Immune Reconstitution Syndrome with Initiation of Treatment of HBV/HIV Co-infection: Activity Flare associated with E antigen Seroconversion
Michael W. Rowley
, Amitkumar Patel†,§, Wendi Zhou‡,||, Mark Wong§,||, Anil B. Seetharam§,||
,§,
Corresponding author
* Department of Internal Medicine, Banner University Medical Center Phoenix, Phoenix, AZ, USA
† Department of Gastroenterology, Banner University Medical Center Phoenix, Phoenix, AZ, USA
‡ Department of Pathology, Banner University Medical Center Phoenix, Phoenix, AZ, USA
§ Transplant and Advanced Liver Disease Center, Banner University Medical Center Phoenix, Phoenix, AZ, USA
|| University of Arizona College of Medicine Phoenix, Phoenix, AZ, USA
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Rowley, Amitkumar Patel, Wendi Zhou, Mark Wong, Anil B. Seetharam" "autores" => array:5 [ 0 => array:4 [ "nombre" => "Michael W." "apellidos" => "Rowley" "email" => array:1 [ 0 => "michael.rowley.banner@gmail.com" ] "referencia" => array:3 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "aff1" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">§</span>" "identificador" => "aff4" ] 2 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor1" ] ] ] 1 => array:3 [ "nombre" => "Amitkumar" "apellidos" => "Patel" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">†</span>" "identificador" => "aff2" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">§</span>" "identificador" => "aff4" ] ] ] 2 => array:3 [ "nombre" => "Wendi" "apellidos" => "Zhou" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">‡</span>" "identificador" => "aff3" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">||</span>" "identificador" => "aff5" ] ] ] 3 => array:3 [ "nombre" => "Mark" "apellidos" => "Wong" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">§</span>" "identificador" => "aff4" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">||</span>" "identificador" => "aff5" ] ] ] 4 => array:3 [ "nombre" => "Anil B." "apellidos" => "Seetharam" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">§</span>" "identificador" => "aff4" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">||</span>" "identificador" => "aff5" ] ] ] ] "afiliaciones" => array:5 [ 0 => array:3 [ "entidad" => "Department of Internal Medicine, Banner University Medical Center Phoenix, Phoenix, AZ, USA" "etiqueta" => "*" "identificador" => "aff1" ] 1 => array:3 [ "entidad" => "Department of Gastroenterology, Banner University Medical Center Phoenix, Phoenix, AZ, USA" "etiqueta" => "†" "identificador" => "aff2" ] 2 => array:3 [ "entidad" => "Department of Pathology, Banner University Medical Center Phoenix, Phoenix, AZ, USA" "etiqueta" => "‡" "identificador" => "aff3" ] 3 => array:3 [ "entidad" => "Transplant and Advanced Liver Disease Center, Banner University Medical Center Phoenix, Phoenix, AZ, USA" "etiqueta" => "§" "identificador" => "aff4" ] 4 => array:3 [ "entidad" => "University of Arizona College of Medicine Phoenix, Phoenix, AZ, USA" "etiqueta" => "||" "identificador" => "aff5" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor1" "etiqueta" => "*" "correspondencia" => "Correspondence and reprint request:" ] ] ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "f0010" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2404 "Ancho" => 2075 "Tamanyo" => 1007768 ] ] "descripcion" => array:1 [ "en" => "<p id="sp0010" class="elsevierStyleSimplePara elsevierViewall">Liver biopsy. A. Low power view showing active hepatitis with disarray and inflammation. B. Portal tract with mixed infiltrate, interface activity and hepatocyte injury (swelling and apoptosis), C-D. Lobular activity and pericentral inflammation with hepatocyte dropout, hemorrhage, and cholestasis. Plasma cells are present. E. Trichrome stain showing mild porta fibrosis. F. Hepatitis B core antigen stain with nuclear staining and significant focal cytoplasmic staining.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="s0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0020">Introduction</span><p id="p0010" class="elsevierStylePara elsevierViewall">Hepatitis B virus (HBV) infection is common with an estimated 2 billion people having evidence of past or present infection.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">1</span></a> While the United States is considered a low prevalence region of the world, 0.3% of Americans are Hepatitis B surface antigen (HBsAg) positive—translating to 800,000 with active infection.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">2</span></a> Partly due to shared modes of transmission with Human Immunodeficiency Virus (HIV), an estimated 10% of HIV patients are co-infected with HBV.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">3</span></a> Those who acquire HIV/HBV concomitantly have a significantly higher risk to progression of chronic hepatitis B-21% <span class="elsevierStyleItalic">vs.