Original article
High prevalence of antibodies against hepatitis E virus in HIV-infected patients with unexplained liver disease
Prevalencia elevada de anticuerpos frente al virus de la hepatitis E en pacientes infectados por el VIH con enfermedad hepática de origen incierto
Nicolás Merchantea, Manuel Parra-Sáncheza, Antonio Rivero-Juárezb, Celia Cifuentesa, Ángela Camachob, Juan Macíasa, Loreto Martínez-Dueñasb, Elisabet Pérez-Navarroa, Antonio Riverob, Juan A. Pinedaa,
Corresponding author
a Unidad de Enfermedades Infecciosas y Microbiología, Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario de Valme, Sevilla, Spain
b Unidad de Enfermedades Infecciosas, Hospital Universitario Reina Sofía, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Córdoba, Spain
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Pineda" "autores" => array:10 [ 0 => array:3 [ "nombre" => "Nicolás" "apellidos" => "Merchante" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 1 => array:3 [ "nombre" => "Manuel" "apellidos" => "Parra-Sánchez" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 2 => array:3 [ "nombre" => "Antonio" "apellidos" => "Rivero-Juárez" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 3 => array:3 [ "nombre" => "Celia" "apellidos" => "Cifuentes" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 4 => array:3 [ "nombre" => "Ángela" "apellidos" => "Camacho" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 5 => array:3 [ "nombre" => "Juan" "apellidos" => "Macías" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 6 => array:3 [ "nombre" => "Loreto" "apellidos" => "Martínez-Dueñas" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 7 => array:3 [ "nombre" => "Elisabet" "apellidos" => "Pérez-Navarro" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 8 => array:3 [ "nombre" => "Antonio" "apellidos" => "Rivero" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 9 => array:4 [ "nombre" => "Juan A." "apellidos" => "Pineda" "email" => array:1 [ 0 => "japineda@telefonica.net" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Unidad de Enfermedades Infecciosas y Microbiología, Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario de Valme, Sevilla, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Unidad de Enfermedades Infecciosas, Hospital Universitario Reina Sofía, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Córdoba, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Prevalencia elevada de anticuerpos frente al virus de la hepatitis E en pacientes infectados por el VIH con enfermedad hepática de origen incierto" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Autochthonous hepatitis E virus (HEV) is an emerging infection in HIV patients in developed countries.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1–4</span></a> Epidemiological data from Spain have suggested that HIV may be an independent risk factor for autochthonous HEV.<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5,6</span></a> In a retrospective study, HEV infection accounted for 4% acute liver abnormalities in HIV-infected individuals.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> Besides HEV-related unexplained acute elevations of liver enzymes, chronic HEV infection with rapid progression to cirrhosis has been reported in HIV-infected patients.<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">8–10</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Unexplained elevations of liver stiffness (LS) were found in 11% of the HIV-infected patients without hepatitis B virus (HBV) or hepatitis C virus (HCV) co-infection from our cohort.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> Liver histology proved several sort of liver damage virtually in all patients with unexplained elevations of LS.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> In those with normal values of LS, sequential examinations revealed that 7% of them developed persistent elevations of LS, which were mainly attributed to fatty liver disease.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> However, previous HEV infection was not routinely investigated in these patients. In fact, it has been hypothesized that subclinical hepatic steatosis or fibrosis could be a host risk factor for clinical disease expression in patients exposed to HEV.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Our objective was to look for evidence of HEV exposure in HIV-infected patients with unexplained elevations of LS.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Study design and patients</span><p id="par0020" class="elsevierStylePara elsevierViewall">This was a case-control study conducted in two hospitals from Southern Spain. We selected as cases all patients fulfilling criteria of abnormal LS of uncertain origin as previously described among those who attended both institutions.<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">11,12</span></a> Briefly, we selected HIV-infected patients with a LS<span class="elsevierStyleHsp" style=""></span>≥<span class="elsevierStyleHsp" style=""></span>7.2<span class="elsevierStyleHsp" style=""></span>kiloPascals (kPa) in two consecutive visits, without previous exposure to HBV or HCV as determined by a negative hepatitis B surface antigen, negative HCV antibodies and a negative serum DNA HBV and RNA HCV PCR assessment, and without evidence of other causes of liver disease. Forty-four patients fulfilled these criteria before 30th June 2011. Of them, 31 (70%) had an available frozen serum sample collected at the date of LS assessment and were included as cases in the study. These cases were paired with HIV-infected patients, without evidence of active HCV or HBV coinfection, selected from the same cohort with a LS<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>7.2<span class="elsevierStyleHsp" style=""></span>kPa who were matched by age, sex, CD4 cell count and study center.