Reactivation of hepatitis B associated with immunosuppressants and chemotherapy. Natural history, risk factors and recommendations for prevention

array:24 ["pii" => "S2387020618305448" "issn" => "23870206" "doi" => "10.1016/j.medcle.2018.12.006" "estado" => "S300" "fechaPublicacion" => "2019-02-01" "aid" => "4645" "copyright" => "Elsevier España, S.L.U.. All rights reserved" "copyrightAnyo" => "2018" "documento" => "article" "crossmark" => 1 "subdocumento" => "rev" "cita" => "Med Clin. 2019;152:107-14" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "Traduccion" => array:1 [ "es" => array:19 [ "pii" => "S0025775318305670" "issn" => "00257753" "doi" => "10.1016/j.medcli.2018.08.018" "estado" => "S300" "fechaPublicacion" => "2019-02-01" "aid" => "4645" "copyright" => "Elsevier España, S.L.U." "documento" => "article" "crossmark" => 1 "subdocumento" => "rev" "cita" => "Med Clin. 2019;152:107-14" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 73 "formatos" => array:2 [ "HTML" => 39 "PDF" => 34 ] ] "es" => array:13 [ "idiomaDefecto" => true "cabecera" => "Revisión" "titulo" => "Reactivación de la hepatitis B asociada a agentes inmunodepresores y a quimioterapia. Historia natural, factores de riesgo y recomendaciones para prevenirla" "tienePdf" => "es" "tieneTextoCompleto" => "es" "tieneResumen" => array:2 [ 0 => "es" 1 => "en" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "107" "paginaFinal" => "114" ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "Reactivation of hepatitis B associated with immunosuppressants and chemotherapy. Natural history, risk factors and recommendations for prevention" ] ] "contieneResumen" => array:2 [ "es" => true "en" => true ] "contieneTextoCompleto" => array:1 [ "es" => true ] "contienePdf" => array:1 [ "es" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figura 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 2108 "Ancho" => 2500 "Tamanyo" => 270823 ] ] "descripcion" => array:1 [ "es" => "Cómo actuar en pacientes que van a recibir quimioterapia, tratamientos inmunosupresores o biológicos. Pacientes con HBsAg negativo y anti-HBc positivo con o sin anti-HBs. ALT: alanina-aminotransferasa; anti-HBc: anticuerpo frente al antígeno del core del VHB; anti-HBs: anticuerpo frente al antígeno de superficie; ETV: entecavir; HBsAg: antígeno de superficie del VHB; IS: inmunodepresores; QT: quimioterapia; RTX: rituximab; TAF: tenofovir-alafenamida; TDF: tenofovir; VHB: virus de la hepatitis B." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Rosa Maria Morillas, David López Sisamón" "autores" => array:2 [ 0 => array:2 [ "nombre" => "Rosa Maria" "apellidos" => "Morillas" ] 1 => array:2 [ "nombre" => "David" "apellidos" => "López Sisamón" ] ] ] ] ] "idiomaDefecto" => "es" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S2387020618305448" "doi" => "10.1016/j.medcle.2018.12.006" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2387020618305448?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0025775318305670?idApp=UINPBA00004N" "url" => "/00257753/0000015200000003/v1_201901250619/S0025775318305670/v1_201901250619/es/main.assets" ] ] "itemSiguiente" => array:19 [ "pii" => "S2387020618305424" "issn" => "23870206" "doi" => "10.1016/j.medcle.2018.07.016" "estado" => "S300" "fechaPublicacion" => "2019-02-01" "aid" => "4578" "copyright" => "Elsevier España, S.L.U." "documento" => "article" "crossmark" => 1 "subdocumento" => "sco" "cita" => "Med Clin. 2019;152:115-7" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "en" => array:10 [ "idiomaDefecto" => true "cabecera" => "Special article" "titulo" => "The problem of the fragmentation of hospital medicine" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "115" "paginaFinal" => "117" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "El problema de la fragmentación de la medicina hospitalaria" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Eduardo Montero Ruiz, Luis Manzano Espinosa" "autores" => array:2 [ 0 => array:2 [ "nombre" => "Eduardo" "apellidos" => "Montero Ruiz" ] 1 => array:2 [ "nombre" => "Luis" "apellidos" => "Manzano Espinosa" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0025775318304287" "doi" => "10.1016/j.medcli.2018.07.001" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0025775318304287?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2387020618305424?idApp=UINPBA00004N" "url" => "/23870206/0000015200000003/v1_201901290746/S2387020618305424/v1_201901290746/en/main.assets" ] "itemAnterior" => array:18 [ "pii" => "S2387020618305461" "issn" => "23870206" "doi" => "10.1016/j.medcle.2018.03.037" "estado" => "S300" "fechaPublicacion" => "2019-02-01" "aid" => "4517" "copyright" => "Elsevier España, S.L.U." "documento" => "simple-article" "crossmark" => 1 "subdocumento" => "crp" "cita" => "Med Clin. 2019;152:104-6" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "Clinical report" "titulo" => "Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia: Report of two cases" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "104" "paginaFinal" => "106" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Hiperplasia neuroendocrina difusa pulmonar idiopática: estudio de dos casos" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1869 "Ancho" => 2482 "Tamanyo" => 439747 ] ] "descripcion" => array:1 [ "en" => "(a) Hematoxylin and eosin staining technique showing the mucosa of a terminal bronchiole with cilia in the epithelium and neuroendocrine cells (asterisk). (b) The same area showing positivity for CD 56 with immunohistochemistry that corresponds with a neuroendocrine cell hyperplasia (asterisk, objective magnification 60×). (c) Paratracheal lymph node of case number 1 stained with hematoxylin and eosin technique showing a little focus of neuroendocrine epithelial cells that corresponds with a metastatic typical carcinoid marked with an asterisk (objective magnification 20×). Insert: immunohistochemical technique using cytokeratins, which highlights the metastatic neuroendocrine cells. (d) CT of case number 2. We can observe a subcentimeter nodule in the middle lobe (arrow) and a bilateral mosaic pattern." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Eva García-Fontán, Montserrat Blanco Ramos, Jose Soro García, Rommel Carrasco, Miguel Ángel Cañizares, Ana González Piñeiro" "autores" => array:6 [ 0 => array:2 [ "nombre" => "Eva" "apellidos" => "García-Fontán" ] 1 => array:2 [ "nombre" => "Montserrat" "apellidos" => "Blanco Ramos" ] 2 => array:2 [ "nombre" => "Jose Soro" "apellidos" => "García" ] 3 => array:2 [ "nombre" => "Rommel" "apellidos" => "Carrasco" ] 4 => array:2 [ "nombre" => "Miguel Ángel" "apellidos" => "Cañizares" ] 5 => array:2 [ "nombre" => "Ana" "apellidos" => "González Piñeiro" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2387020618305461?idApp=UINPBA00004N" "url" => "/23870206/0000015200000003/v1_201901290746/S2387020618305461/v1_201901290746/en/main.assets" ] "en" => array:20 [ "idiomaDefecto" => true "cabecera" => "Review" "titulo" => "Reactivation of hepatitis B associated with immunosuppressants and chemotherapy. Natural history, risk factors and recommendations for prevention" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "107" "paginaFinal" => "114" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Rosa Maria Morillas, David López Sisamón" "autores" => array:2 [ 0 => array:4 [ "nombre" => "Rosa Maria" "apellidos" => "Morillas" "email" => array:1 [ 0 => "rmorillas.germanstrias@gencat.cat" ] "referencia" => array:3 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "David" "apellidos" => "López Sisamón" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "c" "identificador" => "aff0015" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "Sección de Hepatología, Servicio de Aparato Digestivo, Hospital Universitario Germans Trias i Pujol, Badalona, Barcelona, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "CIBERehd-Instituto de Salud Carlos III, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Unidad de Farmacia Oncológica ICO-Badalona, Hospital Universitario Germans Trias i Pujol, Badalona, Barcelona, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Reactivación de la hepatitis B asociada a agentes inmunodepresores y a quimioterapia. Historia natural, factores de riesgo y recomendaciones para prevenirla" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 2108 "Ancho" => 2500 "Tamanyo" => 280567 ] ] "descripcion" => array:1 [ "en" => "Steps to take when treating patients who will receive chemotherapy or immunosuppressive or biological treatments. HBsA negative and anti-HBc positive patients with or without anti-HBs. ALT: alanine aminotransferase; anti-HBc: antibody against the hepatitis B core antigen; anti-HBs: antibody against surface antigen; ETV: entecavir; HBsAg: HBV surface antigen; IS: immunosuppressants; QT: chemotherapy; RTX: rituximab; TAF: tenofovir-alafenamide; TDF: tenofovir; HBV: hepatitis B virus." ] ] ] "textoCompleto" => "IntroductionThe risk of reactivation of hepatitis B virus (HBV) has gained importance in recent years due to the increasingly frequent use of chemotherapy and potent immunosuppressants in patients with neoplastic processes, and also increasingly in non-neoplastic processes in various medical specialties This expansion of new treatments for malignant and non-malignant disorders has increased the population of patients who have a probability of HBV reactivation. A recently published study has estimated that the population at risk of HBV reactivation in Spain stands at 89,053 new people per year.<a class="elsevierStyleCrossRef" href="#bib0315">1</a>Although the risk of reactivation of hepatitis B in patients treated with immunosuppressants has been known for years and that recommendations on this matter exist, data from certain surveys indicate that studies into the HBV infection serological profile before initiating immunosuppressive treatment is not a universal practice.<a class="elsevierStyleCrossRefs" href="#bib0320">2,3</a> A survey conducted in 2012 showed that 26% of Spanish specialists declared that they were not aware of existing recommendations or prevention and treatment guidelines regarding the reactivation of HBV in patients treated with risky therapies.<a class="elsevierStyleCrossRef" href="#bib0325">3</a> Regarding HBV screening practices prior to initiating treatment with chemotherapy and/or immunosuppressants, 37% of respondents stated that they never or only sometimes valued the presence of HBV risk factors, while 34% and 35% stated that they never or only sometimes requested the determination of HBV surface antigen (HBsAg) or antibody against HBV core antigen (anti-HBc), respectively.<a class="elsevierStyleCrossRef" href="#bib0325">3</a> This is a high figure, considering the serious consequences that a reactivation of an HBV infection may entail. Therefore, exposing the importance of this issue and the recommendations to follow is essential. Raising greater awareness of the possibility of HBV reactivation among health professionals prescribing these treatments, the adoption of routine tests for HBV detection and linking the results of screening with antiviral prophylaxis to reduce the incidence of this deadly but preventable disorder is needed.Population at riskReactivations of this virus have been reported in three groups of patients: patients receiving chemotherapy for solid<a class="elsevierStyleCrossRefs" href="#bib0330">4–6</a> and haematologic<a class="elsevierStyleCrossRefs" href="#bib0345">7,8</a> tumours, patients treated with immunomodulators<a class="elsevierStyleCrossRef" href="#bib0355">9</a> or biological treatments<a class="elsevierStyleCrossRefs" href="#bib0360">10,11</a> and patients receiving immunosuppression for solid organ<a class="elsevierStyleCrossRefs" href="#bib0370">12,13</a> or bone marrow<a class="elsevierStyleCrossRefs" href="#bib0380">14,15</a> transplantation.The frequency of reactivation in HBsAg positive patients receiving chemotherapy for solid tumours has been estimated to be approximately 50%, but the rate exceeds 50% in malignant haematological diseases and allogeneic transplant recipients of haemopoietic progenitors and in renal and cardiac transplant patients (between 50 and 96%).<a class="elsevierStyleCrossRef" href="#bib0315">1</a> HBV reactivation in positive anti-HBc patients is lower, between 6 and 10% in patients treated with chemotherapy and 0.9% in solid organ transplant patients.<a class="elsevierStyleCrossRef" href="#bib0315">1</a>Inhibition of tumour necrosis factor-alpha (TNF-alpha) such as infliximab, etanercept and adalimumab, which are used to treat inflammatory bowel disease, rheumatological diseases, psoriasis and autoimmune diseases, have been associated with reactivation of HBV. A study of 257 cases exposed to anti-TNF agents with different indications concluded that the frequency of reactivation of HBV in HBsAg positive patients was 39%, seven times higher than HBV reactivation in HBsAg negative/anti-HBc positive patients in that cohort.<a class="elsevierStyleCrossRef" href="#bib0390">16</a>Reactivation of hepatitis BThe reactivation of HBV infection is the appearance of viral replication in subjects with chronic infection by HBV and HBsAg positive, or HBsAg negative and anti-HBc positive with or without antibody to surface antigen (anti-HBs), who could develop acute hepatitis and even severe liver failure.<a class="elsevierStyleCrossRef" href="#bib0315">1</a> Based on the patient's baseline virological profile, HBV reactivation can be classified into two categories: reactivation of HBV in patients who are positive for HBsAg in serum, with or without viraemia; and seroreversion, which is defined as the reappearance of HBsAg and the detection of HBV-DNA in serum in individuals that were initially negative for HBsAg and HBV-DNA. Although HBV is considered to be completely cleared during acute hepatitis, it has sometimes been detected in serum many years after the hepatitis was treated, and in spite of the presence of anti-HBs in serum.<a class="elsevierStyleCrossRef" href="#bib0400">18</a> It is believed that the persistence of traces of virus makes it possible to maintain the response of cytotoxic T lymphocytes and keep the virus under control, usually for life. Immunosuppressive treatment can break this balance.Natural history of HBV reactivationHBV reactivation is characterised by a first asymptomatic phase that provides a window to start treatment. In HBsAg positive patients, this phase is characterised by a rapid increase in the level of HBV-DNA followed by an increase in transaminases; and in HBsAg negative patients, by the reappearance of HBsAg and then by an increase in HBV-DNA followed by an increase in transaminases.<a class="elsevierStyleCrossRef" href="#bib0405">19</a> Although most patients usually remain asymptomatic, a small number may experience constitutional symptoms, discomfort in the upper right quadrant of the abdomen, and jaundice. Some patients may progress to liver failure characterised by an increase in prothrombin time and appearance of ascites and encephalopathy, mortality also increases significantly in this group.<a class="elsevierStyleCrossRef" href="#bib0400">18</a>If the reactivation of HBV is detected and antiviral treatment is initiated, HBV-DNA and the level of transaminases decrease rapidly. This can also occur spontaneously in some patients, coinciding with the completion of the immunosuppressive treatment or chemotherapy cycle that produced the reactivation of HBV. However, spontaneous improvement after developing acute liver failure is rare and if the disease is not detected or treated, the risk of death is high.<a class="elsevierStyleCrossRef" href="#bib0395">17</a>These phases do not necessarily follow each other as they have just been listed; some subjects may only develop a transient increase in viraemia with or without an increase in transaminases and no clinical consequences.<a class="elsevierStyleCrossRef" href="#bib0395">17</a>Onset of HBV reactivationThe onset time of a HBV reactivation can vary depending on the state of the host, the underlying disease and the type of immunosuppressive treatment. Although it may occur at the start or at any time during treatment, it is more likely to occur at the end or even up to a year after the completion of the entire treatment cycle, due to the phenomenon of immune reconstitution.<a class="elsevierStyleCrossRefs" href="#bib0395">17–19</a>Risk factorsReactivation does not occur in all patients with HBsAg positive or anti-HBc positive. A variety of factors related to the host,<a class="elsevierStyleCrossRefs" href="#bib0410">20,21</a> the virus<a class="elsevierStyleCrossRefs" href="#bib0420">22–27</a> and the type of treatment the patient received have been associated with a higher risk of HBV reactivation (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>). Regarding the type and degree of immunosuppression, an increase of HBV reactivation in patients who have undergone more intensive immunosuppressive treatments has been reported, such as the use of rituximab in monotherapy or in combination with glucocorticoids in a chemotherapy regimen.<a class="elsevierStyleCrossRef" href="#bib0345">7</a> Conversely, reactivation in bone marrow transplant patients is almost universal in HBsAg positive patients and has rates of approximately 50% in patients with anti-HBc positive.<a class="elsevierStyleCrossRefs" href="#bib0380">14,19,28–30</a><elsevierMultimedia ident="tbl0005"></elsevierMultimedia>Reactivation risk according to the type of immunosuppressive treatment receivedDue to its immunosuppressive activity, any chemotherapeutic or immunosuppressive agent could be capable of provoking reactivation. The risk of reactivation can be divided into high risk (if the reactivation rate of HBV is ≥10%), moderate risk (if the risk of reactivation is between 1% and 10%) and low risk (if the risk of reactivation is <1%), depending on the type of immunosuppressive therapy stratified by the presence or absence of HBsAg and presence of anti-HBc positive with or without anti-HBs.<a class="elsevierStyleCrossRef" href="#bib0400">18</a>Patients with HBsAg positiveAmong the patients with HBsAg positive, we stratified the immunosuppressive treatments according to the risk of reactivation (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>).<elsevierMultimedia ident="tbl0010"></elsevierMultimedia>Treatments with a high risk of reactivation:<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005">1.Therapies that deplete B cells, such as rituximab, ofatumumab, natalizumab, obinutuzumab, blinatumomab, alemtuzumab, ibritumomab, and ocrelizumab, significantly increase the risk of reactivation in HBsAg positive and HBsAg negative patients and anti-HBc positive patients.<a class="elsevierStyleCrossRef" href="#bib0465">31</a> This class of drug can cause a severe reactivation of HBV, in addition to an increased risk of liver failure and mortality associated with the reactivation of HBV if it is not diagnosed and treated quickly.</li><li class="elsevierStyleListItem" id="lsti0010">2.Anthracycline derivatives, such as doxorubicin, epirubicin, daunorubicin and idarubicin.<a class="elsevierStyleCrossRef" href="#bib0460">30</a></li><li class="elsevierStyleListItem" id="lsti0015">3.Chronic treatment with prednisone, either at medium doses (10–20mg/day orally) or high doses (>20mg/day orally) for more than four weeks increases the likelihood of HBV reactivation.<a class="elsevierStyleCrossRef" href="#bib0470">32</a></li><li class="elsevierStyleListItem" id="lsti0020">4.TNF-alpha inhibitors, such as infliximab, adalimumab, certolizumab and golimumab, used in the treatment of inflammatory bowel disease and rheumatologic conditions such as rheumatoid arthritis, also have a high risk of HBV reactivation (range, 12–39%) in HBsAg positive patients.<a class="elsevierStyleCrossRefs" href="#bib0390">16,33</a></li></ul>Treatments with a moderate risk of reactivation:<ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0025">1.Systemic chemotherapy other than the situation described above.</li><li class="elsevierStyleListItem" id="lsti0030">2.Less potent inhibitors of TNF-alpha such as etanercept.<a class="elsevierStyleCrossRef" href="#bib0475">33</a></li><li class="elsevierStyleListItem" id="lsti0035">3.Inhibitors of cytokine or integrin such as abatacept, ustekinumab, mogamulizumab, natalizumab, vedolizumab and tocilizumab, commonly used in inflammatory bowel disease and in rheumatological and dermatological diseases.<a class="elsevierStyleCrossRef" href="#bib0465">31</a></li><li class="elsevierStyleListItem" id="lsti0040">4.Tyrosine kinase inhibitors such as imatinib, nilotinib, dasatinib, bosutinib, ponatinib, ibrutinib and idelalisib, which are commonly used in the treatment of chronic myeloid leukaemia and gastrointestinal stromal tumours, among others.<a class="elsevierStyleCrossRef" href="#bib0480">34</a></li><li class="elsevierStyleListItem" id="lsti0045">5.Proteasome inhibitors such as bortezomib, carfilzomib or ixazomib, which are commonly used for the treatment of multiple myeloma.<a class="elsevierStyleCrossRef" href="#bib0485">35</a></li><li class="elsevierStyleListItem" id="lsti0050">6.Histone deacetylase (HDI) inhibitors such as romidepsin, vorinostat or panobinostat, which are used in the treatment of T-cell lymphomas.<a class="elsevierStyleCrossRef" href="#bib0490">36</a></li><li class="elsevierStyleListItem" id="lsti0055">7.Low-dose corticosteroid therapy such as prednisone at 10mg/day orally for four weeks, can increase the risk of reactivation up to 10% in HBsAg positive individuals.<a class="elsevierStyleCrossRef" href="#bib0470">32</a></li><li class="elsevierStyleListItem" id="lsti0060">8.There is evidence that immunophilin inhibitors such as cyclosporine and tacrolimus may also increase the risk of reactivation of HBV.<a class="elsevierStyleCrossRef" href="#bib0400">18</a></li></ul>Treatments with a low risk of reactivation:<ul class="elsevierStyleList" id="lis0015"><li class="elsevierStyleListItem" id="lsti0065">1.Methotrexate, azathioprine or therapies based on 6-mercaptopurine.<a class="elsevierStyleCrossRef" href="#bib0470">32</a></li><li class="elsevierStyleListItem" id="lsti0070">2.Injections or intraarticular glucocorticoid treatment with a low dose of prednisone of lower than 10mg/day orally, have a minimal risk of reactivation.<a class="elsevierStyleCrossRef" href="#bib0470">32</a></li></ul>Immune checkpoint inhibitors and anti-PD-L1 (e.g. Nivolumab which strengthens T-lymphocytes responses including antitumour response by blocking PD-1, preventing its binding to PD ligands and PD-L2-L1) and anti-CTLA4 (e.g. ipilimumab), are increasingly used in the treatment of various cancers.<a class="elsevierStyleCrossRef" href="#bib0495">37</a> When these biological products began to be used, health professionals had doubts about whether they could predispose patients to the reactivation of HBV but no case has been reported. In addition, its mechanism of action is based on activating the immune system's response, so a reactivation of HBV is unlikely.HBsA negative and anti-HBc positive patientsWe also stratified the immunosuppressive treatments according to the risk of reactivation among HBsA negative and anti-HBc positive patients (<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>). It should be noted that the increased risk of reactivation in these patients lies in B-cell-depletion therapies such as rituximab, ofatumumab, natalizumab, obinutuzumab, blinatumomab, alemtuzumab, ibritumomab and ocrelizumab.<a class="elsevierStyleCrossRef" href="#bib0400">18</a> Recent studies have described an increased risk of reactivation in HBsAg negative and anti-HBc positive patients exposed to transarterial chemoembolisation in the context of hepatocellular carcinoma of 9.3–11%<a class="elsevierStyleCrossRefs" href="#bib0500">38,39</a>; these figures could suggest the appropriateness of prophylaxis in future guides.<elsevierMultimedia ident="tbl0015"></elsevierMultimedia>HBV reactivation mechanismsThe mechanism to which reactivation is attributed to is associated with, firstly, an increase in the replication of HBV and the expression of its antigens in hepatocytes during immunosuppression, and secondly, a destruction of infected hepatocytes mediated by T-lymphocytes during immune recovery. The intensity of viral replication and subsequent liver damage appear to be directly associated with the potency of cytotoxic or immunosuppressive treatment.When HBV infects a susceptible person, the virus penetrates the hepatocytes and its DNA is integrated into the hepatocyte DNA, becoming a covalent, closed, circular DNA (cccDNA). The cccDNA is transcribed in the nucleus of the hepatocyte, forming RNA that is subsequently translated into the cytoplasm, forming new viral particles. The cccDNA serves as a template for the formation of new viruses that will infect new hepatocytes and will remain in the nucleus of the hepatocyte until it is destroyed. The cccDNA is quite stable in the infected cells and can persist in a latent state as a reservoir for the reactivation of HBV.<a class="elsevierStyleCrossRefs" href="#bib0315">1,40</a> Different studies have shown that cccDNA can persist in patients’ liver for decades after a supposed recovery from HBV infection. This persistence occurs despite the anti-HBV immune response being activated. Clinical studies have also shown that nucleoside analogue therapy can potently suppress HBV-DNA, but that cccDNA reduction after one year of treatment is modest.<a class="elsevierStyleCrossRef" href="#bib0400">18</a> Similar results have been reported for the extraordinary stability of cccDNA in animal models.<a class="elsevierStyleCrossRef" href="#bib0400">18</a> All these observations support the concept that HBV infection is quite difficult to eradicate and its persistence, although low, explains the potential for HBV reactivation in any individual that has been infected with the virus.During viral replication, several antigens are expressed inside the hepatocytes; some are expressed in the cell membrane (HBcAg) and others are released as circulating particles into the bloodstream (HBsAg and HBeAg). The host's immune system recognises these antigens as foreign and triggers an immune response. On one hand, a Th1 response that activates CD8 cells and the formation of TNF-alpha is activated, causing the destruction of infected hepatocytes. On the other hand, a Th-2 response is activated and B lymphocytes produce antibodies against different antigens that neutralise circulating viruses, preventing infections from new hepatocytes. If the immune response is effective, all infected hepatocytes are destroyed and resolution of infection is obtained.<a class="elsevierStyleCrossRef" href="#bib0400">18</a> Innate immunity probably also plays a role in the control of HBV infection.<a class="elsevierStyleCrossRef" href="#bib0400">18</a> Although these immune mechanisms are sufficient to control HBV replication, they are probably not powerful enough to eradicate all infected cell niches harbouring latent HBV cccDNA or to eliminate low-level HBV replication that escapes the action of specific immune cells. These cells are, therefore, a reservoir of persistent HBV and a source of HBV reactivation when the mechanisms of immune control are disturbed or suppressed.For example, rituximab, a monoclonal antibody, works against the CD20 antigen and depletes the B lymphocyte population and antibody levels; it thus decreases immune response and favours the replication of HBV. It has a selective action on B lymphocytes, which is prolonged, and can last as long as a year. Although the control of HBV infection is mainly due to HBV-specific cytotoxic T lymphocytes, B lymphocytes are necessary for the presentation of antigens, so their depletion can allow HBV to escape control of the cytotoxic T lymphocytes. Glucocorticoids act on the HBV genome, facilitating replication and increasing HBV-DNA levels, and these two effects may explain the higher rate of reactivation with regimens containing glucocorticoids and rituximab.<a class="elsevierStyleCrossRefs" href="#bib0515">41,42</a>Studying the serological profile of HBV before starting immunosuppressive treatmentsTo try to avoid the unfavourable clinical events resulting from HBV reactivation, the European guide<a class="elsevierStyleCrossRef" href="#bib0395">17</a> and latest consensus documents<a class="elsevierStyleCrossRefs" href="#bib0525">43–45</a> currently recommend carrying out serological screening of HBV on all patients who will undergo chemotherapy or immunosuppressive or biological treatments. At least HBsAg, anti-HBc and anti-HBs should be screened for. HBV-DNA will be detected in HBsAg positive or HBsA negative patients and anti-HBc positive patients (<a class="elsevierStyleCrossRefs" href="#fig0005">Figs. 1 and 2</a>).<elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia>Patients with negative serologyPatients with negative serology (HBsAg, anti-HBc and anti-HBs) are susceptible to infection and should be vaccinated as soon as possible (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>). The quantitative anti-HBs response should be documented several weeks after the last dose. Non-responders should receive another three-dose cycle when possible.Immunocompromised patients may require higher doses of the vaccine or a vaccine booster to obtain anti-HBs response.<a class="elsevierStyleCrossRefs" href="#bib0395">17,46</a>Patients with HBsAg positiveAll candidates for chemotherapy or HBsAg positive immunosuppressive therapy should be referred to a specialist for an assessment and diagnosis of their HBV infection stage. All these patients should start a potent nucleoside or nucleotide analogue (AN) treatment or prophylaxis<a class="elsevierStyleCrossRef" href="#bib0395">17</a> (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>).If the patient is HBsAg positive, HBV-DNA should be requested. If HBV-DNA is greater than 2000UI/ml, they should follow conventional antiviral treatment with an AN which should be initiated before starting chemotherapy or immunosuppressive treatment and maintained until accepted objectives are obtained (seroconversion of HBeAg in HBeAg positive patients and negativization of HBsAg in HBeAg negative patients), otherwise the risk of reactivation after treatment interruption is high.<a class="elsevierStyleCrossRef" href="#bib0395">17</a> If HBV-DNA is less than 2000IU/ml or undetectable, current recommendations suggest prophylactic treatment with AN.<a class="elsevierStyleCrossRef" href="#bib0395">17</a>Prophylactic administration of lamivudine has been shown to reduce the risk of HBV reactivation and associated morbidity and mortality.<a class="elsevierStyleCrossRefs" href="#bib0410">20,47,48</a> However, there is a residual risk of HBV reactivation in approximately 10% of patients with chronic HBV infection with low viraemia (HBV-DNA<2000UI/ml) treated with prophylactic lamivudine, and a higher rate in those with higher viraemia levels.<a class="elsevierStyleCrossRef" href="#bib0395">17</a> In addition, episodes of HBV exacerbation have been reported due to the development of resistance, as it is a drug with a low genetic barrier to the appearance of resistance (20% and 30% after one and two years of treatment, respectively). There are studies that suggest that stronger and less resistant nucleoside (entecavir) or nucleotides (tenofovir and tenofovir-alafenamide) analogues can be used successfully in these patients.<a class="elsevierStyleCrossRefs" href="#bib0555">49–51</a> In addition, a recent meta-analysis has shown that entecavir and tenofovir are the most effective treatments for the prevention of HBV reactivation.<a class="elsevierStyleCrossRef" href="#bib0570">52</a> Thus, the prophylactic antiviral treatment of choice recommended in guidelines is entecavir, tenofovir or tenofovir-alafenamide.<a class="elsevierStyleCrossRef" href="#bib0395">17</a>The antiviral regimen should be initiated preferably two or three weeks before immunosuppressive treatment or chemotherapy and never later than the first dose, maintained during treatment and continued for a minimum of 12 months (18 months for regimens based on rituximab or anti-CD20 antibodies) after the suspension of immunosuppressive treatment and discontinued only if the underlying disease is in remission.