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"Sánchez-Delgado" "email" => array:1 [ 0 => "jsanchezd@tauli.cat" ] "referencia" => array:3 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">d</span>" "identificador" => "aff0020" ] 2 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] ] "afiliaciones" => array:5 [ 0 => array:3 [ "entidad" => "Servicio de Medicina Interna, Parc Taulí Hospital Universitari, Institut d’Investigació i Innovació Parc Taulí I3PT, Universitat Autònoma de Barcelona, Sabadell, Barcelona, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Servicio de Medicina Intensiva, Parc Taulí Hospital Universitari, Institut d’Investigació i Innovació Parc Taulí I3PT, Universitat Autònoma de Barcelona, Sabadell, Barcelona, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Unidad de Hepatología, Servicio de Aparato Digestivo, Parc Taulí Hospital Universitari, Institut d’Investigació i Innovació Parc Taulí I3PT, Universitat Autònoma de Barcelona, Sabadell, Barcelona, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Centro de Investigación Biomédica y en Red enfermedades hepáticas y digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain" "etiqueta" => "d" "identificador" => "aff0020" ] 4 => array:3 [ "entidad" => "Servicio de Enfermedades Infecciosas, Parc Taulí Hospital Universitari, Institut d’Investigació i Innovació Parc Taulí I3PT, Universitat Autònoma de Barcelona, Sabadell, Barcelona, Spain" "etiqueta" => "e" "identificador" => "aff0025" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Reactivación de tuberculosis peritoneal y pleural durante el tratamiento de la hepatitis C con antivirales de acción directa" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 860 "Ancho" => 950 "Tamanyo" => 94579 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Right-sided pleural effusion.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Hepatitis C virus (HCV) infection is a major health problem in Europe and the Mediterranean countries in particular, where prevalence rates range from 0.31 to 0.42%.</p><p id="par0010" class="elsevierStylePara elsevierViewall">Patients with chronic HCV infection have a higher prevalence of tuberculosis (TB) compared to the general population. The epidemiological context of both diseases is similar in certain cases, such as in people suffering from intravenous drug addiction, prisoners and the homeless. HCV treatment with peginterferon and ribavirin was previously associated with a greater risk of TB reactivation,<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">1,2</span></a> but experience relating to the reactivation of infections with new direct-acting antivirals (DAAs) is limited.</p><p id="par0015" class="elsevierStylePara elsevierViewall">We present the case of a 59-year-old man who was born in Guinea and has been living in Spain since the age of 10. He presented with liver cirrhosis (LC) due to hepatitis B virus (HBeAg negative, HBV DNA 1753<span class="elsevierStyleHsp" style=""></span>IU/ml) and HCV (genotype 2a, HCV RNA 2470203<span class="elsevierStyleHsp" style=""></span>IU/ml); Child–Pugh A (5 points); negative HIV antibodies; a FibroScan<span class="elsevierStyleSup">®</span> score of 69.1<span class="elsevierStyleHsp" style=""></span>kPa; and no oesophageal varices. He also had grade 1 ascites a few months prior, which resolved after diuretic therapy and a low-sodium diet. Since there was only a small amount of ascitic fluid, it was not possible to obtain a sample for analysis. The patient started entecavir at the beginning of December 2015. In mid-December, he began treatment with sofosbuvir and ribavirin.</p><p id="par0020" class="elsevierStylePara elsevierViewall">He was admitted to hospital in February 2016 with a one-month history of asthenia, anorexia, 10<span class="elsevierStyleHsp" style=""></span>kg weight loss and febrile episodes of up to 38.7<span class="elsevierStyleHsp" style=""></span>°C, mainly at night. His only diagnostic sign was persistent constipation in the few weeks prior. The cardiovascular and respiratory examination was unremarkable and his abdomen showed signs of grade 2 ascites. The patient's laboratory tests revealed leucocyte levels of 3850<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">9</span>, Hb 146<span class="elsevierStyleHsp" style=""></span>g/l; Platelets 213<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">9</span>, AST/ALT 65/57<span class="elsevierStyleHsp" style=""></span>U/l, bilirubin 0.8<span class="elsevierStyleHsp" style=""></span>mg/dl; INR 1.1. ESR 52<span class="elsevierStyleHsp" style=""></span>mm/h, CRP 7.9<span class="elsevierStyleHsp" style=""></span>mg/dl, CA-125 115.6<span class="elsevierStyleHsp" style=""></span>U/ml; HCV RNA undetectable and HBV DNA <20<span class="elsevierStyleHsp" style=""></span>IU/ml. A chest X-ray showed minimal right-sided pleural effusion with no consolidation. A series of blood cultures were negative.