Rituximab-Containing Treatment Regimens May Imply a Long-Term Risk for Difficult-To-Treat Chronic Hepatitis E

Marten Schulz, Paula Biedermann, Claus-Thomas Bock, Jörg Hofmann, Mira Choi, Frank Tacke, Leif Gunnar Hanitsch and Tobias Mueller
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Marten Schulz: Department of Hepatology and Gastroenterology, Charité—Universitätsmedizin Berlin, CVK, 13353 Berlin, Germany
Paula Biedermann: Division of Viral Gastroenteritis, Hepatitis Pathogens and Enteroviruses, Department of Infectious Diseases, Robert Koch Institute, 13353 Berlin, Germany
Claus-Thomas Bock: Division of Viral Gastroenteritis, Hepatitis Pathogens and Enteroviruses, Department of Infectious Diseases, Robert Koch Institute, 13353 Berlin, Germany
Jörg Hofmann: Institute of Virology, Charité Universitätsmedizin Berlin, Labor Berlin—Charité-Vivantes GmbH, 13353 Berlin, Germany
Mira Choi: Department of Nephrology and Intensive Care Medicine, Charité Universitätsmedizin Berlin, 13353 Berlin, Germany
Frank Tacke: Department of Hepatology and Gastroenterology, Charité—Universitätsmedizin Berlin, CVK, 13353 Berlin, Germany
Leif Gunnar Hanitsch: Institute of Medical Immunology, Charité—Universitätsmedizin Berlin, 13353 Berlin, Germany
Tobias Mueller: Department of Hepatology and Gastroenterology, Charité—Universitätsmedizin Berlin, CVK, 13353 Berlin, Germany

IJERPH, 2020, vol. 17, issue 1, 1-11

Abstract: 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.

Keywords: hepatitis E; rituximab; ribavirin resistance; hypogammaglobulinemia: CD4+ T cell lymphopenia (search for similar items in EconPapers)
JEL-codes: I I1 I3 Q Q5 (search for similar items in EconPapers)
Date: 2020
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