<a class="elsevierStyleCrossRef" href="#bib0395">17</a>Monitoring patients’ liver function tests and HBV-DNA every three to six months during prophylactic treatment and for at least 12 months after cessation is recommended since a large proportion of HBV reactivations appear after discontinuation of antiviral treatment.<a class="elsevierStyleCrossRef" href="#bib0395">17</a>HBsA negative and anti-HBc positive patients with or without anti-HBsThe risk of reactivation of HBV in this group of patients varies widely according to the virological profile, the underlying disease and the type and duration of the immunosuppressant regimen used. These patients should be tested for HBV-DNA before immunosuppression (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>). If HBV-DNA levels are detectable, the same prophylactic regimen is recommended for HBsAg positive patients.<a class="elsevierStyleCrossRef" href="#bib0395">17</a>If serum DNA levels are not detectable:<ul class="elsevierStyleList" id="lis0020"><li class="elsevierStyleListItem" id="lsti0075">•In the high-risk group (>10%), including patients who need to be treated with anti-B lymphocytes or T monoclonal antibodies or who will have a bone marrow or haematopoietic progenitors transplant, recommendation suggest starting antiviral prophylaxis, which should be continued for at least 18 months after suspension of immunosuppression. Monitoring should continue for at least 12 months after withdrawal of prophylaxis with AN. With lamivudine, episodes of reactivation related to the appearance of resistance have been reported,<a class="elsevierStyleCrossRefs" href="#bib0575">53–55</a> such that prophylaxis with entecavir, tenofovir or tenofovir-afenfenamide is indicated for these patients – who will also undergo an estimated treatment duration of longer than 12 months.<a class="elsevierStyleCrossRefs" href="#bib0395">17,56,57</a></li><li class="elsevierStyleListItem" id="lsti0080">•Conducting periodic checks of HBsAg and/or HBV-DNA and transaminases every one to three months during and after immunosuppression is recommended in the moderate (<10%) or low (<1%)HBV reactivation risk groups,<a class="elsevierStyleCrossRefs" href="#bib0600">58,59</a> initiating antiviral treatment as soon as possible if there is an elevation of viraemia or a reappearance of HBsAg, regardless of transaminase levels. In individualised clinical cases, characterised by long-term immunosuppression, poor compliance with control tests or if periodic measurements of HBsAg and viral DNA cannot be guaranteed, initiating prophylaxis is recommended.<a class="elsevierStyleCrossRef" href="#bib0395">17</a> Universal prophylaxis against an unknown risk of HBV reactivation with new biological products is also recommended.</li></ul>Tools to prevent reactivationSeveral tools have been reported that can assist in the prevention of HBV reactivation, from educational intervention with training projects to the application of alerts in electronic prescription systems. In a centre in England, a guide based on international recommendations for HBV screening and initiation of antiviral prophylaxis in patients receiving immunosuppression or chemotherapy was delivered to all doctors, in addition to 30min training sessions. After the educational intervention, a significant increase in the detection of HBV in patients, before receiving rituximab, was seen: from 19% to 78%.<a class="elsevierStyleCrossRef" href="#bib0610">60</a>New technologies, information technologies and assisted electronic prescription systems are an opportunity to implement HBV screening and prevent reactivation. The implementation of an alert system in computers or linked to electronic assisted prescription programs have been shown to increase the detection rate of HBsAg by up to 85.5%<a class="elsevierStyleCrossRef" href="#bib0615">61</a> or even more.<a class="elsevierStyleCrossRef" href="#bib0620">62</a> In a study conducted in a centre in Spain, an alert was implemented into the electronic prescribing system to remind medical professionals of the possible risk of viral reactivation when prescribing biological therapies and requesting a serological profile of (HBsAg, anti-HBc and anti-HBs) those patients who had not carried out these tests.<a class="elsevierStyleCrossRef" href="#bib0620">62</a> The warning system increased the detection rate from less than 50% to 94% for HBsAg and from less than 30% to 85% for anti-HBc in patients who were prescribed a biological treatment.<a class="elsevierStyleCrossRef" href="#bib0620">62</a>ConclusionsPerforming serological screening of HBV in all patients who are going to receive chemotherapy or immunosuppressive or biological treatments is essential; the results should then be linked with antiviral prophylaxis to reduce the incidence of HBV reactivation, a potentially fatal but preventable disorder.There are studies that show the feasibility of implementing tools that can help in preventing HBV reactivation and which can increase the HBV detection rate. Their use facilitates the identification of patients with a high risk of reactivation and allows doctors to prescribe prophylactic measures in accordance with current guidelines.Conflict of interestR.M. Morillas: speaker fees from Gilead, AbbVie, Merck and Intercept. Advisory Board for Merck, Gilead, AbbVie and Intercept. Dr López declares no conflict of interest." "textoCompletoSecciones" => array:1 [ "secciones" => array:16 [ 0 => array:3 [ "identificador" => "xres1142225" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1072949" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1142224" "titulo" => "Resumen" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0010" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1072950" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Population at risk" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Reactivation of hepatitis B" ] 7 => array:2 [ "identificador" => "sec0020" "titulo" => "Natural history of HBV reactivation" ] 8 => array:2 [ "identificador" => "sec0025" "titulo" => "Onset of HBV reactivation" ] 9 => array:3 [ "identificador" => "sec0030" "titulo" => "Risk factors" "secciones" => array:1 [ 0 => array:3 [ "identificador" => "sec0035" "titulo" => "Reactivation risk according to the type of immunosuppressive treatment received" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0040" "titulo" => "Patients with HBsAg positive" ] 1 => array:2 [ "identificador" => "sec0045" "titulo" => "HBsA negative and anti-HBc positive patients" ] ] ] ] ] 10 => array:2 [ "identificador" => "sec0050" "titulo" => "HBV reactivation mechanisms" ] 11 => array:3 [ "identificador" => "sec0055" "titulo" => "Studying the serological profile of HBV before starting immunosuppressive treatments" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0060" "titulo" => "Patients with negative serology" ] 1 => array:2 [ "identificador" => "sec0065" "titulo" => "Patients with HBsAg positive" ] 2 => array:2 [ "identificador" => "sec0070" "titulo" => "HBsA negative and anti-HBc positive patients with or without anti-HBs" ] ] ] 12 => array:2 [ "identificador" => "sec0075" "titulo" => "Tools to prevent reactivation" ] 13 => array:2 [ "identificador" => "sec0080" "titulo" => "Conclusions" ] 14 => array:2 [ "identificador" => "sec0085" "titulo" => "Conflict of interest" ] 15 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2018-07-26" "fechaAceptado" => "2018-08-31" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1072949" "palabras" => array:4 [ 0 => "Hepatitis B reactivation" 1 => "Immunosuppressive and biological modifier therapies" 2 => "Management strategies" 3 => "Prophylaxis" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1072950" "palabras" => array:4 [ 0 => "Reactivación de la hepatitis B" 1 => "Inmunodepresores y tratamientos biológicos" 2 => "Estrategias de manejo" 3 => "Profilaxis" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "Although the risk of reactivation of hepatitis B in patients treated with immunosuppressants has been known for years and, if there are recommendations, data from some surveys indicate that the study of the serological profile of HBV infection before starting immunosuppressive treatment is not universal practice. Taking into account the serious consequences that the reactivation of the infection with HBV may entail, we believe that it is necessary to disclose the importance of this problem among the health professionals who prescribe these treatments as well as the recommendations to be followed. In fact, in recent years, the use of chemotherapy and potent immunosuppressants in patients with neoplastic processes and in non-neoplastic pathology of various specialties has been increasingly frequent, increasing the population of patients at risk of reactivation of HBV." ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "A pesar de que el riesgo de reactivación de la hepatitis B en los pacientes tratados con inmunosupresores es conocido desde hace años y de la existencia de recomendaciones, los datos procedentes de algunas encuestas indican que el estudio del perfil serológico de la infección por el VHB antes de iniciar el tratamiento inmunosupresor no es una práctica universal. Teniendo en cuenta las consecuencias graves que puede comportar la reactivación de la infección por el VHB, creemos que es necesario divulgar la importancia de este problema entre los profesionales sanitarios que prescriben estos tratamientos así como de las recomendaciones a seguir. De hecho, en los últimos años, es cada vez más frecuente el empleo de quimioterapia e inmunosupresores potentes en pacientes con procesos neoplásicos y en patología no neoplásica de diversas especialidades, aumentando la población de pacientes con riesgo de reactivación del VHB." ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: Morillas RM, López Sisamón D. Reactivación de la hepatitis B asociada a agentes inmunodepresores y a quimioterapia. Historia natural, factores de riesgo y recomendaciones para prevenirla. Med Clin (Barc). 2019;152:107–114." ] ] "multimedia" => array:5 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1648 "Ancho" => 2167 "Tamanyo" => 180971 ] ] "descripcion" => array:1 [ "en" => "Steps to take when treating patients who will receive chemotherapy or immunosuppressive or biological treatments. HBsAg positive patients. Anti-HBc: antibody against the hepatitis B core antigen; anti-HBs: antibody against surface antigen; ETV: entecavir; HBsAg: HBV surface antigen; IS: immunosuppressants; QT: chemotherapy; RTX: rituximab; TAF: tenofovir-alafenamide; TDF: tenofovir; HBV: hepatitis B virus." ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 2108 "Ancho" => 2500 "Tamanyo" => 280567 ] ] "descripcion" => array:1 [ "en" => "Steps to take when treating patients who will receive chemotherapy or immunosuppressive or biological treatments. HBsA negative and anti-HBc positive patients with or without anti-HBs. ALT: alanine aminotransferase; anti-HBc: antibody against the hepatitis B core antigen; anti-HBs: antibody against surface antigen; ETV: entecavir; HBsAg: HBV surface antigen; IS: immunosuppressants; QT: chemotherapy; RTX: rituximab; TAF: tenofovir-alafenamide; TDF: tenofovir; HBV: hepatitis B virus." ] ] 2 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "ALT: alanine aminotransferase; HBeAg: HBV e-antigen; HBV: hepatitis B virus." "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 " rowspan="5" align="left" valign="top">Related to the host</td><td class="td" title="table-entry " align="left" valign="top">Sex male \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Young patients \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">ALT levels before initiation of treatment \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Presence of cirrhosis \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Diagnosis of lymphoma \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " rowspan="3" align="left" valign="top">Related to the virus</td><td class="td" title="table-entry " align="left" valign="top">Baseline viral load >104UI/ml \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">HBeAg positive before initiation of treatment \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">HBV genotype not A \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Related to the treatment \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">More intensive immunosuppressive therapy (e.g. rituximab or patients who have received bone marrow transplant) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1949181.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Risk factors for HBV reactivation." ] ] 3 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at2" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "HBsAg: HBV surface antigen; TNF-α: tumour necrosis factor alpha; HBV: hepatitis B virus." "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 " rowspan="20" align="left" valign="top">Treatments with high risk of reactivation (reactivation rate ≥10%)</td><td class="td" title="table-entry " align="left" valign="top">B cell depletion therapy \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Natalizumab \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Rituximab \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Ofatumumab \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Obinutuzumab \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Blinatumomab \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Alemtuzumab \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Ibritumomab \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Ocrelizumab \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Anthracycline derivatives \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Doxorubicin \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Epirubicin \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Daunorubicin \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Idarubicin \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Dosage of 10–20mg/day of prednisone or >20mg/day for more than four weeks \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Potent inhibitors of TNF-α \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Infliximab \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Adalimumab \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Certolizumab \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Golimumab \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " rowspan="35" align="left" valign="top">Treatments with moderate risk of reactivation (reactivation rate 1–10%)</td><td class="td" title="table-entry " align="left" valign="top">Systemic chemotherapy \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Less potent inhibitors of TNF-α \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Etanercept \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Inhibitors of cytokine or integrin \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Abatacept \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Ustekinumab \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Mogamulizumab \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Vedolizumab \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Tocilizumab \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Immunomodulators \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Thalidomide \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Lenalidomide \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Pomalidomide \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Tyrosine kinase inhibitors \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Imatinib \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Nilotinib \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Dasatinib \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Bosutinib \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Ponatinib \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Ibrutinib \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Idelalisib \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Proteosome inhibitors \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Bortezomib \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Carfilzomib \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Ixazomib \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Histone deacetylase inhibitors \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Romidepsin \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Vorinostat \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Panobinostat \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Dosage of 10mg/day of prednisone/day for more than four weeks \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Immunosuppressants \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Ciclosporin \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Tacrolimus \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Everolimus \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Temsirolimus \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " rowspan="4" align="left" valign="top">Treatments with a low risk of reactivation (reactivation rate <1%)</td><td class="td" title="table-entry " align="left" valign="top">Methotrexate \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Azathioprine \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">6-mercaptopurine \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Dosage of <10mg/day of prednisone \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1949182.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Risk of reactivation associated with immunosuppressive treatment in HBsAg positive patients." ] ] 4 => array:8 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at3" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "Anti-HBc: antibody against the hepatitis B core antigen; HBsAg: HBV surface antigen; HBV: hepatitis B virus." "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 " rowspan="9" align="left" valign="top">Treatments with high risk of reactivation (reactivation rate ≥10%)</td><td class="td" title="table-entry " align="left" valign="top">B cell depletion therapies \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Natalizumab \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Rituximab \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Ofatumumab \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Obinutuzumab \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Blinatumomab \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Alemtuzumab \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Ibritumomab \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Ocrelizumab \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " rowspan="45" align="left" valign="top">Treatments with moderate risk of reactivation (reactivation rate 1–10%)</td><td class="td" title="table-entry " align="left" valign="top">Treatment with high doses of corticosteroids \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Anthracycline derivatives \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Doxorubicin \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Epirubicin \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Daunorubicin \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Idarubicin \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Potent inhibitors of tumour necrosis factor alpha \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Infliximab \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Adalimumab \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Certolizumab \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Golimumab \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Systemic chemotherapy \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Inhibitors of cytokine or integrin \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Abatacept \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Ustekinumab \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Mogamulizumab \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Vedolizumab \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Tocilizumab \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Immunomodulators \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Thalidomide \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Lenalidomide \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Pomalidomide \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Tyrosine kinase inhibitors \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Imatinib \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Nilotinib \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Dasatinib \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Bosutinib \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Ponatinib \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Ibrutinib \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Idelalisib \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Proteosome inhibitors \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Bortezomib \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Carfilzomib \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Ixazomib \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Histone deacetylase inhibitors \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Romidepsin \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Vorinostat \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Panobinostat \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Chronic treatment with corticosteroids \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Dosage of 10mg/day of prednisone for more than four weeks \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Immunosuppressants \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Ciclosporin \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Tacrolimus \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Everolimus \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Temsirolimus \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " rowspan="4" align="left" valign="top">Treatments with a low risk of reactivation (reactivation rate <1%)</td><td class="td" title="table-entry " align="left" valign="top">Methotrexate \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Azathioprine \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">6-mercaptopurine \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Chronic treatment with glucocorticoids at doses of <10mg/day \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1949183.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Risk of reactivation associated with immunosuppressive treatment in HBsAg negative and anti-HBc positive patients." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:62 [ 0 => array:3 [ "identificador" => "bib0315" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hepatitis B: reactivation and current clinical impact" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "B. Alvarez Suárez" 1 => "J. de-la-Revilla-Negro" 2 => "B. Ruiz-Antorán" 3 => "J.L. Calleja Panero" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Rev Esp Enferm Dig" "fecha" => "2010" "volumen" => "102" "paginaInicial" => "542" "paginaFinal" => "552" ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0320" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Screening for hepatitis B in chemotherapy patients: survey of current oncology patients" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "T.T. Tran" 1 => "M.O. Rakoski" 2 => "P. Martin" 3 => "F. Poordad" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1365-2036.2009.04158.x" "Revista" => array:6 [ "tituloSerie" => "Aliment Pharmacol Ther" "fecha" => "2010" "volumen" => "31" "paginaInicial" => "240" "paginaFinal" => "246" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19814747" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0325" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Prácticas de cribado del virus de la hepatitis B previo a las terapias de riesgo de reactivación vírica en diferentes especialidades médicas. Proyecto HEBRA" "autores" => array:1 [ 0 => array:3 [ "colaboracion" => "en representación del grupo HEBRA" "etal" => false "autores" => array:4 [ 0 => "M. García-Bengoechea" 1 => "C. Hernández-López" 2 => "J. Crespo" 3 => "F. Gea" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Med Clin (Barc)" "fecha" => "2012" "volumen" => "139" "paginaInicial" => "498" "paginaFinal" => "501" ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0330" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hepatitis B reactivation in patients with hepatocellular carcinoma undergoing systematic chemotherapy" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "W. Yeo" 1 => "K.C. Lam" 2 => "B. Zee" 3 => "P.S. Chan" 4 => "F.K. Mo" 5 => "W.M. Ho" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1093/annonc/mdh430" "Revista" => array:6 [ "tituloSerie" => "Ann Oncol" "fecha" => "2004" "volumen" => "15" "paginaInicial" => "1661" "paginaFinal" => "1666" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15520068" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0335" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Prevention of hepatitis B virus reactivation in patients with nasopharyngeal carcinoma with lamivudine" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "W. Yeo" 1 => "E.P. Hui" 2 => "A.T. Chan" 3 => "W.M. Ho" 4 => "K.C. Lam" 5 => "P.K. Chan" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Am J Clin Oncol" "fecha" => "2005" "volumen" => "28" "paginaInicial" => "379" "paginaFinal" => "384" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16062080" "web" => "Medline" ] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0340" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hepatitis B virus reactivation in breast cancer patients undergoing cytotoxic chemotherapy and the role of preemptive lamivudine administration" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "M.S. Dai" 1 => "P.F. Wu" 2 => "R.Y. Shyu" 3 => "J.J. Lu" 4 => "T.Y. Chao" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1478-3231.2004.0964.x" "Revista" => array:6 [ "tituloSerie" => "Liver Int" "fecha" => "2004" "volumen" => "24" "paginaInicial" => "540" "paginaFinal" => "546" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15566502" "web" => "Medline" ] ] ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0345" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Steroid-free chemotherapy decreases risk of hepatitis B virus (HBV) reactivation in HBV-carriers with lymphoma" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A. Cheng" 1 => "C. Hsiung" 2 => "I. Su" 3 => "P. Chen" 4 => "M. Chang" 5 => "C. Tsao" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Hepatology" "fecha" => "2003" "volumen" => "37" "paginaInicial" => "1320" "paginaFinal" => "1328" ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0350" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Efficacy of lamivudine to prevent hepatitis reactivation in hepatitis B virus-infected patients treated for non-Hodgkin lymphoma" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M. Persico" 1 => "F. de Marino" 2 => "G.D. Russo" 3 => "A. Morante" 4 => "B. Rotoli" 5 => "R. Torella" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:7 [ "tituloSerie" => "Blood" "fecha" => "2002" "volumen" => "15" "paginaInicial" => "724" "paginaFinal" => "725" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/14414776" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0165032714006867" "estado" => "S300" "issn" => "01650327" ] ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib0355" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hepatitis B reactivation in a chronic hepatitis B surface antigen carrier with rheumatoid arthritis treated with infliximab and low dose methotrexate" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "P. Ostuni" 1 => "C. Botsios" 2 => "L. Punzi" 3 => "P. Sfriso" 4 => "S. Todesco" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Ann Rheum Dis" "fecha" => "2003" "volumen" => "62" "paginaInicial" => "686" "paginaFinal" => "687" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12810441" "web" => "Medline" ] ] ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib0360" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Use of tumor necrosis factor α inhibitors in patients with chronic hepatitis B infection" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "M.B. Carroll" 1 => "M.I. Bond" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.semarthrit.2007.10.011" "Revista" => array:6 [ "tituloSerie" => "Semin Arthritis Rheum" "fecha" => "2007" "volumen" => "38" "paginaInicial" => "208" "paginaFinal" => "217" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18221983" "web" => "Medline" ] ] ] ] ] ] ] ] 10 => array:3 [ "identificador" => "bib0365" "etiqueta" => "11" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Chronic hepatitis B reactivation following infliximab therapy in Crohn's disease patients: need for primary prophylaxis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "M. Esteve" 1 => "C. Saro" 2 => "F. Gonzalez-Huix" 3 => "F. Suarez" 4 => "M. Forné" 5 => "J.M. Viver" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/gut.2004.040675" "Revista" => array:7 [ "tituloSerie" => "Gut" "fecha" => "2004" "volumen" => "53" "paginaInicial" => "1363" "paginaFinal" => "1365" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15306601" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0924933818301433" "estado" => "S300" "issn" => "09249338" ] ] ] ] ] ] ] 11 => array:3 [ "identificador" => "bib0370" "etiqueta" => "12" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Redevelopment of hepatitis B surface antigen after renal transplantation" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "P. Marcellin" 1 => "E. Giostra" 2 => "M. Martino-Peignoux" 3 => "M.A. Loriot" 4 => "M.L. Jaengle" 5 => "P. Wolf" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Gastroenterology" "fecha" => "1991" "volumen" => "100" "paginaInicial" => "1432" "paginaFinal" => "1434" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/2013388" "web" => "Medline" ] ] ] ] ] ] ] ] 12 => array:3 [ "identificador" => "bib0375" "etiqueta" => "13" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Transmission of hepatitis B by transplantation of livers from donors positive for antibody to hepatitis B core antigen. The National Institute of Diabetes and Digestive and Kidney Diseases Liver Transplantation Database" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "R.C. Dickson" 1 => "J.E. Everhart" 2 => "J.R. Lake" 3 => "Y. Wei" 4 => "E.C. Seaberg" 5 => "R.H. Wiesner" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Gastroenterology" "fecha" => "1997" "volumen" => "113" "paginaInicial" => "1668" "paginaFinal" => "1674" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9352871" "web" => "Medline" ] ] ] ] ] ] ] ] 13 => array:3 [ "identificador" => "bib0380" "etiqueta" => "14" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Progressive disappearance of anti-hepatitis surface antigen antibody and reverse seroconversion after allogeneic hematopoietic stem cell transplantation in patients with previous hepatitis B virus infection" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M. Onozawa" 1 => "S. Hashino" 2 => "K. Izumiyama" 3 => "K. Kahata" 4 => "M. Chuma" 5 => "A. Mori" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Transplantation" "fecha" => "2005" "volumen" => "79" "paginaInicial" => "616" "paginaFinal" => "619" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15753855" "web" => "Medline" ] ] ] ] ] ] ] ] 14 => array:3 [ "identificador" => "bib0385" "etiqueta" => "15" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Reactivation of HBV following allogeneic bone marrow transplantation: new outlook (the hepatitis B virus and the bone marrow transplant)" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "S. Otero López-Cubero" 1 => "I. Espigado" 2 => "J. Aguilar Reina" 3 => "R. Parody" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Rev Esp Enferm Dig" "fecha" => "1999" "volumen" => "91" "paginaInicial" => "229" "paginaFinal" => "230" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10231356" "web" => "Medline" ] ] ] ] ] ] ] ] 15 => array:3 [ "identificador" => "bib0390" "etiqueta" => "16" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hepatitis