normal&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">F0-1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">18&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Female&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">32&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">48,200&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Normal&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">A0F0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">37&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Female&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">31&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">468,000&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Normal&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">A0F0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">33&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Male&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">58&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">999,000&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Normal&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">A0F0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">40&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Female&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">27&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1,120,000&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Normal&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">F0-1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">A0F0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab1359758.png"
              ]
            ]
          ]
          "notaPie" => array:1 [
            0 => array:3 [
              "identificador" => "tblfn0015"
              "etiqueta" => "a"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0015">Peak values, but which did not meet criteria for chronic hepatitis in follow-up (ALT and HBV-DNA generally low and/or below the upper limit of normal).</p>"
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">Patients in indeterminate state in follow-up.</p>"
        ]
      ]
      6 => array:8 [
        "identificador" => "tbl0025"
        "etiqueta" => "Table 5"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at5"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0090" class="elsevierStyleSimplePara elsevierViewall">ALT, alanine transaminase; HBsAg, hepatitis B surface antigen; HCC, hepatocellular carcinoma; HE, hepatic encephalopathy; NA, not analysable; OAD, oedematous ascitic decompensation; VGIB, variceal gastrointestinal bleeding.</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Inactive carriers (n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>98)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Indeterminate (n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>8)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">p</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Age (years)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">39.80<span class="elsevierStyleHsp" style=""></span>&plusmn;<span class="elsevierStyleHsp" style=""></span>11.37&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">36.09<span class="elsevierStyleHsp" style=""></span>&plusmn;<span class="elsevierStyleHsp" style=""></span>11.90&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0.378&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Sex (men)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">42.27%&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">37.50%&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0.395&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Foreign patients&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">38.78%&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">25%&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0.196&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Follow-up time (months)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">39.82<span class="elsevierStyleHsp" style=""></span>&plusmn;<span class="elsevierStyleHsp" style=""></span>19.91&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">45.25<span class="elsevierStyleHsp" style=""></span>&plusmn;<span class="elsevierStyleHsp" style=""></span>16&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0.454&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Mean peak ALT (mIU/mL)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">41.68<span class="elsevierStyleHsp" style=""></span>&plusmn;<span class="elsevierStyleHsp" style=""></span>43.24&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">44.63<span class="elsevierStyleHsp" style=""></span>&plusmn;<span class="elsevierStyleHsp" style=""></span>23.42&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0.851&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Mean peak HBV-DNA (IU/mL)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3482.16<span class="elsevierStyleHsp" style=""></span>&plusmn;<span class="elsevierStyleHsp" style=""></span>4255.23&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">346,350.00<span class="elsevierStyleHsp" style=""></span>&plusmn;<span class="elsevierStyleHsp" style=""></span>465,811.87&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#60;0.001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">HBsAg clearance&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">5 (5.10%)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0.011&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Cirrhosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0.157&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Disease-related complications (OAD, HCC, VGIB, HE)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2 (both HCC)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0.077&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Reactivations&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">N/A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Need for treatment&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0.039&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">HBV-related death&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0.157&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab1359760.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">Comparison of inactive carriers vs patients in indeterminate state.</p>"
        ]
      ]
      7 => array:8 [
        "identificador" => "tbl0030"
        "etiqueta" => "Table 6"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at6"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0100" class="elsevierStyleSimplePara elsevierViewall">ALT, alanine transaminase; HBsAg, hepatitis B surface antigen.</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="char" valign="top" scope="col" style="border-bottom: 2px solid black">n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>126&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="char" valign="top" scope="col" style="border-bottom: 2px solid black">HBsAg clearance n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>5 (3.97%)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="char" valign="top" scope="col" style="border-bottom: 2px solid black">No HBsAg clearance n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>121 (96.03%)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="char" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">p</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">ALT at diagnosis (mU/mL)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">25.80<span class="elsevierStyleHsp" style=""></span>&plusmn;<span class="elsevierStyleHsp" style=""></span>17.81&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">31.97<span class="elsevierStyleHsp" style=""></span>&plusmn;<span class="elsevierStyleHsp" style=""></span>28.72&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0.421&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Peak ALT (mU/mL)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">34.00<span class="elsevierStyleHsp" style=""></span>&plusmn;<span class="elsevierStyleHsp" style=""></span>22.53&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">43.74<span class="elsevierStyleHsp" style=""></span>&plusmn;<span class="elsevierStyleHsp" style=""></span>44.94&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0.566&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">HBV-DNA at diagnosis (IU/mL)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">21.60<span class="elsevierStyleHsp" style=""></span>&plusmn;<span class="elsevierStyleHsp" style=""></span>48.30&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">5214.70<span class="elsevierStyleHsp" style=""></span>&plusmn;<span class="elsevierStyleHsp" style=""></span>16,074&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0.002&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Peak HBV-DNA (IU/mL)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1089.60<span class="elsevierStyleHsp" style=""></span>&plusmn;<span class="elsevierStyleHsp" style=""></span>1869.56&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">31,100.22<span class="elsevierStyleHsp" style=""></span>&plusmn;<span class="elsevierStyleHsp" style=""></span>154,440.70&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0.053&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab1359756.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0095" class="elsevierStyleSimplePara elsevierViewall">Comparison of ALT and HBV-DNA between patients with and without HBsAg loss.</p>"
