Genotype f prevails in Venezuelan urban patients with chronic hepatitis B(a)
Irma V. Machado
, María del Pilar Fortes*, Berta Vargas-Lovelle*, Aleidy C. Trómpiz*, Danerys A. López*, Roberto V. León†, Merita Senior‡, Lucy Dagher§, Carmen E. López||, Elena Pestaña¶, Román Bacalao**, Miguel E. Garassini§
,
Corresponding author
* Laboratorio Clínico Especializado Intediag-HV (Integración Diagnóstica en Hepatitis Viral), Caracas, Venezuela
† Hospital General “Domingo Luciani” and Instituto Médico La Floresta, Caracas
‡ Hospital de Clínicas Caracas
§ Centro Médico Docente La Trinidad, Caracas
|| Hospital de Niños “J.M. de Los Ríos”, Caracas
¶ Fundación Zuliana del Hígado, Maracaibo, Estado Zulia and Policlínica Metropolitana, Caracas
** Centro Médico de Caracas
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"documento" => "article" "crossmark" => 0 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "fla" "cita" => "Ann Hepatol. 2010;9:177-80" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 52 "formatos" => array:3 [ "EPUB" => 7 "HTML" => 22 "PDF" => 23 ] ] "en" => array:11 [ "idiomaDefecto" => true "titulo" => "Serum concentrations of substance P in cholestasis" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "177" "paginaFinal" => "180" ] ] "contieneResumen" => array:1 [ "en" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "f0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 606 "Ancho" => 1002 "Tamanyo" => 28123 ] ] "descripcion" => array:1 [ "en" => "<p id="sp0005" class="elsevierStyleSimplePara elsevierViewall">Mean ± SE serum concentrations of substance P in the study groups. The mean serum concentration of substance P in the group of patients with chronic liver disease (CLD) and pruritus (n = 13) was significantly higher than that of patients with chronic liver disease without pruritus (n = 17), (p < 0.0001), and that of the control group of subjects (n = 12) (p < 0.0001). The mean serum concentration of substance P from the group of patients with cholestasis without pruritus was not significantly different from that of the control group of subjects.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Mayur Trivedi, Nora V. Bergasa" "autores" => array:2 [ 0 => array:2 [ "nombre" => "Mayur" "apellidos" => "Trivedi" ] 1 => array:3 [ "preGrado" => "M.D." "nombre" => "Nora" "apellidos" => "V. Bergasa" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1665268119316588?idApp=UINPBA00004N" "url" => "/16652681/0000000900000002/v1_201907070740/S1665268119316588/v1_201907070740/en/main.assets" ] "itemAnterior" => array:19 [ "pii" => "S1665268119316564" "issn" => "16652681" "doi" => "10.1016/S1665-2681(19)31656-4" "estado" => "S300" "fechaPublicacion" => "2010-04-01" "aid" => "71342" "copyright" => "Fundación Clínica Médica Sur, A.C." 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The number of patients at each time value changes based on patient compliance with bloodwork each week, and with those that need to be removed from this figure as they required a repeat injection, such that n values are shown at each week.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Janakie Singham, Erica D. Greanya, Kirby Lau, Siegfried R. Erb, Nilu Partovi, Eric M. Yoshida" "autores" => array:6 [ 0 => array:2 [ "nombre" => "Janakie" "apellidos" => "Singham" ] 1 => array:2 [ "nombre" => "Erica D." "apellidos" => "Greanya" ] 2 => array:2 [ "nombre" => "Kirby" "apellidos" => "Lau" ] 3 => array:2 [ "nombre" => "Siegfried R." "apellidos" => "Erb" ] 4 => array:2 [ "nombre" => "Nilu" "apellidos" => "Partovi" ] 5 => array:2 [ "nombre" => "Eric M." "apellidos" => "Yoshida" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1665268119316564?idApp=UINPBA00004N" "url" => "/16652681/0000000900000002/v1_201907070740/S1665268119316564/v1_201907070740/en/main.assets" ] "en" => array:16 [ "idiomaDefecto" => true "titulo" => "Genotype f prevails in Venezuelan urban patients with chronic hepatitis B<a class="elsevierStyleCrossRef" href="#fn1"><span class="elsevierStyleSup">(a)</span></a>" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "172" "paginaFinal" => "176" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Irma V. Machado, María del Pilar Fortes, Berta Vargas-Lovelle, Aleidy C. Trómpiz, Danerys A. López, Roberto V. León, Merita Senior, Lucy Dagher, Carmen E. López, Elena Pestaña, Román Bacalao, Miguel E. Garassini" "autores" => array:12 [ 0 => array:4 [ "nombre" => "Irma" "apellidos" => "V. 