Case and Research Letter
Risk of hepatitis B virus reactivation in patients treated with anti-TNFα agents for immune-mediated inflammatory diseases
Riesgo de reactivación de la hepatitis B en los pacientes tratados con agentes anti-TNFα para enfermedades inflamatorias inmuno-mediadas
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A. Gran ampolla subepidérmica con gran destrucción tisular subyacente abarcando la dermis y el tejido celular subcutáneo (tinción de hematoxilina y eosina ×<span class="elsevierStyleHsp" style=""></span>2, magnificación ×<span class="elsevierStyleHsp" style=""></span>20). B. Se observa un infiltrado neutrofílico denso con destrucción del colágeno dérmico y vasculitis asociada (tinción de hematoxilina y eosina ×<span class="elsevierStyleHsp" style=""></span>10, magnificación ×<span class="elsevierStyleHsp" style=""></span>100). C. Detalle en el que se observan neutrófilos infiltrando densamente la dermis y rodeando estructuras filamentosas discretamente perceptibles (tinción de hematoxilina y eosina ×<span class="elsevierStyleHsp" style=""></span>20, magnificación ×<span class="elsevierStyleHsp" style=""></span>200). D. A mayor detalle y con tinción de PAS se visualizan estructuras lineales tabicadas y en ángulo agudo compatible con el diagnóstico clínico y microbiológico de aspergilosis cutánea (tinción de PAS ×<span class="elsevierStyleHsp" style=""></span>40 magnificación ×<span class="elsevierStyleHsp" style=""></span>400).</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "P. Fonda-Pascual, P. Fernández-González, O.M. Moreno-Arrones, L. Miguel-Gómez" "autores" => array:4 [ 0 => array:2 [ "nombre" => "P." "apellidos" => "Fonda-Pascual" ] 1 => array:2 [ "nombre" => "P." "apellidos" => "Fernández-González" ] 2 => array:2 [ "nombre" => "O.M." "apellidos" => "Moreno-Arrones" ] 3 => array:2 [ "nombre" => "L." "apellidos" => "Miguel-Gómez" ] ] ] ] ] "idiomaDefecto" => "es" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S1578219018300131" "doi" => "10.1016/j.adengl.2018.02.011" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1578219018300131?idApp=UINPBA000044" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0001731017303873?idApp=UINPBA000044" "url" => "/00017310/0000010900000003/v1_201804020403/S0001731017303873/v1_201804020403/es/main.assets" ] "itemAnterior" => array:19 [ "pii" => "S0001731017304659" "issn" => "00017310" "doi" => "10.1016/j.ad.2017.07.012" "estado" => "S300" "fechaPublicacion" => "2018-04-01" "aid" => "1774" "copyright" => "AEDV" "documento" => "simple-article" "crossmark" => 1 "subdocumento" => "crp" "cita" => "Actas Dermosifiliogr. 2018;109:284-5" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 175 "formatos" => array:3 [ "EPUB" => 14 "HTML" => 87 "PDF" => 74 ] ] "en" => array:11 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Case and Research Letter</span>" "titulo" => "Bullous Sweet's syndrome with myositis" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "284" "paginaFinal" => "285" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Síndrome de Sweet ampollar con miositis" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1218 "Ancho" => 1625 "Tamanyo" => 345842 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">(a) Painful, erosive lesions on the upper chest with peripheral tense blisters (insert). (b) Histological features showing dense neutrophil infiltration throughout the edematous dermis. (c) Higher magnification showed neutrophil infiltration. (d) MRI examination revealed edematous swelling on the right gluteus maximus muscle.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "K. Sato, T. Miura, M. Ohtsuka, T. Yamamoto" "autores" => array:4 [ 0 => array:2 [ "nombre" => "K." "apellidos" => "Sato" ] 1 => array:2 [ "nombre" => "T." "apellidos" => "Miura" ] 2 => array:2 [ "nombre" => "M." "apellidos" => "Ohtsuka" ] 3 => array:2 [ "nombre" => "T." "apellidos" => "Yamamoto" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S1578219018300945" "doi" => "10.1016/j.adengl.2017.07.017" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1578219018300945?idApp=UINPBA000044" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0001731017304659?idApp=UINPBA000044" "url" => "/00017310/0000010900000003/v1_201804020403/S0001731017304659/v1_201804020403/en/main.assets" ] "en" => array:15 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Case and Research Letter</span>" "titulo" => "Risk of hepatitis B virus reactivation in patients treated with anti-TNFα agents for immune-mediated inflammatory diseases" "tieneTextoCompleto" => true "saludo" => "Dear Editor:" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "285" "paginaFinal" => "287" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "R. Pereira, I. Raposo, F. Nery, T. Torres" "autores" => array:4 [ 0 => array:3 [ "nombre" => "R." "apellidos" => "Pereira" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 1 => array:3 [ "nombre" => "I." "apellidos" => "Raposo" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "F." "apellidos" => "Nery" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] 