B virus (HBV) reactivation in patients receiving tumor necrosis factor (TNF)-targeted therapy: analysis of 257 cases" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "R. Pérez-Alvarez" 1 => "C. Díaz-Lagares" 2 => "F. García-Hernández" 3 => "L. Lopez-Roses" 4 => "P. Brito-Zerón" 5 => "M. Pérez-de-Lis" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/MD.0b013e3182380a76" "Revista" => array:6 [ "tituloSerie" => "Medicine" "fecha" => "2011" "volumen" => "90" "paginaInicial" => "359" "paginaFinal" => "371" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22033451" "web" => "Medline" ] ] ] ] ] ] ] ] 16 => array:3 [ "identificador" => "bib0395" "etiqueta" => "17" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "EASL 2017 Clinical Guidelines on the management of hepatitis B virus infection" "autores" => array:1 [ 0 => array:2 [ "colaboracion" => "European Association for the Study of the Liver" "etal" => false ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jhep.2017.03.021" "Revista" => array:6 [ "tituloSerie" => "J Hepatol" "fecha" => "2017" "volumen" => "67" "paginaInicial" => "370" "paginaFinal" => "398" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28427875" "web" => "Medline" ] ] ] ] ] ] ] ] 17 => array:3 [ "identificador" => "bib0400" "etiqueta" => "18" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hepatitis B reactivation associated with immune suppressive and biological modifier therapies: current concepts, management strategies and future directions" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "R. Loomba" 1 => "T.J. Liang" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1053/j.gastro.2017.02.009" "Revista" => array:6 [ "tituloSerie" => "Gastroenterology" "fecha" => "2017" "volumen" => "152" "paginaInicial" => "1297" "paginaFinal" => "1309" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28219691" "web" => "Medline" ] ] ] ] ] ] ] ] 18 => array:3 [ "identificador" => "bib0405" "etiqueta" => "19" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Reactivation of hepatitis B" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "J. Hoofnagle" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/hep.22945" "Revista" => array:7 [ "tituloSerie" => "Hepatology" "fecha" => "2009" "volumen" => "49" "numero" => "Suppl." "paginaInicial" => "S156" "paginaFinal" => "S165" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19399803" "web" => "Medline" ] ] ] ] ] ] ] ] 19 => array:3 [ "identificador" => "bib0410" "etiqueta" => "20" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Systematic review: the effect of preventive lamivudine on hepatitis B reactivation during chemotherapy" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "R. Loomba" 1 => "A. Rowley" 2 => "R. Wesley" 3 => "T.J. Liang" 4 => "J.H. Hoofnagle" 5 => "F. Pucino" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Ann Intern Med" "fecha" => "2008" "volumen" => "148" "paginaInicial" => "519" "paginaFinal" => "528" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18378948" "web" => "Medline" ] ] ] ] ] ] ] ] 20 => array:3 [ "identificador" => "bib0415" "etiqueta" => "21" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Frequency of hepatitis B virus reactivation in cancer patients undergoing cytotoxic chemotherapy: a prospective study of 626 patients with identification of risk factors" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "W. Yeo" 1 => "P.K. Chan" 2 => "S. Zhong" 3 => "W.M. Ho" 4 => "J.L. Steinberg" 5 => "J.S. Tam" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:7 [ "tituloSerie" => "J Med Virol" "fecha" => "2000" "volumen" => "62" "paginaInicial" => "299" "paginaFinal" => "307" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11055239" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0895435616001438" "estado" => "S300" "issn" => "08954356" ] ] ] ] ] ] ] 21 => array:3 [ "identificador" => "bib0420" "etiqueta" => "22" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Lamivudine for the prevention of hepatitis B virus reactivation in hepatitis B s-antigen seropositive cancer patients undergoing cytotoxic chemotherapy" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "W. Yeo" 1 => "P.K. Chan" 2 => "W.M. Ho" 3 => "B. Zee" 4 => "K.C. Lam" 5 => "K.I. Lei" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1200/JCO.2004.05.161" "Revista" => array:6 [ "tituloSerie" => "J Clin Oncol" "fecha" => "2004" "volumen" => "22" "paginaInicial" => "927" "paginaFinal" => "934" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/14990649" "web" => "Medline" ] ] ] ] ] ] ] ] 22 => array:3 [ "identificador" => "bib0425" "etiqueta" => "23" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hepatitis B virus reactivation in breast cancer patients receiving cytotoxic chemotherapy: a prospective study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "W. Yeo" 1 => "P.K. Chan" 2 => "P. Hui" 3 => "W.M. Ho" 4 => "K.C. Lam" 5 => "W.H. Kwan" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/jmv.10430" "Revista" => array:6 [ "tituloSerie" => "J Med Virol" "fecha" => "2003" "volumen" => "70" "paginaInicial" => "553" "paginaFinal" => "561" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12794717" "web" => "Medline" ] ] ] ] ] ] ] ] 23 => array:3 [ "identificador" => "bib0430" "etiqueta" => "24" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Diagnosis, prevention and management of hepatitis B virus reactivation during anticancer therapy" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "W. Yeo" 1 => "P.J. Johnson" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/hep.21051" "Revista" => array:6 [ "tituloSerie" => "Hepatology" "fecha" => "2006" "volumen" => "43" "paginaInicial" => "209" "paginaFinal" => "220" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16440366" "web" => "Medline" ] ] ] ] ] ] ] ] 24 => array:3 [ "identificador" => "bib0435" "etiqueta" => "25" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Rates and risk factors for hepatitis B reactivation in a cohort of persons in the inactive phase of chronic hepatitis B-Alaska, 2001–2010" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "R.A. Tohme" 1 => "L. Bulkow" 2 => "C.E. Homan" 3 => "S. Neus" 4 => "B.J. McMahon" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jcv.2013.08.012" "Revista" => array:6 [ "tituloSerie" => "J Clin Virol" "fecha" => "2013" "volumen" => "58" "paginaInicial" => "396" "paginaFinal" => "400" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24001884" "web" => "Medline" ] ] ] ] ] ] ] ] 25 => array:3 [ "identificador" => "bib0440" "etiqueta" => "26" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Clinical and virological factors associated with hepatitis B virus reactivation in HBsAg-negative and anti-HBc antibodies positive patients undergoing chemotherapy and/or autologous stem cell transplantation for cancer" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "P. Borentain" 1 => "P. Colson" 2 => "D. Coso" 3 => "E. Bories" 4 => "A. Charbonnier" 5 => "A.M. Stoppa" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1365-2893.2009.01239.x" "Revista" => array:6 [ "tituloSerie" => "J Viral Hepat" "fecha" => "2010" "volumen" => "17" "paginaInicial" => "807" "paginaFinal" => "815" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20002298" "web" => "Medline" ] ] ] ] ] ] ] ] 26 => array:3 [ "identificador" => "bib0445" "etiqueta" => "27" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Clinical characteristics and molecular analysis of hepatitis B virus reactivation in hepatitis B surface antigen-negative patients during or after immunosuppressive or cytotoxic chemotherapy" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "K. Hayashi" 1 => "M. Ishigami" 2 => "Y. Ishizu" 3 => "T. Kuzuya" 4 => "T. Honda" 5 => "Y. Tachi" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s00535-016-1187-z" "Revista" => array:6 [ "tituloSerie" => "J Gastroenterol" "fecha" => "2016" "volumen" => "51" "paginaInicial" => "1081" "paginaFinal" => "1089" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26943169" "web" => "Medline" ] ] ] ] ] ] ] ] 27 => array:3 [ "identificador" => "bib0450" "etiqueta" => "28" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Reverse seroconversion of hepatitis B alter allogeneic bone marrow transplantation: a retrospective study of 37 patients with pretransplant antiHBs and antiHBc" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "N. Dhedin" 1 => "C. Douvin" 2 => "M. Kuentz" 3 => "M.F. Saint Marc" 4 => "O. Remen" 5 => "C. Rieux" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Transplantation" "fecha" => "1998" "volumen" => "66" "paginaInicial" => "616" "paginaFinal" => "619" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9753342" "web" => "Medline" ] ] ] ] ] ] ] ] 28 => array:3 [ "identificador" => "bib0455" "etiqueta" => "29" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hepatitis B reactivation with clinical flare in allogeneic stem cell transplant with chronic graft-versus-host disease" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "P. Seth" 1 => "A.A. Alrajhi" 2 => "I. Kagevi" 3 => "M.A. Chaudhary" 4 => "E. Colcol" 5 => "E. Sahovic" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/sj.bmt.1703614" "Revista" => array:6 [ "tituloSerie" => "Bone Marrow Transplant" "fecha" => "2002" "volumen" => "30" "paginaInicial" => "189" "paginaFinal" => "194" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12189538" "web" => "Medline" ] ] ] ] ] ] ] ] 29 => array:3 [ "identificador" => "bib0460" "etiqueta" => "30" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Reactivation of resolved hepatitis B virus infection after allogeneic haematopoietic stem cell transplantation" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "A. Knöll" 1 => "S. Boehm" 2 => "J. Hahn" 3 => "E. Holler" 4 => "W. Jilg" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/sj.bmt.1704457" "Revista" => array:6 [ "tituloSerie" => "Bone Marrow Transplant" "fecha" => "2004" "volumen" => "33" "paginaInicial" => "925" "paginaFinal" => "929" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15004543" "web" => "Medline" ] ] ] ] ] ] ] ] 30 => array:3 [ "identificador" => "bib0465" "etiqueta" => "31" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Reactivation of hepatitis B virus infection after cytotoxic chemotherapy or immunosuppressive therapy" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "M.L. Manzano-Alonso" 1 => "G. Castellano-Tortajada" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3748/wjg.v17.i12. 1531" "Revista" => array:6 [ "tituloSerie" => "World J Gastroenterol" "fecha" => "2011" "volumen" => "17" "paginaInicial" => "1531" "paginaFinal" => "1537" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21472116" "web" => "Medline" ] ] ] ] ] ] ] ] 31 => array:3 [ "identificador" => "bib0470" "etiqueta" => "32" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "American Gastroenterological Association Institute technical review on prevention and treatment of hepatitis B virus reactivation during immunosuppressive drug therapy" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "R.P. Perrillo" 1 => "R. Gish" 2 => "Y.T. Falck-Ytter" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1053/j.gastro.2014.10.038" "Revista" => array:6 [ "tituloSerie" => "Gastroenterology" "fecha" => "2015" "volumen" => "148" "paginaInicial" => "221" "paginaFinal" => "244" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25447852" "web" => "Medline" ] ] ] ] ] ] ] ] 32 => array:3 [ "identificador" => "bib0475" "etiqueta" => "33" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Reactivation of hepatitis B virus in rheumatoid arthritis patients treated with biological disease-modifying antirheumatic drugs" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "J. Nakamura" 1 => "T. Nagashima" 2 => "K. Nagatani" 3 => "T. Yoshio" 4 => "M. Iwamoto" 5 => "S. Minota" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/1756-185X.12359" "Revista" => array:6 [ "tituloSerie" => "Int J Rheum Dis" "fecha" => "2016" "volumen" => "19" "paginaInicial" => "470" "paginaFinal" => "475" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24698305" "web" => "Medline" ] ] ] ] ] ] ] ] 33 => array:3 [ "identificador" => "bib0480" "etiqueta" => "34" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Risk of hepatitis B virus reactivation in patients treated with ibrutinib" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "S.P. Hammond" 1 => "K. Chen" 2 => "A. Pandit" 3 => "M.S. Davids" 4 => "N.C. Issa" 5 => "F.M. Marty" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1182/blood-2018-01-826495" "Revista" => array:6 [ "tituloSerie" => "Blood" "fecha" => "2018" "volumen" => "131" "paginaInicial" => "1987" "paginaFinal" => "1989" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29490923" "web" => "Medline" ] ] ] ] ] ] ] ] 34 => array:3 [ "identificador" => "bib0485" "etiqueta" => "35" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Incidence and risk factors of hepatitis B virus reactivation in patients with multiple myeloma in an era with novel agents: a nationwide retrospective study in Japan" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "Y. Tsukune" 1 => "M. Sasaki" 2 => "T. Odajima" 3 => "K. Sunami" 4 => "T. Takei" 5 => "Y. Moriuchi" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/s41408-017-0002-2" "Revista" => array:5 [ "tituloSerie" => "Blood Cancer J" "fecha" => "2017" "volumen" => "7" "paginaInicial" => "631" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29167420" "web" => "Medline" ] ] ] ] ] ] ] ] 35 => array:3 [ "identificador" => "bib0490" "etiqueta" => "36" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Reactivation of DNA viruses in association with histone deacetylase inhibitor therapy: a case series report" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "D. Ritchie" 1 => "R.L. Piekarz" 2 => "P. Blombery" 3 => "L.J. Karai" 4 => "S. Pittaluga" 5 => "E.S. Jaffe" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3324/haematol.2009.008607" "Revista" => array:6 [ "tituloSerie" => "Haematologica" "fecha" => "2009" "volumen" => "94" "paginaInicial" => "1618" "paginaFinal" => "1622" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19608677" "web" => "Medline" ] ] ] ] ] ] ] ] 36 => array:3 [ "identificador" => "bib0495" "etiqueta" => "37" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Immune checkpoint blockade in hepatocellular carcinoma: 2017 update" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "M. Kudo" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1159/000449342" "Revista" => array:6 [ "tituloSerie" => "Liver Cancer" "fecha" => "2016" "volumen" => "6" "paginaInicial" => "1" "paginaFinal" => "12" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27995082" "web" => "Medline" ] ] ] ] ] ] ] ] 37 => array:3 [ "identificador" => "bib0500" "etiqueta" => "38" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Reactivation of hepatitis B virus in HBsAg-negative patients with hepatocellular carcinoma" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J.W. Jang" 1 => "Y.W. Kim" 2 => "S.W. Lee" 3 => "J.H. Kwon" 4 => "S.W. Nam" 5 => "S.H. Bae" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1371/journal.pone.0122041" "Revista" => array:5 [ "tituloSerie" => "PLOS ONE" "fecha" => "2015" "volumen" => "10" "paginaInicial" => "e0122041" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25894607" "web" => "Medline" ] ] ] ] ] ] ] ] 38 => array:3 [ "identificador" => "bib0505" "etiqueta" => "39" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Transarterial chemo-lipiodolization can reactivate hepatitis B virus replication in patients with hepatocellular carcinoma" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J.W. Jang" 1 => "J.Y. Choi" 2 => "S.H. Bae" 3 => "C.W. Kim" 4 => "S.K. Yoon" 5 => "S.H. Cho" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jhep.2004.05.014" "Revista" => array:6 [ "tituloSerie" => "J Hepatol" "fecha" => "2004" "volumen" => "41" "paginaInicial" => "427" "paginaFinal" => "435" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15336446" "web" => "Medline" ] ] ] ] ] ] ] ] 39 => array:3 [ "identificador" => "bib0510" "etiqueta" => "40" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hepatitis B virus infection – natural history and clinical consequences" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "D. Ganem" 1 => "A.M. Prince" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMra031087" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med" "fecha" => "2004" "volumen" => "350" "paginaInicial" => "1118" "paginaFinal" => "1129" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15014185" "web" => "Medline" ] ] ] ] ] ] ] ] 40 => array:3 [ "identificador" => "bib0515" "etiqueta" => "41" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Kinetics and risk of de novo hepatitis B infection in HBsAg-negative patients undergoing cytotoxic chemotherapy" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "C.K. Hui" 1 => "W.W. Cheung" 2 => "H. Zhang" 3 => "W. Au" 4 => "Y. Yueng" 5 => "A. Leung" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1053/j.gastro.2006.04.015" "Revista" => array:6 [ "tituloSerie" => "Gastroenterology" "fecha" => "2006" "volumen" => "131" "paginaInicial" => "59" "paginaFinal" => "68" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16831590" "web" => "Medline" ] ] ] ] ] ] ] ] 41 => array:3 [ "identificador" => "bib0520" "etiqueta" => "42" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hepatitis B virus reactivation in lymphoma patients with prior resolved hepatitis B undergoing anticancer therapy with or without rituximab" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "W. Yeo" 1 => "T.C. Chan" 2 => "N.W. Leung" 3 => "W.Y. Lam" 4 => "F.K. Mo" 5 => "M.T. Chu" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1200/JCO.2008.18.0182" "Revista" => array:6 [ "tituloSerie" => "J Clin Oncol" "fecha" => "2009" "volumen" => "27" "paginaInicial" => "605" "paginaFinal" => "611" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19075267" "web" => "Medline" ] ] ] ] ] ] ] ] 42 => array:3 [ "identificador" => "bib0525" "etiqueta" => "43" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Documento de Consenso de la AEEH sobre el tratamiento de la infección por el virus de la hepatitis B (2012)" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M. Buti" 1 => "J. García-Samaniego" 2 => "M. Prieto" 3 => "M. Rodríguez" 4 => "J.M. Sánchez-Tapias" 5 => "E. Suárez" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.gastrohep.2012.04.006" "Revista" => array:6 [ "tituloSerie" => "Gastroenterol Hepatol" "fecha" => "2012" "volumen" => "35" "paginaInicial" => "512" "paginaFinal" => "528" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22749508" "web" => "Medline" ] ] ] ] ] ] ] ] 43 => array:3 [ "identificador" => "bib0530" "etiqueta" => "44" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "AASLD guidelines for treatment of chronic hepatitis B" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "N.A. Terrault" 1 => "N.H. Bzowej" 2 => "K.M. Chang" 3 => "J.P. Hwang" 4 => "M.M. Jonas" 5 => "M.H. Murad" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/hep.28156" "Revista" => array:6 [ "tituloSerie" => "Hepatology" "fecha" => "2016" "volumen" => "63" "paginaInicial" => "261" "paginaFinal" => "283" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26566064" "web" => "Medline" ] ] ] ] ] ] ] ] 44 => array:3 [ "identificador" => "bib0535" "etiqueta" => "45" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Asian-Pacific consensus statement on the management of chronic hepatitis B: a 2015 update" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "S.K. Sarin" 1 => "M. Kumar" 2 => "G.K. Lau" 3 => "Z. Abbas" 4 => "H.L.Y. Chan" 5 => "C.J. Chen" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s12072-016-9707-8" "Revista" => array:6 [ "tituloSerie" => "Hepatol Int" "fecha" => "2016" "volumen" => "10" "paginaInicial" => "1" "paginaFinal" => "98" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26856325" "web" => "Medline" ] ] ] ] ] ] ] ] 45 => array:3 [ "identificador" => "bib0540" "etiqueta" => "46" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Optimal management of hepatitis B virus infection – EASL Special Conference" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "P. Lampertico" 1 => "M. Maini" 2 => "G. Papatheodoridis" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jhep.2015.06.026" "Revista" => array:7 [ "tituloSerie" => "J Hepatol" "fecha" => "2015" "volumen" => "63" "paginaInicial" => "1238" "paginaFinal" => "1253" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26150256" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0005791615300057" "estado" => "S300" "issn" => "00057916" ] ] ] ] ] ] ] 46 => array:3 [ "identificador" => "bib0545" "etiqueta" => "47" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Systematic review: lamivudine prophylaxis for chemotherapy-induced reactivation of chronic hepatitis B virus infection" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "H.E. Kohrt" 1 => "D.L. Ouyang" 2 => "E.B. Keeffe" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1365-2036.2006.03081.x" "Revista" => array:6 [ "tituloSerie" => "Aliment Pharmacol Ther" "fecha" => "2006" "volumen" => "24" "paginaInicial" => "1003" "paginaFinal" => "1016" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16984494" "web" => "Medline" ] ] ] ] ] ] ] ] 47 => array:3 [ "identificador" => "bib0550" "etiqueta" => "48" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Lamivudine prevents reactivation of hepatitis B and reduce mortality in immunosuppressed patients: systematic review and meta-analysis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "L. Katz" 1 => "A. Fraser" 2 => "A. Gafter-Gvili" 3 => "L. Leibovici" 4 => "R. Tur-Kaspa" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1365-2893.2007.00902.x" "Revista" => array:6 [ "tituloSerie" => "J Viral Hepat" "fecha" => "2008" "volumen" => "15" "paginaInicial" => "89" "paginaFinal" => "102" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18184191" "web" => "Medline" ] ] ] ] ] ] ] ] 48 => array:3 [ "identificador" => "bib0555" "etiqueta" => "49" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Entecavir vs. lamivudine for prevention of hepatitis B virus reactivation among patients with untreated diffuse large B-cell lymphoma receiving R-CHOP chemotherapy: a randomized clinical trial" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "H. Huang" 1 => "X. Li" 2 => "J. Zhu" 3 => "S. Ye" 4 => "H. Zhang" 5 => "W. Wang" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1001/jama.2014.15704" "Revista" => array:6 [ "tituloSerie" => "JAMA" "fecha" => "2014" "volumen" => "312" "paginaInicial" => "2521" "paginaFinal" => "2530" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25514302" "web" => "Medline" ] ] ] ] ] ] ] ] 49 => array:3 [ "identificador" => "bib0560" "etiqueta" => "50" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Tenofovir for treatment of hepatitis B virus reactivation in patients with chronic GVHD" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "I. Hilgendorf" 1 => "M. Loebermann" 2 => "K. Borchert" 3 => "C. Junghanss" 4 => "M. Freund" 5 => "M. Schmitt" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/bmt.2010.290" "Revista" => array:6 [ "tituloSerie" => "Bone Marrow Transplant" "fecha" => "2011" "volumen" => "46" "paginaInicial" => "1274" "paginaFinal" => "1275" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21151183" "web" => "Medline" ] ] ] ] ] ] ] ] 50 => array:3 [ "identificador" => "bib0565" "etiqueta" => "51" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A comparison of entecavir and lamivudine for the prophylaxis of hepatitis B virus reactivation in solid tumor patients undergoing systemic cytotoxic chemotherapy" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "W.C. Chen" 1 => "J.S. Cheng" 2 => "P.H. Chiang" 3 => "F.W. Tsay" 4 => "H.H. Chan" 5 => "H.W. Chang" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1371/journal.pone.0131545" "Revista" => array:5 [ "tituloSerie" => "PLOS ONE" "fecha" => "2015" "volumen" => "10" "paginaInicial" => "e0131545" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26121480" "web" => "Medline" ] ] ] ] ] ] ] ] 51 => array:3 [ "identificador" => "bib0570" "etiqueta" => "52" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Systematic review with network meta-analysis: comparative efficacy of oral nucleos(t)ide analogues for the prevention of chemotherapy-induced hepatitis B virus reactivation" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M.Y. Zhang" 1 => "G.Q. Zhu" 2 => "K.Q. Shi" 3 => "J.N. Zheng" 4 => "Z. Cheng" 5 => "Z.L. Zou" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.18632/oncotarget.8907" "Revista" => array:6 [ "tituloSerie" => "Oncotarget" "fecha" => "2016" "volumen" => "7" "paginaInicial" => "30642" "paginaFinal" => "30658" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27121321" "web" => "Medline" ] ] ] ] ] ] ] ] 52 => array:3 [ "identificador" => "bib0575" "etiqueta" => "53" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Universal prophylaxis with lamivudine prevents hepatitis B reactivation in HBsAg-negative/anti-HBC positive patients undergoing rituximab-based chemotherapy for non-Hodgkin b cell lymphoma – final results" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "G. Grossi" 1 => "A. Loglio" 2 => "M. Viganò" 3 => "M. Cappelletti" 4 => "M.C. Goldaniga" 5 => "L. Farina" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Hepatology" "fecha" => "2016" "volumen" => "64" "paginaInicial" => "88A" "itemHostRev" => array:3 [ "pii" => "S016503271630739X" "estado" => "S300" "issn" => "01650327" ] ] ] ] ] ] ] 53 => array:3 [ "identificador" => "bib0580" "etiqueta" => "54" "referencia" => array:1 [ 0 => array:3 [ "comentario" => "e1–8" "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Persistent risk of HBV reactivation despite extensive lamivudine prophylaxis in haematopoietic stem cell transplant recipients who are anti-HBc-positive or HBV-negative recipients with an anti-HBc-positive donor" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "C. Cerva" 1 => "L. Colagrossi" 2 => "G. Maffongelli" 3 => "R. Salpini" 4 => "D. di Carlo" 5 => "V. Malagnino" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.cmi.2016.07.021" "Revista" => array:5 [ "tituloSerie" => "Clin Microbiol Infect" "fecha" => "2016" "volumen" => "22" "paginaInicial" => "946" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27475741" "web" => "Medline" ] ] ] ] ] ] ] ] 54 => array:3 [ "identificador" => "bib0585" "etiqueta" => "55" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hepatitis B reactivation in HBsAgnegative/HBcAb-positive patients receiving rituximab for lymphoma: a meta-analysis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "L. Mozessohn" 1 => "K.K. Chan" 2 => "J.J. Feld" 3 => "L.K. Hicks" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/jvh.12402" "Revista" => array:6 [ "tituloSerie" => "J Viral Hepat" "fecha" => "2015" "volumen" => "22" "paginaInicial" => "842" "paginaFinal" => "849" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25765930" "web" => "Medline" ] ] ] ] ] ] ] ] 55 => array:3 [ "identificador" => "bib0590" "etiqueta" => "56" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Randomized controlled trial of entecavir prophylaxis for rituximab-associated hepatitis B virus reactivation in patients with lymphoma and resolved hepatitis B" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "Y.H. Huang" 1 => "L.T. Hsiao" 2 => "Y.C. Hong" 3 => "T.J. Chiou" 4 => "Bin YuY" 5 => "J.P. Gau" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1200/JCO.2012.48.5938" "Revista" => array:6 [ "tituloSerie" => "J Clin Oncol" "fecha" => "2013" "volumen" => "31" "paginaInicial" => "2765" "paginaFinal" => "2772" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23775967" "web" => "Medline" ] ] ] ] ] ] ] ] 56 => array:3 [ "identificador" => "bib0595" "etiqueta" => "57" "referencia" => array:1 [ 0 => array:3 [ "comentario" => "e0184550ee184551184" "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Randomized prospective study evaluating tenofovir disoproxil fumarate prophylaxis against hepatitis B virus reactivation in anti-HBc-positive patients with rituximab-based regimens to treat hematologic malignancies: The Preblin Study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M. Buti" 1 => "M.L. Manzano" 2 => "R.M. Morillas" 3 => "M. García-Retortillo" 4 => "L. Martín" 5 => "M. Prieto" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1371/journal.pone.0189910" "Revista" => array:4 [ "tituloSerie" => "PLOS ONE" "fecha" => "2017" "volumen" => "12" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29287100" "web" => "Medline" ] ] ] ] ] ] ] ] 57 => array:3 [ "identificador" => "bib0600" "etiqueta" => "58" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Management of patients with hepatitis B in special populations" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "E. Cholongitas" 1 => "K. Tziomalos" 2 => "C. Pipili" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3748/wjg.v21.i6.1738" "Revista" => array:6 [ "tituloSerie" => "World J Gastroenterol" "fecha" => "2015" "volumen" => "21" "paginaInicial" => "1738" "paginaFinal" => "1748" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25684938" "web" => "Medline" ] ] ] ] ] ] ] ] 58 => array:3 [ "identificador" => "bib0605" "etiqueta" => "59" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Reactivation of hepatitis B virus during targeted therapies for cancer and immune mediated disorders" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "M. Viganò" 1 => "G. Serra" 2 => "G. Casella" 3 => "G. Grossi" 4 => "P. Lampertico" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1080/14712598.2016.1177017" "Revista" => array:6 [ "tituloSerie" => "Expert Opin Biol Ther" "fecha" => "2016" "volumen" => "16" "paginaInicial" => "917" "paginaFinal" => "926" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27088278" "web" => "Medline" ] ] ] ] ] ] ] ] 59 => array:3 [ "identificador" => "bib0610" "etiqueta" => "60" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Improving testing for hepatitis B before treatment with rituximab" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J.K. Dysson" 1 => "L. Jopson" 2 => "S. Ng" 3 => "M. Lowery" 4 => "J. Harwood" 5 => "S. Waugh" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/MEG.0000000000000689" "Revista" => array:6 [ "tituloSerie" => "Eur J Gastroenterol Hepatol" "fecha" => "2016" "volumen" => "28" "paginaInicial" => "1172" "paginaFinal" => "1178" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27388147" "web" => "Medline" ] ] ] ] ] ] ] ] 60 => array:3 [ "identificador" => "bib0615" "etiqueta" => "61" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The compliance of doctors with viral hepatitis B screening and antiviral prophylaxis in cancer patients receiving cytotoxic chemotherapy using hospital-based screening reminder system" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "W.C. Sun" 1 => "P.I. Hsu" 2 => "H.C. Yu" 3 => "K.H. Lin" 4 => "F.W. Tsay" 5 => "H.M. Wang" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:4 [ "tituloSerie" => "PLOS ONE" "fecha" => "2015" "volumen" => "10" "paginaInicial" => "ee0116978" ] ] ] ] ] ] 61 => array:3 [ "identificador" => "bib0620" "etiqueta" => "62" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Computerized physician order entry-based system to prevent HBV reactivation in patients treated with biological agents: The PRESCRIB Project" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "B. Sampedro" 1 => "C. Hernández-López" 2 => "J.R. Ferrandiz" 3 => "A. Illaro" 4 => "E. Fábrega" 5 => "A. Cuadrado" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/hep.27103" "Revista" => array:6 [ "tituloSerie" => "Hepatology" "fecha" => "2014" "volumen" => "60" "paginaInicial" => "106" "paginaFinal" => "113" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24585503" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/23870206/0000015200000003/v1_201901290746/S2387020618305448/v1_201901290746/en/main.assets" "Apartado" => array:4 [ "identificador" => "44147" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Review" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/23870206/0000015200000003/v1_201901290746/S2387020618305448/v1_201901290746/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2387020618305448?idApp=UINPBA00004N"]