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"apellidos" => "Garassini" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">§</span>" "identificador" => "aff4" ] ] ] ] "afiliaciones" => array:7 [ 0 => array:3 [ "entidad" => "Laboratorio Clínico Especializado Intediag-HV (<span class="elsevierStyleItalic">Integración Diagnóstica en Hepatitis Viral</span>), Caracas, Venezuela" "etiqueta" => "*" "identificador" => "aff1" ] 1 => array:3 [ "entidad" => "Hospital General “Domingo Luciani” and Instituto Médico La Floresta, Caracas" "etiqueta" => "<span class="elsevierStyleSup">†</span>" "identificador" => "aff2" ] 2 => array:3 [ "entidad" => "Hospital de Clínicas Caracas" "etiqueta" => "<span class="elsevierStyleSup">‡</span>" "identificador" => "aff3" ] 3 => array:3 [ "entidad" => "Centro Médico Docente La Trinidad, Caracas" "etiqueta" => "<span class="elsevierStyleSup">§</span>" "identificador" => "aff4" ] 4 => array:3 [ "entidad" => "Hospital de Niños “J.M. de Los Ríos”, Caracas" "etiqueta" => "<span class="elsevierStyleSup">||</span>" "identificador" => "aff5" ] 5 => array:3 [ "entidad" => "Fundación Zuliana del Hígado, Maracaibo, Estado Zulia and Policlínica Metropolitana, Caracas" "etiqueta" => "<span class="elsevierStyleSup">¶</span>" "identificador" => "aff6" ] 6 => array:3 [ "entidad" => "Centro Médico de Caracas" "etiqueta" => "**" "identificador" => "aff7" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor1" "etiqueta" => "*" "correspondencia" => "Correspondence and reprint request:" ] ] ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "f0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 711 "Ancho" => 999 "Tamanyo" => 49412 ] ] "descripcion" => array:1 [ "en" => "<p id="sp0005" class="elsevierStyleSimplePara elsevierViewall">HBV DNA viral loads shown by the group of urban patients with CHB, genotype F, e-antigen positive and e-antigen negative. HBV DNA levels expressed as log<span class="elsevierStyleInf">10</span> IU/mL, were significantly higher (P = 0.0001) in 74 patients with CHB e-antigen positive compared to 16 patients with CHB e-antigen negative.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Introduction</span><p id="p0005" class="elsevierStylePara elsevierViewall">Hepatitis B virus (HBV) has been classified into 8 genotypes (A-H) by means of molecular evolutionary genetics analysis.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> There is growing evidence that HBV genotypes may influence the natural history of liver disease including mode of transmission, disease progression, seroconversion to HBe antibody, presence of HBV mutants and response to therapy.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> Today, the application of nucleic acid tests for clinical management of chronic hepatitis B (CHB) is almost mandatory.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> This battery of tests includes measurement of viral load and genotyping of emergent resistant viral mutants during therapy.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> Moreover, in countries with high prevalence of HBsAg chronic carriers, HBV genotyping has been introduced as valuable test in the clinical management of CHB.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a></p><p id="p0010" class="elsevierStylePara elsevierViewall">Epidemiological data suggest that 7 to 12 million Latin Americans are infected with hepatitis B virus.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> Currently in Venezuela, the mean morbidity rate of HBV is approximately 3.8 x 100.000 inhabitants. Moreover, Venezuela is classified as having an intermediate prevalence of hepatitis B surface antigen (HBsAg) in urban areas.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> Venezuelan aborigine population is categorized as having the highest rate of HBsAg,<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> and HBV genotype F has been well-documented as the most prevalent.