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Reactivation of peritoneal and pleural tuberculosis during hepatitis C treatment with direct-acting antivirals
Reactivación de tuberculosis peritoneal y pleural durante el tratamiento de la hepatitis C con antivirales de acción directa
Marc Pedrosaa, Sara Nogalesb, Mercedes Vergarac,d, Mireia Miquelc,d, Meritxell Casasc, Blai Dalmauc, Bernat Fonte, Jordi Sánchez-Delgadoc,d,
Corresponding author
jsanchezd@tauli.cat

Corresponding author.
a Servicio de Medicina Interna, Parc Taulí Hospital Universitari, Institut d’Investigació i Innovació Parc Taulí I3PT, Universitat Autònoma de Barcelona, Sabadell, Barcelona, Spain
b Servicio de Medicina Intensiva, Parc Taulí Hospital Universitari, Institut d’Investigació i Innovació Parc Taulí I3PT, Universitat Autònoma de Barcelona, Sabadell, Barcelona, Spain
c 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
d Centro de Investigación Biomédica y en Red enfermedades hepáticas y digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain
e Servicio de Enfermedades Infecciosas, Parc Taulí Hospital Universitari, Institut d’Investigació i Innovació Parc Taulí I3PT, Universitat Autònoma de Barcelona, Sabadell, Barcelona, Spain
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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Hepatitis C virus &#40;HCV&#41; infection is a major health problem in Europe and the Mediterranean countries in particular&#44; where prevalence rates range from 0&#46;31 to 0&#46;42&#37;&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">Patients with chronic HCV infection have a higher prevalence of tuberculosis &#40;TB&#41; compared to the general population&#46; The epidemiological context of both diseases is similar in certain cases&#44; such as in people suffering from intravenous drug addiction&#44; prisoners and the homeless&#46; HCV treatment with peginterferon and ribavirin was previously associated with a greater risk of TB reactivation&#44;<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">1&#44;2</span></a> but experience relating to the reactivation of infections with new direct-acting antivirals &#40;DAAs&#41; is limited&#46;</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&#46; He presented with liver cirrhosis &#40;LC&#41; due to hepatitis B virus &#40;HBeAg negative&#44; HBV DNA 1753<span class="elsevierStyleHsp" style=""></span>IU&#47;ml&#41; and HCV &#40;genotype 2a&#44; HCV RNA 2470203<span class="elsevierStyleHsp" style=""></span>IU&#47;ml&#41;&#59; Child&#8211;Pugh A &#40;5 points&#41;&#59; negative HIV antibodies&#59; a FibroScan<span class="elsevierStyleSup">&#174;</span> score of 69&#46;1<span class="elsevierStyleHsp" style=""></span>kPa&#59; and no oesophageal varices&#46; He also had grade 1 ascites a few months prior&#44; which resolved after diuretic therapy and a low-sodium diet&#46; Since there was only a small amount of ascitic fluid&#44; it was not possible to obtain a sample for analysis&#46; The patient started entecavir at the beginning of December 2015&#46; In mid-December&#44; he began treatment with sofosbuvir and ribavirin&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">He was admitted to hospital in February 2016 with a one-month history of asthenia&#44; anorexia&#44; 10<span class="elsevierStyleHsp" style=""></span>kg weight loss and febrile episodes of up to 38&#46;7<span class="elsevierStyleHsp" style=""></span>&#176;C&#44; mainly at night&#46; His only diagnostic sign was persistent constipation in the few weeks prior&#46; The cardiovascular and respiratory examination was unremarkable and his abdomen showed signs of grade 2 ascites&#46; The patient&#39;s laboratory tests revealed leucocyte levels of 3850<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">9</span>&#44; Hb 146<span class="elsevierStyleHsp" style=""></span>g&#47;l&#59; Platelets 213<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">9</span>&#44; AST&#47;ALT 65&#47;57<span class="elsevierStyleHsp" style=""></span>U&#47;l&#44; bilirubin 0&#46;8<span class="elsevierStyleHsp" style=""></span>mg&#47;dl&#59; INR 1&#46;1&#46; ESR 52<span class="elsevierStyleHsp" style=""></span>mm&#47;h&#44; CRP 7&#46;9<span class="elsevierStyleHsp" style=""></span>mg&#47;dl&#44; CA-125 115&#46;6<span class="elsevierStyleHsp" style=""></span>U&#47;ml&#59; HCV RNA undetectable and HBV DNA &#60;20<span class="elsevierStyleHsp" style=""></span>IU&#47;ml&#46; A chest X-ray showed minimal right-sided pleural effusion with no consolidation&#46; A series of blood cultures were negative&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">Abdominal paracentesis was carried out&#44; removing 3&#46;5<span class="elsevierStyleHsp" style=""></span>l of ascitic fluid with 400<span class="elsevierStyleHsp" style=""></span>leukocytes&#47;mm<span class="elsevierStyleSup">3</span> &#40;95&#37; lymphocytes&#41;&#46; Proteins&#44; albumin and adenosine deaminase &#40;ADA&#41; were not determined at any time due to suspected decompensated LC&#46; A CT scan of the chest and abdomen was performed&#44; revealing multiple 2&#8211;3<span class="elsevierStyleHsp" style=""></span>mm subpleural nodules&#44; free perihepatic and perisplenic fluid&#44; as well as peritoneal thickening and a diffuse increase in mesenteric density&#46; Right-sided pleural effusion &#40;<a class="elsevierStyleCrossRefs" href="#fig0005">Figs&#46; 1 and 2</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0030" class="elsevierStylePara elsevierViewall">Thoracentesis was also performed&#44; which showed pleural fluid with protein levels of 58<span class="elsevierStyleHsp" style=""></span>g&#47;l&#44; leukocytes of 1325&#47;mm<span class="elsevierStyleSup">3</span> &#40;99&#37; lymphocytes&#41;&#44; ADA of 42&#46;3<span class="elsevierStyleHsp" style=""></span>U&#47;l &#40;upper limit of normal&#41; and pleural fluid CRP positive for <span class="elsevierStyleItalic">Mycobacterium tuberculosis</span>&#46; QuantiFERON-TB<span class="elsevierStyleSup">&#174;</span> &#62;4<span class="elsevierStyleHsp" style=""></span>IU&#47;ml&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Given the above results&#44; 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&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">DAA