        ]
      ]
    ]
    "bibliografia" => array:2 [
      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0005"
          "bibliografiaReferencia" => array:55 [
            0 => array:3 [
              "identificador" => "bib0280"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The natural history and treatment of chronic hepatitis B: a critical evaluation of standard treatment criteria and end points"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "C.L. Lai"
                            1 => "M.F. Yeun"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Ann Intern Med"
                        "fecha" => "2007"
                        "volumen" => "147"
                        "paginaInicial" => "58"
                        "paginaFinal" => "61"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17606962"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib0285"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A mathematical model to estimate global hepatitis B disease burden and vaccination impact"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "S.T. Goldstein"
                            1 => "F. Zhou"
                            2 => "S.C. Hadler"
                            3 => "B.P. Bell"
                            4 => "E.E. Mast"
                            5 => "H.S. Margolis"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1093/ije/dyi206"
                      "Revista" => array:6 [
                        "tituloSerie" => "Int J Epidemiol"
                        "fecha" => "2005"
                        "volumen" => "34"
                        "paginaInicial" => "1329"
                        "paginaFinal" => "1339"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16249217"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib0290"
              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Hepatitis B e antigen-negative chronic hepatitis B"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "S.J. Hadziyannis"
                            1 => "D. Vassilopoulos"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1053/jhep.2001.27834"
                      "Revista" => array:6 [
                        "tituloSerie" => "Hepatology"
                        "fecha" => "2001"
                        "volumen" => "34"
                        "paginaInicial" => "617"
                        "paginaFinal" => "624"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11584355"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            3 => array:3 [
              "identificador" => "bib0295"
              "etiqueta" => "4"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Identification of HBV variants which cannot produce precore derived HBeAg and may be responsible for severe hepatitis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "M.R. Brunetto"
                            1 => "M. Stemler"
                            2 => "F. Schodel"
                            3 => "H. Will"
                            4 => "A. Ottobrelli"
                            5 => "M. Rizzetto"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Ital J Gastroenterol"
                        "fecha" => "1989"
                        "volumen" => "21"
                        "paginaInicial" => "151"
                        "paginaFinal" => "154"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            4 => array:3 [
              "identificador" => "bib0300"
              "etiqueta" => "5"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "World-wide epidemiology of HBeAg negative chronic hepatitis B and associated precore and core promoter variants"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "M.L. Funk"
                            1 => "D.M. Rosenberg"
                            2 => "A.S. Lok"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "J Viral Hepatol"
                        "fecha" => "2002"
                        "volumen" => "9"
                        "paginaInicial" => "52"
                        "paginaFinal" => "61"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            5 => array:3 [
              "identificador" => "bib0305"
              "etiqueta" => "6"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Prevalence of HBV precore/core promoter variants in the United States"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "C.J. Chu"
                            1 => "E.B. Keeffe"
                            2 => "S.H. Han"
                            3 => "R.P. Perrillo"
                            4 => "A.D. Min"
                            5 => "C. Soldevila-Pico"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1053/jhep.2003.50352"
                      "Revista" => array:6 [
                        "tituloSerie" => "Hepatology"
                        "fecha" => "2003"
                        "volumen" => "38"
                        "paginaInicial" => "619"
                        "paginaFinal" => "628"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12939588"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            6 => array:3 [
              "identificador" => "bib0310"
              "etiqueta" => "7"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Characteristics of patients with chronic hepatitis B in France: Predominant frequency of HBe antigen negative cases"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "J.P. Zarski"
                            1 => "P. Marcellin"
                            2 => "V. Leroy"
                            3 => "C. Trepo"
                            4 => "D. Samuel"
                            5 => "N. Ganne-Carrie"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jhep.2006.03.007"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Hepatol"
                        "fecha" => "2006"
                        "volumen" => "45"
                        "paginaInicial" => "355"
                        "paginaFinal" => "360"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16750585"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            7 => array:3 [
              "identificador" => "bib0315"
              "etiqueta" => "8"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Characteristics of patients with chronic hepatitis B virus infection. Analysis of a series of 474 patients"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "R. G&oacute;mez Rodr&iacute;guez"
                            1 => "A. Guardiola Ar&eacute;valo"
                            2 => "A.Z. G&oacute;mez Moreno"
                            3 => "A. Garc&iacute;a Vela"
                            4 => "C. G&oacute;mez Hernando"
                            5 => "R. Rodr&iacute;guez Merlo"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.gastrohep.2012.10.006"
                      "Revista" => array:6 [
                        "tituloSerie" => "Gastroenterol Hepatol"
                        "fecha" => "2013"
                        "volumen" => "36"
                        "paginaInicial" => "243"
                        "paginaFinal" => "253"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23414836"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            8 => array:3 [
              "identificador" => "bib0320"
              "etiqueta" => "9"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Incidencia diagn&oacute;stica de AgH Bs positivo. Caracter&iacute;sticas epidemiol&oacute;gicas, cl&iacute;nicas y virol&oacute;gicas"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "E. Poves Mart&iacute;nez"
                            1 => "D. Del Pozo Prieto"
                            2 => "B. Costero Pastor"
                            3 => "G. Borrego Rodr&iacute;guez"
                            4 => "I. Beceiro Pedro&ntilde;o"
                            5 => "C. Sanz Garc&iacute;a"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Rev Esp Enferm Dig"
                        "fecha" => "2012"
                        "volumen" => "104"
                        "paginaInicial" => "10"
                        "paginaFinal" => "15"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22300111"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            9 => array:3 [
              "identificador" => "bib0325"
              "etiqueta" => "10"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "HBeAg-positive chronic hepatitis B treatment with oral antiviral agents: Experience and results in clinical practice"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "R.M. Mart&iacute;n-Mateos"