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> However, there is scarce data regarding HBV genotypes in HBsAg chronic carriers from Venezuelan urban populations. The present study was designed to identify the prevalence of HBV genotypes in native HBsAg chronic carriers in Venezuelan urban areas. In addition, we correlated the predominant HBV genotype with epidemiological, serological and virological features of the HBV infection.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Subjects and Methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Patient population</span><p id="p0015" class="elsevierStylePara elsevierViewall">This study was approved by the Institutional Research Ethics Committee, and written informed consent was obtained from each participant. Patients with chronic HBV infection from different urban Venezuelan cities and referred to our tertiary diagnostic center (Intediag-HV, Caracas) were recruited into this study. Patients were not on treatment at the time of the investigation. Non-Venezuelan migrant patients were excluded from the study. Serum samples from each patient were collected, aliquoted and stored at-20 °C until analysis.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Serological and virological tests</span><p id="p0020" class="elsevierStylePara elsevierViewall">Hepatitis B e antigen (HBeAg) and antibodies (anti-HBe) were determined using the Axsym™ immunoassay system (Abbott Laboratories; Chicago, IL, USA). HBV DNA serum levels were measured by real-time PCR (Real-Art® HBV PCR assay, (Artus-Biotech, Qiagen, Hamburg, Germany)<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">8</span></a><span class="elsevierStyleSup">-</span><a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> HBV genotypes were identified by PCR using type-specific primers in accordance to a commercial assay (Human Hepatitis B Virus Genotyping, Genekam Biote-chnology AG, Duisburg, Germany).<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> Briefly, a nested PCR is carried-out based on differences in the conserved nucleotides in the envelope ORFs followed by a second PCR using two mixes of primers (group 1: A 68 bp, B 281 bp, C 122 bp; group 2: D 119 bp, E 167 bp, F 97 bp) to differentiate the HBV genotypes based on amplicon length.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Statistical analysis</span><p id="p0025" class="elsevierStylePara elsevierViewall">Viral loads data were presented as mean ± standard deviation (SD). In all cases, the Kolmogorov-</p><p id="p0030" class="elsevierStylePara elsevierViewall">Smirnov test was applied to test for normal distribution (Graphpad Instant software for Window version 305). Unpaired Student <span class="elsevierStyleItalic">t</span> test was employed to compare differences in means of viral load levels between the e-antigen positive and the e-antigen negative HBsAg chronic carriers. The significance level was assessed at <span class="elsevierStyleItalic">p</span> < 0.05.</p></span></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Results</span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Patient population</span><p id="p0035" class="elsevierStylePara elsevierViewall">Our study population comprised of 90 patients with chronic HBV infection from different Venezuelan urban cities. Patients were classified in two groups. Group A consisted of 21 children and adolescents (mean age 10 ± 6 years, 11 males and 10 females). The majority of patients were in the immune-tolerant phase of the infection and showing normal values of alanine-aminotransferase (ALT). Only two patients have mild elevation of ALT. Patients acquired HBV either via blood transfusion or health-care measures during chemotherapy. Group B comprised of 69 adults (mean age 46 ± 12 years, 36 males and 33 females), and they presented elevations (> 2.5 fold normal value) or fluctuations of ALT values. They mainly acquired HBV by sexual contact.</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">HBeAg and anti-HBe</span><p id="p0040" class="elsevierStylePara elsevierViewall">All patients from group A were e-antigen positive. In group B, 53 patients showed e-antigen positive and 16 patients presented e-antigen negative with positive anti-HBe antibodies. Overall, 74 patients (82.2%) showed CHB e-antigen positive and 16 patients (17.8%) CHB e-antigen negative.