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Laboratory procedures</span><p id="par0025" class="elsevierStylePara elsevierViewall">All plasma samples were tested for the presence of HEV-specific IgG antibodies using both the Wantai HEV-IgG ELISA kit (Beijing Wantai Biological Pharmacy Enterprise CO., LTD., Beijing, China) and the recomWell HEV IgG ELISA (Mikrogen GmbH, Neuried, Germany). Confirmatory testing was performed using the recomLine HEV IgM/IgG immunoassay (Mikrogen GmbH, Neuried, Germany). Samples were analyzed according to the manufacturer's instructions. We defined exposure to HEV as the detection of serum HEV antibodies by at least one of the two ELISA assays, provided that it was confirmed by Immunoblot. A real-time PCR RNA assay was conducted in all plasma samples to identify subjects with active HEV infection.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Statistical analysis</span><p id="par0030" class="elsevierStylePara elsevierViewall">Continuous variables are expressed as median (Q1–Q3). Categorical variables are presented as numbers (percentage). Continuous variables were compared using the Wilcoxon test whereas the frequencies were compared by the McNemar test. Data were analyzed using SPSS 19.0 (SPSS Inc., Chicago, IL, USA).</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Ethical aspects</span><p id="par0035" class="elsevierStylePara elsevierViewall">This study has been designed and performed according to the Helsinki declaration and was approved by the Ethics Committee of Hospital Universitario de Valme.</p></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Results</span><p id="par0040" class="elsevierStylePara elsevierViewall">The main features of the study population are depicted in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>. Among cases, 8 (26%) patients showed a LS<span class="elsevierStyleHsp" style=""></span>≥<span class="elsevierStyleHsp" style=""></span>14.6<span class="elsevierStyleHsp" style=""></span>kPa and 9 (29%) had a LS<span class="elsevierStyleHsp" style=""></span>≥<span class="elsevierStyleHsp" style=""></span>9<span class="elsevierStyleHsp" style=""></span>kPa but <14.6<span class="elsevierStyleHsp" style=""></span>kPa. Twelve (39%) cases had elevated levels of liver enzymes whereas this was observed in 7 (22%) controls (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.3).</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0045" class="elsevierStylePara elsevierViewall">Exposure to HEV was demonstrated, according to the criteria used in this study, in 9 (29%) of the cases whereas it was shown in 5 (16%) of the controls (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.3) (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>). Serum HEV RNA was detected only in one case and in no control. This patient had a documented chronic hepatitis E with progression to cirrhosis.</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Discussion</span><p id="par0050" class="elsevierStylePara elsevierViewall">Our study suggests that previous exposure to HEV is higher among HIV-infected patients with unexplained elevations of LS than in the HIV population with normal values of LS. This finding supports the hypothesis that HEV infection may underlie some of the unexplained cases of liver disease in HIV-infected patients and may contribute to liver injury in this setting. Although no statistically significant differences have been observed in this study, this fact may have been a consequence of the limited power of the analyzed sample. However, the prevalence of HEV exposure was almost double in cases in comparison with controls. This datum suggests that significant differences might have been reached if a larger sample had been analyzed and warrants further studies to confirm this finding.</p><p id="par0055" class="elsevierStylePara elsevierViewall">The seroprevalence of anti-HEV found in our HIV population with normal values of liver LS was high, namely 16% according to the criteria used in this study. This figure is higher than the seroprevalence reported in other HIV-cohorts, which have ranged from 1.5% to 11.2%<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5,14–21</span></a> and is also greater than the seroprevalence in the general population in Spain, which ranges between 0.6 and 7.3%.<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> Additionally, the anti-HEV seroprevalence found in our study is slightly higher than the 14% seroprevalence reported in a recent study conducted in 448 HIV-infected individuals in Spain.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> Although variability in the strategy and procedures for serological testing could partly explain these differences, it is well documented that seroprevalence varies between countries and within countries,<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a> which may have accounted for these differences in a great extent. Further investigations should clarify if the high anti-HEV seroprevalence in HIV-infected patients with unexplained liver disease found in our study reflects a higher risk for HEV infection in this population or if, alternatively, HEV infection is a potential contributor to liver disease in this setting.