Statistics

Review

Reactivation of hepatitis B associated with immunosuppressants and chemotherapy. Natural history, risk factors and recommendations for prevention

Reactivación de la hepatitis B asociada a agentes inmunodepresores y a quimioterapia. Historia natural, factores de riesgo y recomendaciones para prevenirla

Rosa Maria Morillasa,b,

Corresponding author

rmorillas.germanstrias@gencat.cat

Corresponding author.

, David López Sisamónc

a Sección de Hepatología, Servicio de Aparato Digestivo, Hospital Universitario Germans Trias i Pujol, Badalona, Barcelona, Spain

b CIBERehd-Instituto de Salud Carlos III, Spain

c Unidad de Farmacia Oncológica ICO-Badalona, Hospital Universitario Germans Trias i Pujol, Badalona, Barcelona, Spain

Read

Times
was read the article

Total PDF

Total HTML

Share statistics

 array:24 [
  "pii" => "S2387020618305448"
  "issn" => "23870206"
  "doi" => "10.1016/j.medcle.2018.12.006"
  "estado" => "S300"
  "fechaPublicacion" => "2019-02-01"
  "aid" => "4645"
  "copyright" => "Elsevier Espa&#241;a&#44; S&#46;L&#46;U&#46;. All rights reserved"
  "copyrightAnyo" => "2018"
  "documento" => "article"
  "crossmark" => 1
  "subdocumento" => "rev"
  "cita" => "Med Clin. 2019;152:107-14"
  "abierto" => array:3 [
    "ES" => false
    "ES2" => false
    "LATM" => false
  ]
  "gratuito" => false
  "lecturas" => array:1 [
    "total" => 0
  ]
  "Traduccion" => array:1 [
    "es" => array:19 [
      "pii" => "S0025775318305670"
      "issn" => "00257753"
      "doi" => "10.1016/j.medcli.2018.08.018"
      "estado" => "S300"
      "fechaPublicacion" => "2019-02-01"
      "aid" => "4645"
      "copyright" => "Elsevier Espa&#241;a&#44; S&#46;L&#46;U&#46;"
      "documento" => "article"
      "crossmark" => 1
      "subdocumento" => "rev"
      "cita" => "Med Clin. 2019;152:107-14"
      "abierto" => array:3 [
        "ES" => false
        "ES2" => false
        "LATM" => false
      ]
      "gratuito" => false
      "lecturas" => array:2 [
        "total" => 73
        "formatos" => array:2 [
          "HTML" => 39
          "PDF" => 34
        ]
      ]
      "es" => array:13 [
        "idiomaDefecto" => true
        "cabecera" => "<span class="elsevierStyleTextfn">Revisi&#243;n</span>"
        "titulo" => "Reactivaci&#243;n de la hepatitis B asociada a agentes inmunodepresores y a quimioterapia&#46; Historia natural&#44; factores de riesgo y recomendaciones para prevenirla"
        "tienePdf" => "es"
        "tieneTextoCompleto" => "es"
        "tieneResumen" => array:2 [
          0 => "es"
          1 => "en"
        ]
        "paginas" => array:1 [
          0 => array:2 [
            "paginaInicial" => "107"
            "paginaFinal" => "114"
          ]
        ]
        "titulosAlternativos" => array:1 [
          "en" => array:1 [
            "titulo" => "Reactivation of hepatitis B associated with immunosuppressants and chemotherapy&#46; Natural history&#44; risk factors and recommendations for prevention"
          ]
        ]
        "contieneResumen" => array:2 [
          "es" => true
          "en" => true
        ]
        "contieneTextoCompleto" => array:1 [
          "es" => true
        ]
        "contienePdf" => array:1 [
          "es" => true
        ]
        "resumenGrafico" => array:2 [
          "original" => 0
          "multimedia" => array:7 [
            "identificador" => "fig0010"
            "etiqueta" => "Figura 2"
            "tipo" => "MULTIMEDIAFIGURA"
            "mostrarFloat" => true
            "mostrarDisplay" => false
            "figura" => array:1 [
              0 => array:4 [
                "imagen" => "gr2.jpeg"
                "Alto" => 2108
                "Ancho" => 2500
                "Tamanyo" => 270823
              ]
            ]
            "descripcion" => array:1 [
              "es" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">C&#243;mo actuar en pacientes que van a recibir quimioterapia&#44; tratamientos inmunosupresores o biol&#243;gicos&#46; Pacientes con HBsAg negativo y anti-HBc positivo con o sin anti-HBs&#46;</p> <p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">ALT&#58; alanina-aminotransferasa&#59; anti-HBc&#58; anticuerpo frente al ant&#237;geno del core del VHB&#59; anti-HBs&#58; anticuerpo frente al ant&#237;geno de superficie&#59; ETV&#58; entecavir&#59; HBsAg&#58; ant&#237;geno de superficie del VHB&#59; IS&#58; inmunodepresores&#59; QT&#58; quimioterapia&#59; RTX&#58; rituximab&#59; TAF&#58; tenofovir-alafenamida&#59; TDF&#58; tenofovir&#59; VHB&#58; virus de la hepatitis B&#46;</p>"
            ]
          ]
        ]
        "autores" => array:1 [
          0 => array:2 [
            "autoresLista" => "Rosa Maria Morillas, David L&#243;pez Sisam&#243;n"
            "autores" => array:2 [
              0 => array:2 [
                "nombre" => "Rosa Maria"
                "apellidos" => "Morillas"
              ]
              1 => array:2 [
                "nombre" => "David"
                "apellidos" => "L&#243;pez Sisam&#243;n"
              ]
            ]
          ]
        ]
      ]
      "idiomaDefecto" => "es"
      "Traduccion" => array:1 [
        "en" => array:9 [
          "pii" => "S2387020618305448"
          "doi" => "10.1016/j.medcle.2018.12.006"
          "estado" => "S300"
          "subdocumento" => ""
          "abierto" => array:3 [
            "ES" => false
            "ES2" => false
            "LATM" => false
          ]
          "gratuito" => false
          "lecturas" => array:1 [
            "total" => 0
          ]
          "idiomaDefecto" => "en"
          "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2387020618305448?idApp=UINPBA00004N"
        ]
      ]
      "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0025775318305670?idApp=UINPBA00004N"
      "url" => "/00257753/0000015200000003/v1_201901250619/S0025775318305670/v1_201901250619/es/main.assets"
    ]
  ]
  "itemSiguiente" => array:19 [
    "pii" => "S2387020618305424"
    "issn" => "23870206"
    "doi" => "10.1016/j.medcle.2018.07.016"
    "estado" => "S300"
    "fechaPublicacion" => "2019-02-01"
    "aid" => "4578"
    "copyright" => "Elsevier Espa&#241;a&#44; S&#46;L&#46;U&#46;"
    "documento" => "article"
    "crossmark" => 1
    "subdocumento" => "sco"
    "cita" => "Med Clin. 2019;152:115-7"
    "abierto" => array:3 [
      "ES" => false
      "ES2" => false
      "LATM" => false
    ]
    "gratuito" => false
    "lecturas" => array:1 [
      "total" => 0
    ]
    "en" => array:10 [
      "idiomaDefecto" => true
      "cabecera" => "<span class="elsevierStyleTextfn">Special article</span>"
      "titulo" => "The problem of the fragmentation of hospital medicine"
      "tienePdf" => "en"
      "tieneTextoCompleto" => "en"
      "paginas" => array:1 [
        0 => array:2 [
          "paginaInicial" => "115"
          "paginaFinal" => "117"
        ]
      ]
      "titulosAlternativos" => array:1 [
        "es" => array:1 [
          "titulo" => "El problema de la fragmentaci&#243;n de la medicina hospitalaria"
        ]
      ]
      "contieneTextoCompleto" => array:1 [
        "en" => true
      ]
      "contienePdf" => array:1 [
        "en" => true
      ]
      "autores" => array:1 [
        0 => array:2 [
          "autoresLista" => "Eduardo Montero Ruiz, Luis Manzano Espinosa"
          "autores" => array:2 [
            0 => array:2 [
              "nombre" => "Eduardo"
              "apellidos" => "Montero Ruiz"
            ]
            1 => array:2 [
              "nombre" => "Luis"
              "apellidos" => "Manzano Espinosa"
            ]
          ]
        ]
      ]
    ]
    "idiomaDefecto" => "en"
    "Traduccion" => array:1 [
      "es" => array:9 [
        "pii" => "S0025775318304287"
        "doi" => "10.1016/j.medcli.2018.07.001"
        "estado" => "S300"
        "subdocumento" => ""
        "abierto" => array:3 [
          "ES" => false
          "ES2" => false
          "LATM" => false
        ]
        "gratuito" => false
        "lecturas" => array:1 [
          "total" => 0
        ]
        "idiomaDefecto" => "es"
        "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0025775318304287?idApp=UINPBA00004N"
      ]
    ]
    "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2387020618305424?idApp=UINPBA00004N"
    "url" => "/23870206/0000015200000003/v1_201901290746/S2387020618305424/v1_201901290746/en/main.assets"
  ]
  "itemAnterior" => array:18 [
    "pii" => "S2387020618305461"
    "issn" => "23870206"
    "doi" => "10.1016/j.medcle.2018.03.037"
    "estado" => "S300"
    "fechaPublicacion" => "2019-02-01"
    "aid" => "4517"
    "copyright" => "Elsevier Espa&#241;a&#44; S&#46;L&#46;U&#46;"
    "documento" => "simple-article"
    "crossmark" => 1
    "subdocumento" => "crp"
    "cita" => "Med Clin. 2019;152:104-6"
    "abierto" => array:3 [
      "ES" => false
      "ES2" => false
      "LATM" => false
    ]
    "gratuito" => false
    "lecturas" => array:1 [
      "total" => 0
    ]
    "en" => array:13 [
      "idiomaDefecto" => true
      "cabecera" => "<span class="elsevierStyleTextfn">Clinical report</span>"
      "titulo" => "Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia&#58; Report of two cases"
      "tienePdf" => "en"
      "tieneTextoCompleto" => "en"
      "tieneResumen" => array:2 [
        0 => "en"
        1 => "es"
      ]
      "paginas" => array:1 [
        0 => array:2 [
          "paginaInicial" => "104"
          "paginaFinal" => "106"
        ]
      ]
      "titulosAlternativos" => array:1 [
        "es" => array:1 [
          "titulo" => "Hiperplasia neuroendocrina difusa pulmonar idiop&#225;tica&#58; estudio de dos casos"
        ]
      ]
      "contieneResumen" => array:2 [
        "en" => true
        "es" => true
      ]
      "contieneTextoCompleto" => array:1 [
        "en" => true
      ]
      "contienePdf" => array:1 [
        "en" => true
      ]
      "resumenGrafico" => array:2 [
        "original" => 0
        "multimedia" => array:7 [
          "identificador" => "fig0005"
          "etiqueta" => "Fig&#46; 1"
          "tipo" => "MULTIMEDIAFIGURA"
          "mostrarFloat" => true
          "mostrarDisplay" => false
          "figura" => array:1 [
            0 => array:4 [
              "imagen" => "gr1.jpeg"
              "Alto" => 1869
              "Ancho" => 2482
              "Tamanyo" => 439747
            ]
          ]
          "descripcion" => array:1 [
            "en" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">&#40;a&#41; Hematoxylin and eosin staining technique showing the mucosa of a terminal bronchiole with cilia in the epithelium and neuroendocrine cells &#40;asterisk&#41;&#46; &#40;b&#41; The same area showing positivity for CD 56 with immunohistochemistry that corresponds with a neuroendocrine cell hyperplasia &#40;asterisk&#44; objective magnification 60&#215;&#41;&#46; &#40;c&#41; Paratracheal lymph node of case number 1 stained with hematoxylin and eosin technique showing a little focus of neuroendocrine epithelial cells that corresponds with a metastatic typical carcinoid marked with an asterisk &#40;objective magnification 20&#215;&#41;&#46; Insert&#58; immunohistochemical technique using cytokeratins&#44; which highlights the metastatic neuroendocrine cells&#46; &#40;d&#41; CT of case number 2&#46; We can observe a subcentimeter nodule in the middle lobe &#40;arrow&#41; and a bilateral mosaic pattern&#46;</p>"
          ]
        ]
      ]
      "autores" => array:1 [
        0 => array:2 [
          "autoresLista" => "Eva Garc&#237;a-Font&#225;n, Montserrat Blanco Ramos, Jose Soro Garc&#237;a, Rommel Carrasco, Miguel &#193;ngel Ca&#241;izares, Ana Gonz&#225;lez Pi&#241;eiro"
          "autores" => array:6 [
            0 => array:2 [
              "nombre" => "Eva"
              "apellidos" => "Garc&#237;a-Font&#225;n"
            ]
            1 => array:2 [
              "nombre" => "Montserrat"
              "apellidos" => "Blanco Ramos"
            ]
            2 => array:2 [
              "nombre" => "Jose Soro"
              "apellidos" => "Garc&#237;a"
            ]
            3 => array:2 [
              "nombre" => "Rommel"
              "apellidos" => "Carrasco"
            ]
            4 => array:2 [
              "nombre" => "Miguel &#193;ngel"
              "apellidos" => "Ca&#241;izares"
            ]
            5 => array:2 [
              "nombre" => "Ana"
              "apellidos" => "Gonz&#225;lez Pi&#241;eiro"
            ]
          ]
        ]
      ]
    ]
    "idiomaDefecto" => "en"
    "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2387020618305461?idApp=UINPBA00004N"
    "url" => "/23870206/0000015200000003/v1_201901290746/S2387020618305461/v1_201901290746/en/main.assets"
  ]
  "en" => array:20 [
    "idiomaDefecto" => true
    "cabecera" => "<span class="elsevierStyleTextfn">Review</span>"
    "titulo" => "Reactivation of hepatitis B associated with immunosuppressants and chemotherapy&#46; Natural history&#44; risk factors and recommendations for prevention"
    "tieneTextoCompleto" => true
    "paginas" => array:1 [
      0 => array:2 [
        "paginaInicial" => "107"
        "paginaFinal" => "114"
      ]
    ]
    "autores" => array:1 [
      0 => array:4 [
        "autoresLista" => "Rosa Maria Morillas, David L&#243;pez Sisam&#243;n"
        "autores" => array:2 [
          0 => array:4 [
            "nombre" => "Rosa Maria"
            "apellidos" => "Morillas"
            "email" => array:1 [
              0 => "rmorillas&#46;germanstrias&#64;gencat&#46;cat"
            ]
            "referencia" => array:3 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">a</span>"
                "identificador" => "aff0005"
              ]
              1 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">b</span>"
                "identificador" => "aff0010"
              ]
              2 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">&#42;</span>"
                "identificador" => "cor0005"
              ]
            ]
          ]
          1 => array:3 [
            "nombre" => "David"
            "apellidos" => "L&#243;pez Sisam&#243;n"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">c</span>"
                "identificador" => "aff0015"
              ]
            ]
          ]
        ]
        "afiliaciones" => array:3 [
          0 => array:3 [
            "entidad" => "Secci&#243;n de Hepatolog&#237;a&#44; Servicio de Aparato Digestivo&#44; Hospital Universitario Germans Trias i Pujol&#44; Badalona&#44; Barcelona&#44; Spain"
            "etiqueta" => "a"
            "identificador" => "aff0005"
          ]
          1 => array:3 [
            "entidad" => "CIBERehd-Instituto de Salud Carlos III&#44; Spain"
            "etiqueta" => "b"
            "identificador" => "aff0010"
          ]
          2 => array:3 [
            "entidad" => "Unidad de Farmacia Oncol&#243;gica ICO-Badalona&#44; Hospital Universitario Germans Trias i Pujol&#44; Badalona&#44; Barcelona&#44; Spain"
            "etiqueta" => "c"
            "identificador" => "aff0015"
          ]
        ]
        "correspondencia" => array:1 [
          0 => array:3 [
            "identificador" => "cor0005"
            "etiqueta" => "&#8270;"
            "correspondencia" => "Corresponding author&#46;"
          ]
        ]
      ]
    ]
    "titulosAlternativos" => array:1 [
      "es" => array:1 [
        "titulo" => "Reactivaci&#243;n de la hepatitis B asociada a agentes inmunodepresores y a quimioterapia&#46; Historia natural&#44; factores de riesgo y recomendaciones para prevenirla"
      ]
    ]
    "resumenGrafico" => array:2 [
      "original" => 0
      "multimedia" => array:7 [
        "identificador" => "fig0010"
        "etiqueta" => "Fig&#46; 2"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr2.jpeg"
            "Alto" => 2108
            "Ancho" => 2500
            "Tamanyo" => 280567
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Steps to take when treating patients who will receive chemotherapy or immunosuppressive or biological treatments&#46; HBsA negative and anti-HBc positive patients with or without anti-HBs&#46; ALT&#58; alanine aminotransferase&#59; anti-HBc&#58; antibody against the hepatitis B core antigen&#59; anti-HBs&#58; antibody against surface antigen&#59; ETV&#58; entecavir&#59; HBsAg&#58; HBV surface antigen&#59; IS&#58; immunosuppressants&#59; QT&#58; chemotherapy&#59; RTX&#58; rituximab&#59; TAF&#58; tenofovir-alafenamide&#59; TDF&#58; tenofovir&#59; HBV&#58; hepatitis B virus&#46;</p>"
        ]
      ]
    ]
    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">The risk of reactivation of hepatitis B virus &#40;HBV&#41; has gained importance in recent years due to the increasingly frequent use of chemotherapy and potent immunosuppressants in patients with neoplastic processes&#44; and also increasingly in non-neoplastic processes in various medical specialties This expansion of new treatments for malignant and non-malignant disorders has increased the population of patients who have a probability of HBV reactivation&#46; A recently published study has estimated that the population at risk of HBV reactivation in Spain stands at 89&#44;053 new people per year&#46;<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">1</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Although the risk of reactivation of hepatitis B in patients treated with immunosuppressants has been known for years and that recommendations on this matter exist&#44; data from certain surveys indicate that studies into the HBV infection serological profile before initiating immunosuppressive treatment is not a universal practice&#46;<a class="elsevierStyleCrossRefs" href="#bib0320"><span class="elsevierStyleSup">2&#44;3</span></a> A survey conducted in 2012 showed that 26&#37; of Spanish specialists declared that they were not aware of existing recommendations or prevention and treatment guidelines regarding the reactivation of HBV in patients treated with risky therapies&#46;<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">3</span></a> Regarding HBV screening practices prior to initiating treatment with chemotherapy and&#47;or immunosuppressants&#44; 37&#37; of respondents stated that they never or only sometimes valued the presence of HBV risk factors&#44; while 34&#37; and 35&#37; stated that they never or only sometimes requested the determination of HBV surface antigen &#40;HBsAg&#41; or antibody against HBV core antigen &#40;anti-HBc&#41;&#44; respectively&#46;<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">3</span></a> This is a high figure&#44; considering the serious consequences that a reactivation of an HBV infection may entail&#46; Therefore&#44; exposing the importance of this issue and the recommendations to follow is essential&#46; Raising greater awareness of the possibility of HBV reactivation among health professionals prescribing these treatments&#44; the adoption of routine tests for HBV detection and linking the results of screening with antiviral prophylaxis to reduce the incidence of this deadly but preventable disorder is needed&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Population at risk</span><p id="par0015" class="elsevierStylePara elsevierViewall">Reactivations of this virus have been reported in three groups of patients&#58; patients receiving chemotherapy for solid<a class="elsevierStyleCrossRefs" href="#bib0330"><span class="elsevierStyleSup">4&#8211;6</span></a> and haematologic<a class="elsevierStyleCrossRefs" href="#bib0345"><span class="elsevierStyleSup">7&#44;8</span></a> tumours&#44; patients treated with immunomodulators<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">9</span></a> or biological treatments<a class="elsevierStyleCrossRefs" href="#bib0360"><span class="elsevierStyleSup">10&#44;11</span></a> and patients receiving immunosuppression for solid organ<a class="elsevierStyleCrossRefs" href="#bib0370"><span class="elsevierStyleSup">12&#44;13</span></a> or bone marrow<a class="elsevierStyleCrossRefs" href="#bib0380"><span class="elsevierStyleSup">14&#44;15</span></a> transplantation&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">The frequency of reactivation in HBsAg positive patients receiving chemotherapy for solid tumours has been estimated to be approximately 50&#37;&#44; but the rate exceeds 50&#37; in malignant haematological diseases and allogeneic transplant recipients of haemopoietic progenitors and in renal and cardiac transplant patients &#40;between 50 and 96&#37;&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">1</span></a> HBV reactivation in positive anti-HBc patients is lower&#44; between 6 and 10&#37; in patients treated with chemotherapy and 0&#46;9&#37; in solid organ transplant patients&#46;<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">1</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Inhibition of tumour necrosis factor-alpha &#40;TNF-alpha&#41; such as infliximab&#44; etanercept and adalimumab&#44; which are used to treat inflammatory bowel disease&#44; rheumatological diseases&#44; psoriasis and autoimmune diseases&#44; have been associated with reactivation of HBV&#46; A study of 257 cases exposed to anti-TNF agents with different indications concluded that the frequency of reactivation of HBV in HBsAg positive patients was 39&#37;&#44; seven times higher than HBV reactivation in HBsAg negative&#47;anti-HBc positive patients in that cohort&#46;<a class="elsevierStyleCrossRef" href="#bib0390"><span class="elsevierStyleSup">16</span></a></p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Reactivation of hepatitis B</span><p id="par0030" class="elsevierStylePara elsevierViewall">The reactivation of HBV infection is the appearance of viral replication in subjects with chronic infection by HBV and HBsAg positive&#44; or HBsAg negative and anti-HBc positive with or without antibody to surface antigen &#40;anti-HBs&#41;&#44; who could develop acute hepatitis and even severe liver failure&#46;<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">1</span></a> Based on the patient&#39;s baseline virological profile&#44; HBV reactivation can be classified into two categories&#58; reactivation of HBV in patients who are positive for HBsAg in serum&#44; with or without viraemia&#59; and seroreversion&#44; which is defined as the reappearance of HBsAg and the detection of HBV-DNA in serum in individuals that were initially negative for HBsAg and HBV-DNA&#46; Although HBV is considered to be completely cleared during acute hepatitis&#44; it has sometimes been detected in serum many years after the hepatitis was treated&#44; and in spite of the presence of anti-HBs in serum&#46;<a class="elsevierStyleCrossRef" href="#bib0400"><span class="elsevierStyleSup">18</span></a> It is believed that the persistence of traces of virus makes it possible to maintain the response of cytotoxic T lymphocytes and keep the virus under control&#44; usually for life&#46; Immunosuppressive treatment can break this balance&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Natural history of HBV reactivation</span><p id="par0035" class="elsevierStylePara elsevierViewall">HBV reactivation is characterised by a first asymptomatic phase that provides a window to start treatment&#46; In HBsAg positive patients&#44; this phase is characterised by a rapid increase in the level of HBV-DNA followed by an increase in transaminases&#59; and in HBsAg negative patients&#44; by the reappearance of HBsAg and then by an increase in HBV-DNA followed by an increase in transaminases&#46;<a class="elsevierStyleCrossRef" href="#bib0405"><span class="elsevierStyleSup">19</span></a> Although most patients usually remain asymptomatic&#44; a small number may experience constitutional symptoms&#44; discomfort in the upper right quadrant of the abdomen&#44; and jaundice&#46; Some patients may progress to liver failure characterised by an increase in prothrombin time and appearance of ascites and encephalopathy&#44; mortality also increases significantly in this group&#46;<a class="elsevierStyleCrossRef" href="#bib0400"><span class="elsevierStyleSup">18</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">If the reactivation of HBV is detected and antiviral treatment is initiated&#44; HBV-DNA and the level of transaminases decrease rapidly&#46; This can also occur spontaneously in some patients&#44; coinciding with the completion of the immunosuppressive treatment or chemotherapy cycle that produced the reactivation of HBV&#46; However&#44; spontaneous improvement after developing acute liver failure is rare and if the disease is not detected or treated&#44; the risk of death is high&#46;<a class="elsevierStyleCrossRef" href="#bib0395"><span class="elsevierStyleSup">17</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">These phases do not necessarily follow each other as they have just been listed&#59; some subjects may only develop a transient increase in viraemia with or without an increase in transaminases and no clinical consequences&#46;<a class="elsevierStyleCrossRef" href="#bib0395"><span class="elsevierStyleSup">17</span></a></p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Onset of HBV reactivation</span><p id="par0050" class="elsevierStylePara elsevierViewall">The onset time of a HBV reactivation can vary depending on the state of the host&#44; the underlying disease and the type of immunosuppressive treatment&#46; Although it may occur at the start or at any time during treatment&#44; it is more likely to occur at the end or even up to a year after the completion of the entire treatment cycle&#44; due to the phenomenon of immune reconstitution&#46;<a class="elsevierStyleCrossRefs" href="#bib0395"><span class="elsevierStyleSup">17&#8211;19</span></a></p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Risk factors</span><p id="par0055" class="elsevierStylePara elsevierViewall">Reactivation does not occur in all patients with HBsAg positive or anti-HBc positive&#46; A variety of factors related to the host&#44;<a class="elsevierStyleCrossRefs" href="#bib0410"><span class="elsevierStyleSup">20&#44;21</span></a> the virus<a class="elsevierStyleCrossRefs" href="#bib0420"><span class="elsevierStyleSup">22&#8211;27</span></a> and the type of treatment the patient received have been associated with a higher risk of HBV reactivation &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46; Regarding the type and degree of immunosuppression&#44; an increase of HBV reactivation in patients who have undergone more intensive immunosuppressive treatments has been reported&#44; such as the use of rituximab in monotherapy or in combination with glucocorticoids in a chemotherapy regimen&#46;<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">7</span></a> Conversely&#44; reactivation in bone marrow transplant patients is almost universal in HBsAg positive patients and has rates of approximately 50&#37; in patients with anti-HBc positive&#46;<a class="elsevierStyleCrossRefs" href="#bib0380"><span class="elsevierStyleSup">14&#44;19&#44;28&#8211;30</span></a></p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Reactivation risk according to the type of immunosuppressive treatment received</span><p id="par0060" class="elsevierStylePara elsevierViewall">Due to its immunosuppressive activity&#44; any chemotherapeutic or immunosuppressive agent could be capable of provoking reactivation&#46; The risk of reactivation can be divided into high risk &#40;if the reactivation rate of HBV is &#8805;10&#37;&#41;&#44; moderate risk &#40;if the risk of reactivation is between 1&#37; and 10&#37;&#41; and low risk &#40;if the risk of reactivation is &#60;1&#37;&#41;&#44; depending on the type of immunosuppressive therapy stratified by the presence or absence of HBsAg and presence of anti-HBc positive with or without anti-HBs&#46;<a class="elsevierStyleCrossRef" href="#bib0400"><span