3 => array:4 [ "nombre" => "T." "apellidos" => "Torres" "email" => array:1 [ 0 => "torres.tiago@outlook.com" ] "referencia" => array:3 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] 2 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "Instituto de Ciências Biomédicas Abel Salazar, University of Porto, Portugal" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Department of Dermatology, Centro Hospitalar do Porto, Portugal" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Hepato-Pancreatic Unit, Centro Hospitalar do Porto, Porto, Portugal" "etiqueta" => "c" "identificador" => "aff0015" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Riesgo de reactivación de la hepatitis B en los pacientes tratados con agentes anti-TNFα para enfermedades inflamatorias inmuno-mediadas" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">TNFα inhibitors revolutionized the treatment of immune-mediated inflammatory diseases (IMIDs). Due to their immunosuppressive nature, these therapies increase susceptibility for new infections and may alter the natural course of latent infections.<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">1,2</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Occult HBV infection is defined as the persistence of viral genome in the liver tissue of individuals serologically negative for HBV surface antigen (HBsAg).<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">3</span></a> Patients with positive antibodies to HBV core antigen (anti-HBc) and negative HBsAg and HBV-DNA, with or without antibodies to HBV surface antigen (anti-HBs) are potential occult HBV carriers<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">3</span></a> and may reactivate under immunosuppressive therapy.<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">1,2</span></a> Studies in subjects with past HBV infection treated with anti-TNFα therapy for inflammatory bowel disease (IBD) and rheumatic diseases estimated a reactivation rate between 1.7% and 5% of patients.<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">1,2</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">The aim of this retrospective study was to evaluate the rate of reactivation in anti-HBc positive/HBsAg negative patients treated with TNFα inhibitors for psoriasis, rheumatologic diseases and IBD.</p><p id="par0020" class="elsevierStylePara elsevierViewall">Patients treated with TNFα inhibitors for IMIDs from January 2000 to December 2014, for at least one month were retrospectively included. Information regarding patients’ HBV screening serology (HBsAg, anti-HBc and anti-HBs antibodies) and HBV-DNA (in anti-HBc positive patients) prior to the initiation of TNFα inhibitors as well as HBsAg seroconversion, HBV-DNA <span class="elsevierStyleItalic">de novo</span> detection and ALT/AST levels during anti-TNF therapy were collected. HBV reactivation was defined as titer elevation up to 2–3 times the upper limit of normal ALT, in combination with <span class="elsevierStyleItalic">de novo</span> detection of HBV-DNA or HBsAg seroconversion. Furthermore, patients’ demographic, clinical and therapeutic characteristics were recorded. This study was approved by the hospital's Institutional Review Board.</p><p id="par0025" class="elsevierStylePara elsevierViewall">From 389 patients treated with TNFα inhibitors during the study period, 26 (9%) patients were anti-HBc positive/HBsAg negative and one patient presented with a serologic profile compatible with chronic hepatitis B. The mean observation time was 43.6<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>28.7 months. Subjects’ demographic and clinical data are reported in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>. Nineteen (73.1%) patients were anti-HBs positive in the pre-treatment screening. HBV-DNA levels were available in 7 (26.9%) patients, being undetectable in all of them. Additionally, during follow-up, HBV-DNA levels were measured in 7 additional patients (that had not been measured before treatment) amounting to 53.8% patients with undetectable HBV-DNA levels. In these patients, HBV-DNA levels were measured every 6months for a 2-years period. No rise of the aminotransferases values was observed in any patient during follow-up. At the end of the observational period, no case of reactivation was observed regardless of anti-HBs positivity.</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0030" class="elsevierStylePara elsevierViewall">Patients with past HBV infection (anti-HBc positive/HBsAg negative patients) can arbor an occult infection, and be susceptible to reactivation when exposed to immunosuppression, including TNFα inhibitors. This risk is highly depends on the agent's target and mechanism of action.<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">4,5</span></a> Although it is accepted that TNFα inhibitors may lead to HBV reactivation in these patients, the reactivation rates are much lower when compared to HBsAg positive patients.