</p><p id="par0060" class="elsevierStylePara elsevierViewall">Our study has some limitations. First, as stated above, is the lack of power to find significant differences. However, identifying HIV-infected patients without hepatitis coinfection bearing unexplained liver disease is not easy, because reliable screening test as transient elastography is not routinely carried out in such a population. Because of this, we believe that these results are of interest, even without statistically significant difference, as they may prompt specific multicentric studies with larger sample sizes to be undertaken. The relevance that HEV may have as cause of unexplained liver disease in the HIV infection clearly justify these studies. Second, the serological diagnosis of HEV is not well standardized and lacks of a current widely accepted definition for HEV exposure. However, we have used several assays for the detection of anti-HEV antibodies and stringent criteria for minimizing variability in procedure results, including a confirmatory immunoblot test, also used by other experts.<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a> Additionally, the persistence of anti-HEV antibodies in the mid- and long-term is not completely known. Consequently, this and all previously published cross-sectional studies looking at the prevalence of anti-HEV antibodies may underestimate previous exposure to HEV due to loss of antibodies over time. Finally, although cases and controls were matched by relevant factors such as age, sex and CD4 count, the small sample size precluded us to include other matching factors as alcohol consumption or exposure to certain antiretroviral drugs as didanosine.</p><p id="par0065" class="elsevierStylePara elsevierViewall">In summary, although this study should be considered preliminary, according to its results, previous HEV infection seems to be more frequent among HIV-infected patients with unexplained liver disease and it may be involved in the development of the latter disorder. On the contrary, active chronic hepatitis E is rare in this setting, but rapid progression to cirrhosis is a concern. Chronic hepatitis E should be considered in any HIV-infected patients with unexplained abnormal liver function tests, including abnormal LS, as effective treatment of HEV may induce reversal of liver injury.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a></p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Conflict of interest</span><p id="par0075" class="elsevierStylePara elsevierViewall">None.</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Funding</span><p id="par0070" class="elsevierStylePara elsevierViewall">This work was partly supported by the <span class="elsevierStyleGrantSponsor" id="gs1">Red de Investigación en SIDA</span> (<span class="elsevierStyleGrantNumber" refid="gs1">ISCIII-RETIC RD06/006</span> and <span class="elsevierStyleGrantNumber" refid="gs1">ISCIII-RETIC RD12/0017</span>) and the <span class="elsevierStyleGrantSponsor" id="gs2">Fundación Progreso y Salud de la Junta de Andalucía</span> (grants references: PI: <span class="elsevierStyleGrantNumber" refid="gs2">0208/2009</span> and <span class="elsevierStyleGrantNumber" refid="gs2">0036/2010</span>). JM is the recipient of a grant from the <span class="elsevierStyleGrantSponsor" id="gs3">Servicio Andaluz de Salud de la Junta de Andalucía</span> (<span class="elsevierStyleGrantNumber" refid="gs3">B-0037</span>). JAP is the recipient of an intensification grant from the <span class="elsevierStyleGrantSponsor" id="gs4">Instituto de Salud Carlos III</span> (grant number <span class="elsevierStyleGrantNumber" refid="gs4">Programa-I3SNS</span>). The Unit of Infectious Diseases and Microbiology, Hospital Universitario de Valme (Seville, Spain) has received human resources research support from <span class="elsevierStyleGrantSponsor" id="gs5">Servicio Andaluz de Salud de la Junta de Andalucía</span> (Reference <span class="elsevierStyleGrantNumber" refid="gs5">B-0037</span>).</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:11 [ 0 => array:3 [ "identificador" => "xres560439" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Objective" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec576680" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres560438" "titulo" => "Resumen" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Objetivo" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec576679" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Methods" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Study design and patients" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Laboratory procedures" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Statistical analysis" ] 3 => array:2 [ "identificador" => "sec0030" "titulo" => "Ethical aspects" ] ] ] 6 => array:2 [ "identificador" => "sec0035" "titulo" => "Results" ] 7 => array:2 [ "identificador" => "sec0040" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0050" "titulo" => "Conflict of interest" ] 9 => array:2 [ "identificador" => "sec0045" "titulo" => "Funding" ] 10 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2014-03-09" "fechaAceptado" => "2014-10-17" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec576680" "palabras" => array:5 [ 0 => "Hepatitis E virus" 1 => "HIV" 2 => "Liver fibrosis" 3 => "Cirrhosis" 4 => "Liver stiffness" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec576679" "palabras" => array:5 [ 0 => "Virus de la hepatitis E" 1 => "VIH" 2 => "Fibrosis hepática" 3 => "Cirrosis" 4 => "Rigidez hepática" ] ] ] ] "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 look for evidence of hepatitis E virus (HEV) exposure in HIV-infected patients with unexplained elevations of liver stiffness (LS).