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  3. Chronic Hepatitis E Virus Infection during Lymphoplasmacytic Lymphoma and Ibrutinib Treatment

Chronic Hepatitis E Virus Infection during Lymphoplasmacytic Lymphoma and Ibrutinib Treatment

  • Pathogens. 2019 Aug 22;8(3):129. doi: 10.3390/pathogens8030129.
Bernhard Schlevogt 1,  Volker Kinast 2 3,  Julia Reusch 4,  Andrea Kerkhoff 4,  Dimas Praditya 2 3,  Daniel Todt 3,  Hartmut H Schmidt 1,  Eike Steinmann 5,  Patrick Behrendt 6 7 8
Affiliations

Affiliations

  • 1 Department of Medicine B for Gastroenterology and Hepatology, University Hospital Muenster, 48149 Münster, Germany.
  • 2 Institute of Experimental Virology, TWINCORE Centre for Experimental and Clinical Infection Research, a Joint Venture between the Medical School Hannover (MHH) and the Helmholtz Centre for Infection Research (HZI), 30625 Hannover, Germany.
  • 3 Department for Molecular and Medical Virology, Faculty of Medicine, Ruhr University Bochum, 44801 Bochum, Germany.
  • 4 Department of Medicine A, Hematology, Oncology and Pneumology, University Hospital Muenster, 48149 Münster, Germany.
  • 5 Department for Molecular and Medical Virology, Faculty of Medicine, Ruhr University Bochum, 44801 Bochum, Germany. eike.steinmann@ruhr-uni-bochum.de.
  • 6 Institute of Experimental Virology, TWINCORE Centre for Experimental and Clinical Infection Research, a Joint Venture between the Medical School Hannover (MHH) and the Helmholtz Centre for Infection Research (HZI), 30625 Hannover, Germany. Behrendt.Patrick@mh-hannover.de.
  • 7 Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, 30625 Hannover, Germany. Behrendt.Patrick@mh-hannover.de.
  • 8 German Centre for Infection Research (DZIF), Partner-Site Hannover-Braunschweig, 30625 Hannover, Germany. Behrendt.Patrick@mh-hannover.de.
PMID: 31443360 DOI: 10.3390/pathogens8030129
Abstract

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.

Keywords

Bruton’s tyrosine kinase; chronification; hepatitis E virus; ibrutinib; immunosuppression; lymphoplasmacytic lymphoma.

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