                            1 => "V.F. Moreira Vicente"
                            2 => "L. T&eacute;llez-Villajos"
                            3 => "C. Garc&iacute;a-S&aacute;nchez"
                            4 => "M.T. Maroto-Castellanos"
                            5 => "F.J. Garc&iacute;a-Alonso"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.gastrohep.2013.11.011"
                      "Revista" => array:6 [
                        "tituloSerie" => "Gastroenterol Hepatol"
                        "fecha" => "2014"
                        "volumen" => "37"
                        "paginaInicial" => "280"
                        "paginaFinal" => "288"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24462611"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            10 => array:3 [
              "identificador" => "bib0330"
              "etiqueta" => "11"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The long-term outcome of interferon-treated and untreated patients with HBeAg-negative chronic hepatitis B"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "G.V. Papatheodoridis"
                            1 => "E. Manesis"
                            2 => "J.J. Hadziyannis"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Hepatol"
                        "fecha" => "2001"
                        "volumen" => "34"
                        "paginaInicial" => "306"
                        "paginaFinal" => "313"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11281561"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            11 => array:3 [
              "identificador" => "bib0335"
              "etiqueta" => "12"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Precore and core promoter mutations of hepatitis B virus and hepatitis B e antigen-negative chronic hepatitis B in Korea"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "B.C. Yoo"
                            1 => "J.W. Park"
                            2 => "H.J. Kim"
                            3 => "D.H. Lee"
                            4 => "Y.J. Cha"
                            5 => "S.M. Park"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:7 [
                        "tituloSerie" => "J Hepatol"
                        "fecha" => "2003"
                        "volumen" => "38"
                        "paginaInicial" => "98"
                        "paginaFinal" => "103"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12480566"
                            "web" => "Medline"
                          ]
                        ]
                        "itemHostRev" => array:3 [
                          "pii" => "S0735109705029219"
                          "estado" => "S300"
                          "issn" => "07351097"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            12 => array:3 [
              "identificador" => "bib0340"
              "etiqueta" => "13"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Clinical, demographic and epidemiological characteristics of patients with hepatitis B followed at a university hospital in Southeastern Brazil: predominance of HBeAg negative cases"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "S.G. Chach&aacute;"
                            1 => "C. Ferreira Sda"
                            2 => "T.V. Costa"
                            3 => "L.C. Almeida Filho"
                            4 => "M.G. Villanova"
                            5 => "F.F. Souza"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Rev Soc Bras Med Trop"
                        "fecha" => "2011"
                        "volumen" => "44"
                        "paginaInicial" => "13"
                        "paginaFinal" => "17"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21340400"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            13 => array:3 [
              "identificador" => "bib0345"
              "etiqueta" => "14"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Intraobserver and interobserver variations in liver biopsy interpretation in patients with chronic hepatitis C"
                      "autores" => array:1 [
                        0 => array:2 [
                          "colaboracion" => "The METAVIR Cooperative Study Group"
                          "etal" => false
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Hepatology"
                        "fecha" => "1994"
                        "volumen" => "1"
                        "paginaInicial" => "15"
                        "paginaFinal" => "20"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            14 => array:3 [
              "identificador" => "bib0350"
              "etiqueta" => "15"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Dual cut-off transient elastography to assess liver fibrosis in chronic hepatitis B: A cohort study with internal validation"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "M. Vigan&ograve;"
                            1 => "S. Paggi"
                            2 => "P. Lampertico"
                            3 => "M. Fraquelli"
                            4 => "S. Massironi"
                            5 => "G. Ronchi"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/j.1365-2036.2011.04722.x"
                      "Revista" => array:6 [
                        "tituloSerie" => "Aliment Pharmacol Ther"
                        "fecha" => "2011"
                        "volumen" => "34"
                        "paginaInicial" => "353"
                        "paginaFinal" => "362"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21631559"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            15 => array:3 [
              "identificador" => "bib0355"
              "etiqueta" => "16"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Chronic hepatitis B: update 2009. AASLD practical guidelines"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "A. Lok"
                            1 => "B.J. McMahon"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/hep.23190"
                      "Revista" => array:6 [
                        "tituloSerie" => "Hepatology"
                        "fecha" => "2009"
                        "volumen" => "50"
                        "paginaInicial" => "661"
                        "paginaFinal" => "662"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19714720"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            16 => array:3 [
              "identificador" => "bib0360"
              "etiqueta" => "17"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "EASL clinical practice guidelines: Management of chronic hepatitis B virus infection"
                      "autores" => array:1 [
                        0 => array:2 [
                          "colaboracion" => "European Association for the Study of the Liver"
                          "etal" => false
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jhep.2012.02.010"
                      "Revista" => array:7 [
                        "tituloSerie" => "J Hepatol"
                        "fecha" => "2012"
                        "volumen" => "57"
                        "paginaInicial" => "167"
                        "paginaFinal" => "185"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22436845"
                            "web" => "Medline"
                          ]
                        ]
                        "itemHostRev" => array:3 [
                          "pii" => "S0735109711028397"
                          "estado" => "S300"
                          "issn" => "07351097"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            17 => array:3 [
              "identificador" => "bib0365"
              "etiqueta" => "18"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Hepatitis B e antigen negative chronic hepatitis B: from clinical recognition to pathogenesis and treatment"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "S.J. Hadziyannis"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Viral Hepat Rev"
                        "fecha" => "1995"
                        "volumen" => "1"
                        "paginaInicial" => "7"
                        "paginaFinal" => "36"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            18 => array:3 [
              "identificador" => "bib0370"
              "etiqueta" => "19"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Efficacy of long-term lamivudine monotherapy in patients with hepatitis B e antigen-negative chronic hepatitis B"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "S.J. Hadziyannis"
                            1 => "G.V. Papatheodoridis"
                            2 => "E. Dimou"
                            3 => "A. Laras"
                            4 => "C. Papaioannou"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1053/jhep.2000.17915"