</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Case–control study conducted in 31 HIV-infected patients with unexplained elevations of LS and in 31 HIV-controls with normal LS, matched by age, sex and CD4 cell-counts. Serum HEV antibodies were tested by two ELISA procedures and by Immunoblot. We defined exposure to HEV as the detection of serum HEV antibodies by at least one of the two ELISA assays, provided that it was confirmed by Immunoblot. A real-time PCR RNA assay was conducted in all plasma samples to identify subjects with active HEV infection.</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Exposure to HEV was demonstrated, according to the criteria used in this study, in 9 (29%) of the cases, whereas it was shown in 5 (16%) of the controls (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>.3). Serum HEV RNA was detected in none of the controls and in only in one case. This patient had a documented chronic hepatitis E with progression to cirrhosis.</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">HEV antibodies are frequently found in HIV-infected patients with unexplained liver disease.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Objective" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] "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">Evaluar la existencia de exposición previa al virus de la hepatitis E (VHE) en pacientes infectados por el VIH con elevaciones inexplicadas de rigidez hepatica (RH).</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Métodos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Estudio caso-control realizado en 31 pacientes con infección por el VIH y elevaciones inexplicadas de RH y 31 controles infectados por el VIH con RH normal, apareados por edad, sexo y recuento de células CD4. Se investigó la presencia de anticuerpos en suero frente al VHE mediante dos técnicas de ELISA y por Inmunoblot. La exposición previa al VHE se definió como la detección de anticuerpos séricos mediante al menos una de las dos técnicas de ELISA que se confirmó posteriormente mediante Inmunoblot. En todos los pacientes se realizó una PCR en tiempo real para identificar a aquellos pacientes con infección activa por el VHE.</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Se demostró la presencia de exposición previa al VHE, de acuerdo a los criterios usados en el estudio, en 9 (29%) de los casos y en 5 (16%) de los controles (p<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.3). La PCR en tiempo real confirmó la presencia de RNA del VHE en el suero de uno de los casos y en ninguno de los controles. Este paciente presentó una hepatitis crónica por VHE documentada con progresión a cirrosis.</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Los pacientes infectados por VIH con enfermedad hepática de origen inexplicado presentan una frecuencia elevada de anticuerpos frente al VHE.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Objetivo" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] ] "multimedia" => array:1 [ 0 => array:7 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "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">Parameter \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">Cases (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>31) \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">Controls (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>31) \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> bivariate \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleItalic">Age, median (Q1–Q3)</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">50 (41–60) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">49 (46–55) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.8 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="4" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="4" align="left" valign="top"><span class="elsevierStyleItalic">Sex</span></td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Male \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">25 (80) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">25 (80) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.0 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Female \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">6 (20) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">6 (20) \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></tr><tr title="table-row"><td class="td" title="table-entry " colspan="4" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="4" align="left" valign="top"><span class="elsevierStyleItalic">Risk factor</span></td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Heterosexual \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">19 (61%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">18 (58%) \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></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Male-to-male \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5 (16%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">7 (23%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.7 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Other \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">7 (23%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">6 (19%) \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></tr><tr title="table-row"><td class="td" title="table-entry " colspan="4" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleItalic">Body