Johann von Felden1, Laurent Alric2, Sven Pischke3, Celia Aitken4, Stefan Schlabe5, Ulrich Spengler5, Maria Teresa Giordani6, Paul Schnitzler7, Dominik Bettinger8, Robert Thimme9, Alienor Xhaard10, Mascha Binder11, Francis Ayuk12, Ansgar W Lohse13, Jan J Cornelissen14, Robert A de Man15, Vincent Mallet16. 1. I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Divisions of Liver Diseases and Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York City, NY, USA. Electronic address: j.von-felden@uke.de. 2. Department of Internal Medicine and Digestive Diseases, CHU Purpan, Toulouse, France; UMR 152, IRD Toulouse 3 University, France. 3. I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; German Centre for Infection Research (DZIF), Hamburg site, Hamburg, Germany. 4. Virology, NHS Greater Glasgow and Clyde, Glasgow, United Kingdom. 5. Department of Internal Medicine I, University of Bonn, Bonn, Germany. 6. Infectious Diseases and Tropical Medicine Unit, San Bortolo Hospital, Vicenza, Italy. 7. Department of Infectious Diseases, Virology, University of Heidelberg, Germany. 8. Department of Medicine II, Medical Center University of Freiburg, Germany; Berta-Ottenstein-Program, Faculty of Medicine, University of Freiburg, Germany. 9. Department of Medicine II, Medical Center University of Freiburg, Germany. 10. Service d'hématologie-greffe, Hôpital Saint-Louis, Université Paris Diderot, Paris, France. 11. Department of Oncology, Hematology and Bone Marrow Transplantation, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany. 12. Department of Stem Cell Transplantation, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany. 13. I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. 14. Department of Haematology, Erasmus Medical Centre, Rotterdam, Netherlands. 15. Department of Gastroenterology and Hepatology, Erasmus MC University Medical Centre, Rotterdam, Netherlands. 16. Hepatology Service, Assistance Publique - Hôpitaux de Paris, Hôpital Cochin, Université Paris Descartes, Paris, France; Institut National de la Santé et de la Recherche Médicale unité 1223, Institut Pasteur, Paris, France. Electronic address: vincent.mallet@aphp.fr.
Abstract
BACKGROUND & AIMS: The burden of hepatitis E virus (HEV) infection among patients with haematological malignancy has only been scarcely reported. Therefore, we aimed to describe this burden in patients with haematological malignancies, including those receiving allogeneic haematopoietic stem cell transplantation. METHODS: We conducted a retrospective, multicentre 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. The primary endpoint was HEV-associated mortality; the 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 8 (16%) patients, including 1 patient with iNHL and 1 patient >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 5 (10%) patients, and associated with liver-related mortality in 2 patients. Hepatitis E progressed to chronic hepatitis in 17 (34%) patients overall, and in 10 (47.6%) and 6 (50%) alloHSCT and iNHL patients, respectively. Hepatitis E was associated with acute or acute-on-chronic liver failure in 4 (8%) patients with 75% mortality. Ribavirin was administered to 24 (48%) patients, with an HEV clearance rate of 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 <24 and <12 weeks after diagnosis of hepatitis E, respectively. Immunosuppressive treatment reductions were associated with mortality in 2 patients (28.6%). CONCLUSION: Hepatitis E is associated with mortality and liver-related morbidity in patients with haematological malignancy. Blood-borne transmission contributes to the burden. Ribavirin should be initiated early, whereas reduction 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 disease or among stem cell transplant recipients in complete remission. Hepatitis E virus infection evolved to chronic hepatitis in 5 (45.5%) patients exposed to a rituximab-containing regimen and 10 (47.6%) stem cell transplant recipients. Reducing immunosuppressive therapy because of hepatitis E was associated with mortality, while early ribavirin treatment was safe and effective. Crown
BACKGROUND & AIMS: The burden of hepatitis E virus (HEV) infection among patients with haematological malignancy has only been scarcely reported. Therefore, we aimed to describe this burden in patients with haematological malignancies, including those receiving allogeneic haematopoietic stem cell transplantation. METHODS: We conducted a retrospective, multicentre 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. The primary endpoint was HEV-associated mortality; the 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 8 (16%) patients, including 1 patient with iNHL and 1 patient >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 5 (10%) patients, and associated with liver-related mortality in 2 patients. Hepatitis E progressed to chronic hepatitis in 17 (34%) patients overall, and in 10 (47.6%) and 6 (50%) alloHSCT and iNHL patients, respectively. Hepatitis E was associated with acute or acute-on-chronic liver failure in 4 (8%) patients with 75% mortality. Ribavirin was administered to 24 (48%) patients, with an HEV clearance rate of 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 <24 and <12 weeks after diagnosis of hepatitis E, respectively. Immunosuppressive treatment reductions were associated with mortality in 2 patients (28.6%). CONCLUSION:Hepatitis E is associated with mortality and liver-related morbidity in patients with haematological malignancy. Blood-borne transmission contributes to the burden. Ribavirin should be initiated early, whereas reduction 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 disease or among stem cell transplant recipients in complete remission. Hepatitis E virus infection evolved to chronic hepatitis in 5 (45.5%) patients exposed to a rituximab-containing regimen and 10 (47.6%) stem cell transplant recipients. Reducing immunosuppressive therapy because of hepatitis E was associated with mortality, while early ribavirin treatment was safe and effective. Crown
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