                      "Revista" => array:6 [
                        "tituloSerie" => "Hepatology"
                        "fecha" => "2000"
                        "volumen" => "32"
                        "paginaInicial" => "847"
                        "paginaFinal" => "851"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11003633"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            19 => array:3 [
              "identificador" => "bib0375"
              "etiqueta" => "20"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Analysis of liver disease, nuclear HBcAg, viral replication, and hepatitis B virus DNA in liver and serum of HBeAg vs. anti-HBe positive carriers of hepatitis B virus"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "S.J. Hadziyannis"
                            1 => "H.M. Lieberman"
                            2 => "G.G. Karvountzis"
                            3 => "D.A. Shafritz"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Hepatology"
                        "fecha" => "1983"
                        "volumen" => "3"
                        "paginaInicial" => "656"
                        "paginaFinal" => "662"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/6618432"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            20 => array:3 [
              "identificador" => "bib0380"
              "etiqueta" => "21"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Evaluation of liver biopsy in Egyptian HBeAg-negative chronic hepatitis B patients at initial presentation: Implications for therapy"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "A.R. El-Zayadi"
                            1 => "H.M. Badran"
                            2 => "A. Saied"
                            3 => "S. Shawky"
                            4 => "Attia Mel-D"
                            5 => "K. Zalata"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/ajg.2009.30"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Gastroenterol"
                        "fecha" => "2009"
                        "volumen" => "104"
                        "paginaInicial" => "906"
                        "paginaFinal" => "911"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19293791"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            21 => array:3 [
              "identificador" => "bib0385"
              "etiqueta" => "22"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Virologic and histologic features of chronic hepatitis B virus-infected asymptomatic patients with persistently normal ALT"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "M. Kumar"
                            1 => "S.K. Sarin"
                            2 => "S. Hissar"
                            3 => "C. Pande"
                            4 => "P. Sakhuja"
                            5 => "B.C. Sharma"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1053/j.gastro.2008.02.075"
                      "Revista" => array:7 [
                        "tituloSerie" => "Gastroenterology"
                        "fecha" => "2008"
                        "volumen" => "134"
                        "paginaInicial" => "1376"
                        "paginaFinal" => "1384"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18471514"
                            "web" => "Medline"
                          ]
                        ]
                        "itemHostRev" => array:3 [
                          "pii" => "S0735109797883350"
                          "estado" => "S300"
                          "issn" => "07351097"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            22 => array:3 [
              "identificador" => "bib0390"
              "etiqueta" => "23"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The role of serial measurement of serum HBV DNA levels in patients with chronic HBeAg(&#8722;) hepatitis B infection: association with liver disease progression. A prospective cohort study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "G. Zacharakis"
                            1 => "J. Koskinas"
                            2 => "S. Kotsiou"
                            3 => "F. Tzara"
                            4 => "N. Vafeiadis"
                            5 => "M. Papoutselis"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jhep.2008.06.009"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Hepatol"
                        "fecha" => "2008"
                        "volumen" => "49"
                        "paginaInicial" => "884"
                        "paginaFinal" => "891"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18674840"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            23 => array:3 [
              "identificador" => "bib0395"
              "etiqueta" => "24"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Liver fibrosis progression is uncommon in patients with inactive chronic hepatitis B: a prospective cohort study with paired transient elastography examination"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "G.L. Wong"
                            1 => "H.L. Chan"
                            2 => "Z. Yu"
                            3 => "H.Y. Chan"
                            4 => "C.H. Tse"
                            5 => "V.W. Wong"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:4 [
                        "tituloSerie" => "J Gastroenterol Hepatol"
                        "fecha" => "2013"
                        "paginaInicial" => "1842"
                        "paginaFinal" => "1848"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            24 => array:3 [
              "identificador" => "bib0400"
              "etiqueta" => "25"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Changing epidemiology of HCV and HBV infections in Northern Italy: a survey in the general population"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "P. Fabris"
                            1 => "V. Baldo"
                            2 => "T. Baldovin"
                            3 => "E. Bellotto"
                            4 => "M. Rassu"
                            5 => "R. Trivello"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1097/MCG.0b013e318030e3ab"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Clin Gastroenterol"
                        "fecha" => "2008"
                        "volumen" => "42"
                        "paginaInicial" => "527"
                        "paginaFinal" => "532"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18277889"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            25 => array:3 [
              "identificador" => "bib0405"
              "etiqueta" => "26"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The burden and recent epidemiological changes of the main chronic liver diseases in a Greek referral tertiary centre"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "I.P. Giannousis"
                            1 => "G.V. Papatheodoridis"
                            2 => "M.J. Deutsch"
                            3 => "S.G. Manolakopoulos"
                            4 => "E.K. Manesis"
                            5 => "J.S. Koskinas"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1097/MEG.0b013e328331115b"
                      "Revista" => array:6 [
                        "tituloSerie" => "Eur J Gastroenterol Hepatol"
                        "fecha" => "2010"
                        "volumen" => "22"
                        "paginaInicial" => "172"
                        "paginaFinal" => "179"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19738477"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            26 => array:3 [
              "identificador" => "bib0410"
              "etiqueta" => "27"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Histological changes in Chinese chronic hepatitis B patients with ALT lower than two times upper limits of normal"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "E.-Q. Chen"
                            1 => "F.-J. Huang"
                            2 => "L.-L. He"
                            3 => "L. Bai"
                            4 => "L.-C. Wang"
                            5 => "T.-Y. Zhou"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s10620-009-0724-5"
                      "Revista" => array:6 [
                        "tituloSerie" => "Dig Dis Sci"
                        "fecha" => "2010"
                        "volumen" => "55"
                        "paginaInicial" => "432"
                        "paginaFinal" => "437"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19241166"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            27 => array:3 [
              "identificador" => "bib0415"
              "etiqueta" => "28"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Hepatitis B virus DNA in saliva from children with chronic hepatitis B infection: implications for saliva as a potential mode of horizontal transmission"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "I.L. Heiberg"