mass index, median (Q1–Q3)</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">26 (23–29) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">24 (23–29) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleItalic">CD4 cell count, median (Q1–Q3)</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">451 (165–671) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">484 (273–610) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="4" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="4" align="left" valign="top"><span class="elsevierStyleItalic">RNA HIV viral load</span></td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><50<span class="elsevierStyleHsp" style=""></span>copies/mL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">24 (77%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">26 (84%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.7 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>≥50<span class="elsevierStyleHsp" style=""></span>copies/mL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">7 (23%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5 (16%) \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></tr><tr title="table-row"><td class="td" title="table-entry " colspan="4" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleItalic">Alanine aminotransferase, IU/mL</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">32 (23–51) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">27 (20–41) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.08 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleItalic">Aspartate aminotransferase, IU/mL</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">29 (23–41) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">24 (20–31) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.04 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="4" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="4" align="left" valign="top"><span class="elsevierStyleItalic">Exposure to HEV</span><a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a></td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Positive \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">9 (29) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5 (16) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.3 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Negative \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">22 (71) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">26 (84) \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></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab906713.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "a" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Exposure to HEV was defined as a positive detection of IgG antibodies by one of the ELISA that was further confirmed by the Immunoblot.</p>" ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Features of the study population.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:24 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hepatitis E" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "J.H. 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| 2023 August | 12 | 2 | 14 |
| 2023 July | 24 | 7 | 31 |
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| 2021 December | 12 | 15 | 27 |
| 2021 November | 27 | 14 | 41 |
| 2021 October | 42 | 13 | 55 |
| 2021 September | 16 | 16 | 32 |
| 2021 August | 35 | 9 | 44 |
| 2021 July | 29 | 15 | 44 |
| 2021 June | 22 | 13 | 35 |
| 2021 May | 13 | 16 | 29 |
| 2021 April | 39 | 18 | 57 |
| 2021 March | 24 | 18 | 42 |
| 2021 February | 22 | 15 | 37 |
| 2021 January | 16 | 19 | 35 |
| 2020 December | 14 | 19 | 33 |
| 2020 November | 16 | 18 | 34 |
| 2020 October | 18 | 9 | 27 |
| 2020 September | 38 | 16 | 54 |
| 2020 August | 23 | 20 | 43 |
| 2020 July | 19 | 6 | 25 |
| 2020 June | 25 | 19 | 44 |
| 2020 May | 25 | 14 | 39 |
| 2020 April | 18 | 10 | 28 |
| 2020 March | 19 | 4 | 23 |
| 2020 February | 29 | 10 | 39 |
| 2020 January | 24 | 13 | 37 |
| 2019 December | 35 | 16 | 51 |
| 2019 November | 17 | 15 | 32 |
| 2019 October | 5 | 14 | 19 |
| 2019 September | 23 | 6 | 29 |
| 2019 August | 24 | 7 | 31 |
| 2019 July | 28 | 15 | 43 |
| 2019 June | 42 | 26 | 68 |
| 2019 May | 110 | 68 | 178 |
| 2019 April | 30 | 35 | 65 |
| 2019 March | 14 | 16 | 30 |
| 2019 February | 13 | 11 | 24 |
| 2019 January | 20 | 16 | 36 |
| 2018 December | 15 | 11 | 26 |
| 2018 November | 19 | 12 | 31 |
| 2018 October | 30 | 10 | 40 |
| 2018 September | 29 | 6 | 35 |
| 2018 August | 19 | 7 | 26 |
| 2018 July | 3 | 4 | 7 |
| 2018 June | 7 | 4 | 11 |
| 2018 May | 8 | 8 | 16 |
| 2018 April | 7 | 2 | 9 |
| 2018 March | 7 | 0 | 7 |
| 2018 February | 8 | 3 | 11 |
| 2018 January | 9 | 2 | 11 |
| 2017 December | 10 | 4 | 14 |
| 2017 November | 11 | 6 | 17 |
| 2017 October | 10 | 1 | 11 |
| 2017 September | 17 | 2 | 19 |
| 2017 August | 13 | 2 | 15 |
| 2017 July | 2 | 3 | 5 |
| 2017 June | 9 | 7 | 16 |
| 2017 May | 16 | 1 | 17 |
| 2017 April | 20 | 4 | 24 |
| 2017 March | 7 | 34 | 41 |
| 2017 February | 8 | 7 | 15 |
| 2017 January | 12 | 3 | 15 |
| 2016 December | 20 | 4 | 24 |
| 2016 November | 19 | 7 | 26 |
| 2016 October | 51 | 3 | 54 |
| 2016 September | 39 | 11 | 50 |
| 2016 August | 27 | 4 | 31 |
| 2016 July | 17 | 4 | 21 |
| 2016 June | 20 | 13 | 33 |
| 2016 May | 14 | 1 | 15 |
| 2016 April | 7 | 21 | 28 |
| 2016 March | 10 | 12 | 22 |
| 2016 February | 25 | 19 | 44 |
| 2016 January | 27 | 25 | 52 |
| 2015 December | 28 | 19 | 47 |
| 2015 November | 44 | 28 | 72 |
| 2015 October | 77 | 79 | 156 |
Show all