</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">HBV DNA circulating viral load and HBV genotypes</span><p id="p0045" class="elsevierStylePara elsevierViewall">The whole group showed HBV DNA levels ranging from 4.1 to 8.8 log<span class="elsevierStyleInf">10</span> IU/mL. No difference in viral load was found between groups A and B patient e-antigen positive. However, HBV DNA levels were significantly higher (P = 0.0001) in CHB patients with e-antigen positive compared with those with CHB e-antigen negative (see <a class="elsevierStyleCrossRef" href="#f0005">Figure 1</a>). Genotype F hepatitis B predominated in 88 patients (97.8%). Only two non-related patients (child and adult), both with CHB e-antigen positive, showed to be co-infected with genotype A and genotype F hepatitis B (<a class="elsevierStyleCrossRef" href="#f0010">Figure 2</a>).</p><elsevierMultimedia ident="f0005"></elsevierMultimedia><elsevierMultimedia ident="f0010"></elsevierMultimedia></span></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Discussion</span><p id="p0050" class="elsevierStylePara elsevierViewall">We have demonstrated that HBV genotype F prevails in Venezuelan urban populations infected with hepatitis B virus regardless of the immune status of patients. This genotype was identified in either CHB e-antigen positive or e-antigen negative cases. Moreover, HBV genotype F was observed in patients who acquired the infection by different modes of transmission (sexual, blood transfusion, chemotherapy). Only two patients, both in the active phase of the disease, were co-infected with genotypes A and F.</p><p id="p0055" class="elsevierStylePara elsevierViewall">HBV genotype F prevails in Amerindians from Western and Southern Venezuela.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> In addition, the circulation of this genotype has been reported in other communities such as hemodialysis patients and few patients with chronic hepatitis B.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> Our results are in good agreement with previously repor-ted data in South America. Indeed, genotype F has been predominantly found in groups of HBV patients from Colombia (Venezuela’s eastern-border country),<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> but differs from those observed in Brazil (Venezuela’s southern border country) where the frequency of genotype F is lower even in northern areas of this country.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> This disparity could be related to differences in the ethnic origins of Brazilian inhabitants. Unlike the Venezuelan hybrid mestizo population (Mongoloid, Negroid and Caucasian), the Native Amerindian inhabitants have only made a minor contribution to the Brazilian population as a whole,<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> We have now envisaged future genoty-ping studies including non-Venezuelan migrant HBV patients to determine whether this population exhibits a different genotype pattern. Interestingly, we thus far have identified two patients with genotype F and one with genotype F C C among five HBV carrier immigrants from China. This suggests a high grade of circulation and transmission of genotype F among our urban populations.</p><p id="p0060" class="elsevierStylePara elsevierViewall">Based on previous reports, HBV genotype A has been associated to CHB e-antigen positive while genotypes B, C and D (often present precore mutants) are serologically associated with positive anti-HBe antibodies.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> One of few published articles on HBV infection and genotype F documented that this pa-tient population, who were all HBeAg positive, had the lowest rate of remission.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> Furthermore, the proportion of patients who presented with hepatic decompensation or died were higher than those infected with genotype A or D. In addition, none of these subjects cleared HBsAg from the serum. We have previously reported that over 60% of our adults HBV carriers have the presence of anti-HBe antibodies but they are clinically in inactive state.