                            1 => "M. Hoegh"
                            2 => "S. Ladelund"
                            3 => "H.G. Niesters"
                            4 => "B. Hogh"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1097/INF.0b013e3181d8e009"
                      "Revista" => array:6 [
                        "tituloSerie" => "Pediatr Infect Dis J"
                        "fecha" => "2010"
                        "volumen" => "29"
                        "paginaInicial" => "465"
                        "paginaFinal" => "467"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20335824"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            28 => array:3 [
              "identificador" => "bib0420"
              "etiqueta" => "29"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Reactivation of hepatitis B virus infection after cytotoxic chemotherapy or immunosuppressive therapy"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "M.L. Manzano"
                            1 => "G. Castellano"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.3748/wjg.v17.i12. 1531"
                      "Revista" => array:6 [
                        "tituloSerie" => "World J Gastroenterol"
                        "fecha" => "2011"
                        "volumen" => "17"
                        "paginaInicial" => "1531"
                        "paginaFinal" => "1537"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21472116"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            29 => array:3 [
              "identificador" => "bib0425"
              "etiqueta" => "30"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Follow-up and indications for liver biopsy in HBeAg-negative chronic hepatitis B virus infection with persistently normal ALT: a systematic review"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "G.V. Papatheodoridis"
                            1 => "S. Manolakopoulos"
                            2 => "Y.F. Liaw"
                            3 => "A. Lok"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jhep.2011.11.030"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Hepatol"
                        "fecha" => "2012"
                        "volumen" => "57"
                        "paginaInicial" => "196"
                        "paginaFinal" => "202"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22450396"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            30 => array:3 [
              "identificador" => "bib0430"
              "etiqueta" => "31"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Is there a meaningful serum HBV DNA cut-off level for therapeutic decisions in HBeAg-negative chronic hepatitis B virus infection?"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "G.V. Papatheodoridis"
                            1 => "E.K. Manesis"
                            2 => "S. Manolakopoulos"
                            3 => "I.S. Elefsiniotis"
                            4 => "J. Goulis"
                            5 => "J. Giannousis"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/hep.22518"
                      "Revista" => array:6 [
                        "tituloSerie" => "Hepatology"
                        "fecha" => "2008"
                        "volumen" => "48"
                        "paginaInicial" => "1451"
                        "paginaFinal" => "1459"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18924246"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            31 => array:3 [
              "identificador" => "bib0435"
              "etiqueta" => "32"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Longitudinal changes in serum HBV DNA levels and predictors of progression during the natural course of HBeAg-negative chronic hepatitis B virus infection"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "G.V. Papatheodoridis"
                            1 => "N. Chrysanthos"
                            2 => "E. Hadziyannis"
                            3 => "E. Cholongitas"
                            4 => "E.K. Manesis"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/j.1365-2893.2007.00957.x"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Viral Hepat"
                        "fecha" => "2008"
                        "volumen" => "15"
                        "paginaInicial" => "434"
                        "paginaFinal" => "441"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18194171"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            32 => array:3 [
              "identificador" => "bib0440"
              "etiqueta" => "33"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Long-term outcome of hepatitis B e antigen-negative hepatitis B surface antigen carriers in relation to changes of alanine aminotransferase levels over time"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "D.I. Tai"
                            1 => "S.M. Lin"
                            2 => "I.S. Sheen"
                            3 => "C.M. Chu"
                            4 => "D.Y. Lin"
                            5 => "Y.F. Liaw"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/hep.22878"
                      "Revista" => array:6 [
                        "tituloSerie" => "Hepatology"
                        "fecha" => "2009"
                        "volumen" => "49"
                        "paginaInicial" => "1859"
                        "paginaFinal" => "1867"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19378345"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            33 => array:3 [
              "identificador" => "bib0445"
              "etiqueta" => "34"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Long-term outcome of HBV carriers with negative HBe antigen and normal aminotransferase"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "K. Ikeda"
                            1 => "Y. Arase"
                            2 => "S. Saitoh"
                            3 => "M. Kobayashi"
                            4 => "T. Someya"
                            5 => "T. Hosaka"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.amjmed.2006.04.036"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Med"
                        "fecha" => "2006"
                        "volumen" => "119"
                        "paginaInicial" => "977"
                        "paginaFinal" => "985"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17071167"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            34 => array:3 [
              "identificador" => "bib0450"
              "etiqueta" => "35"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Quantitative serum HBV DNA levels during different stages of chronic hepatitis B infection"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "C.J. Chu"
                            1 => "M. Hussain"
                            2 => "A.S.F. Lok"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1053/jhep.2002.36949"
                      "Revista" => array:6 [
                        "tituloSerie" => "Hepatology"
                        "fecha" => "2002"
                        "volumen" => "36"
                        "paginaInicial" => "1408"
                        "paginaFinal" => "1415"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12447866"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            35 => array:3 [
              "identificador" => "bib0455"
              "etiqueta" => "36"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Serial HBV DNA levels in patients with persistently normal transaminase over 10 years following spontaneous HBeAg seroconversion"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "Y.-C. Chen"
                            1 => "S.-F. Huang"
                            2 => "C.-M. Chu"
                            3 => "Y.-F. Liaw"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/j.1365-2893.2011.01450.x"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Viral Hepat"
                        "fecha" => "2012"
                        "volumen" => "19"
                        "paginaInicial" => "138"
                        "paginaFinal" => "146"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22239503"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            36 => array:3 [
              "identificador" => "bib0460"
              "etiqueta" => "37"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The liver histology and frequency and clearance of the hepatitis B surface antigen (HBsAg) in chronic carriers"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "R.E. Sampliner"
                            1 => "F.A. Hamilton"
                            2 => "O.A. Iseri"
                            3 => "E. Tabor"
                            4 => "J. Boitnott"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Med Sci"
                        "fecha" => "1979"