class="elsevierStyleSup">18</span></a></p><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Patients with HBsAg positive</span><p id="par0065" class="elsevierStylePara elsevierViewall">Among the patients with HBsAg positive&#44; we stratified the immunosuppressive treatments according to the risk of reactivation &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;<span class="elsevierStyleItalic">&#46;</span></p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0070" class="elsevierStylePara elsevierViewall">Treatments with a high risk of reactivation&#58;<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">1&#46;</span><p id="par0075" class="elsevierStylePara elsevierViewall">Therapies that deplete B cells&#44; such as rituximab&#44; ofatumumab&#44; natalizumab&#44; obinutuzumab&#44; blinatumomab&#44; alemtuzumab&#44; ibritumomab&#44; and ocrelizumab&#44; significantly increase the risk of reactivation in HBsAg positive and HBsAg negative patients and anti-HBc positive patients&#46;<a class="elsevierStyleCrossRef" href="#bib0465"><span class="elsevierStyleSup">31</span></a> This class of drug can cause a severe reactivation of HBV&#44; in addition to an increased risk of liver failure and mortality associated with the reactivation of HBV if it is not diagnosed and treated quickly&#46;</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">2&#46;</span><p id="par0080" class="elsevierStylePara elsevierViewall">Anthracycline derivatives&#44; such as doxorubicin&#44; epirubicin&#44; daunorubicin and idarubicin&#46;<a class="elsevierStyleCrossRef" href="#bib0460"><span class="elsevierStyleSup">30</span></a></p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">3&#46;</span><p id="par0085" class="elsevierStylePara elsevierViewall">Chronic treatment with prednisone&#44; either at medium doses &#40;10&#8211;20<span class="elsevierStyleHsp" style=""></span>mg&#47;day orally&#41; or high doses &#40;&#62;20<span class="elsevierStyleHsp" style=""></span>mg&#47;day orally&#41; for more than four weeks increases the likelihood of HBV reactivation&#46;<a class="elsevierStyleCrossRef" href="#bib0470"><span class="elsevierStyleSup">32</span></a></p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">4&#46;</span><p id="par0090" class="elsevierStylePara elsevierViewall">TNF-alpha inhibitors&#44; such as infliximab&#44; adalimumab&#44; certolizumab and golimumab&#44; used in the treatment of inflammatory bowel disease and rheumatologic conditions such as rheumatoid arthritis&#44; also have a high risk of HBV reactivation &#40;range&#44; 12&#8211;39&#37;&#41; in HBsAg positive patients&#46;<a class="elsevierStyleCrossRefs" href="#bib0390"><span class="elsevierStyleSup">16&#44;33</span></a></p></li></ul></p><p id="par0095" class="elsevierStylePara elsevierViewall">Treatments with a moderate risk of reactivation&#58;<ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">1&#46;</span><p id="par0100" class="elsevierStylePara elsevierViewall">Systemic chemotherapy other than the situation described above&#46;</p></li><li class="elsevierStyleListItem" id="lsti0030"><span class="elsevierStyleLabel">2&#46;</span><p id="par0105" class="elsevierStylePara elsevierViewall">Less potent inhibitors of TNF-alpha such as etanercept&#46;<a class="elsevierStyleCrossRef" href="#bib0475"><span class="elsevierStyleSup">33</span></a></p></li><li class="elsevierStyleListItem" id="lsti0035"><span class="elsevierStyleLabel">3&#46;</span><p id="par0110" class="elsevierStylePara elsevierViewall">Inhibitors of cytokine or integrin such as abatacept&#44; ustekinumab&#44; mogamulizumab&#44; natalizumab&#44; vedolizumab and tocilizumab&#44; commonly used in inflammatory bowel disease and in rheumatological and dermatological diseases&#46;<a class="elsevierStyleCrossRef" href="#bib0465"><span class="elsevierStyleSup">31</span></a></p></li><li class="elsevierStyleListItem" id="lsti0040"><span class="elsevierStyleLabel">4&#46;</span><p id="par0115" class="elsevierStylePara elsevierViewall">Tyrosine kinase inhibitors such as imatinib&#44; nilotinib&#44; dasatinib&#44; bosutinib&#44; ponatinib&#44; ibrutinib and idelalisib&#44; which are commonly used in the treatment of chronic myeloid leukaemia and gastrointestinal stromal tumours&#44; among others&#46;<a class="elsevierStyleCrossRef" href="#bib0480"><span class="elsevierStyleSup">34</span></a></p></li><li class="elsevierStyleListItem" id="lsti0045"><span class="elsevierStyleLabel">5&#46;</span><p id="par0120" class="elsevierStylePara elsevierViewall">Proteasome inhibitors such as bortezomib&#44; carfilzomib or ixazomib&#44; which are commonly used for the treatment of multiple myeloma&#46;<a class="elsevierStyleCrossRef" href="#bib0485"><span class="elsevierStyleSup">35</span></a></p></li><li class="elsevierStyleListItem" id="lsti0050"><span class="elsevierStyleLabel">6&#46;</span><p id="par0125" class="elsevierStylePara elsevierViewall">Histone deacetylase &#40;HDI&#41; inhibitors such as romidepsin&#44; vorinostat or panobinostat&#44; which are used in the treatment of T-cell lymphomas&#46;<a class="elsevierStyleCrossRef" href="#bib0490"><span class="elsevierStyleSup">36</span></a></p></li><li class="elsevierStyleListItem" id="lsti0055"><span class="elsevierStyleLabel">7&#46;</span><p id="par0130" class="elsevierStylePara elsevierViewall">Low-dose corticosteroid therapy such as prednisone at 10<span class="elsevierStyleHsp" style=""></span>mg&#47;day orally for four weeks&#44; can increase the risk of reactivation up to 10&#37; in HBsAg positive individuals&#46;<a class="elsevierStyleCrossRef" href="#bib0470"><span class="elsevierStyleSup">32</span></a></p></li><li class="elsevierStyleListItem" id="lsti0060"><span class="elsevierStyleLabel">8&#46;</span><p id="par0135" class="elsevierStylePara elsevierViewall">There is evidence that immunophilin inhibitors such as cyclosporine and tacrolimus may also increase the risk of reactivation of HBV&#46;<a class="elsevierStyleCrossRef" href="#bib0400"><span class="elsevierStyleSup">18</span></a></p></li></ul></p><p id="par0140" class="elsevierStylePara elsevierViewall">Treatments with a low risk of reactivation&#58;<ul class="elsevierStyleList" id="lis0015"><li class="elsevierStyleListItem" id="lsti0065"><span class="elsevierStyleLabel">1&#46;</span><p id="par0145" class="elsevierStylePara elsevierViewall">Methotrexate&#44; azathioprine or therapies based on 6-mercaptopurine&#46;<a class="elsevierStyleCrossRef" href="#bib0470"><span class="elsevierStyleSup">32</span></a></p></li><li class="elsevierStyleListItem" id="lsti0070"><span class="elsevierStyleLabel">2&#46;</span><p id="par0150" class="elsevierStylePara elsevierViewall">Injections or intraarticular glucocorticoid treatment with a low dose of prednisone of lower than 10<span class="elsevierStyleHsp" style=""></span>mg&#47;day orally&#44; have a minimal risk of reactivation&#46;<a class="elsevierStyleCrossRef" href="#bib0470"><span class="elsevierStyleSup">32</span></a></p></li></ul></p><p id="par0155" class="elsevierStylePara elsevierViewall">Immune checkpoint inhibitors and anti-PD-L1 &#40;e&#46;g&#46; Nivolumab which strengthens T-lymphocytes responses including antitumour response by blocking PD-1&#44; preventing its binding to PD ligands and PD-L2-L1&#41; and anti-CTLA4 &#40;e&#46;g&#46; ipilimumab&#41;&#44; are increasingly used in the treatment of various cancers&#46;<a class="elsevierStyleCrossRef" href="#bib0495"><span class="elsevierStyleSup">37</span></a> When these biological products began to be used&#44; health professionals had doubts about whether they could predispose patients to the reactivation of HBV but no case has been reported&#46; In addition&#44; its mechanism of action is based on activating the immune system&#39;s response&#44; so a reactivation of HBV is unlikely&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">HBsA negative and anti-HBc positive patients</span><p id="par0160" class="elsevierStylePara elsevierViewall">We also stratified the immunosuppressive treatments according to the risk of reactivation among HBsA negative and anti-HBc positive patients &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46; It should be noted that the increased risk of reactivation in these patients lies in B-cell-depletion therapies such as rituximab&#44; ofatumumab&#44; natalizumab&#44; obinutuzumab&#44; blinatumomab&#44; alemtuzumab&#44; ibritumomab and ocrelizumab&#46;<a class="elsevierStyleCrossRef" href="#bib0400"><span class="elsevierStyleSup">18</span></a> Recent studies have described an increased risk of reactivation in HBsAg negative and anti-HBc positive patients exposed to transarterial chemoembolisation in the context of hepatocellular carcinoma of 9&#46;3&#8211;11&#37;<a class="elsevierStyleCrossRefs" href="#bib0500"><span class="elsevierStyleSup">38&#44;39</span></a>&#59; these figures could suggest the appropriateness of prophylaxis in future guides&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia></span></span></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">HBV reactivation mechanisms</span><p id="par0165" class="elsevierStylePara elsevierViewall">The mechanism to which reactivation is attributed to is associated with&#44; firstly&#44; an increase in the replication of HBV and the expression of its antigens in hepatocytes during immunosuppression&#44; and secondly&#44; a destruction of infected hepatocytes mediated by T-lymphocytes during immune recovery&#46; The intensity of viral replication and subsequent liver damage appear to be directly associated with the potency of cytotoxic or immunosuppressive treatment&#46;</p><p id="par0170" class="elsevierStylePara elsevierViewall">When HBV infects a susceptible person&#44; the virus penetrates the hepatocytes and its DNA is integrated into the hepatocyte DNA&#44; becoming a covalent&#44; closed&#44; circular DNA &#40;cccDNA&#41;&#46; The cccDNA is transcribed in the nucleus of the hepatocyte&#44; forming RNA that is subsequently translated into the cytoplasm&#44; forming new viral particles&#46; The cccDNA serves as a template for the formation of new viruses that will infect new hepatocytes and will remain in the nucleus of the hepatocyte until it is destroyed&#46; The cccDNA is quite stable in the infected cells and can persist in a latent state as a reservoir for the reactivation of HBV&#46;<a class="elsevierStyleCrossRefs" href="#bib0315"><span class="elsevierStyleSup">1&#44;40</span></a> Different studies have shown that cccDNA can persist in patients&#8217; liver for decades after a supposed recovery from HBV infection&#46; This persistence occurs despite the anti-HBV immune response being activated&#46; Clinical studies have also shown that nucleoside analogue therapy can potently suppress HBV-DNA&#44; but that cccDNA reduction after one year of treatment is modest&#46;<a class="elsevierStyleCrossRef" href="#bib0400"><span class="elsevierStyleSup">18</span></a> Similar results have been reported for the extraordinary stability of cccDNA in animal models&#46;<a class="elsevierStyleCrossRef" href="#bib0400"><span class="elsevierStyleSup">18</span></a> All these observations support the concept that HBV infection is quite difficult to eradicate and its persistence&#44; although low&#44; explains the potential for HBV reactivation in any individual that has been infected with the virus&#46;</p><p id="par0175" class="elsevierStylePara elsevierViewall">During viral replication&#44; several antigens are expressed inside the hepatocytes&#59; some are expressed in the cell membrane &#40;HBcAg&#41; and others are released as circulating particles into the bloodstream &#40;HBsAg and HBeAg&#41;&#46; The host&#39;s immune system recognises these antigens as foreign and triggers an immune response&#46; On one hand&#44; a Th1 response that activates CD8 cells and the formation of TNF-alpha is activated&#44; causing the destruction of infected hepatocytes&#46; On the other hand&#44; a Th-2 response is activated and B lymphocytes produce antibodies against different antigens that neutralise circulating viruses&#44; preventing infections from new hepatocytes&#46; If the immune response is effective&#44; all infected hepatocytes are destroyed and resolution of infection is obtained&#46;<a class="elsevierStyleCrossRef" href="#bib0400"><span class="elsevierStyleSup">18</span></a> Innate immunity probably also plays a role in the control of HBV infection&#46;<a class="elsevierStyleCrossRef" href="#bib0400"><span class="elsevierStyleSup">18</span></a> Although these immune mechanisms are sufficient to control HBV replication&#44; they are probably not powerful enough to eradicate all infected cell niches harbouring latent HBV cccDNA or to eliminate low-level HBV replication that escapes the action of specific immune cells&#46; These cells are&#44; therefore&#44; a reservoir of persistent HBV and a source of HBV reactivation when the mechanisms of immune control are disturbed or suppressed&#46;</p><p id="par0180" class="elsevierStylePara elsevierViewall">For example&#44; rituximab&#44; a monoclonal antibody&#44; works against the CD20 antigen and depletes the B lymphocyte population and antibody levels&#59; it thus decreases immune response and favours the replication of HBV&#46; It has a selective action on B lymphocytes&#44; which is prolonged&#44; and can last as long as a year&#46; Although the control of HBV infection is mainly due to HBV-specific cytotoxic T lymphocytes&#44; B lymphocytes are necessary for the presentation of antigens&#44; so their depletion can allow HBV to escape control of the cytotoxic T lymphocytes&#46; Glucocorticoids act on the HBV genome&#44; facilitating replication and increasing HBV-DNA levels&#44; and these two effects may explain the higher rate of reactivation with regimens containing glucocorticoids and rituximab&#46;<a class="elsevierStyleCrossRefs" href="#bib0515"><span class="elsevierStyleSup">41&#44;42</span></a></p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Studying the serological profile of HBV before starting immunosuppressive treatments</span><p id="par0185" class="elsevierStylePara elsevierViewall">To try to avoid the unfavourable clinical events resulting from HBV reactivation&#44; the European guide<a class="elsevierStyleCrossRef" href="#bib0395"><span class="elsevierStyleSup">17</span></a> and latest consensus documents<a class="elsevierStyleCrossRefs" href="#bib0525"><span class="elsevierStyleSup">43&#8211;45</span></a> currently recommend carrying out serological screening of HBV on all patients who will undergo chemotherapy or immunosuppressive or biological treatments&#46; At least HBsAg&#44; anti-HBc and anti-HBs should be screened for&#46; HBV-DNA will be detected in HBsAg positive or HBsA negative patients and anti-HBc positive patients &#40;<a class="elsevierStyleCrossRefs" href="#fig0005">Figs&#46; 1 and 2</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Patients with negative serology</span><p id="par0190" class="elsevierStylePara elsevierViewall">Patients with negative serology &#40;HBsAg&#44; anti-HBc and anti-HBs&#41; are susceptible to infection and should be vaccinated as soon as possible &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46; The quantitative anti-HBs response should be documented several weeks after the last dose&#46; Non-responders should receive another three-dose cycle when possible&#46;</p><p id="par0195" class="elsevierStylePara elsevierViewall">Immunocompromised patients may require higher doses of the vaccine or a vaccine booster to obtain anti-HBs response&#46;<a class="elsevierStyleCrossRefs" href="#bib0395"><span class="elsevierStyleSup">17&#44;46</span></a></p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Patients with HBsAg positive</span><p id="par0200" class="elsevierStylePara elsevierViewall">All candidates for chemotherapy or HBsAg positive immunosuppressive therapy should be referred to a specialist for an assessment and diagnosis of their HBV infection stage&#46; All these patients should start a potent nucleoside or nucleotide analogue &#40;AN&#41; treatment or prophylaxis<a class="elsevierStyleCrossRef" href="#bib0395"><span class="elsevierStyleSup">17</span></a> &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46;</p><p id="par0205" class="elsevierStylePara elsevierViewall">If the patient is HBsAg positive&#44; HBV-DNA should be requested&#46; If HBV-DNA is greater than 2000<span class="elsevierStyleHsp" style=""></span>UI&#47;ml&#44; they should follow conventional antiviral treatment with an AN which should be initiated before starting chemotherapy or immunosuppressive treatment and maintained until accepted objectives are obtained &#40;seroconversion of HBeAg in HBeAg positive patients and negativization of HBsAg in HBeAg negative patients&#41;&#44; otherwise the risk of reactivation after treatment interruption is high&#46;<a class="elsevierStyleCrossRef" href="#bib0395"><span class="elsevierStyleSup">17</span></a> If HBV-DNA is less than 2000<span class="elsevierStyleHsp" style=""></span>IU&#47;ml or undetectable&#44; current recommendations suggest prophylactic treatment with AN&#46;<a class="elsevierStyleCrossRef" href="#bib0395"><span class="elsevierStyleSup">17</span></a></p><p id="par0210" class="elsevierStylePara elsevierViewall">Prophylactic administration of lamivudine has been shown to reduce the risk of HBV reactivation and associated morbidity and mortality&#46;<a class="elsevierStyleCrossRefs" href="#bib0410"><span class="elsevierStyleSup">20&#44;47&#44;48</span></a> However&#44; there is a residual risk of HBV reactivation in approximately 10&#37; of patients with chronic HBV infection with low viraemia &#40;HBV-DNA<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>2000<span class="elsevierStyleHsp" style=""></span>UI&#47;ml&#41; treated with prophylactic lamivudine&#44; and a higher rate in those with higher viraemia levels&#46;<a class="elsevierStyleCrossRef" href="#bib0395"><span class="elsevierStyleSup">17</span></a> In addition&#44; episodes of HBV exacerbation have been reported due to the development of resistance&#44; as it is a drug with a low genetic barrier to the appearance of resistance &#40;20&#37; and 30&#37; after one and two years of treatment&#44; respectively&#41;&#46; There are studies that suggest that stronger and less resistant nucleoside &#40;entecavir&#41; or nucleotides &#40;tenofovir and tenofovir-alafenamide&#41; analogues can be used successfully in these patients&#46;<a class="elsevierStyleCrossRefs" href="#bib0555"><span class="elsevierStyleSup">49&#8211;51</span></a> In addition&#44; a recent meta-analysis has shown that entecavir and tenofovir are the most effective treatments for the prevention of HBV reactivation&#46;<a class="elsevierStyleCrossRef" href="#bib0570"><span class="elsevierStyleSup">52</span></a> Thus&#44; the prophylactic antiviral treatment of choice recommended in guidelines is entecavir&#44; tenofovir or tenofovir-alafenamide&#46;<a class="elsevierStyleCrossRef" href="#bib0395"><span class="elsevierStyleSup">17</span></a></p><p id="par0215" class="elsevierStylePara elsevierViewall">The antiviral regimen should be initiated preferably two or three weeks before immunosuppressive treatment or chemotherapy and never later than the first dose&#44; maintained during treatment and continued for a minimum of 12 months &#40;18 months for regimens based on rituximab or anti-CD20 antibodies&#41; after the suspension of immunosuppressive treatment and discontinued only if the underlying disease is in remission&#46;<a class="elsevierStyleCrossRef" href="#bib0395"><span class="elsevierStyleSup">17</span></a></p><p id="par0220" class="elsevierStylePara elsevierViewall">Monitoring patients&#8217; liver function tests and HBV-DNA every three to six months during prophylactic treatment and for at least 12 months after cessation is recommended since a large proportion of HBV reactivations appear after discontinuation of antiviral treatment&#46;<a class="elsevierStyleCrossRef" href="#bib0395"><span class="elsevierStyleSup">17</span></a></p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">HBsA negative and anti-HBc positive patients with or without anti-HBs</span><p id="par0225" class="elsevierStylePara elsevierViewall">The risk of reactivation of HBV in this group of patients varies widely according to the virological profile&#44; the underlying disease and the type and duration of the immunosuppressant regimen used&#46; These patients should be tested for HBV-DNA before immunosuppression &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46; If HBV-DNA levels are detectable&#44; the same prophylactic regimen is recommended for HBsAg positive patients&#46;<a class="elsevierStyleCrossRef" href="#bib0395"><span class="elsevierStyleSup">17</span></a></p><p id="par0230" class="elsevierStylePara elsevierViewall">If serum DNA levels are not detectable&#58;<ul class="elsevierStyleList" id="lis0020"><li class="elsevierStyleListItem" id="lsti0075"><span class="elsevierStyleLabel">&#8226;</span><p id="par0235" class="elsevierStylePara elsevierViewall">In the high-risk group &#40;&#62;10&#37;&#41;&#44; including patients who need to be treated with anti-B lymphocytes or T monoclonal antibodies or who will have a bone marrow or haematopoietic progenitors transplant&#44; recommendation suggest starting antiviral prophylaxis&#44; which should be continued for at least 18 months after suspension of immunosuppression&#46; Monitoring should continue for at least 12 months after withdrawal of prophylaxis with AN&#46; With lamivudine&#44; episodes of reactivation related to the appearance of resistance have been reported&#44;<a class="elsevierStyleCrossRefs" href="#bib0575"><span class="elsevierStyleSup">53&#8211;55</span></a> such that prophylaxis with entecavir&#44; tenofovir or tenofovir-afenfenamide is indicated for these patients &#8211; who will also undergo an estimated treatment duration of longer than 12 months&#46;<a class="elsevierStyleCrossRefs" href="#bib0395"><span class="elsevierStyleSup">17&#44;56&#44;57</span></a></p></li><li class="elsevierStyleListItem" id="lsti0080"><span class="elsevierStyleLabel">&#8226;</span><p id="par0240" class="elsevierStylePara elsevierViewall">Conducting periodic checks of HBsAg and&#47;or HBV-DNA and transaminases every one to three months during and after immunosuppression is recommended in the moderate &#40;&#60;10&#37;&#41; or low &#40;&#60;1&#37;<span class="elsevierStyleMonospace">&#41;</span>HBV reactivation risk groups&#44;<a class="elsevierStyleCrossRefs" href="#bib0600"><span class="elsevierStyleSup">58&#44;59</span></a> initiating antiviral treatment as soon as possible if there is an elevation of viraemia or a reappearance of HBsAg&#44; regardless of transaminase levels&#46; In individualised clinical cases&#44; characterised by long-term immunosuppression&#44; poor compliance with control tests or if periodic measurements of HBsAg and viral DNA cannot be guaranteed&#44; initiating prophylaxis is recommended&#46;<a class="elsevierStyleCrossRef" href="#bib0395"><span class="elsevierStyleSup">17</span></a> Universal prophylaxis against an unknown risk of HBV reactivation with new biological products is also recommended&#46;</p></li></ul></p></span></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Tools to prevent reactivation</span><p id="par0245" class="elsevierStylePara elsevierViewall">Several tools have been reported that can assist in the prevention of HBV reactivation&#44; from educational intervention with training projects to the application of alerts in electronic prescription systems&#46; In a centre in England&#44; a guide based on international recommendations for HBV screening and initiation of antiviral prophylaxis in patients receiving immunosuppression or chemotherapy was delivered to all doctors&#44; in addition to 30<span class="elsevierStyleHsp" style=""></span>min training sessions&#46; After the educational intervention&#44; a significant increase in the detection of HBV in patients&#44; before receiving rituximab&#44; was seen&#58; from 19&#37; to 78&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0610"><span class="elsevierStyleSup">60</span></a></p><p id="par0250" class="elsevierStylePara elsevierViewall">New technologies&#44; information technologies and assisted electronic prescription systems are an opportunity to implement HBV screening and prevent reactivation&#46; The implementation of an alert system in computers or linked to electronic assisted prescription programs have been shown to increase the detection rate of HBsAg by up to 85&#46;5&#37;<a class="elsevierStyleCrossRef" href="#bib0615"><span class="elsevierStyleSup">61</span></a> or even more&#46;<a class="elsevierStyleCrossRef" href="#bib0620"><span class="elsevierStyleSup">62</span></a> In a study conducted in a centre in Spain&#44; an alert was implemented into the electronic prescribing system to remind medical professionals of the possible risk of viral reactivation when prescribing biological therapies and requesting a serological profile of &#40;HBsAg&#44; anti-HBc and anti-HBs&#41; those patients who had not carried out these tests&#46;<a class="elsevierStyleCrossRef" href="#bib0620"><span class="elsevierStyleSup">62</span></a> The warning system increased the detection rate from less than 50&#37; to 94&#37; for HBsAg and from less than 30&#37; to 85&#37; for anti-HBc in patients who were prescribed a biological treatment&#46;<a class="elsevierStyleCrossRef" href="#bib0620"><span class="elsevierStyleSup">62</span></a></p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Conclusions</span><p id="par0255" class="elsevierStylePara elsevierViewall">Performing serological screening of HBV in all patients who are going to receive chemotherapy or immunosuppressive or biological treatments is essential&#59; the results should then be linked with antiviral prophylaxis to reduce the incidence of HBV reactivation&#44; a potentially fatal but preventable disorder&#46;</p><p id="par0260" class="elsevierStylePara elsevierViewall">There are studies that show the feasibility of implementing tools that can help in preventing HBV reactivation and which can increase the HBV detection rate&#46; Their use facilitates the identification of patients with a high risk of reactivation and allows doctors to prescribe prophylactic measures in accordance with current guidelines&#46;</p></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Conflict of interest</span><p id="par0265" class="elsevierStylePara elsevierViewall">R&#46;M&#46; Morillas&#58; speaker fees from Gilead&#44; AbbVie&#44; Merck and Intercept&#46; Advisory Board for Merck&#44; Gilead&#44; AbbVie and Intercept&#46; Dr L&#243;pez declares no conflict of interest&#46;</p></span></span>"
    "textoCompletoSecciones" => array:1 [
      "secciones" => array:16 [
        0 => array:3 [
          "identificador" => "xres1142225"
          "titulo" => "Abstract"
          "secciones" => array:1 [
            0 => array:1 [
              "identificador" => "abst0005"
            ]
          ]
        ]
        1 => array:2 [
          "identificador" => "xpalclavsec1072949"
          "titulo" => "Keywords"
        ]
        2 => array:3 [
          "identificador" => "xres1142224"
          "titulo" => "Resumen"
          "secciones" => array:1 [
            0 => array:1 [
              "identificador" => "abst0010"
            ]
          ]
        ]
        3 => array:2 [
          "identificador" => "xpalclavsec1072950"
          "titulo" => "Palabras clave"
        ]
        4 => array:2 [
          "identificador" => "sec0005"
          "titulo" => "Introduction"
        ]
        5 => array:2 [
          "identificador" => "sec0010"
          "titulo" => "Population at risk"
        ]
        6 => array:2 [
          "identificador" => "sec0015"