</span> 7%.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">4</span></a> Hepatitis Be antigen (HBeAg) to antibody (HBeAb) seroconversion rates are significantly lower in coinfected populations.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">5</span></a> In addition, HIV/HBV co-infected patients experience more rapid progression of fibrosis and subsequent complications including cirrhosis, hepatocellular carcinoma and need for liver transplantation.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">6</span></a> Such rapid progression is evident even in patients with lower HBV viral loads and alanine aminotransferase (ALT) levels.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">7</span></a> Current guidelines recommend treatment of all co-infected patients with antiviral therapy targeting both HIV and HBV.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">8</span></a></p><p id="p0015" class="elsevierStylePara elsevierViewall">Immune Reconstitution Syndrome (IRIS) is a recognized complication with initiation of highly active antiretroviral therapy (HAART) for acquired immune deficiency syndrome (AIDS) in HIV/HBV patients. HBV flares are seen in 20-25% of patients after initiation of HAART, an estimated 1-5% of whom develop clinical hepatitis.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">9</span></a> In this report, we present a case of HAART initiation for HIV that led to a flare of HBV activity despite antiviral therapy directed towards both. Liver biopsy and longitudinal serologic evaluation lend support to the hypothesis that the flare in activity was representative of IRIS. Importantly, we document eAg/eAb seroconversion with this phenomenon.</p></span><span id="s0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0025">Case</span><p id="p0020" class="elsevierStylePara elsevierViewall">A 57-year-old male originally from Nigeria presented with a 2-week history of right upper quadrant abdominal pain, nausea, fatigue and confusion. Medical history was significant for a recent diagnosis of HIV/HBV co-infection 2 months prior, identified when he presented with ataxia attributed to neurotoxoplasmosis. At that time, labs were notable for low CD4 count, positive HIV and HBV viral loads, and normal AST/ALT consistent with AIDS and immune tolerant, chronic HBV (<a class="elsevierStyleCrossRef" href="#t0010">Table 1</a>). Hepatitis C antibody was negative. He was treated for Toxoplasmosis with pyrimethamine, leucovorin and clindamycin as well as initiated on HAART with emtricitabine, tenofovir and reltegravir. Sulfamethoxazole-trimethoprim was also started for pneumocystis jiroveci pneumonia prophylaxis. He remained on therapy for 2 months without incident; with outpatient, labs showing normal aminotransferases at 1 month of therapy.</p><elsevierMultimedia ident="t0010"></elsevierMultimedia><p id="p0025" class="elsevierStylePara elsevierViewall">On re-presentation, labs were notable for significantly elevated AST/ALT consistent with a hepatocellular type liver injury pattern despite improvements in both HIV and HBV viral loads (<a class="elsevierStyleCrossRef" href="#t0010">Table 1</a>). There was also evidence of HBV eAg to eAb seroconversion. HBV genotyping revealed genotype E with C1858T precore mutation but no polymerase or basal core promotor mutations. The patient was admitted for further workup and management. An abdominal ultrasound and CT scan revealed no focal lesions, nodularity or fatty infiltration of the liver. A repeat MRI showed almost complete resolution of his brain lesions from toxoplasmosis. Toxicology was consulted to help determine the etiology of the patient’s liver injury. Given the temporal association with the initiation of multiple new medications, drug induced liver injury was initially considered likely. Sulfamethoxazole-trimethoprim and azithromycin were determined to be the most likely culprits, although the patient had no rash, fever, lymphadenopathy or eosinophilia typical of a hypersensitivity reaction from the former agent. Infectious disease and hepatology were also consulted and his antiviral therapy was continued while is prophylaxis medications were held. The significant transaminitis only minimally improved however and on hospital day 7, a liver biopsy was performed.</p><p id="p0030" class="elsevierStylePara elsevierViewall">On H&E stain, moderate to severe active hepatitis with central zone dropout, focal periportal hepatocyte dropout of mild to moderate degree, and diffuse lobular activity with mixed inflammatory infiltrates and cellular necrosis were seen (<a class="elsevierStyleCrossRef" href="#f0010">Figures 1A</a>-<a class="elsevierStyleCrossRef" href="#f0010">Figures 1D</a>). There was mild periportal fibrosis on trichrome stain (<a class="elsevierStyleCrossRef" href="#f0010">Figures 1E</a>). Typical of HBV infection, HBcAg staining showed multiple positive nuclear straining and significant focal cytoplasmic staining (<a class="elsevierStyleCrossRef" href="#f0010">Figure 1F</a>). There were rare HBsAg staining and no evidence of drug toxicity.