The Burden of Hepatitis E among Patients with Hematological Malignancies: a Retrospective European Cohort Study

Abstract Background The burden of hepatitis E virus (HEV) infection has been scarcely reported among patients with haematological malignancy. Methods We conducted a retrospective, multi-centre cohort study across 11 European centres and collected clinical characteristics of 50 patients with haematological malignancy and RNA-positive, clinically overt hepatitis E between April 2014 and March 2017. Primary endpoint was HEV-associated mortality; secondary endpoint was HEV-associated liver-related morbidity. Results The most frequent underlying haematological malignancies were aggressive non-Hodgkin lymphoma (NHL) (34%), indolent NHL (iNHL) (24%), and acute leukaemia (36%). Twenty-one (42%) patients had received allogeneic haematopoietic stem cell transplantation (alloHSCT). Death with ongoing hepatitis E occurred in eight (16%) patients, including one with iNHL and one >100 days after alloHSCT in complete remission, and was associated with male sex (p=0.040), cirrhosis (p=0.006) and alloHSCT (p=0.056). Blood-borne transmission of hepatitis E was demonstrated in five (10%) patients, and associated with liver-related mortality in two patients. Hepatitis E progressed to chronic hepatitis in 17 (34%) patients overall, and in ten (47.6%) and six (50%) alloHSCT and iNHL patients, respectively. Hepatitis E was associated with acute or acute-on-chronic liver failure in four (8%) patients with 75% mortality. Ribavirin was administered to 24 (48%) patients and HEV clearance rate was 79.2%. Ribavirin treatment was associated with lower mortality (p=0.037) and by trend with lower rates of chronicity (p=0.407) when initiated Conclusion Hepatitis E is associated with mortality and liver-related morbidity in haematological patients. Blood-borne transmission contributes to the burden. Ribavirin should be initiated early, whereas alleviation of immunosuppressive treatment requires caution. Lay Summary Little is known about the burden of hepatitis E among patients with haematological malignancy. We conducted a retrospective European cohort study among 50 patients with haematological malignancy, including haematopoietic stem cell transplant recipients, with clinically significant HEV infection and found that hepatitis E is associated with hepatic and extrahepatic mortality, including among patients with indolent haematological disease or among haematopoietic stem cell transplant recipients in complete remission. Hepatitis E virus infection evolved to chronic hepatitis in five (45.5%) patients exposed to a rituximab-containing regimen and ten (47.6%) haematopoietic stem cell transplant recipients. Contaminated blood-products contributed to the burden. Alleviation of immunosuppressive therapy for hepatitis E was associated with mortality. Early ribavirin treatment was safe and effective.