          "titulo" => "Reactivation of hepatitis B"
        ]
        7 => array:2 [
          "identificador" => "sec0020"
          "titulo" => "Natural history of HBV reactivation"
        ]
        8 => array:2 [
          "identificador" => "sec0025"
          "titulo" => "Onset of HBV reactivation"
        ]
        9 => array:3 [
          "identificador" => "sec0030"
          "titulo" => "Risk factors"
          "secciones" => array:1 [
            0 => array:3 [
              "identificador" => "sec0035"
              "titulo" => "Reactivation risk according to the type of immunosuppressive treatment received"
              "secciones" => array:2 [
                0 => array:2 [
                  "identificador" => "sec0040"
                  "titulo" => "Patients with HBsAg positive"
                ]
                1 => array:2 [
                  "identificador" => "sec0045"
                  "titulo" => "HBsA negative and anti-HBc positive patients"
                ]
              ]
            ]
          ]
        ]
        10 => array:2 [
          "identificador" => "sec0050"
          "titulo" => "HBV reactivation mechanisms"
        ]
        11 => array:3 [
          "identificador" => "sec0055"
          "titulo" => "Studying the serological profile of HBV before starting immunosuppressive treatments"
          "secciones" => array:3 [
            0 => array:2 [
              "identificador" => "sec0060"
              "titulo" => "Patients with negative serology"
            ]
            1 => array:2 [
              "identificador" => "sec0065"
              "titulo" => "Patients with HBsAg positive"
            ]
            2 => array:2 [
              "identificador" => "sec0070"
              "titulo" => "HBsA negative and anti-HBc positive patients with or without anti-HBs"
            ]
          ]
        ]
        12 => array:2 [
          "identificador" => "sec0075"
          "titulo" => "Tools to prevent reactivation"
        ]
        13 => array:2 [
          "identificador" => "sec0080"
          "titulo" => "Conclusions"
        ]
        14 => array:2 [
          "identificador" => "sec0085"
          "titulo" => "Conflict of interest"
        ]
        15 => array:1 [
          "titulo" => "References"
        ]
      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2018-07-26"
    "fechaAceptado" => "2018-08-31"
    "PalabrasClave" => array:2 [
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec1072949"
          "palabras" => array:4 [
            0 => "Hepatitis B reactivation"
            1 => "Immunosuppressive and biological modifier therapies"
            2 => "Management strategies"
            3 => "Prophylaxis"
          ]
        ]
      ]
      "es" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec1072950"
          "palabras" => array:4 [
            0 => "Reactivaci&#243;n de la hepatitis B"
            1 => "Inmunodepresores y tratamientos biol&#243;gicos"
            2 => "Estrategias de manejo"
            3 => "Profilaxis"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:2 [
      "en" => array:2 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Although the risk of reactivation of hepatitis B in patients treated with immunosuppressants has been known for years and&#44; if there are recommendations&#44; data from some surveys indicate that the study of the serological profile of HBV infection before starting immunosuppressive treatment is not universal practice&#46; Taking into account the serious consequences that the reactivation of the infection with HBV may entail&#44; we believe that it is necessary to disclose the importance of this problem among the health professionals who prescribe these treatments as well as the recommendations to be followed&#46; In fact&#44; in recent years&#44; the use of chemotherapy and potent immunosuppressants in patients with neoplastic processes and in non-neoplastic pathology of various specialties has been increasingly frequent&#44; increasing the population of patients at risk of reactivation of HBV&#46;</p></span>"
      ]
      "es" => array:2 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">A pesar de que el riesgo de reactivaci&#243;n de la hepatitis B en los pacientes tratados con inmunosupresores es conocido desde hace a&#241;os y de la existencia de recomendaciones&#44; los datos procedentes de algunas encuestas indican que el estudio del perfil serol&#243;gico de la infecci&#243;n por el VHB antes de iniciar el tratamiento inmunosupresor no es una pr&#225;ctica universal&#46; Teniendo en cuenta las consecuencias graves que puede comportar la reactivaci&#243;n de la infecci&#243;n por el VHB&#44; creemos que es necesario divulgar la importancia de este problema entre los profesionales sanitarios que prescriben estos tratamientos as&#237; como de las recomendaciones a seguir&#46; De hecho&#44; en los &#250;ltimos a&#241;os&#44; es cada vez m&#225;s frecuente el empleo de quimioterapia e inmunosupresores potentes en pacientes con procesos neopl&#225;sicos y en patolog&#237;a no neopl&#225;sica de diversas especialidades&#44; aumentando la poblaci&#243;n de pacientes con riesgo de reactivaci&#243;n del VHB&#46;</p></span>"
      ]
    ]
    "NotaPie" => array:1 [
      0 => array:2 [
        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Morillas RM&#44; L&#243;pez Sisam&#243;n D&#46; Reactivaci&#243;n de la hepatitis B asociada a agentes inmunodepresores y a quimioterapia&#46; Historia natural&#44; factores de riesgo y recomendaciones para prevenirla&#46; Med Clin &#40;Barc&#41;&#46; 2019&#59;152&#58;107&#8211;114&#46;</p>"
      ]
    ]
    "multimedia" => array:5 [
      0 => array:7 [
        "identificador" => "fig0005"
        "etiqueta" => "Fig&#46; 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
            "Alto" => 1648
            "Ancho" => 2167
            "Tamanyo" => 180971
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Steps to take when treating patients who will receive chemotherapy or immunosuppressive or biological treatments&#46; HBsAg positive patients&#46; Anti-HBc&#58; antibody against the hepatitis B core antigen&#59; anti-HBs&#58; antibody against surface antigen&#59; ETV&#58; entecavir&#59; HBsAg&#58; HBV surface antigen&#59; IS&#58; immunosuppressants&#59; QT&#58; chemotherapy&#59; RTX&#58; rituximab&#59; TAF&#58; tenofovir-alafenamide&#59; TDF&#58; tenofovir&#59; HBV&#58; hepatitis B virus&#46;</p>"
        ]
      ]
      1 => array:7 [
        "identificador" => "fig0010"
        "etiqueta" => "Fig&#46; 2"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr2.jpeg"
            "Alto" => 2108
            "Ancho" => 2500
            "Tamanyo" => 280567
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Steps to take when treating patients who will receive chemotherapy or immunosuppressive or biological treatments&#46; HBsA negative and anti-HBc positive patients with or without anti-HBs&#46; ALT&#58; alanine aminotransferase&#59; anti-HBc&#58; antibody against the hepatitis B core antigen&#59; anti-HBs&#58; antibody against surface antigen&#59; ETV&#58; entecavir&#59; HBsAg&#58; HBV surface antigen&#59; IS&#58; immunosuppressants&#59; QT&#58; chemotherapy&#59; RTX&#58; rituximab&#59; TAF&#58; tenofovir-alafenamide&#59; TDF&#58; tenofovir&#59; HBV&#58; hepatitis B virus&#46;</p>"
        ]
      ]
      2 => array:8 [
        "identificador" => "tbl0005"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at1"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">ALT&#58; alanine aminotransferase&#59; HBeAg&#58; HBV e-antigen&#59; HBV&#58; hepatitis B virus&#46;</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  " rowspan="5" align="left" valign="top">Related to the host</td><td class="td" title="table-entry  " align="left" valign="top">Sex male&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Young patients&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">ALT levels before initiation of treatment&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Presence of cirrhosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Diagnosis of lymphoma&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " rowspan="3" align="left" valign="top">Related to the virus</td><td class="td" title="table-entry  " align="left" valign="top">Baseline viral load &#62;10<span class="elsevierStyleSup">4</span><span class="elsevierStyleHsp" style=""></span>UI&#47;ml&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">HBeAg positive before initiation of treatment&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">HBV genotype not A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Related to the treatment&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">More intensive immunosuppressive therapy &#40;e&#46;g&#46; rituximab or patients who have received bone marrow transplant&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab1949181.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Risk factors for HBV reactivation&#46;</p>"
        ]
      ]
      3 => array:8 [
        "identificador" => "tbl0010"
        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at2"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">HBsAg&#58; HBV surface antigen&#59; TNF-&#945;&#58; tumour necrosis factor alpha&#59; HBV&#58; hepatitis B virus&#46;</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  " rowspan="20" align="left" valign="top">Treatments with high risk of reactivation &#40;reactivation rate &#8805;10&#37;&#41;</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">B cell depletion therapy</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Natalizumab&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Rituximab&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Ofatumumab&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Obinutuzumab&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Blinatumomab&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Alemtuzumab&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Ibritumomab&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Ocrelizumab&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Anthracycline derivatives</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Doxorubicin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Epirubicin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Daunorubicin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Idarubicin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Dosage of 10&#8211;20</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">mg&#47;day of prednisone or &#62;20</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">mg&#47;day for more than four weeks</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Potent inhibitors of TNF-</span>&#945;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Infliximab&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Adalimumab&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Certolizumab&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Golimumab&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " rowspan="35" align="left" valign="top">Treatments with moderate risk of reactivation &#40;reactivation rate 1&#8211;10&#37;&#41;</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">Systemic chemotherapy</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Less potent inhibitors of TNF-</span>&#945;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Etanercept&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Inhibitors of cytokine or integrin</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Abatacept&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Ustekinumab&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Mogamulizumab&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Vedolizumab&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Tocilizumab&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Immunomodulators</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Thalidomide&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Lenalidomide&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Pomalidomide&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Tyrosine kinase inhibitors</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Imatinib&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Nilotinib&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Dasatinib&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Bosutinib&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Ponatinib&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Ibrutinib&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Idelalisib&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Proteosome inhibitors</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Bortezomib&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Carfilzomib&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Ixazomib&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Histone deacetylase inhibitors</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Romidepsin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Vorinostat&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Panobinostat&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Dosage of 10</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">mg&#47;day of prednisone&#47;day for more than four weeks</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Immunosuppressants</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Ciclosporin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Tacrolimus&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Everolimus&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Temsirolimus&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " rowspan="4" align="left" valign="top">Treatments with a low risk of reactivation &#40;reactivation rate &#60;1&#37;&#41;</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">Methotrexate</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Azathioprine</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">6-mercaptopurine</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Dosage of &#60;10</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">mg&#47;day of prednisone</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab1949182.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Risk of reactivation associated with immunosuppressive treatment in HBsAg positive patients&#46;</p>"
        ]
      ]
      4 => array:8 [
        "identificador" => "tbl0015"
        "etiqueta" => "Table 3"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at3"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Anti-HBc&#58; antibody against the hepatitis B core antigen&#59; HBsAg&#58; HBV surface antigen&#59; HBV&#58; hepatitis B virus&#46;</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  " rowspan="9" align="left" valign="top">Treatments with high risk of reactivation &#40;reactivation rate &#8805;10&#37;&#41;</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">B cell depletion therapies</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Natalizumab&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Rituximab&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Ofatumumab&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Obinutuzumab&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Blinatumomab&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Alemtuzumab&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Ibritumomab&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Ocrelizumab&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " rowspan="45" align="left" valign="top">Treatments with moderate risk of reactivation &#40;reactivation rate 1&#8211;10&#37;&#41;</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">Treatment with high doses of corticosteroids</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Anthracycline derivatives</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Doxorubicin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Epirubicin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Daunorubicin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Idarubicin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Potent inhibitors of tumour necrosis factor alpha</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Infliximab&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Adalimumab&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Certolizumab&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Golimumab&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Systemic chemotherapy</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Inhibitors of cytokine or integrin</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Abatacept&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Ustekinumab&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Mogamulizumab&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Vedolizumab&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Tocilizumab&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Immunomodulators</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Thalidomide&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Lenalidomide&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Pomalidomide&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Tyrosine kinase inhibitors</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Imatinib&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Nilotinib&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Dasatinib&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Bosutinib&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Ponatinib&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Ibrutinib&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Idelalisib&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Proteosome inhibitors</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Bortezomib&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Carfilzomib&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Ixazomib&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Histone deacetylase inhibitors</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Romidepsin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Vorinostat&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Panobinostat&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Chronic treatment with corticosteroids</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Dosage of 10<span class="elsevierStyleHsp" style=""></span>mg&#47;day of prednisone for more than four weeks&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Immunosuppressants</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Ciclosporin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Tacrolimus&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Everolimus&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Temsirolimus&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " rowspan="4" align="left" valign="top">Treatments with a low risk of reactivation &#40;reactivation rate &#60;1&#37;&#41;</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">Methotrexate</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Azathioprine</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">6-mercaptopurine</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Chronic treatment with glucocorticoids at doses of &#60;10</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">mg&#47;day</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab1949183.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Risk of reactivation associated with immunosuppressive treatment in HBsAg negative and anti-HBc positive patients&#46;</p>"
        ]
      ]
    ]
    "bibliografia" => array:2 [
      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0015"
          "bibliografiaReferencia" => array:62 [
            0 => array:3 [
              "identificador" => "bib0315"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Hepatitis B&#58; reactivation and current clinical impact"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "B&#46; Alvarez Su&#225;rez"
                            1 => "J&#46; de-la-Revilla-Negro"
                            2 => "B&#46; Ruiz-Antor&#225;n"
                            3 => "J&#46;L&#46; Calleja Panero"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Rev Esp Enferm Dig"
                        "fecha" => "2010"
                        "volumen" => "102"
                        "paginaInicial" => "542"
                        "paginaFinal" => "552"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib0320"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Screening for hepatitis B in chemotherapy patients&#58; survey of current oncology patients"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "T&#46;T&#46; Tran"
                            1 => "M&#46;O&#46; Rakoski"
                            2 => "P&#46; Martin"
                            3 => "F&#46; Poordad"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/j.1365-2036.2009.04158.x"
                      "Revista" => array:6 [
                        "tituloSerie" => "Aliment Pharmacol Ther"
                        "fecha" => "2010"
                        "volumen" => "31"
                        "paginaInicial" => "240"
                        "paginaFinal" => "246"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19814747"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib0325"
              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Pr&#225;cticas de cribado del virus de la hepatitis B previo a las terapias de riesgo de reactivaci&#243;n v&#237;rica en diferentes especialidades m&#233;dicas&#46; Proyecto HEBRA"
                      "autores" => array:1 [
                        0 => array:3 [
                          "colaboracion" => "en representaci&#243;n del grupo HEBRA"
                          "etal" => false
                          "autores" => array:4 [
                            0 => "M&#46; Garc&#237;a-Bengoechea"
                            1 => "C&#46; Hern&#225;ndez-L&#243;pez"
                            2 => "J&#46; Crespo"
                            3 => "F&#46; Gea"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Med Clin &#40;Barc&#41;"
                        "fecha" => "2012"
                        "volumen" => "139"
                        "paginaInicial" => "498"
                        "paginaFinal" => "501"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            3 => array:3 [
              "identificador" => "bib0330"
              "etiqueta" => "4"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Hepatitis B reactivation in patients with hepatocellular carcinoma undergoing systematic chemotherapy"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "W&#46; Yeo"
                            1 => "K&#46;C&#46; Lam"
                            2 => "B&#46; Zee"
                            3 => "P&#46;S&#46; Chan"
                            4 => "F&#46;K&#46; Mo"
                            5 => "W&#46;M&#46; Ho"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1093/annonc/mdh430"
                      "Revista" => array:6 [
                        "tituloSerie" => "Ann Oncol"
                        "fecha" => "2004"
                        "volumen" => "15"
                        "paginaInicial" => "1661"
                        "paginaFinal" => "1666"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15520068"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            4 => array:3 [
              "identificador" => "bib0335"
              "etiqueta" => "5"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Prevention of hepatitis B virus reactivation in patients with nasopharyngeal carcinoma with lamivudine"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "W&#46; Yeo"
                            1 => "E&#46;P&#46; Hui"
                            2 => "A&#46;T&#46; Chan"
                            3 => "W&#46;M&#46; Ho"
                            4 => "K&#46;C&#46; Lam"
                            5 => "P&#46;K&#46; Chan"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Clin Oncol"
                        "fecha" => "2005"
                        "volumen" => "28"
                        "paginaInicial" => "379"
                        "paginaFinal" => "384"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16062080"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            5 => array:3 [
              "identificador" => "bib0340"
              "etiqueta" => "6"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Hepatitis B virus reactivation in breast cancer patients undergoing cytotoxic chemotherapy and the role of preemptive lamivudine administration"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "M&#46;S&#46; Dai"
                            1 => "P&#46;F&#46; Wu"
                            2 => "R&#46;Y&#46; Shyu"
                            3 => "J&#46;J&#46; Lu"
                            4 => "T&#46;Y&#46; Chao"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/j.1478-3231.2004.0964.x"
                      "Revista" => array:6 [
                        "tituloSerie" => "Liver Int"
                        "fecha" => "2004"
                        "volumen" => "24"
                        "paginaInicial" => "540"
                        "paginaFinal" => "546"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15566502"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            6 => array:3 [
              "identificador" => "bib0345"
              "etiqueta" => "7"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Steroid-free chemotherapy decreases risk of hepatitis B virus &#40;HBV&#41; reactivation in HBV-carriers with lymphoma"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "A&#46; Cheng"
                            1 => "C&#46; Hsiung"
                            2 => "I&#46; Su"
                            3 => "P&#46; Chen"
                            4 => "M&#46; Chang"
                            5 => "C&#46; Tsao"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Hepatology"
                        "fecha" => "2003"
                        "volumen" => "37"
                        "paginaInicial" => "1320"
                        "paginaFinal" => "1328"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            7 => array:3 [
              "identificador" => "bib0350"
              "etiqueta" => "8"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Efficacy of lamivudine to prevent hepatitis reactivation in hepatitis B virus-infected patients treated for non-Hodgkin lymphoma"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "M&#46; Persico"
                            1 => "F&#46; de Marino"
                            2 => "G&#46;D&#46; Russo"
                            3 => "A&#46; Morante"
                            4 => "B&#46; Rotoli"
                            5 => "R&#46; Torella"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:7 [
                        "tituloSerie" => "Blood"
                        "fecha" => "2002"
                        "volumen" => "15"
                        "paginaInicial" => "724"
                        "paginaFinal" => "725"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/14414776"
                            "web" => "Medline"
                          ]
                        ]
                        "itemHostRev" => array:3 [
                          "pii" => "S0165032714006867"
                          "estado" => "S300"
                          "issn" => "01650327"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            8 => array:3 [
              "identificador" => "bib0355"
