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Chronic Hepatitis E Virus Infection during Lymphoplasmacytic Lymphoma and Ibrutinib Treatment

Hepatitis E virus (HEV) is an increasingly recognised pathogen, affecting several hundred thousand individuals in western countries each year. Importantly, the majority of immunocompromised individuals are not able to clear HEV but develop a chronic course of infection. In the case of lymphoma, whic...

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Autores principales: Schlevogt, Bernhard, Kinast, Volker, Reusch, Julia, Kerkhoff, Andrea, Praditya, Dimas, Todt, Daniel, Schmidt, Hartmut H., Steinmann, Eike, Behrendt, Patrick
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6789582/
https://www.ncbi.nlm.nih.gov/pubmed/31443360
http://dx.doi.org/10.3390/pathogens8030129
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author Schlevogt, Bernhard
Kinast, Volker
Reusch, Julia
Kerkhoff, Andrea
Praditya, Dimas
Todt, Daniel
Schmidt, Hartmut H.
Steinmann, Eike
Behrendt, Patrick
author_facet Schlevogt, Bernhard
Kinast, Volker
Reusch, Julia
Kerkhoff, Andrea
Praditya, Dimas
Todt, Daniel
Schmidt, Hartmut H.
Steinmann, Eike
Behrendt, Patrick
author_sort Schlevogt, Bernhard
collection PubMed
description Hepatitis E virus (HEV) is an increasingly recognised pathogen, affecting several hundred thousand individuals in western countries each year. Importantly, the majority of immunocompromised individuals are not able to clear HEV but develop a chronic course of infection. In the case of lymphoma, which is an inherent immunosuppressive disease per se, chemotherapy can even further exacerbate the immunosuppressive status. As the mechanism of HEV chronification is barely understood, it is important to gain knowledge about the influence of chemotherapeutic drugs on the HEV replication cycle to guide rational clinical management of HEV infection in such patients. In this case report, a 70 year old man was diagnosed with lymphoplasmacytic lymphoma. As we observed the occurrence of chronic HEV after treatment with the Bruton’s tyrosine kinase (BTK) inhibitor ibrutinib in vivo, we investigated the influence of BTK signaling and ibrutinib treatment in the HEV replication cycle in vitro. First, we detected an HEV-induced mobilisation of BTK in human liver cells during HEV replication. A moderate antiviral effect against HEV replicating isolates including genotypes 1 and 3 was observed, suggesting that ibrutinib did not support HEV replication in a direct manner. Combinatory treatments of ibrutinib with ribavirin indicated that ibrutinib did not influence the antiviral effect of ribavirin. Taken together, chemotherapy targeting cellular factors for the treatment of lymphomas may be a neglected risk factor for the chronification of HEV. For ibrutinib, despite the upregulation of its target BTK during HEV replication, we observed neither a proviral effect on HEV replication nor an influence on the antiviral effect of ribavirin, suggesting that the chronification of HEV may be favoured by its immunosuppressive effect.
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spelling pubmed-67895822019-10-16 Chronic Hepatitis E Virus Infection during Lymphoplasmacytic Lymphoma and Ibrutinib Treatment Schlevogt, Bernhard Kinast, Volker Reusch, Julia Kerkhoff, Andrea Praditya, Dimas Todt, Daniel Schmidt, Hartmut H. Steinmann, Eike Behrendt, Patrick Pathogens Case Report Hepatitis E virus (HEV) is an increasingly recognised pathogen, affecting several hundred thousand individuals in western countries each year. Importantly, the majority of immunocompromised individuals are not able to clear HEV but develop a chronic course of infection. In the case of lymphoma, which is an inherent immunosuppressive disease per se, chemotherapy can even further exacerbate the immunosuppressive status. As the mechanism of HEV chronification is barely understood, it is important to gain knowledge about the influence of chemotherapeutic drugs on the HEV replication cycle to guide rational clinical management of HEV infection in such patients. In this case report, a 70 year old man was diagnosed with lymphoplasmacytic lymphoma. As we observed the occurrence of chronic HEV after treatment with the Bruton’s tyrosine kinase (BTK) inhibitor ibrutinib in vivo, we investigated the influence of BTK signaling and ibrutinib treatment in the HEV replication cycle in vitro. First, we detected an HEV-induced mobilisation of BTK in human liver cells during HEV replication. A moderate antiviral effect against HEV replicating isolates including genotypes 1 and 3 was observed, suggesting that ibrutinib did not support HEV replication in a direct manner. Combinatory treatments of ibrutinib with ribavirin indicated that ibrutinib did not influence the antiviral effect of ribavirin. Taken together, chemotherapy targeting cellular factors for the treatment of lymphomas may be a neglected risk factor for the chronification of HEV. For ibrutinib, despite the upregulation of its target BTK during HEV replication, we observed neither a proviral effect on HEV replication nor an influence on the antiviral effect of ribavirin, suggesting that the chronification of HEV may be favoured by its immunosuppressive effect. MDPI 2019-08-22 /pmc/articles/PMC6789582/ /pubmed/31443360 http://dx.doi.org/10.3390/pathogens8030129 Text en © 2019 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 Case Report
Schlevogt, Bernhard
Kinast, Volker
Reusch, Julia
Kerkhoff, Andrea
Praditya, Dimas
Todt, Daniel
Schmidt, Hartmut H.
Steinmann, Eike
Behrendt, Patrick
Chronic Hepatitis E Virus Infection during Lymphoplasmacytic Lymphoma and Ibrutinib Treatment
title Chronic Hepatitis E Virus Infection during Lymphoplasmacytic Lymphoma and Ibrutinib Treatment
title_full Chronic Hepatitis E Virus Infection during Lymphoplasmacytic Lymphoma and Ibrutinib Treatment
title_fullStr Chronic Hepatitis E Virus Infection during Lymphoplasmacytic Lymphoma and Ibrutinib Treatment
title_full_unstemmed Chronic Hepatitis E Virus Infection during Lymphoplasmacytic Lymphoma and Ibrutinib Treatment
title_short Chronic Hepatitis E Virus Infection during Lymphoplasmacytic Lymphoma and Ibrutinib Treatment
title_sort chronic hepatitis e virus infection during lymphoplasmacytic lymphoma and ibrutinib treatment
topic Case Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6789582/
https://www.ncbi.nlm.nih.gov/pubmed/31443360
http://dx.doi.org/10.3390/pathogens8030129
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