</p><elsevierMultimedia ident="f0010"></elsevierMultimedia><p id="p0035" class="elsevierStylePara elsevierViewall">The patient’s clinical, laboratory and histological findings suggested HBV-related IRIS. HAART was continued and appropriate toxoplasmosis and prophylaxis therapy were restarted. He was discharged on hospital day 12 after symptoms and transaminitis improved significantly. Subsequently, AST/ALT levels normalized and HIV and HBV viral loads (were undetectable 3 months after discharge (<a class="elsevierStyleCrossRef" href="#t0010">Table 1</a>).</p></span><span id="s0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0030">Discussion</span><p id="p0040" class="elsevierStylePara elsevierViewall">IRIS is an inflammatory disorder associated with paradoxical worsening of a pre-existing infection, either previously recognized or occult.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">10</span></a> The condition is commonly seen in AIDS patients although transplant patients may be affected. Diagnostic features include AIDS with low CD4 count; positive virologic/immunological response to HAART; clinical manifestations of an inflammatory condition; temporal association between initiation of HAART and onset; absence of other causes such as drug reactions, noncompliance or ineffective HAART therapy and other infection.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">11</span></a> The most common associated GI pathogen is HBV. Typical onset is 2-8 weeks after initiation of HAART. Symptoms include B-symptoms, anorexia, nausea, fatigue, tender hepatomegaly and jaundice. IRIS is usually self-limiting and HAART and HBV treatment are usually continued.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">9</span></a></p><p id="p0045" class="elsevierStylePara elsevierViewall">The molecular mechanism of liver injury in IRIS appears to be different than for injury in non-HIV infected patients. Injury in mono-infected patients is caused by immune-mediated damage of HBV-infected hepatocytes. Multiple cytokines are implicated including tumor necrosis factor (TNF)-a, interferon (IFN)-y and activated natural killer (NK) cells. Ultimately both HBV-specific and predominately nonspecific CD8+ T cells present to the liver and cause damage to hepatocytes.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">12</span></a> The IRIS immune response is associated with recruitment of monocytes and CD8 + T cells to the liver but is not thought to involve NK cell-mediated immunity.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">13</span></a></p><p id="p0050" class="elsevierStylePara elsevierViewall">Our case is nicely illustrative IRIS/flare of HBV activity with imitation of HAART. Serial viral PCR showed clear evidence of effective treatment of both his HIV and HBV with decreasing viral loads. Serum markers at presentation were consistent with immune tolerance with minimally elevated AST/ALT and positive HBeAg. At representation, injury associated with immune clearance was seen: increasing AST/ALT, eAg/eAb seroconversion, and decreasing viral loads. Interestingly, no similar flare of his neurologic symptoms to suggest toxoplasmosis related IRIS which has also been described.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">14</span></a> The patient was continued on HAART including tenofovir throughout his course and improved with symptomatic management. Interestingly, our patient had genotype E HBV with C1858T precore mutation, found almost exclusively in Africa. In one study from India, HIV/HBV co-infected patients had different profiles of mutations than mono-infected patients.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">15</span></a> To the best of our knowledge phenotypic diversity has not been studied in genotype E patients.</p><p id="p0055" class="elsevierStylePara elsevierViewall">We found only one other study which addressed the features of HIV/HBV related IRIS on liver biopsy.<a class="elsevierStyleCrossRef" href="#bib0085">16</a>Two patients’ biopsies showed evidence of mild lobular hepatitis and mild lymphocytic inflammation which was diffusely positive for CD3 and CD8. These patients were both asymptomatic and had milder elevations of AST/ALT levels compared to our patient. eAg/eAb seroconversion was not documented in these cases. However, histological findings were similar and point to IRIS as the causative process instead of worsening HBV infection or drug toxicity.</p><p id="p0060" class="elsevierStylePara elsevierViewall">While HBV related IRIS is relatively common, AST/ ALT levels rarely reach >10 times the normal limit.