<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">17</span></a><span class="elsevierStyleSup">-</span><a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> In addition, more than 80% of patients with active disease presented CHB e-antigen positive and 12% to 18% CHB e-antigen negative.<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> In the present study, we also found that 82% of patients had CHB e-antigen positive and significantly higher viral load. Taken together, although these results demonstrate that genotype F is mainly associated with CHB e-an-tigen positive, we have to be aware that an important segment of our HBsAg carriers with positive anti-HBe antibodies might represent CHB e-antigen negative instead of inactive HBV carrier state. Therefore, we have to make the effort to quantify HBV-DNA levels to assess the appropriate diagnosis and management of these patients.<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a></p><p id="p0065" class="elsevierStylePara elsevierViewall">A recently published study among Alaska Native young populations infected with HBV demonstrated that genotype F strain compared to genotypes A, B, C or D was significantly associated with the occurrence of hepatocellular carcinoma (HCC).<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a> The incidence of HBV-induced HCC has not been accurately established in our country. However, Leon, <span class="elsevierStyleItalic">et αl.</span> reported that over a 8-year period they had diagnosed 14 patients infected with HBV (40-50 years old) who developed HCC, twelve of them already with liver cirrhosis and two without.<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> Another study compiling 68 Venezuelan patients with HCC, most of them in the sixth decade of life, described HBV as the main etiologic agent in 347 of cases.<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a> The development of cirrhosis and liver cancer during the fourth and sixth decade of life has also been described in other Latin American countries, where HBV transmission occurs primarily from sexual contact like in Venezuelan urban areas.<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a> On the other hand, the progress to chronic liver disease and HCC in Asian HBV carriers, who have acquired the infection perinatally, occurs early in childhood.<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">27</span></a> In Venezuela, these complications in HBV-infected children have been described in four (10.2 7) out of thirty nine children over a 9-year follow-up.<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a> However, they acquired the infection during chemotherapy rather than perinatally. This finding is not surprising since nosocomial HBV infection in Venezuela remains a common unsolved problem nationwide from many decades ago.<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">30</span></a> It is noteworthy to mention that thus far our children and adolescents with CHB do not seroconvert earlier to antiH-Be antibodies.</p><p id="p0070" class="elsevierStylePara elsevierViewall">In conclusion, we have demonstrated that genotype F is the main circulating HBV strain among HB-sAg carriers from Venezuelan urban areas. This genotype is associated mostly with CHB e-antigen positive and showed a high rate of transmission. Progression to cirrhosis and hepatocellular carcinoma could be major clinical events of this patient population independently of age at acquisition or transmission route. Longitudinal studies are encouraged to further describe the natural history of this disease in Venezuela.