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a> The prevalence of patients with past HBV (9%) found in this study was similar to other published studies in patients with IMIDs.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">6</span></a> A systematic review including 168 anti-HBc positive/HBsAg negative patients with RA, spondyloarthropathies, psoriasis and IBD found HBV reactivation 5.4% of patients<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a> while a meta-analysis including 468 anti-HBc positive/HBsAg negative patients treated with TNFα inhibitors for rheumatologic diseases, HBV reactivation was observed in 1.7% with a percentage of HBV reactivation ranging from 0 to 8.3%.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">2</span></a> As seen in other studies, including with patients with psoriasis, no cases of HBV reactivation were observed in this study.<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">7,8</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">All patients that had HBV DNA measured during screening, maintained their levels below detection threshold during follow-up (measured every 6 months for 2 years and then yearly). However, detectable baseline viral loads have been found in this subset of patients.<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">9</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">The title of anti-HBs may influence the risk of reactivation of HBV.<span class="elsevierStyleSup">9</span> In this study, 73.1% patients were anti-HBs positive in the pre-treatment screening, and may have been important decreasing the risk of HBV reactivation.</p><p id="par0045" class="elsevierStylePara elsevierViewall">The main limitation of this study is its retrospective nature and the small and heterogenic sample, the long period of inclusion (as intra-hospital and international recommendations has changed along time) and the inexistence of HBV DNA data for some of the anti-HBc positive/HBsAg negative patients (preventing to determine HBV occult infection).</p><p id="par0050" class="elsevierStylePara elsevierViewall">Current guidelines state that candidates for chemotherapy and immunosuppressive therapy who are anti-HBc positive/HBsAg negative, regardless of anti-HBs status and with undetectable serum HBV-DNA should be followed carefully by means of ALT and HBV-DNA testing and treated with nucleotide analogs therapy only upon confirmation of HBV reactivation before ALT elevation.<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">10</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">Treatment with anti-TNFα agents is safe in anti-HBc positive/HBsAg negative patients. HBV reactivation is probably related to the presence of HBV in circulation rather than to the serologic status of previous exposure. Nonetheless, and as expressed in current guidelines, screening for HBV serologic markers prior to initiation of anti-TNFα therapy is of major importance since it may dictate if prophylactic treatment, vaccination or monitoring should be taken to minimize the risks related to hepatitis B flare/reactivation.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflict of interests</span><p id="par0060" class="elsevierStylePara elsevierViewall">Rui Pereira, Inês Lobo and Filipe Nery have no conflicts of interest to disclosure.</p><p id="par0075" class="elsevierStylePara elsevierViewall">Tiago Torres has participated in clinical trials sponsored by AbbVie, Amgen, and Novartis and has received honoraria for acting as a consultant and/or as a speaker at events sponsored by AbbVie, Boehringer Ingelheim, Celgene, Janssen, Leo-Pharma, Eli-Lilly, MSD, Novartis, and Pfizer.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Conflict of interests" ] 1 => array:2 [ "identificador" => "xack341064" "titulo" => "Acknowledgments" ] 2 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "multimedia" => array:1 [ 0 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">CD, Chron's disease; RA, rheumatoid arthritis; AS, ankylosing spondylitis; Ps, psoriasis; PsA, psoriatic arthritis; TNF, tumor necrosis factor; MTX, methotrexate; AZA, azathioprine; CsA, cyclosporine A; CS, corticosteroids.</p>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleItalic">Patients</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">26 (100%) \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">Female gender, N (%)</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">10 (38.5) \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">Age in years, mean</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">±</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">SD</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">52.65<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>14.12 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" 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">Disease duration in