<a class="elsevierStyleCrossRef" href="#bib0090">17</a> Frank decompensated liver failure is even rarer, typically limited to patients with advanced cirrhosis.<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">18</span></a> IRIS related hepatic flare has been shown to rapidly lower HBV DNA and HBsAg levels.<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">19</span></a> We postulate that the severity of the patient’s hepatic flare was ultimately beneficial in rapid clearance of HBV and development of HBe antibodies which is much less common in HIV/HBV patients.</p><p id="p0065" class="elsevierStylePara elsevierViewall">The diagnosis of IRIS can be challenging. Hepatotoxicity with HAART medications is common but criteria for IRIS include ruling out drug toxicity. Given the known associated hepatotoxicity of HIV medications, treatment is sometimes stopped or adjusted in patients with worsening liver function. However, patients are at risk for severe worsening HBV infection with cessation of treatment. Given the very low likelihood of acute liver failure, continuing HAART and HBV treatment is most often appropriate. It is therefore important that providers have a high index of suspicion for IRIS in newly treated HIV/HBV co-infection and manage it appropriately.</p></span><span id="s0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0035">Abbreviations</span><p id="p0070" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="l0010"><li class="elsevierStyleListItem" id="u0010"><span class="elsevierStyleLabel">•</span><p id="p0075" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">Ab:</span> antibody.</p></li><li class="elsevierStyleListItem" id="u0015"><span class="elsevierStyleLabel">•</span><p id="p0080" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">Ag:</span> antigen.</p></li><li class="elsevierStyleListItem" id="u0020"><span class="elsevierStyleLabel">•</span><p id="p0085" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">AIDS:</span> acquired immune deficiency syndrome.</p></li><li class="elsevierStyleListItem" id="u0025"><span class="elsevierStyleLabel">•</span><p id="p0090" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">ALT:</span> alanine aminotransferase.</p></li><li class="elsevierStyleListItem" id="u0030"><span class="elsevierStyleLabel">•</span><p id="p0095" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">HAART:</span> highly active antiretroviral therapy.</p></li><li class="elsevierStyleListItem" id="u0035"><span class="elsevierStyleLabel">•</span><p id="p0100" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">HBeAb:</span> hepatitis Be antibody.</p></li><li class="elsevierStyleListItem" id="u0040"><span class="elsevierStyleLabel">•</span><p id="p0105" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">HBeAg:</span> hepatitis Be antigen.</p></li><li class="elsevierStyleListItem" id="u0045"><span class="elsevierStyleLabel">•</span><p id="p0110" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">HBsAg:</span> hepatitis B surface antigen.</p></li><li class="elsevierStyleListItem" id="u0050"><span class="elsevierStyleLabel">•</span><p id="p0115" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">HBV:</span> hepatitis B virus.</p></li><li class="elsevierStyleListItem" id="u0055"><span class="elsevierStyleLabel">•</span><p id="p0120" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">IRIS:</span> immune reconstitution syndrome.</p></li></ul></p></span><span id="s0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0040">Conflict of Interest</span><p id="p0125" class="elsevierStylePara elsevierViewall">The authors declares that there is no conflict of interest regarding the publication of this article.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:8 [ 0 => array:3 [ "identificador" => "xres1224768" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abs0010" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1138834" "titulo" => "Key words" ] 2 => array:2 [ "identificador" => "s0010" "titulo" => "Introduction" ] 3 => array:2 [ "identificador" => "s0015" "titulo" => "Case" ] 4 => array:2 [ "identificador" => "s0020" "titulo" => "Discussion" ] 5 => array:2 [ "identificador" => "s0025" "titulo" => "Abbreviations" ] 6 => array:2 [ "identificador" => "s0030" "titulo" => "Conflict of Interest" ] 7 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2017-05-02" "fechaAceptado" => "2017-07-17" "PalabrasClave" => array:1 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Key words" "identificador" => "xpalclavsec1138834" "palabras" => array:4 [ 0 => "Acquired Immune Deficiency Syndrome" 1 => "AIDS" 2 => "Hepatitis B" 3 => "Human Immunodeficiency Virus" ] ] ] ] "tieneResumen" => true "resumen" => array:1 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "<span id="abs0010" class="elsevierStyleSection