                        "volumen" => "277"
                        "paginaInicial" => "17"
                        "paginaFinal" => "22"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/425995"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            37 => array:3 [
              "identificador" => "bib0465"
              "etiqueta" => "38"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The long-term serological course of asymptomatic hepatitis B virus carriers and the development of primary hepatocellular carcinoma"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "W.L.M. Alward"
                            1 => "B.J. McMahon"
                            2 => "D.B. Hall"
                            3 => "W.L. Heyward"
                            4 => "D.P. Francis"
                            5 => "T.R. Bender"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Infect Dis"
                        "fecha" => "1985"
                        "volumen" => "151"
                        "paginaInicial" => "604"
                        "paginaFinal" => "609"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/2982971"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            38 => array:3 [
              "identificador" => "bib0470"
              "etiqueta" => "39"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Incidence, determinants and significance of delayed clearance of serum HBsAg in chronic hepatitis B virus infection: a prospective study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "Y.F. Liaw"
                            1 => "I.S. Sheen"
                            2 => "T.J. Chen"
                            3 => "C.M. Chu"
                            4 => "C.C. Pao"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Hepatology"
                        "fecha" => "1991"
                        "volumen" => "13"
                        "paginaInicial" => "627"
                        "paginaFinal" => "631"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/2010157"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            39 => array:3 [
              "identificador" => "bib0475"
              "etiqueta" => "40"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Spontaneous loss of HBsAg in children with chronic hepatitis B virus infection"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "H.Y. Hsu"
                            1 => "M.H. Chang"
                            2 => "C.Y. Lee"
                            3 => "J.S. Chen"
                            4 => "H.C. Hsu"
                            5 => "D.S. Chen"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Hepatology"
                        "fecha" => "1992"
                        "volumen" => "15"
                        "paginaInicial" => "382"
                        "paginaFinal" => "386"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/1544619"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            40 => array:3 [
              "identificador" => "bib0480"
              "etiqueta" => "41"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Natural history of chronic HBV carriers in northern Italy: morbidity and mortality after 30 years"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "M. Manno"
                            1 => "C. Camm&agrave;"
                            2 => "F. Schepis"
                            3 => "F. Bassi"
                            4 => "R. Gelmini"
                            5 => "F. Giannini"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Gastroenterology"
                        "fecha" => "2004"
                        "volumen" => "127"
                        "paginaInicial" => "756"
                        "paginaFinal" => "763"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15362032"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            41 => array:3 [
              "identificador" => "bib0485"
              "etiqueta" => "42"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "HBsAg seroclearance in asymptomatic carriers of high endemic areas: Appreciably high rates during a long-term follow-up"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "C.M. Chu"
                            1 => "Y.F. Liaw"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/hep.21612"
                      "Revista" => array:6 [
                        "tituloSerie" => "Hepatology"
                        "fecha" => "2007"
                        "volumen" => "45"
                        "paginaInicial" => "1187"
                        "paginaFinal" => "1192"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17465003"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            42 => array:3 [
              "identificador" => "bib0490"
              "etiqueta" => "43"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "HBsAg seroclearance in chronic hepatitis B in Asian patients: replicative level and risk of hepatocellular carcinoma"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "M.F. Yuen"
                            1 => "D.K. Wong"
                            2 => "J. Fung"
                            3 => "P. Ip"
                            4 => "D. But"
                            5 => "I. Hung"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1053/j.gastro.2008.07.008"
                      "Revista" => array:6 [
                        "tituloSerie" => "Gastroenterology"
                        "fecha" => "2008"
                        "volumen" => "135"
                        "paginaInicial" => "1192"
                        "paginaFinal" => "1199"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18722377"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            43 => array:3 [
              "identificador" => "bib0495"
              "etiqueta" => "44"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Serum hepatitis B DNA levels and liver histology in inactive HBsAg carriers"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "M. Martinot-Peignoux"
                            1 => "N. Boyer"
                            2 => "M. Colombat"
                            3 => "R. Akremi"
                            4 => "B.-N. Pham"
                            5 => "S. Ollivier"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Hepatol"
                        "fecha" => "2002"
                        "volumen" => "36"
                        "paginaInicial" => "543"
                        "paginaFinal" => "548"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11943427"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            44 => array:3 [
              "identificador" => "bib0500"
              "etiqueta" => "45"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "HBsAg seroclearance in chronic hepatitis B in the Chinese: virological, histological, and clinical aspects"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "M.F. Yuen"
                            1 => "D.K. Wong"
                            2 => "E. Sablon"
                            3 => "E. Tse"
                            4 => "I.O. Ng"
                            5 => "H.J. Yuan"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/hep.20240"
                      "Revista" => array:6 [
                        "tituloSerie" => "Hepatology"
                        "fecha" => "2004"
                        "volumen" => "39"
                        "paginaInicial" => "1694"
                        "paginaFinal" => "1701"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15185311"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            45 => array:3 [
              "identificador" => "bib0505"
              "etiqueta" => "46"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Sero-clearance of hepatitis B surface antigen in chronic carriers does not necessarily imply a good prognosis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "T.I. Huo"
                            1 => "J.C. Wu"
                            2 => "P.C. Lee"
                            3 => "G.Y. Chau"
                            4 => "W.Y. Lui"
                            5 => "S.H. Tsay"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/hep.510280130"
                      "Revista" => array:6 [
                        "tituloSerie" => "Hepatology"
                        "fecha" => "1998"
                        "volumen" => "28"
                        "paginaInicial" => "231"
                        "paginaFinal" => "236"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9657117"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            46 => array:3 [
              "identificador" => "bib0510"
              "etiqueta" => "47"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The development of cirrhosis in patients with chronic type B hepatitis: a prospective study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "Y.F. Liaw"
                            1 => "D.I. Tai"