              "etiqueta" => "9"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Hepatitis B reactivation in a chronic hepatitis B surface antigen carrier with rheumatoid arthritis treated with infliximab and low dose methotrexate"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "P&#46; Ostuni"
                            1 => "C&#46; Botsios"
                            2 => "L&#46; Punzi"
                            3 => "P&#46; Sfriso"
                            4 => "S&#46; Todesco"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Ann Rheum Dis"
                        "fecha" => "2003"
                        "volumen" => "62"
                        "paginaInicial" => "686"
                        "paginaFinal" => "687"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12810441"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            9 => array:3 [
              "identificador" => "bib0360"
              "etiqueta" => "10"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Use of tumor necrosis factor &#945; inhibitors in patients with chronic hepatitis B infection"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "M&#46;B&#46; Carroll"
                            1 => "M&#46;I&#46; Bond"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.semarthrit.2007.10.011"
                      "Revista" => array:6 [
                        "tituloSerie" => "Semin Arthritis Rheum"
                        "fecha" => "2007"
                        "volumen" => "38"
                        "paginaInicial" => "208"
                        "paginaFinal" => "217"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18221983"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            10 => array:3 [
              "identificador" => "bib0365"
              "etiqueta" => "11"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Chronic hepatitis B reactivation following infliximab therapy in Crohn&#39;s disease patients&#58; need for primary prophylaxis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "M&#46; Esteve"
                            1 => "C&#46; Saro"
                            2 => "F&#46; Gonzalez-Huix"
                            3 => "F&#46; Suarez"
                            4 => "M&#46; Forn&#233;"
                            5 => "J&#46;M&#46; Viver"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1136/gut.2004.040675"
                      "Revista" => array:7 [
                        "tituloSerie" => "Gut"
                        "fecha" => "2004"
                        "volumen" => "53"
                        "paginaInicial" => "1363"
                        "paginaFinal" => "1365"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15306601"
                            "web" => "Medline"
                          ]
                        ]
                        "itemHostRev" => array:3 [
                          "pii" => "S0924933818301433"
                          "estado" => "S300"
                          "issn" => "09249338"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            11 => array:3 [
              "identificador" => "bib0370"
              "etiqueta" => "12"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Redevelopment of hepatitis B surface antigen after renal transplantation"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "P&#46; Marcellin"
                            1 => "E&#46; Giostra"
                            2 => "M&#46; Martino-Peignoux"
                            3 => "M&#46;A&#46; Loriot"
                            4 => "M&#46;L&#46; Jaengle"
                            5 => "P&#46; Wolf"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Gastroenterology"
                        "fecha" => "1991"
                        "volumen" => "100"
                        "paginaInicial" => "1432"
                        "paginaFinal" => "1434"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/2013388"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            12 => array:3 [
              "identificador" => "bib0375"
              "etiqueta" => "13"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Transmission of hepatitis B by transplantation of livers from donors positive for antibody to hepatitis B core antigen&#46; The National Institute of Diabetes and Digestive and Kidney Diseases Liver Transplantation Database"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "R&#46;C&#46; Dickson"
                            1 => "J&#46;E&#46; Everhart"
                            2 => "J&#46;R&#46; Lake"
                            3 => "Y&#46; Wei"
                            4 => "E&#46;C&#46; Seaberg"
                            5 => "R&#46;H&#46; Wiesner"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Gastroenterology"
                        "fecha" => "1997"
                        "volumen" => "113"
                        "paginaInicial" => "1668"
                        "paginaFinal" => "1674"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9352871"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            13 => array:3 [
              "identificador" => "bib0380"
              "etiqueta" => "14"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Progressive disappearance of anti-hepatitis surface antigen antibody and reverse seroconversion after allogeneic hematopoietic stem cell transplantation in patients with previous hepatitis B virus infection"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "M&#46; Onozawa"
                            1 => "S&#46; Hashino"
                            2 => "K&#46; Izumiyama"
                            3 => "K&#46; Kahata"
                            4 => "M&#46; Chuma"
                            5 => "A&#46; Mori"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Transplantation"
                        "fecha" => "2005"
                        "volumen" => "79"
                        "paginaInicial" => "616"
                        "paginaFinal" => "619"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15753855"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            14 => array:3 [
              "identificador" => "bib0385"
              "etiqueta" => "15"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Reactivation of HBV following allogeneic bone marrow transplantation&#58; new outlook &#40;the hepatitis B virus and the bone marrow transplant&#41;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "S&#46; Otero L&#243;pez-Cubero"
                            1 => "I&#46; Espigado"
                            2 => "J&#46; Aguilar Reina"
                            3 => "R&#46; Parody"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Rev Esp Enferm Dig"
                        "fecha" => "1999"
                        "volumen" => "91"
                        "paginaInicial" => "229"
                        "paginaFinal" => "230"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10231356"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            15 => array:3 [
              "identificador" => "bib0390"
              "etiqueta" => "16"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Hepatitis B virus &#40;HBV&#41; reactivation in patients receiving tumor necrosis factor &#40;TNF&#41;-targeted therapy&#58; analysis of 257 cases"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "R&#46; P&#233;rez-Alvarez"
                            1 => "C&#46; D&#237;az-Lagares"
                            2 => "F&#46; Garc&#237;a-Hern&#225;ndez"
                            3 => "L&#46; Lopez-Roses"
                            4 => "P&#46; Brito-Zer&#243;n"
                            5 => "M&#46; P&#233;rez-de-Lis"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1097/MD.0b013e3182380a76"
                      "Revista" => array:6 [
                        "tituloSerie" => "Medicine"
                        "fecha" => "2011"
                        "volumen" => "90"
                        "paginaInicial" => "359"
                        "paginaFinal" => "371"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22033451"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            16 => array:3 [
              "identificador" => "bib0395"
              "etiqueta" => "17"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "EASL 2017 Clinical Guidelines on the management of hepatitis B virus infection"
                      "autores" => array:1 [
                        0 => array:2 [
                          "colaboracion" => "European Association for the Study of the Liver"
                          "etal" => false
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jhep.2017.03.021"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Hepatol"
                        "fecha" => "2017"
                        "volumen" => "67"
                        "paginaInicial" => "370"
                        "paginaFinal" => "398"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28427875"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            17 => array:3 [
              "identificador" => "bib0400"
              "etiqueta" => "18"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Hepatitis B reactivation associated with immune suppressive and biological modifier therapies&#58; current concepts&#44; management strategies and future directions"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "R&#46; Loomba"
                            1 => "T&#46;J&#46; Liang"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1053/j.gastro.2017.02.009"
                      "Revista" => array:6 [
                        "tituloSerie" => "Gastroenterology"
                        "fecha" => "2017"
                        "volumen" => "152"
                        "paginaInicial" => "1297"
                        "paginaFinal" => "1309"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28219691"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            18 => array:3 [
              "identificador" => "bib0405"
              "etiqueta" => "19"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Reactivation of hepatitis B"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "J&#46; Hoofnagle"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/hep.22945"
                      "Revista" => array:7 [
                        "tituloSerie" => "Hepatology"
                        "fecha" => "2009"
                        "volumen" => "49"
                        "numero" => "Suppl&#46;"
                        "paginaInicial" => "S156"
                        "paginaFinal" => "S165"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19399803"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            19 => array:3 [
              "identificador" => "bib0410"
              "etiqueta" => "20"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Systematic review&#58; the effect of preventive lamivudine on hepatitis B reactivation during chemotherapy"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "R&#46; Loomba"
                            1 => "A&#46; Rowley"
                            2 => "R&#46; Wesley"
                            3 => "T&#46;J&#46; Liang"
                            4 => "J&#46;H&#46; Hoofnagle"
                            5 => "F&#46; Pucino"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Ann Intern Med"
                        "fecha" => "2008"
                        "volumen" => "148"
                        "paginaInicial" => "519"
                        "paginaFinal" => "528"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18378948"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            20 => array:3 [
              "identificador" => "bib0415"
              "etiqueta" => "21"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Frequency of hepatitis B virus reactivation in cancer patients undergoing cytotoxic chemotherapy&#58; a prospective study of 626 patients with identification of risk factors"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "W&#46; Yeo"
                            1 => "P&#46;K&#46; Chan"
                            2 => "S&#46; Zhong"
                            3 => "W&#46;M&#46; Ho"
                            4 => "J&#46;L&#46; Steinberg"
                            5 => "J&#46;S&#46; Tam"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:7 [
                        "tituloSerie" => "J Med Virol"
                        "fecha" => "2000"
                        "volumen" => "62"
                        "paginaInicial" => "299"
                        "paginaFinal" => "307"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11055239"
                            "web" => "Medline"
                          ]
                        ]
                        "itemHostRev" => array:3 [
                          "pii" => "S0895435616001438"
                          "estado" => "S300"
                          "issn" => "08954356"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            21 => array:3 [
              "identificador" => "bib0420"
              "etiqueta" => "22"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Lamivudine for the prevention of hepatitis B virus reactivation in hepatitis B s-antigen seropositive cancer patients undergoing cytotoxic chemotherapy"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "W&#46; Yeo"
                            1 => "P&#46;K&#46; Chan"
                            2 => "W&#46;M&#46; Ho"
                            3 => "B&#46; Zee"
                            4 => "K&#46;C&#46; Lam"
                            5 => "K&#46;I&#46; Lei"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1200/JCO.2004.05.161"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Clin Oncol"
                        "fecha" => "2004"
                        "volumen" => "22"
                        "paginaInicial" => "927"
                        "paginaFinal" => "934"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/14990649"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            22 => array:3 [
              "identificador" => "bib0425"
              "etiqueta" => "23"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Hepatitis B virus reactivation in breast cancer patients receiving cytotoxic chemotherapy&#58; a prospective study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "W&#46; Yeo"
                            1 => "P&#46;K&#46; Chan"
                            2 => "P&#46; Hui"
                            3 => "W&#46;M&#46; Ho"
                            4 => "K&#46;C&#46; Lam"
                            5 => "W&#46;H&#46; Kwan"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/jmv.10430"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Med Virol"
                        "fecha" => "2003"
                        "volumen" => "70"
                        "paginaInicial" => "553"
                        "paginaFinal" => "561"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12794717"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            23 => array:3 [
              "identificador" => "bib0430"
              "etiqueta" => "24"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Diagnosis&#44; prevention and management of hepatitis B virus reactivation during anticancer therapy"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "W&#46; Yeo"
                            1 => "P&#46;J&#46; Johnson"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/hep.21051"
                      "Revista" => array:6 [
                        "tituloSerie" => "Hepatology"
                        "fecha" => "2006"
                        "volumen" => "43"
                        "paginaInicial" => "209"
                        "paginaFinal" => "220"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16440366"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            24 => array:3 [
              "identificador" => "bib0435"
              "etiqueta" => "25"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Rates and risk factors for hepatitis B reactivation in a cohort of persons in the inactive phase of chronic hepatitis B-Alaska&#44; 2001&#8211;2010"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "R&#46;A&#46; Tohme"
                            1 => "L&#46; Bulkow"
                            2 => "C&#46;E&#46; Homan"
                            3 => "S&#46; Neus"
                            4 => "B&#46;J&#46; McMahon"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jcv.2013.08.012"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Clin Virol"
                        "fecha" => "2013"
                        "volumen" => "58"
                        "paginaInicial" => "396"
                        "paginaFinal" => "400"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24001884"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            25 => array:3 [
              "identificador" => "bib0440"
              "etiqueta" => "26"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Clinical and virological factors associated with hepatitis B virus reactivation in HBsAg-negative and anti-HBc antibodies positive patients undergoing chemotherapy and&#47;or autologous stem cell transplantation for cancer"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "P&#46; Borentain"
                            1 => "P&#46; Colson"
                            2 => "D&#46; Coso"
                            3 => "E&#46; Bories"
                            4 => "A&#46; Charbonnier"
                            5 => "A&#46;M&#46; Stoppa"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/j.1365-2893.2009.01239.x"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Viral Hepat"
                        "fecha" => "2010"
                        "volumen" => "17"
                        "paginaInicial" => "807"
                        "paginaFinal" => "815"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20002298"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            26 => array:3 [
              "identificador" => "bib0445"
              "etiqueta" => "27"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Clinical characteristics and molecular analysis of hepatitis B virus reactivation in hepatitis B surface antigen-negative patients during or after immunosuppressive or cytotoxic chemotherapy"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "K&#46; Hayashi"
                            1 => "M&#46; Ishigami"
                            2 => "Y&#46; Ishizu"
                            3 => "T&#46; Kuzuya"
                            4 => "T&#46; Honda"
                            5 => "Y&#46; Tachi"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s00535-016-1187-z"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Gastroenterol"
                        "fecha" => "2016"
                        "volumen" => "51"
                        "paginaInicial" => "1081"
                        "paginaFinal" => "1089"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26943169"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            27 => array:3 [
              "identificador" => "bib0450"
              "etiqueta" => "28"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Reverse seroconversion of hepatitis B alter allogeneic bone marrow transplantation&#58; a retrospective study of 37 patients with pretransplant antiHBs and antiHBc"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "N&#46; Dhedin"
                            1 => "C&#46; Douvin"
                            2 => "M&#46; Kuentz"
                            3 => "M&#46;F&#46; Saint Marc"
                            4 => "O&#46; Remen"
                            5 => "C&#46; Rieux"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Transplantation"
                        "fecha" => "1998"
                        "volumen" => "66"
                        "paginaInicial" => "616"
                        "paginaFinal" => "619"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9753342"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            28 => array:3 [
              "identificador" => "bib0455"
              "etiqueta" => "29"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Hepatitis B reactivation with clinical flare in allogeneic stem cell transplant with chronic graft-versus-host disease"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "P&#46; Seth"
                            1 => "A&#46;A&#46; Alrajhi"
                            2 => "I&#46; Kagevi"
                            3 => "M&#46;A&#46; Chaudhary"
                            4 => "E&#46; Colcol"
                            5 => "E&#46; Sahovic"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/sj.bmt.1703614"
                      "Revista" => array:6 [
                        "tituloSerie" => "Bone Marrow Transplant"
                        "fecha" => "2002"
                        "volumen" => "30"
                        "paginaInicial" => "189"
                        "paginaFinal" => "194"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12189538"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            29 => array:3 [
              "identificador" => "bib0460"
              "etiqueta" => "30"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Reactivation of resolved hepatitis B virus infection after allogeneic haematopoietic stem cell transplantation"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "A&#46; Kn&#246;ll"
                            1 => "S&#46; Boehm"
                            2 => "J&#46; Hahn"
                            3 => "E&#46; Holler"
                            4 => "W&#46; Jilg"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/sj.bmt.1704457"
                      "Revista" => array:6 [
                        "tituloSerie" => "Bone Marrow Transplant"
                        "fecha" => "2004"
                        "volumen" => "33"
                        "paginaInicial" => "925"
                        "paginaFinal" => "929"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15004543"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            30 => array:3 [
              "identificador" => "bib0465"
              "etiqueta" => "31"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Reactivation of hepatitis B virus infection after cytotoxic chemotherapy or immunosuppressive therapy"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "M&#46;L&#46; Manzano-Alonso"
                            1 => "G&#46; Castellano-Tortajada"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.3748/wjg.v17.i12. 1531"
                      "Revista" => array:6 [
                        "tituloSerie" => "World J Gastroenterol"
                        "fecha" => "2011"
                        "volumen" => "17"
                        "paginaInicial" => "1531"
                        "paginaFinal" => "1537"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21472116"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            31 => array:3 [
              "identificador" => "bib0470"
              "etiqueta" => "32"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "American Gastroenterological Association Institute technical review on prevention and treatment of hepatitis B virus reactivation during immunosuppressive drug therapy"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "R&#46;P&#46; Perrillo"
                            1 => "R&#46; Gish"
                            2 => "Y&#46;T&#46; Falck-Ytter"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1053/j.gastro.2014.10.038"
                      "Revista" => array:6 [
                        "tituloSerie" => "Gastroenterology"
                        "fecha" => "2015"
                        "volumen" => "148"
                        "paginaInicial" => "221"
                        "paginaFinal" => "244"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25447852"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            32 => array:3 [
              "identificador" => "bib0475"
              "etiqueta" => "33"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Reactivation of hepatitis B virus in rheumatoid arthritis patients treated with biological disease-modifying antirheumatic drugs"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "J&#46; Nakamura"
                            1 => "T&#46; Nagashima"
                            2 => "K&#46; Nagatani"
                            3 => "T&#46; Yoshio"
                            4 => "M&#46; Iwamoto"
                            5 => "S&#46; Minota"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/1756-185X.12359"
                      "Revista" => array:6 [
                        "tituloSerie" => "Int J Rheum Dis"
                        "fecha" => "2016"
                        "volumen" => "19"
                        "paginaInicial" => "470"
                        "paginaFinal" => "475"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24698305"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            33 => array:3 [
              "identificador" => "bib0480"
              "etiqueta" => "34"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Risk of hepatitis B virus reactivation in patients treated with ibrutinib"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "S&#46;P&#46; Hammond"
                            1 => "K&#46; Chen"
                            2 => "A&#46; Pandit"
                            3 => "M&#46;S&#46; Davids"
                            4 => "N&#46;C&#46; Issa"
                            5 => "F&#46;M&#46; Marty"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1182/blood-2018-01-826495"
                      "Revista" => array:6 [
                        "tituloSerie" => "Blood"
                        "fecha" => "2018"
                        "volumen" => "131"
                        "paginaInicial" => "1987"
                        "paginaFinal" => "1989"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29490923"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            34 => array:3 [
              "identificador" => "bib0485"
              "etiqueta" => "35"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Incidence and risk factors of hepatitis B virus reactivation in patients with multiple myeloma in an era with novel agents&#58; a nationwide retrospective study in Japan"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "Y&#46; Tsukune"
                            1 => "M&#46; Sasaki"
                            2 => "T&#46; Odajima"
                            3 => "K&#46; Sunami"
                            4 => "T&#46; Takei"
                            5 => "Y&#46; Moriuchi"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/s41408-017-0002-2"
                      "Revista" => array:5 [
                        "tituloSerie" => "Blood Cancer J"
                        "fecha" => "2017"
                        "volumen" => "7"
                        "paginaInicial" => "631"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29167420"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            35 => array:3 [
              "identificador" => "bib0490"
              "etiqueta" => "36"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Reactivation of DNA viruses in association with histone deacetylase inhibitor therapy&#58; a case series report"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "D&#46; Ritchie"
                            1 => "R&#46;L&#46; Piekarz"
                            2 => "P&#46; Blombery"
                            3 => "L&#46;J&#46; Karai"
                            4 => "S&#46; Pittaluga"
                            5 => "E&#46;S&#46; Jaffe"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.3324/haematol.2009.008607"
                      "Revista" => array:6 [