</p><p id="par0025" class="elsevierStylePara elsevierViewall">Abdominal paracentesis was carried out, removing 3.5<span class="elsevierStyleHsp" style=""></span>l of ascitic fluid with 400<span class="elsevierStyleHsp" style=""></span>leukocytes/mm<span class="elsevierStyleSup">3</span> (95% lymphocytes). Proteins, albumin and adenosine deaminase (ADA) were not determined at any time due to suspected decompensated LC. A CT scan of the chest and abdomen was performed, revealing multiple 2–3<span class="elsevierStyleHsp" style=""></span>mm subpleural nodules, free perihepatic and perisplenic fluid, as well as peritoneal thickening and a diffuse increase in mesenteric density. Right-sided pleural effusion (<a class="elsevierStyleCrossRefs" href="#fig0005">Figs. 1 and 2</a>).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0030" class="elsevierStylePara elsevierViewall">Thoracentesis was also performed, which showed pleural fluid with protein levels of 58<span class="elsevierStyleHsp" style=""></span>g/l, leukocytes of 1325/mm<span class="elsevierStyleSup">3</span> (99% lymphocytes), ADA of 42.3<span class="elsevierStyleHsp" style=""></span>U/l (upper limit of normal) and pleural fluid CRP positive for <span class="elsevierStyleItalic">Mycobacterium tuberculosis</span>. QuantiFERON-TB<span class="elsevierStyleSup">®</span> >4<span class="elsevierStyleHsp" style=""></span>IU/ml.</p><p id="par0035" class="elsevierStylePara elsevierViewall">Given the above results, the case was deemed a reactivation of abdominal and pleural TB in the context of DAA treatment in a patient with cirrhosis due to HBV and HCV.</p><p id="par0040" class="elsevierStylePara elsevierViewall">DAA treatment was stopped on 18/02/2016 and anti-TB therapy initiated, with rifampicin (RIF), isoniazid (INH) and ethambutol (for two months) plus four further months of RIF<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>INH. The patient made good clinical progress thereafter, with his fever disappearing and toxic symptoms and constipation resolving (normal outpatient colonoscopy). The ascites also disappeared without diuretic treatment.</p><p id="par0045" class="elsevierStylePara elsevierViewall">Regarding the HCV infection, he had a sustained virologic response despite only receiving 12 weeks of treatment. A CT scan of the chest and abdomen six months after finishing anti-TB therapy showed that the right-sided pleural effusion of peritoneal fluid and peritoneal fat thickening had resolved, and no pulmonary micronodules were observed.</p><p id="par0050" class="elsevierStylePara elsevierViewall">Reactivations of infections following the use of DAAs are uncommon, although cases are described in relation to the HBV and herpes simplex virus (HSV), among other infections.<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">3–5</span></a> Reported cases of TB reactivation are rare and in relation to dual therapy with interferon and ribavirin or triple therapy with the addition of boceprevir or telaprevir. To date, only one case of miliary TB reactivation has been reported during DAA treatment. Said patient had received treatment with sofosbuvir/ledipasvir and ribavirin.<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">6</span></a> There are various factors which may have led to TB reactivation in the patient, the first being underlying cirrhosis, which has been linked to dysfunction of the neutrophils, lymphocytes and macrophages and to decreased IFN-α and TNF-α production.<a class="elsevierStyleCrossRefs" href="#bib0100"><span class="elsevierStyleSup">7–9</span></a> Conversely, the immune system disorders caused by DAAs are not fully understood. Various studies show reduced lymphocyte activation and normalised natural killer cell function.<a class="elsevierStyleCrossRefs" href="#bib0115"><span class="elsevierStyleSup">10–13</span></a> HSV and HBV reactivations have been reported, as well as a potential increase in hepatocellular carcinoma recurrences in patients treated with DAAs. As in the case described above, establishing a causal relationship with DAA treatment is difficult and the timing of the two infections could simply be a coincidence. This could potentially be the second case of TB reactivation during DAA treatment. Given the low incidence of reported cases of TB reactivation with DAAs to date, we cannot make recommendations in favour of patients being screened prior to beginning treatment.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Pedrosa M, Nogales S, Vergara M, Miquel M, Casas M, Dalmau B, et al. Reactivación de tuberculosis peritoneal y pleural durante el tratamiento de la hepatitis C con antivirales de acción directa. Gastroenterol Hepatol. 2019;42:174–175.</p>" ] ] "multimedia" => array:2 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 771 "Ancho" => 950 "Tamanyo" => 77562 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Peritoneal thickening and diffuse increase in mesenteric density.</p>" ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 860 "Ancho" => 950 "Tamanyo" => 94579 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Right-sided pleural effusion.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:13 [ 0 => array:3 [ "identificador" => "bib0070" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Reactivation of pulmonary tuberculosis during treatment with triple therapy for hepatitis C" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "L. 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