                            2 => "C.M. Chu"
                            3 => "T.J. Chen"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Hepatology"
                        "fecha" => "1988"
                        "volumen" => "8"
                        "paginaInicial" => "493"
                        "paginaFinal" => "496"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/3371868"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            47 => array:3 [
              "identificador" => "bib0515"
              "etiqueta" => "48"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Development of cirrhosis after chronic type B hepatitis: a clinicopathologic and follow-up study of HBeAg-positive asymptomatic patients"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "R. Moreno-Otero"
                            1 => "C. Garc&iacute;a-Monz&oacute;n"
                            2 => "A. Garc&iacute;a-S&aacute;nchez"
                            3 => "L. Garc&iacute;a Buey"
                            4 => "J.M. Pajares"
                            5 => "A.M. di Bisceglie"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Gastroenterol"
                        "fecha" => "1991"
                        "volumen" => "86"
                        "paginaInicial" => "560"
                        "paginaFinal" => "564"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/2028945"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            48 => array:3 [
              "identificador" => "bib0520"
              "etiqueta" => "49"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Factors predictive of liver cirrhosis in patients with chronic hepatitis B: a multivariate analysis in longitudinal study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "T. Huo"
                            1 => "J. Wu"
                            2 => "S. Hwang"
                            3 => "C.R. Lai"
                            4 => "P.C. Lee"
                            5 => "S.H. Tsay"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Eur J Gastroenterol Hepatol"
                        "fecha" => "2000"
                        "volumen" => "12"
                        "paginaInicial" => "687"
                        "paginaFinal" => "693"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10912490"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            49 => array:3 [
              "identificador" => "bib0525"
              "etiqueta" => "50"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "High prevalence of significant liver fibrosis and cirrhosis in chronic hepatitis B patients with normal ALT in central Europe"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "T. G&ouml;bel"
                            1 => "A. Erhardt"
                            2 => "M. Herwig"
                            3 => "C. Poremba"
                            4 => "S.E. Bald us"
                            5 => "A. Sagir"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/jmv.22048"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Med Virol"
                        "fecha" => "2011"
                        "volumen" => "83"
                        "paginaInicial" => "968"
                        "paginaFinal" => "973"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21503908"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            50 => array:3 [
              "identificador" => "bib0530"
              "etiqueta" => "51"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Evaluation of normal or minimally elevated alanine transaminase, age and DNA level in predicting liver histological changes in chronic hepatitis B"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "S. Alam"
                            1 => "N. Ahmad"
                            2 => "G. Mustafa"
                            3 => "A. Shrestha"
                            4 => "A.K. Alam"
                            5 => "M. Khan"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/j.1478-3231.2011.02491.x"
                      "Revista" => array:6 [
                        "tituloSerie" => "Liver Int"
                        "fecha" => "2011"
                        "volumen" => "31"
                        "paginaInicial" => "824"
                        "paginaFinal" => "830"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21645213"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            51 => array:3 [
              "identificador" => "bib0535"
              "etiqueta" => "52"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Natural history of chronic hepatitis B: special emphasis on disease progression and prognostic factors"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "G. Fattovich"
                            1 => "F. Bortolotti"
                            2 => "F. Donato"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jhep.2007.11.011"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Hepatol"
                        "fecha" => "2008"
                        "volumen" => "48"
                        "paginaInicial" => "335"
                        "paginaFinal" => "352"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18096267"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            52 => array:3 [
              "identificador" => "bib0540"
              "etiqueta" => "53"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "C.J. Chen"
                            1 => "H.I. Yang"
                            2 => "J. Su"
                            3 => "C.L. Jen"
                            4 => "S.L. You"
                            5 => "S.N. Lu"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "J Am Med Assoc"
                        "fecha" => "2006"
                        "volumen" => "295"
                        "paginaInicial" => "65"
                        "paginaFinal" => "73"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            53 => array:3 [
              "identificador" => "bib0545"
              "etiqueta" => "54"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Long-term outcome of chronic hepatitis B in Caucasian patients: mortality after 25 years"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "G. Fattovich"
                            1 => "N. Olivari"
                            2 => "M. Pasino"
                            3 => "M. d&#8217;Onofrio"
                            4 => "E. Martone"
                            5 => "F. Donato"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1136/gut.2007.128496"
                      "Revista" => array:6 [
                        "tituloSerie" => "Gut"
                        "fecha" => "2008"
                        "volumen" => "57"
                        "paginaInicial" => "84"
                        "paginaFinal" => "90"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17715267"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            54 => array:3 [
              "identificador" => "bib0550"
              "etiqueta" => "55"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Hepatitis B virus infection increases the risk of cholangiocarcinoma: a meta-analysis and systematic review"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "M. Li"
                            1 => "J. Li"
                            2 => "P. Li"
                            3 => "H. Li"
                            4 => "T. Su"
                            5 => "R. Zhu"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/j.1440-1746.2012.07207.x"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Gastroenterol Hepatol"
                        "fecha" => "2012"
                        "volumen" => "27"
                        "paginaInicial" => "1561"
                        "paginaFinal" => "1568"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22694354"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
          ]
        ]
      ]
    ]
    "agradecimientos" => array:1 [
      0 => array:4 [
        "identificador" => "xack271487"
        "titulo" => "Acknowledgements"
        "texto" => "<p id="par0240" class="elsevierStylePara elsevierViewall">We would like to thank Dr. Marcelino S&aacute;nchez Casado, ICU staff physician in Hospital Virgen de la Salud de Toledo, for his assistance in both the methodology and statistics.</p>"
        "vista" => "all"
      ]
    ]
  ]
  "idiomaDefecto" => "en"
  "url" => "/24443824/0000004000000002/v1_201703060044/S2444382417300275/v1_201703060044/en/main.assets"
  "Apartado" => array:4 [
    "identificador" => "48441"
    "tipo" => "SECCION"
    "en" => array:2 [
      "titulo" => "Original articles"
      "idiomaDefecto" => true
    ]
    "idiomaDefecto" => "en"
  ]
  "PDF" => "https://static.elsevier.es/multimedia/24443824/0000004000000002/v1_201703060044/S2444382417300275/v1_201703060044/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/"
  "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2444382417300275?idApp=UINPBA00004N"
]

