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

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 hem...

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Autores principales: Schulz, Marten, Biedermann, Paula, Bock, Claus-Thomas, Hofmann, Jörg, Choi, Mira, Tacke, Frank, Hanitsch, Leif Gunnar, Mueller, Tobias
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6982013/
https://www.ncbi.nlm.nih.gov/pubmed/31947836
http://dx.doi.org/10.3390/ijerph17010341
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author Schulz, Marten
Biedermann, Paula
Bock, Claus-Thomas
Hofmann, Jörg
Choi, Mira
Tacke, Frank
Hanitsch, Leif Gunnar
Mueller, Tobias
author_facet Schulz, Marten
Biedermann, Paula
Bock, Claus-Thomas
Hofmann, Jörg
Choi, Mira
Tacke, Frank
Hanitsch, Leif Gunnar
Mueller, Tobias
author_sort Schulz, Marten
collection PubMed
description 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.
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spelling pubmed-69820132020-02-07 Rituximab-Containing Treatment Regimens May Imply a Long-Term Risk for Difficult-To-Treat Chronic Hepatitis E Schulz, Marten Biedermann, Paula Bock, Claus-Thomas Hofmann, Jörg Choi, Mira Tacke, Frank Hanitsch, Leif Gunnar Mueller, Tobias Int J Environ Res Public Health Article 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. MDPI 2020-01-03 2020-01 /pmc/articles/PMC6982013/ /pubmed/31947836 http://dx.doi.org/10.3390/ijerph17010341 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Schulz, Marten
Biedermann, Paula
Bock, Claus-Thomas
Hofmann, Jörg
Choi, Mira
Tacke, Frank
Hanitsch, Leif Gunnar
Mueller, Tobias
Rituximab-Containing Treatment Regimens May Imply a Long-Term Risk for Difficult-To-Treat Chronic Hepatitis E
title Rituximab-Containing Treatment Regimens May Imply a Long-Term Risk for Difficult-To-Treat Chronic Hepatitis E
title_full Rituximab-Containing Treatment Regimens May Imply a Long-Term Risk for Difficult-To-Treat Chronic Hepatitis E
title_fullStr Rituximab-Containing Treatment Regimens May Imply a Long-Term Risk for Difficult-To-Treat Chronic Hepatitis E
title_full_unstemmed Rituximab-Containing Treatment Regimens May Imply a Long-Term Risk for Difficult-To-Treat Chronic Hepatitis E
title_short Rituximab-Containing Treatment Regimens May Imply a Long-Term Risk for Difficult-To-Treat Chronic Hepatitis E
title_sort rituximab-containing treatment regimens may imply a long-term risk for difficult-to-treat chronic hepatitis e
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6982013/
https://www.ncbi.nlm.nih.gov/pubmed/31947836
http://dx.doi.org/10.3390/ijerph17010341
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