years, mean</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">±</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">SD</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">19.16<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>11.92 \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>CD, <span class="elsevierStyleItalic">N</span> (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">9 (34.6) \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>RA, <span class="elsevierStyleItalic">N</span> (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4 (15.4) \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>AS, <span class="elsevierStyleItalic">N</span> (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4 (15.4) \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>Ps<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>PsA, <span class="elsevierStyleItalic">N</span> (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">6 (23.1) \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="elsevierStyleHsp" style=""></span>Ps, <span class="elsevierStyleItalic">N</span> (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3 (11.5) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" 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="2" align="left" valign="top"><span class="elsevierStyleItalic">Therapy</span></td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Anti-TNFα, <span class="elsevierStyleItalic">N</span> (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">26 (100) \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>Etanercept, <span class="elsevierStyleItalic">N</span> (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">12 (46.2) \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>Adalimumab, <span class="elsevierStyleItalic">N</span> (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">8 (30.8) \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>Infliximab, <span class="elsevierStyleItalic">N</span> (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">6 (23.1) \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="elsevierStyleHsp" style=""></span>Switch, <span class="elsevierStyleItalic">N</span> (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">7 (26.9) \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>Combined therapy, <span class="elsevierStyleItalic">N</span> (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">13 (50) \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>MTX, <span class="elsevierStyleItalic">N</span> (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">7 (26.9) \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>AZA, <span class="elsevierStyleItalic">N</span> (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4 (15.4) \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>CsA, <span class="elsevierStyleItalic">N</span> (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 (3.8) \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>CS, <span class="elsevierStyleItalic">N</span> (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4 (15.4) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" 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="2" align="left" valign="top"><span class="elsevierStyleItalic">Treatment duration in years</span></td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Etanercept \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3.1 \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="elsevierStyleHsp" style=""></span>Adalimumab \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4.2 \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>Infliximab \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4.9 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1712307.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Baseline characteristics of 26 anti-HBc positive/HBsAg negative patients.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:10 [ 0 => array:3 [ "identificador" => "bib0055" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hepatitis B virus reactivation in patients receiving tumor necrosis factor (TNF)-targeted therapy: analysis of 257 cases" "autores" => array:1 [ 0 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| año/Mes | Html | Total | |
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| 2020 Junio | 43 | 40 | 83 |
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| 2020 Marzo | 24 | 32 | 56 |
| 2020 Enero | 4 | 0 | 4 |
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| 2019 Noviembre | 4 | 0 | 4 |
| 2019 Septiembre | 4 | 0 | 4 |
| 2019 Agosto | 4 | 0 | 4 |
| 2019 Julio | 4 | 0 | 4 |
| 2019 Junio | 3 | 0 | 3 |
| 2019 Mayo | 5 | 0 | 5 |
| 2019 Abril | 2 | 0 | 2 |
| 2019 Febrero | 2 | 0 | 2 |
| 2018 Diciembre | 2 | 4 | 6 |
| 2018 Noviembre | 9 | 4 | 13 |
| 2018 Octubre | 2 | 0 | 2 |
| 2018 Septiembre | 1 | 0 | 1 |
| 2018 Julio | 1 | 0 | 1 |
| 2018 Junio | 1 | 0 | 1 |
| 2018 Mayo | 2 | 2 | 4 |
| 2018 Abril | 20 | 10 | 30 |
| 2018 Febrero | 0 | 11 | 11 |
| 2018 Enero | 0 | 8 | 8 |
| 2017 Diciembre | 0 | 12 | 12 |
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