elsevierViewall"><p id="sp0020" class="elsevierStyleSimplePara elsevierViewall">Immune reconstitution syndrome is a recognized complication with initiation of highly active antiretroviral therapy for acquired immune deficiency syndrome patients co-infected with hepatitis B. Hepatitis B flares are seen in 20%-25% of patients after initiation of highly active antiretroviral therapy, an estimated 1%-5% of whom develop clinical hepatitis. We present a case of highly active antiretroviral therapy initiation for HIV that led to a flare of HBV activity despite antiviral therapy directed towards both. Liver biopsy and longitudinal serologic evaluation lend support to the hypothesis that the flare in activity was representative of IRIS. Importantly, we document eAg/eAb seroconversion with the IRIS phenomenon.</p></span>" ] ] "multimedia" => array:2 [ 0 => array:7 [ "identificador" => "f0010" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2404 "Ancho" => 2075 "Tamanyo" => 1007768 ] ] "descripcion" => array:1 [ "en" => "<p id="sp0010" class="elsevierStyleSimplePara elsevierViewall">Liver biopsy. A. Low power view showing active hepatitis with disarray and inflammation. B. Portal tract with mixed infiltrate, interface activity and hepatocyte injury (swelling and apoptosis), C-D. Lobular activity and pericentral inflammation with hepatocyte dropout, hemorrhage, and cholestasis. Plasma cells are present. E. Trichrome stain showing mild porta fibrosis. F. Hepatitis B core antigen stain with nuclear staining and significant focal cytoplasmic staining.</p>" ] ] 1 => array:8 [ "identificador" => "t0010" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "fuente" => "* <span class="elsevierStyleItalic">HIV/HBV tests: COBAS® AmpliPrep/COBAS® TaqMan®, version 2.0 (Roche Molecular Systems, Inc. Pleasanton, California, USA).</span>" "tabla" => array:1 [ "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="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Prior admit \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Re-admission \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Discharge \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">3 months \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HIV viral load* \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5.32 log copies/mL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.79 log copies/mL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">< 20 copies/mL \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">CD4 Count \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">36 cells/mL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">214 cells/mL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">413 cells/mL \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HBV Surface Ab \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Negative \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Negative \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HBV Surface Ag \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Positive \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Positive \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HBV Core Ab \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Positive \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Positive \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HBV eAg \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Positive \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Negativ \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HBV eAb \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Negative \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Positive \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HBV viral load* \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7.12 log copies/mL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5.34 log copies/mL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2.75 log copies/mL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">< 20 copies/mL \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">AST/ALT \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">39/51 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2435/1987 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">194/214 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">37/30 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Total bilirubin \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.4 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Alkaline Phosphatase \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">74 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">175 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">336 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">105 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2092110.