</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Abbreviations</span><p id="p0075" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="li0005"><li class="elsevierStyleListItem" id="list0005"><span class="elsevierStyleLabel">•</span><p id="p0080" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">HBV:</span> Hepatitis B Virus</p></li><li class="elsevierStyleListItem" id="list0010"><span class="elsevierStyleLabel">•</span><p id="p0085" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">HBsAg:</span> Hepatitis B surface Antigen</p></li><li class="elsevierStyleListItem" id="list0015"><span class="elsevierStyleLabel">•</span><p id="p0090" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">CHB:</span> Chronic hepatitis B</p></li><li class="elsevierStyleListItem" id="list0020"><span class="elsevierStyleLabel">•</span><p id="p0095" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">HBeAg:</span> Hepatitis B e antigen</p></li><li class="elsevierStyleListItem" id="list0025"><span class="elsevierStyleLabel">•</span><p id="p0100" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">anti-HBe:</span> Hepatitis Be antibody</p></li><li class="elsevierStyleListItem" id="list0030"><span class="elsevierStyleLabel">•</span><p id="p0105" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">PCR:</span> Polymerase Chain Reaction</p></li><li class="elsevierStyleListItem" id="list0035"><span class="elsevierStyleLabel">•</span><p id="p0110" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">SD:</span> Standard deviation</p></li><li class="elsevierStyleListItem" id="list0040"><span class="elsevierStyleLabel">•</span><p id="p0115" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">HCC:</span> Hepatocellular carcinoma</p></li></ul></p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:8 [ 0 => array:3 [ "identificador" => "xres1217531" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abs0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1132912" "titulo" => "Key words" ] 2 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 3 => array:3 [ "identificador" => "sec0010" "titulo" => "Subjects and Methods" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Patient population" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Serological and virological tests" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Statistical analysis" ] ] ] 4 => array:3 [ "identificador" => "sec0030" "titulo" => "Results" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0035" "titulo" => "Patient population" ] 1 => array:2 [ "identificador" => "sec0040" "titulo" => "HBeAg and anti-HBe" ] 2 => array:2 [ "identificador" => "sec0045" "titulo" => "HBV DNA circulating viral load and HBV genotypes" ] ] ] 5 => array:2 [ "identificador" => "sec0050" "titulo" => "Discussion" ] 6 => array:2 [ "identificador" => "sec0055" "titulo" => "Abbreviations" ] 7 => array:1 [ "titulo" => "Reference" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "PalabrasClave" => array:1 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Key words" "identificador" => "xpalclavsec1132912" "palabras" => array:5 [ 0 => "Genotype F" 1 => "Chronic hepatitis B" 2 => "e-entigen" 3 => "Anti-eHB antibodies" 4 => "Urban HBV carrier" ] ] ] ] "tieneResumen" => true "resumen" => array:1 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "<span id="abs0005" class="elsevierStyleSection elsevierViewall"><p id="sp0015" class="elsevierStyleSimplePara elsevierViewall">Hepatitis B virus (HBV) has been classified into 8 genotypes (A-H). Genotypes A, D and F have been identified in some South American countries, but in Venezuela studies have been more restricted to aboriginal communities where genotype F is predominant. The aim of the present study was to identify the prevalence of HBV genotypes among native HBsAg carriers in Venezuelan urban areas. In addition, we correlated the predominant HBV genotype with epidemiological, serological and virological features of the infection. Non-Venezuelan migrant patients were excluded from this study. Serum samples from 90 patients (21 children and 69 adults) with chronic hepatitis B (CHB) were analyzed. Seventy-four patients had CHB e-antigen positive and 16 CHB e-antigen negative. HBV DNA serum levels of the whole group ranged from 4.1 to 8.8 log<span class="elsevierStyleInf">1H</span> IU/mL. Patients with CHB e-antigen positive showed significantly higher viral loads (P = 0.0001) than the group with CHB e-antigen negative. Eighty-eight patients (97.8%) exhibited HBV genotype F while two non-related patients (2.2%) were infected with A + F genotypes. Genotype F is the main circulating HBV strain among HBsAg carriers from Venezuelan urban areas. This genotype is associated mostly with CHB e-antigen positive and high rate of transmission. Progression to cirrhosis and hepatocellular carcinoma could be major clinical events of this patient population independently of age at acquisition or transmission route.