treatment was stopped on 18&#47;02&#47;2016 and anti-TB therapy initiated&#44; with rifampicin &#40;RIF&#41;&#44; isoniazid &#40;INH&#41; and ethambutol &#40;for two months&#41; plus four further months of RIF<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>INH&#46; The patient made good clinical progress thereafter&#44; with his fever disappearing and toxic symptoms and constipation resolving &#40;normal outpatient colonoscopy&#41;&#46; The ascites also disappeared without diuretic treatment&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">Regarding the HCV infection&#44; he had a sustained virologic response despite only receiving 12 weeks of treatment&#46; 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&#44; and no pulmonary micronodules were observed&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">Reactivations of infections following the use of DAAs are uncommon&#44; although cases are described in relation to the HBV and herpes simplex virus &#40;HSV&#41;&#44; among other infections&#46;<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">3&#8211;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&#46; To date&#44; only one case of miliary TB reactivation has been reported during DAA treatment&#46; Said patient had received treatment with sofosbuvir&#47;ledipasvir and ribavirin&#46;<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&#44; the first being underlying cirrhosis&#44; which has been linked to dysfunction of the neutrophils&#44; lymphocytes and macrophages and to decreased IFN-&#945; and TNF-&#945; production&#46;<a class="elsevierStyleCrossRefs" href="#bib0100"><span class="elsevierStyleSup">7&#8211;9</span></a> Conversely&#44; the immune system disorders caused by DAAs are not fully understood&#46; Various studies show reduced lymphocyte activation and normalised natural killer cell function&#46;<a class="elsevierStyleCrossRefs" href="#bib0115"><span class="elsevierStyleSup">10&#8211;13</span></a> HSV and HBV reactivations have been reported&#44; as well as a potential increase in hepatocellular carcinoma recurrences in patients treated with DAAs&#46; As in the case described above&#44; establishing a causal relationship with DAA treatment is difficult and the timing of the two infections could simply be a coincidence&#46; This could potentially be the second case of TB reactivation during DAA treatment&#46; Given the low incidence of reported cases of TB reactivation with DAAs to date&#44; we cannot make recommendations in favour of patients being screened prior to beginning treatment&#46;</p></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Pedrosa M&#44; Nogales S&#44; Vergara M&#44; Miquel M&#44; Casas M&#44; Dalmau B&#44; et al&#46; Reactivaci&#243;n de tuberculosis peritoneal y pleural durante el tratamiento de la hepatitis C con antivirales de acci&#243;n directa&#46; Gastroenterol Hepatol&#46; 2019&#59;42&#58;174&#8211;175&#46;</p>"
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                          "etal" => true
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                            0 => "S&#46; Odolini"
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                      "titulo" => "Reactivation of herpesvirus in patients with hepatitis C treated with direct-acting antiviral agents"
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                        0 => array:2 [
                          "etal" => true
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                            0 => "M&#46;C&#46; Perello"
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                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "M&#46;P&#46; Ballester-Ferr&#233;"
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                            2 => "N&#46; Garcia-Gimeno"
                            3 => "F&#46; Mora"
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                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "D&#46;H&#46;E&#46; Wasmuth"
                            1 => "D&#46; Kunz"
                            2 => "E&#46; Yagmur"
                            3 => "A&#46; Timmer-Stranghoner"
                            4 => "D&#46; Vidacek"
                            5 => "E&#46; Siewert"
                          ]
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                  ]
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                    0 => array:2 [
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                        "tituloSerie" => "J Hepatol"
                        "fecha" => "2005"
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              "etiqueta" => "8"
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                      "titulo" => "Altered immune function of monocytes in different stages of patients with acute on chronic liver failure"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "D&#46;T&#46; Xing"
                            1 => "L&#46; Li"
                            2 => "H&#46; Cao"
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                        ]
                      ]
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                  ]
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                        0 => array:2 [
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                            0 => "B&#46; Martin"
                            1 => "N&#46; Hennecke"
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                            3 => "A&#46; Kayser"
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                    0 => array:2 [
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              ]
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              "referencia" => array:1 [
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                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
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                        ]
                      ]
                    ]
                  ]
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Article information
ISSN: 24443824
Original language: English
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