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="sp0015" class="elsevierStyleSimplePara elsevierViewall">Viral serologies.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bs0010" "bibliografiaReferencia" => array:19 [ 0 => array:3 [ "identificador" => "bib0010" "etiqueta" => "1." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Estimations of worldwide prevalence of chronic hepatitis B virus infection: a systematic review of data published between 1965 and 2013." "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "Schweitzer A." 1 => "Horn J." 2 => "Mikolajczk R.T." 3 => "Krause G." 4 => "Ott J.J." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S0140-6736(15)61412-X" "Revista" => array:6 [ "tituloSerie" => "Lancet" "fecha" => "2015" "volumen" => "386" "paginaInicial" => "1546" "paginaFinal" => "1555" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26231459" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0015" "etiqueta" => "2." "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "National health and nutrition examination survey. 2008" ] ] ] 2 => array:3 [ "identificador" => "bib0020" "etiqueta" => "3." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Care of HIV patients with chronic hepatitis B: updated recommendations from the HIV-Hepatitis B Virus International Panel." "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:7 [ 0 => "Soriano V." 1 => "Puoti M." 2 => "Peters M." 3 => "Benhamou Y." 4 => "Sulkowski M." 5 => "Zoulim F." 6 => "Mauss S." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/QAD.0b013e3282f8b46f" "Revista" => array:6 [ "tituloSerie" => "AIDS" "fecha" => "2008" "volumen" => "22" "paginaInicial" => "1399" "paginaFinal" => "1410" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18614862" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0025" "etiqueta" => "4." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Outcome of hepatitis B virus infection in homosexual men and its relation to prior immunodeficiency virus infection." "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:7 [ 0 => "Hadler S.C." 1 => "Judson F.N." 2 => "O’Malley P.M." 3 => "Altman N.L." 4 => "Penley K." 5 => "Buchbinder S." 6 => "Schable C.A." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1093/infdis/163.3.454" "Revista" => array:6 [ "tituloSerie" => "J Infect Dis" "fecha" => "1991" "volumen" => "163" "paginaInicial" => "454" "paginaFinal" => "459" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/1825315" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0030" "etiqueta" => "5." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The influence of human immunodeficiency virus type 1 infection on the development of the HBV carrier state." "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "Bodsworth N.J." 1 => "Cooper D.A." 2 => "Donovan B." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1093/infdis/163.5.1138" "Revista" => array:6 [ "tituloSerie" => "J Infect Dis" "fecha" => "1991" "volumen" => "163" "paginaInicial" => "1138" "paginaFinal" => "1140" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/2019762" "web" => "Medline" ] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0035" "etiqueta" => "6." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hepatitis B in HIV-infected patients." "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "Soriano V." 1 => "Poveda E." 2 => "Vispo E." 3 => "Barreiro P." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.cld.2013.05.008" "Revista" => array:6 [ "tituloSerie" => "Clin Liver Dis" "fecha" => "2013" "volumen" => "17" "paginaInicial" => "489" "paginaFinal" => "4501" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23905818" "web" => "Medline" ] ] ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0040" "etiqueta" => "7." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Predicting cirrhosis risk based on the level of circulating hepatitis B viral load." "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "Iloeje U." 1 => "Yang H." 2 => "Su J." 3 => "Jen C.L." 4 => "You S.L." 5 => "Chen C.J." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1053/j.gastro.2005.11.016" "Revista" => array:6 [ "tituloSerie" => "Gastroenterology" "fecha" => "2006" "volumen" => "130" "paginaInicial" => "678" "paginaFinal" => "686" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16530509" "web" => "Medline" ] ] ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0045" "etiqueta" => "8." "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "Panel on Opportunistic Infections in HIV-Infected Adults and Adolescents. Guidelines for the prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: recommendations from the centers for disease control and prevention, the national institutes of health, and the HIV medicine association of the infectious diseases society of America. Available at http://aidsinfo.nih.gov/contentfiles/Ivguidelines/adultoi.pdf. Accessed Jan 2017" ] ] ] 8 => array:3 [ "identificador" => "bib0050" "etiqueta" => "9." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Assessment of HBV flare in a randomized clinical trial in HIV/HBV coinfected subjects initiating HBV-active antiretroviral therapy in Thailand." "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:7 [ 0 => "Avihingsanon A." 1 => "Matthews G.V." 2 => "Lewin S.R." 3 => "Marks P." 4 => "Sasadeusz J." 5 => "Cooper D.A." 6 => "Bowden S." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1186/1742-6405-9-6" "Revista" => array:6 [ "tituloSerie" => "AIDS Res Ther" "fecha" => "2012" "volumen" => "9" "paginaInicial" => "6" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22405335" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0211139X14002546" "estado" => "S300" "issn" => "0211139X" ] ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib0055" "etiqueta" => "10." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "HIV/AIDS: immune reconstitution inflammatory syndrome: a reappraisal." "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "French M." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1086/595006" "Revista" => array:6 [ "tituloSerie" => "Clin Infect Dis" "fecha" => "2009" "volumen" => "48" "paginaInicial" => "101" "paginaFinal" => "107" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19025493" "web" => "Medline" ] ] ] ] ] ] ] ] 10 => array:3 [ "identificador" => "bib0060" "etiqueta" => "11." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Defining immune reconstitution inflammatory syndrome: evaluation of expert opinion versus 2 case definitions in a South African cohort." "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:7 [ 0 => "Haddow L.J." 1 => "Easterbrook P.J." 2 => "Mosam A." 3 => "Khanyile N.G." 4 => "Parboosing R." 5 => "Moodley P." 6 => "Moosa M.Y." ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Clin Infect Dis" "fecha" => "2009" "volumen" => "29" "paginaInicial" => "1424" "paginaFinal" => "1432" ] ] ] ] ] ] 11 => array:3 [ "identificador" => "bib0065" "etiqueta" => "12." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Exploring the biological basis of hepatitis B e antigen in hepatitis B virus infection." "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "Milich D." 1 => "Liang T.J." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1053/jhep.2003.50453" "Revista" => array:6 [ "tituloSerie" => "Hepatology" "fecha" => "2003" "volumen" => "38" "paginaInicial" => "1075" "paginaFinal" => "1086" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/14578844" "web" => "Medline" ] ] ] ] ] ] ] ] 12 => array:3 [ "identificador" => "bib0070" "etiqueta" => "13." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Immunopathogenesis of hepatitis flare in HIV/HBV coinfected individuals after initiation of HBV-active antiretroviral therapy." "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:7 [ 0 => "Crane M." 1 => "Oliver B." 2 => "Matthews G." 3 => "Avihingsanon A." 4 => "Ubolyam S." 5 => "Markovska V." 6 => "Chang J.J." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1086/597276" "Revista" => array:6 [ "tituloSerie" => "J Infect Dis" "fecha" => "2009" "volumen" => "199" "paginaInicial" => "974" "paginaFinal" => "981" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19231993" "web" => "Medline" ] ] ] ] ] ] ] ] 13 => array:3 [ "identificador" => "bib0075" "etiqueta" => "14." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Toxoplasmosis: a rare cause of IRIS in HIV infected patients. case series." "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:7 [ 0 => "Moroti R." 1 => "Munteanu D." 2 => "Radulescu M." 3 => "Hristea A." 4 => "Niculescu I." 5 => "Mihailescu R." 6 => "Petre R." ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:4 [ "tituloSerie" => "BMC Infect Dis" "fecha" => "2013" "volumen" => "13" "paginaInicial" => "07" ] ] ] ] ] ] 14 => array:3 [ "identificador" => "bib0080" "etiqueta" => "15." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Molecular characterization of HBV strains circulating among the treatment-naive HIV/HBV co-infected patients of eastern India." "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "Saha D." 1 => "Pal A." 2 => "Biswas A." 3 => "Panigrahi R." 4 => "Sarkar N." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1371/journal.pone.0090432" "Revista" => array:6 [ "tituloSerie" => "PLos ONE" "fecha" => "2014" "volumen" => "9" "numero" => "2" "paginaInicial" => "e90432" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24587360" "web" => "Medline" ] ] ] ] ] ] ] ] 15 => array:3 [ "identificador" => "bib0085" "etiqueta" => "16." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hepatitis B virus-related immune reconstitution inflammatory syndrome in two patients coinfected with human immunodeficiency virus diagnosed with a liver biopsy." "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:7 [ 0 => "Mitsumoto F." 1 => "Murata M." 2 => "Kato Y." 3 => "Ura K." 4 => "Takayama K." 5 => "Haramine S." 6 => "Ikezaki H." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.2169/internalmedicine.53.2503" "Revista" => array:6 [ "tituloSerie" => "Intern Med" "fecha" => "2014" "volumen" => "53" "paginaInicial" => "2165" "paginaFinal" => "2170" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25224208" "web" => "Medline" ] ] ] ] ] ] ] ] 16 => array:3 [ "identificador" => "bib0090" "etiqueta" => "17." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Incidence of and risk factors for severe hepatotoxicity associated with antiretroviral combination therapy." "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "Wit F.W." 1 => "Weverling G.J." 2 => "Weel J." 3 => "Jurriaans S." 4 => "Lange J.M." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1086/341084" "Revista" => array:6 [ "tituloSerie" => "J Infect Dis" "fecha" => "2002" "volumen" => "186" "paginaInicial" => "23" "paginaFinal" => "31" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12089658" "web" => "Medline" ] ] ] ] ] ] ] ] 17 => array:3 [ "identificador" => "bib0095" "etiqueta" => "18." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Development of fatal acute liver failure in HIV-HBV coinfected patients." "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "Anderson A.M." 1 => "Mosunjac M.B." 2 => "Palmore M.P." 3 => "Osborn M.K." 4 => "Muir A.J." ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "World J of Gastroenterol" "fecha" => "2010" "volumen" => "16" "paginaInicial" => "4107" "paginaFinal" => "4111" ] ] ] ] ] ] 18 => array:3 [ "identificador" => "bib0100" "etiqueta" => "19." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The kinetics of the HBsAg levels after the initiation of antiretroviral therapy for HBV and HIV coinfected patients." "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:7 [ 0 => "Mitsumoto F." 1 => "Murata M." 2 => "Ura K." 3 => "Takayama K." 4 => "Hiramine S." 5 => "Shimizu M." 6 => "Toyoda K." ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "J of Infect Chemother" "fecha" => "2015" "volumen" => "21" "paginaInicial" => "264" "paginaFinal" => "271" ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/16652681/0000001800000001/v2_201907270857/S1665268119303266/v2_201907270857/en/main.assets" "Apartado" => array:4 [ "identificador" => "77718" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Case Report" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/16652681/0000001800000001/v2_201907270857/S1665268119303266/v2_201907270857/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1665268119303266?idApp=UINPBA00004N" ]
| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 October | 11 | 4 | 15 |
| 2024 September | 24 | 10 | 34 |
| 2024 August | 21 | 19 | 40 |
| 2024 July | 21 | 5 | 26 |
| 2024 June | 34 | 7 | 41 |
| 2024 May | 14 | 8 | 22 |
| 2024 April | 16 | 11 | 27 |
| 2024 March | 35 | 8 | 43 |
| 2024 February | 21 | 5 | 26 |
| 2024 January | 22 | 9 | 31 |
| 2023 December | 9 | 4 | 13 |
| 2023 November | 18 | 8 | 26 |
| 2023 October | 22 | 13 | 35 |
| 2023 September | 9 | 2 | 11 |
| 2023 August | 13 | 13 | 26 |
| 2023 July | 15 | 11 | 26 |
| 2023 June | 26 | 22 | 48 |
| 2023 May | 38 | 21 | 59 |
| 2023 April | 41 | 15 | 56 |
| 2023 March | 18 | 13 | 31 |
| 2023 February | 17 | 9 | 26 |
| 2023 January | 9 | 7 | 16 |
| 2022 December | 27 | 8 | 35 |
| 2022 November | 34 | 8 | 42 |
| 2022 October | 27 | 12 | 39 |
| 2022 September | 24 | 17 | 41 |
| 2022 August | 32 | 17 | 49 |
| 2022 July | 25 | 14 | 39 |
| 2022 June | 25 | 14 | 39 |
| 2022 May | 17 | 8 | 25 |
| 2022 April | 29 | 12 | 41 |
| 2022 March | 37 | 14 | 51 |
| 2022 February | 44 | 9 | 53 |
| 2022 January | 74 | 10 | 84 |
| 2021 December | 39 | 7 | 46 |
| 2021 November | 55 | 9 | 64 |
| 2021 October | 50 | 12 | 62 |
| 2021 September | 45 | 7 | 52 |
| 2021 August | 46 | 11 | 57 |
| 2021 July | 30 | 13 | 43 |
| 2021 June | 21 | 10 | 31 |
| 2021 May | 33 | 10 | 43 |
| 2021 April | 78 | 11 | 89 |
| 2021 March | 27 | 3 | 30 |
| 2021 February | 6 | 5 | 11 |
| 2021 January | 6 | 9 | 15 |
| 2020 December | 5 | 9 | 14 |
| 2020 November | 9 | 7 | 16 |
| 2020 October | 7 | 5 | 12 |
| 2020 September | 7 | 8 | 15 |
| 2020 August | 18 | 10 | 28 |
| 2020 July | 18 | 8 | 26 |
| 2020 June | 9 | 6 | 15 |
| 2020 May | 12 | 5 | 17 |
| 2020 April | 8 | 5 | 13 |
| 2020 March | 6 | 3 | 9 |
| 2020 February | 5 | 3 | 8 |
| 2020 January | 7 | 5 | 12 |
| 2019 December | 15 | 4 | 19 |
| 2019 November | 9 | 2 | 11 |
| 2019 October | 10 | 1 | 11 |
| 2019 September | 14 | 2 | 16 |
| 2019 August | 2 | 1 | 3 |
| 2019 July | 16 | 5 | 21 |
| 2019 June | 8 | 6 | 14 |
| 2019 May | 13 | 13 | 26 |
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