                        "tituloSerie" => "Haematologica"
                        "fecha" => "2009"
                        "volumen" => "94"
                        "paginaInicial" => "1618"
                        "paginaFinal" => "1622"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19608677"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            36 => array:3 [
              "identificador" => "bib0495"
              "etiqueta" => "37"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Immune checkpoint blockade in hepatocellular carcinoma&#58; 2017 update"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "M&#46; Kudo"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1159/000449342"
                      "Revista" => array:6 [
                        "tituloSerie" => "Liver Cancer"
                        "fecha" => "2016"
                        "volumen" => "6"
                        "paginaInicial" => "1"
                        "paginaFinal" => "12"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27995082"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            37 => array:3 [
              "identificador" => "bib0500"
              "etiqueta" => "38"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Reactivation of hepatitis B virus in HBsAg-negative patients with hepatocellular carcinoma"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "J&#46;W&#46; Jang"
                            1 => "Y&#46;W&#46; Kim"
                            2 => "S&#46;W&#46; Lee"
                            3 => "J&#46;H&#46; Kwon"
                            4 => "S&#46;W&#46; Nam"
                            5 => "S&#46;H&#46; Bae"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1371/journal.pone.0122041"
                      "Revista" => array:5 [
                        "tituloSerie" => "PLOS ONE"
                        "fecha" => "2015"
                        "volumen" => "10"
                        "paginaInicial" => "e0122041"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25894607"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            38 => array:3 [
              "identificador" => "bib0505"
              "etiqueta" => "39"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Transarterial chemo-lipiodolization can reactivate hepatitis B virus replication in patients with hepatocellular carcinoma"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "J&#46;W&#46; Jang"
                            1 => "J&#46;Y&#46; Choi"
                            2 => "S&#46;H&#46; Bae"
                            3 => "C&#46;W&#46; Kim"
                            4 => "S&#46;K&#46; Yoon"
                            5 => "S&#46;H&#46; Cho"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jhep.2004.05.014"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Hepatol"
                        "fecha" => "2004"
                        "volumen" => "41"
                        "paginaInicial" => "427"
                        "paginaFinal" => "435"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15336446"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            39 => array:3 [
              "identificador" => "bib0510"
              "etiqueta" => "40"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Hepatitis B virus infection &#8211; natural history and clinical consequences"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "D&#46; Ganem"
                            1 => "A&#46;M&#46; Prince"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1056/NEJMra031087"
                      "Revista" => array:6 [
                        "tituloSerie" => "N Engl J Med"
                        "fecha" => "2004"
                        "volumen" => "350"
                        "paginaInicial" => "1118"
                        "paginaFinal" => "1129"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15014185"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            40 => array:3 [
              "identificador" => "bib0515"
              "etiqueta" => "41"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Kinetics and risk of de novo hepatitis B infection in HBsAg-negative patients undergoing cytotoxic chemotherapy"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "C&#46;K&#46; Hui"
                            1 => "W&#46;W&#46; Cheung"
                            2 => "H&#46; Zhang"
                            3 => "W&#46; Au"
                            4 => "Y&#46; Yueng"
                            5 => "A&#46; Leung"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1053/j.gastro.2006.04.015"
                      "Revista" => array:6 [
                        "tituloSerie" => "Gastroenterology"
                        "fecha" => "2006"
                        "volumen" => "131"
                        "paginaInicial" => "59"
                        "paginaFinal" => "68"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16831590"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            41 => array:3 [
              "identificador" => "bib0520"
              "etiqueta" => "42"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Hepatitis B virus reactivation in lymphoma patients with prior resolved hepatitis B undergoing anticancer therapy with or without rituximab"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "W&#46; Yeo"
                            1 => "T&#46;C&#46; Chan"
                            2 => "N&#46;W&#46; Leung"
                            3 => "W&#46;Y&#46; Lam"
                            4 => "F&#46;K&#46; Mo"
                            5 => "M&#46;T&#46; Chu"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1200/JCO.2008.18.0182"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Clin Oncol"
                        "fecha" => "2009"
                        "volumen" => "27"
                        "paginaInicial" => "605"
                        "paginaFinal" => "611"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19075267"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            42 => array:3 [
              "identificador" => "bib0525"
              "etiqueta" => "43"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Documento de Consenso de la AEEH sobre el tratamiento de la infecci&#243;n por el virus de la hepatitis B &#40;2012&#41;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "M&#46; Buti"
                            1 => "J&#46; Garc&#237;a-Samaniego"
                            2 => "M&#46; Prieto"
                            3 => "M&#46; Rodr&#237;guez"
                            4 => "J&#46;M&#46; S&#225;nchez-Tapias"
                            5 => "E&#46; Su&#225;rez"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.gastrohep.2012.04.006"
                      "Revista" => array:6 [
                        "tituloSerie" => "Gastroenterol Hepatol"
                        "fecha" => "2012"
                        "volumen" => "35"
                        "paginaInicial" => "512"
                        "paginaFinal" => "528"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22749508"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            43 => array:3 [
              "identificador" => "bib0530"
              "etiqueta" => "44"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "AASLD guidelines for treatment of chronic hepatitis B"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "N&#46;A&#46; Terrault"
                            1 => "N&#46;H&#46; Bzowej"
                            2 => "K&#46;M&#46; Chang"
                            3 => "J&#46;P&#46; Hwang"
                            4 => "M&#46;M&#46; Jonas"
                            5 => "M&#46;H&#46; Murad"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/hep.28156"
                      "Revista" => array:6 [
                        "tituloSerie" => "Hepatology"
                        "fecha" => "2016"
                        "volumen" => "63"
                        "paginaInicial" => "261"
                        "paginaFinal" => "283"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26566064"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            44 => array:3 [
              "identificador" => "bib0535"
              "etiqueta" => "45"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Asian-Pacific consensus statement on the management of chronic hepatitis B&#58; a 2015 update"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "S&#46;K&#46; Sarin"
                            1 => "M&#46; Kumar"
                            2 => "G&#46;K&#46; Lau"
                            3 => "Z&#46; Abbas"
                            4 => "H&#46;L&#46;Y&#46; Chan"
                            5 => "C&#46;J&#46; Chen"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s12072-016-9707-8"
                      "Revista" => array:6 [
                        "tituloSerie" => "Hepatol Int"
                        "fecha" => "2016"
                        "volumen" => "10"
                        "paginaInicial" => "1"
                        "paginaFinal" => "98"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26856325"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            45 => array:3 [
              "identificador" => "bib0540"
              "etiqueta" => "46"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Optimal management of hepatitis B virus infection &#8211; EASL Special Conference"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "P&#46; Lampertico"
                            1 => "M&#46; Maini"
                            2 => "G&#46; Papatheodoridis"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jhep.2015.06.026"
                      "Revista" => array:7 [
                        "tituloSerie" => "J Hepatol"
                        "fecha" => "2015"
                        "volumen" => "63"
                        "paginaInicial" => "1238"
                        "paginaFinal" => "1253"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26150256"
                            "web" => "Medline"
                          ]
                        ]
                        "itemHostRev" => array:3 [
                          "pii" => "S0005791615300057"
                          "estado" => "S300"
                          "issn" => "00057916"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            46 => array:3 [
              "identificador" => "bib0545"
              "etiqueta" => "47"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Systematic review&#58; lamivudine prophylaxis for chemotherapy-induced reactivation of chronic hepatitis B virus infection"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "H&#46;E&#46; Kohrt"
                            1 => "D&#46;L&#46; Ouyang"
                            2 => "E&#46;B&#46; Keeffe"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/j.1365-2036.2006.03081.x"
                      "Revista" => array:6 [
                        "tituloSerie" => "Aliment Pharmacol Ther"
                        "fecha" => "2006"
                        "volumen" => "24"
                        "paginaInicial" => "1003"
                        "paginaFinal" => "1016"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16984494"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            47 => array:3 [
              "identificador" => "bib0550"
              "etiqueta" => "48"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Lamivudine prevents reactivation of hepatitis B and reduce mortality in immunosuppressed patients&#58; systematic review and meta-analysis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "L&#46; Katz"
                            1 => "A&#46; Fraser"
                            2 => "A&#46; Gafter-Gvili"
                            3 => "L&#46; Leibovici"
                            4 => "R&#46; Tur-Kaspa"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/j.1365-2893.2007.00902.x"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Viral Hepat"
                        "fecha" => "2008"
                        "volumen" => "15"
                        "paginaInicial" => "89"
                        "paginaFinal" => "102"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18184191"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            48 => array:3 [
              "identificador" => "bib0555"
              "etiqueta" => "49"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Entecavir vs&#46; lamivudine for prevention of hepatitis B virus reactivation among patients with untreated diffuse large B-cell lymphoma receiving R-CHOP chemotherapy&#58; a randomized clinical trial"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "H&#46; Huang"
                            1 => "X&#46; Li"
                            2 => "J&#46; Zhu"
                            3 => "S&#46; Ye"
                            4 => "H&#46; Zhang"
                            5 => "W&#46; Wang"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1001/jama.2014.15704"
                      "Revista" => array:6 [
                        "tituloSerie" => "JAMA"
                        "fecha" => "2014"
                        "volumen" => "312"
                        "paginaInicial" => "2521"
                        "paginaFinal" => "2530"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25514302"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            49 => array:3 [
              "identificador" => "bib0560"
              "etiqueta" => "50"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Tenofovir for treatment of hepatitis B virus reactivation in patients with chronic GVHD"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "I&#46; Hilgendorf"
                            1 => "M&#46; Loebermann"
                            2 => "K&#46; Borchert"
                            3 => "C&#46; Junghanss"
                            4 => "M&#46; Freund"
                            5 => "M&#46; Schmitt"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/bmt.2010.290"
                      "Revista" => array:6 [
                        "tituloSerie" => "Bone Marrow Transplant"
                        "fecha" => "2011"
                        "volumen" => "46"
                        "paginaInicial" => "1274"
                        "paginaFinal" => "1275"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21151183"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            50 => array:3 [
              "identificador" => "bib0565"
              "etiqueta" => "51"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A comparison of entecavir and lamivudine for the prophylaxis of hepatitis B virus reactivation in solid tumor patients undergoing systemic cytotoxic chemotherapy"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "W&#46;C&#46; Chen"
                            1 => "J&#46;S&#46; Cheng"
                            2 => "P&#46;H&#46; Chiang"
                            3 => "F&#46;W&#46; Tsay"
                            4 => "H&#46;H&#46; Chan"
                            5 => "H&#46;W&#46; Chang"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1371/journal.pone.0131545"
                      "Revista" => array:5 [
                        "tituloSerie" => "PLOS ONE"
                        "fecha" => "2015"
                        "volumen" => "10"
                        "paginaInicial" => "e0131545"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26121480"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            51 => array:3 [
              "identificador" => "bib0570"
              "etiqueta" => "52"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Systematic review with network meta-analysis&#58; comparative efficacy of oral nucleos&#40;t&#41;ide analogues for the prevention of chemotherapy-induced hepatitis B virus reactivation"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "M&#46;Y&#46; Zhang"
                            1 => "G&#46;Q&#46; Zhu"
                            2 => "K&#46;Q&#46; Shi"
                            3 => "J&#46;N&#46; Zheng"
                            4 => "Z&#46; Cheng"
                            5 => "Z&#46;L&#46; Zou"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.18632/oncotarget.8907"
                      "Revista" => array:6 [
                        "tituloSerie" => "Oncotarget"
                        "fecha" => "2016"
                        "volumen" => "7"
                        "paginaInicial" => "30642"
                        "paginaFinal" => "30658"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27121321"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            52 => array:3 [
              "identificador" => "bib0575"
              "etiqueta" => "53"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Universal prophylaxis with lamivudine prevents hepatitis B reactivation in HBsAg-negative&#47;anti-HBC positive patients undergoing rituximab-based chemotherapy for non-Hodgkin b cell lymphoma &#8211; final results"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "G&#46; Grossi"
                            1 => "A&#46; Loglio"
                            2 => "M&#46; Vigan&#242;"
                            3 => "M&#46; Cappelletti"
                            4 => "M&#46;C&#46; Goldaniga"
                            5 => "L&#46; Farina"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Hepatology"
                        "fecha" => "2016"
                        "volumen" => "64"
                        "paginaInicial" => "88A"
                        "itemHostRev" => array:3 [
                          "pii" => "S016503271630739X"
                          "estado" => "S300"
                          "issn" => "01650327"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            53 => array:3 [
              "identificador" => "bib0580"
              "etiqueta" => "54"
              "referencia" => array:1 [
                0 => array:3 [
                  "comentario" => "e1&#8211;8"
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Persistent risk of HBV reactivation despite extensive lamivudine prophylaxis in haematopoietic stem cell transplant recipients who are anti-HBc-positive or HBV-negative recipients with an anti-HBc-positive donor"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "C&#46; Cerva"
                            1 => "L&#46; Colagrossi"
                            2 => "G&#46; Maffongelli"
                            3 => "R&#46; Salpini"
                            4 => "D&#46; di Carlo"
                            5 => "V&#46; Malagnino"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.cmi.2016.07.021"
                      "Revista" => array:5 [
                        "tituloSerie" => "Clin Microbiol Infect"
                        "fecha" => "2016"
                        "volumen" => "22"
                        "paginaInicial" => "946"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27475741"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            54 => array:3 [
              "identificador" => "bib0585"
              "etiqueta" => "55"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Hepatitis B reactivation in HBsAgnegative&#47;HBcAb-positive patients receiving rituximab for lymphoma&#58; a meta-analysis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "L&#46; Mozessohn"
                            1 => "K&#46;K&#46; Chan"
                            2 => "J&#46;J&#46; Feld"
                            3 => "L&#46;K&#46; Hicks"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/jvh.12402"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Viral Hepat"
                        "fecha" => "2015"
                        "volumen" => "22"
                        "paginaInicial" => "842"
                        "paginaFinal" => "849"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25765930"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            55 => array:3 [
              "identificador" => "bib0590"
              "etiqueta" => "56"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Randomized controlled trial of entecavir prophylaxis for rituximab-associated hepatitis B virus reactivation in patients with lymphoma and resolved hepatitis B"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "Y&#46;H&#46; Huang"
                            1 => "L&#46;T&#46; Hsiao"
                            2 => "Y&#46;C&#46; Hong"
                            3 => "T&#46;J&#46; Chiou"
                            4 => "Bin YuY"
                            5 => "J&#46;P&#46; Gau"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1200/JCO.2012.48.5938"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Clin Oncol"
                        "fecha" => "2013"
                        "volumen" => "31"
                        "paginaInicial" => "2765"
                        "paginaFinal" => "2772"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23775967"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            56 => array:3 [
              "identificador" => "bib0595"
              "etiqueta" => "57"
              "referencia" => array:1 [
                0 => array:3 [
                  "comentario" => "e0184550ee184551184"
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Randomized prospective study evaluating tenofovir disoproxil fumarate prophylaxis against hepatitis B virus reactivation in anti-HBc-positive patients with rituximab-based regimens to treat hematologic malignancies&#58; The Preblin Study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "M&#46; Buti"
                            1 => "M&#46;L&#46; Manzano"
                            2 => "R&#46;M&#46; Morillas"
                            3 => "M&#46; Garc&#237;a-Retortillo"
                            4 => "L&#46; Mart&#237;n"
                            5 => "M&#46; Prieto"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1371/journal.pone.0189910"
                      "Revista" => array:4 [
                        "tituloSerie" => "PLOS ONE"
                        "fecha" => "2017"
                        "volumen" => "12"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29287100"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            57 => array:3 [
              "identificador" => "bib0600"
              "etiqueta" => "58"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Management of patients with hepatitis B in special populations"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "E&#46; Cholongitas"
                            1 => "K&#46; Tziomalos"
                            2 => "C&#46; Pipili"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.3748/wjg.v21.i6.1738"
                      "Revista" => array:6 [
                        "tituloSerie" => "World J Gastroenterol"
                        "fecha" => "2015"
                        "volumen" => "21"
                        "paginaInicial" => "1738"
                        "paginaFinal" => "1748"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25684938"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            58 => array:3 [
              "identificador" => "bib0605"
              "etiqueta" => "59"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Reactivation of hepatitis B virus during targeted therapies for cancer and immune mediated disorders"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "M&#46; Vigan&#242;"
                            1 => "G&#46; Serra"
                            2 => "G&#46; Casella"
                            3 => "G&#46; Grossi"
                            4 => "P&#46; Lampertico"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1080/14712598.2016.1177017"
                      "Revista" => array:6 [
                        "tituloSerie" => "Expert Opin Biol Ther"
                        "fecha" => "2016"
                        "volumen" => "16"
                        "paginaInicial" => "917"
                        "paginaFinal" => "926"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27088278"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            59 => array:3 [
              "identificador" => "bib0610"
              "etiqueta" => "60"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Improving testing for hepatitis B before treatment with rituximab"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "J&#46;K&#46; Dysson"
                            1 => "L&#46; Jopson"
                            2 => "S&#46; Ng"
                            3 => "M&#46; Lowery"
                            4 => "J&#46; Harwood"
                            5 => "S&#46; Waugh"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1097/MEG.0000000000000689"
                      "Revista" => array:6 [
                        "tituloSerie" => "Eur J Gastroenterol Hepatol"
                        "fecha" => "2016"
                        "volumen" => "28"
                        "paginaInicial" => "1172"
                        "paginaFinal" => "1178"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27388147"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            60 => array:3 [
              "identificador" => "bib0615"
              "etiqueta" => "61"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The compliance of doctors with viral hepatitis B screening and antiviral prophylaxis in cancer patients receiving cytotoxic chemotherapy using hospital-based screening reminder system"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "W&#46;C&#46; Sun"
                            1 => "P&#46;I&#46; Hsu"
                            2 => "H&#46;C&#46; Yu"
                            3 => "K&#46;H&#46; Lin"
                            4 => "F&#46;W&#46; Tsay"
                            5 => "H&#46;M&#46; Wang"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:4 [
                        "tituloSerie" => "PLOS ONE"
                        "fecha" => "2015"
                        "volumen" => "10"
                        "paginaInicial" => "ee0116978"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            61 => array:3 [
              "identificador" => "bib0620"
              "etiqueta" => "62"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Computerized physician order entry-based system to prevent HBV reactivation in patients treated with biological agents&#58; The PRESCRIB Project"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "B&#46; Sampedro"
                            1 => "C&#46; Hern&#225;ndez-L&#243;pez"
                            2 => "J&#46;R&#46; Ferrandiz"
                            3 => "A&#46; Illaro"
                            4 => "E&#46; F&#225;brega"
                            5 => "A&#46; Cuadrado"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/hep.27103"
                      "Revista" => array:6 [
                        "tituloSerie" => "Hepatology"
                        "fecha" => "2014"
                        "volumen" => "60"
                        "paginaInicial" => "106"
                        "paginaFinal" => "113"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24585503"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
          ]
        ]
      ]
    ]
  ]
  "idiomaDefecto" => "en"
  "url" => "/23870206/0000015200000003/v1_201901290746/S2387020618305448/v1_201901290746/en/main.assets"
  "Apartado" => array:4 [
    "identificador" => "44147"
    "tipo" => "SECCION"
    "en" => array:2 [
      "titulo" => "Review"
      "idiomaDefecto" => true
    ]
    "idiomaDefecto" => "en"
  ]
  "PDF" => "https://static.elsevier.es/multimedia/23870206/0000015200000003/v1_201901290746/S2387020618305448/v1_201901290746/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/"
  "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2387020618305448?idApp=UINPBA00004N"
]