</p></span>" ] ] "NotaPie" => array:1 [ 0 => array:3 [ "etiqueta" => "<span class="elsevierStyleSup">(a)</span>" "nota" => "<p class="elsevierStyleNotepara" id="np0005">This project was supported, in part, by an award to Intediag-HV granted by Fondo Pro-Salud 2007, Cámara Venezolana de Fabricantes de Cerveza (CAVEFACE), Venezuela. A preliminary report of this work was presented in an abstract form at the 13<span class="elsevierStyleSup">th</span> International Symposium on Viral Hepatitis and Liver Disease, March, 2009, Washington, USA. www.ishld2009.org/pdf/ISVHLD_Poster_Presentation_Abstractspdf</p>" "identificador" => "fn1" ] ] "multimedia" => array:2 [ 0 => array:7 [ "identificador" => "f0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 711 "Ancho" => 999 "Tamanyo" => 49412 ] ] "descripcion" => array:1 [ "en" => "<p id="sp0005" class="elsevierStyleSimplePara elsevierViewall">HBV DNA viral loads shown by the group of urban patients with CHB, genotype F, e-antigen positive and e-antigen negative. HBV DNA levels expressed as log<span class="elsevierStyleInf">10</span> IU/mL, were significantly higher (P = 0.0001) in 74 patients with CHB e-antigen positive compared to 16 patients with CHB e-antigen negative.</p>" ] ] 1 => array:7 [ "identificador" => "f0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 720 "Ancho" => 844 "Tamanyo" => 34013 ] ] "descripcion" => array:1 [ "en" => "<p id="sp0010" class="elsevierStyleSimplePara elsevierViewall">HBV genotypes identified in urban patients with CHB. Genotype F prevails in 97.8% of urban patients with CHB irrespective of e antigen status. Two not-related patients (2.2%) were infected with genotype A and genotype F.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "Reference" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bs0005" "bibliografiaReferencia" => array:30 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1." 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 2 | 0 | 2 |
| 2024 October | 13 | 1 | 14 |
| 2024 September | 24 | 2 | 26 |
| 2024 August | 17 | 1 | 18 |
| 2024 July | 10 | 3 | 13 |
| 2024 June | 13 | 0 | 13 |
| 2024 May | 13 | 2 | 15 |
| 2024 April | 14 | 2 | 16 |
| 2024 March | 21 | 7 | 28 |
| 2024 February | 21 | 5 | 26 |
| 2024 January | 23 | 1 | 24 |
| 2023 December | 9 | 5 | 14 |
| 2023 November | 24 | 5 | 29 |
| 2023 October | 13 | 2 | 15 |
| 2023 September | 23 | 4 | 27 |
| 2023 August | 13 | 3 | 16 |
| 2023 July | 5 | 2 | 7 |
| 2023 June | 16 | 2 | 18 |
| 2023 May | 52 | 3 | 55 |
| 2023 April | 57 | 1 | 58 |
| 2023 March | 43 | 2 | 45 |
| 2023 February | 21 | 0 | 21 |
| 2023 January | 40 | 10 | 50 |
| 2022 December | 33 | 4 | 37 |
| 2022 November | 40 | 4 | 44 |
| 2022 October | 28 | 7 | 35 |
| 2022 September | 8 | 12 | 20 |
| 2022 August | 14 | 5 | 19 |
| 2022 July | 17 | 9 | 26 |
| 2022 June | 10 | 7 | 17 |
| 2022 May | 9 | 9 | 18 |
| 2022 April | 12 | 10 | 22 |
| 2022 March | 9 | 9 | 18 |
| 2022 February | 9 | 5 | 14 |
| 2022 January | 24 | 7 | 31 |
| 2021 December | 45 | 10 | 55 |
| 2021 November | 22 | 7 | 29 |
| 2021 October | 18 | 9 | 27 |
| 2021 September | 24 | 14 | 38 |
| 2021 August | 7 | 4 | 11 |
| 2021 July | 10 | 7 | 17 |
| 2021 June | 7 | 10 | 17 |
| 2021 May | 10 | 4 | 14 |
| 2021 April | 23 | 13 | 36 |
| 2021 March | 7 | 8 | 15 |
| 2021 February | 8 | 5 | 13 |
| 2021 January | 5 | 14 | 19 |
| 2020 December | 6 | 4 | 10 |
| 2020 November | 6 | 8 | 14 |
| 2020 October | 3 | 5 | 8 |
| 2020 September | 10 | 6 | 16 |
| 2020 August | 14 | 1 | 15 |
| 2020 July | 4 | 2 | 6 |
| 2020 June | 3 | 1 | 4 |
| 2020 May | 6 | 3 | 9 |
| 2020 April | 3 | 0 | 3 |
| 2020 March | 8 | 1 | 9 |
| 2020 February | 4 | 2 | 6 |
| 2020 January | 1 | 3 | 4 |
| 2019 December | 4 | 7 | 11 |
| 2019 November | 4 | 0 | 4 |
| 2019 October | 1 | 2 | 3 |
| 2019 September | 4 | 0 | 4 |
| 2019 August | 1 | 0 | 1 |
| 2019 July | 2 | 8 | 10 |
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