Article information

ISSN: 24443824
Original language: English

DOI:10.1016/j.gastre.2016.11.009

The statistics are updated each day

Year/Month	Html	Pdf	Total

2024 November	9	0	9
2024 October	82	11	93
2024 September	107	11	118
2024 August	101	10	111
2024 July	98	10	108
2024 June	95	5	100
2024 May	104	3	107
2024 April	106	7	113
2024 March	140	8	148
2024 February	147	14	161
2024 January	224	10	234
2023 December	149	12	161
2023 November	150	9	159
2023 October	156	13	169
2023 September	107	6	113
2023 August	135	9	144
2023 July	159	12	171
2023 June	108	13	121
2023 May	142	9	151
2023 April	123	2	125
2023 March	117	9	126
2023 February	109	12	121
2023 January	93	14	107
2022 December	56	8	64
2022 November	60	6	66
2022 October	60	16	76
2022 September	72	20	92
2022 August	38	8	46
2022 July	40	10	50
2022 June	43	14	57
2022 May	52	5	57
2022 April	54	11	65
2022 March	84	7	91
2022 February	54	4	58
2022 January	78	8	86
2021 December	44	16	60
2021 November	36	5	41
2021 October	38	12	50
2021 September	54	15	69
2021 August	51	14	65
2021 July	25	8	33
2021 June	27	11	38
2021 May	50	12	62
2021 April	176	42	218
2021 March	114	11	125
2021 February	66	16	82
2021 January	81	12	93
2020 December	79	9	88
2020 November	72	5	77
2020 October	49	5	54
2020 September	47	10	57
2020 August	52	23	75
2020 July	53	9	62
2020 June	62	13	75
2020 May	63	8	71
2020 April	59	6	65
2020 March	106	11	117
2020 February	83	10	93
2020 January	75	5	80
2019 December	62	16	78
2019 November	25	4	29
2019 October	32	7	39
2019 September	38	5	43
2019 August	20	0	20
2019 July	14	12	26
2019 June	23	22	45
2019 May	66	44	110
2019 April	24	7	31
2019 March	3	3	6
2019 February	13	5	18

Show all

Indexed in:

Follow us:

Subscribe:

Statistics

Indexed in:

Follow us:

Subscribe:

Statistics

Subscribe to our newsletter