{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T03:04:26Z","timestamp":1791860666523,"version":"4.3.4"},"reference-count":37,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2020,1,3]],"date-time":"2020-01-03T00:00:00Z","timestamp":1578009600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJERPH"],"abstract":"<jats:p>Hepatitis E virus (HEV) infection is an emerging disease in industrialized countries which is usually characterized by a self-limited course. However, there is an increased risk of HEV persistence in immunocompromised risk populations, comprising patients following solid organ transplantation or hematological malignancies. Recently, chronic HEV infection following rituximab-containing treatment regimens has been described. Here we report five patients with chronic hepatitis E after prior rituximab therapy for various indications. We determined the immunological characteristics of these patients and analyzed the development of ribavirin (RBV) treatment failure-associated mutations in the HEV genome. One patient became chronically HEV-infected 110 months after administration of rituximab (RTX). Immunological characterization revealed that all patients exhibited significant hypogammaglobulinemia and CD4+ T cell lymphopenia. One patient permanently cleared HEV following weight-based ribavirin treatment while three patients failed to reach a sustained virological response. In depth mutational analysis confirmed the presence of specific mutations associated with RBV treatment failure in these patients. Our cases indicate that rituximab-containing treatment regimens might imply a relevant risk for persistent HEV infection even years after the last rituximab application. Moreover, we provide further evidence to prior observations suggesting that chronically HEV infected patients following RTX-containing treatment regimens might be difficult to treat.<\/jats:p>","DOI":"10.3390\/ijerph17010341","type":"journal-article","created":{"date-parts":[[2020,1,3]],"date-time":"2020-01-03T11:55:07Z","timestamp":1578052507000},"page":"341","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Rituximab-Containing Treatment Regimens May Imply a Long-Term Risk for Difficult-To-Treat Chronic Hepatitis E"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0298-0156","authenticated-orcid":false,"given":"Marten","family":"Schulz","sequence":"first","affiliation":[{"name":"Department of Hepatology and Gastroenterology, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, CVK, 13353 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula","family":"Biedermann","sequence":"additional","affiliation":[{"name":"Division of Viral Gastroenteritis, Hepatitis Pathogens and Enteroviruses, Department of Infectious Diseases, Robert Koch Institute, 13353 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2773-486X","authenticated-orcid":false,"given":"Claus-Thomas","family":"Bock","sequence":"additional","affiliation":[{"name":"Division of Viral Gastroenteritis, Hepatitis Pathogens and Enteroviruses, Department of Infectious Diseases, Robert Koch Institute, 13353 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00f6rg","family":"Hofmann","sequence":"additional","affiliation":[{"name":"Institute of Virology, Charit\u00e9 Universit\u00e4tsmedizin Berlin, Labor Berlin\u2014Charit\u00e9-Vivantes GmbH, 13353 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mira","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Intensive Care Medicine, Charit\u00e9 Universit\u00e4tsmedizin Berlin, 13353 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Tacke","sequence":"additional","affiliation":[{"name":"Department of Hepatology and Gastroenterology, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, CVK, 13353 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leif Gunnar","family":"Hanitsch","sequence":"additional","affiliation":[{"name":"Institute of Medical Immunology, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, 13353 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3426-5421","authenticated-orcid":false,"given":"Tobias","family":"Mueller","sequence":"additional","affiliation":[{"name":"Department of Hepatology and Gastroenterology, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, CVK, 13353 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,1,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1016\/j.jinf.2018.09.012","article-title":"Epidemiologic estimates of hepatitis E virus infection in European countries","volume":"77","author":"Horn","year":"2018","journal-title":"J. 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