Hepatitis E virus: an underestimated opportunistic pathogen in recipients of allogeneic hematopoietic stem cell transplantation.

Hepatitis E virus (HEV) is increasingly acknowledged as a cause of hepatitis in healthy individuals as well as immunocompromised patients. Little is known of HEV infection in recipients of allogeneic hematopoietic stem cell transplantation (alloHSCT). Therefore, we set out to study the incidence and sequelae of HEV as a cause of hepatitis in a recent cohort of 328 alloHSCT recipients. HEV RNA was tested in episodes of liver enzyme abnormalities. In addition, HEV RNA and HEV serology were assessed pre- and post-alloHSCT. We found 8 cases (2.4%) of HEV infection, of which 5 had developed chronic HEV infection. Seroprevalence pre-alloHSCT was 13%. Four patients died with HEV viremia, with signs of ongoing hepatitis, having a median time of infection of 4.1 months. The 4 surviving patients cleared HEV after a median period of 6.3 months. One patient was diagnosed with HEV reactivation after a preceding infection prior to alloHSCT. Although the incidence of developing acute HEV post-alloHSCT is relatively low, the probability of developing chronic hepatitis in severely immunocompromised patients is high. Therefore, alloHSCT recipients should be screened pretransplantation by HEV serology and RNA. Furthermore, a differential diagnosis including hepatitis E is mandatory in all alloHSCT patients with severe liver enzyme abnormalities.

[1]  S. Görg,et al.  Seroprevalence and incidence of hepatitis E virus infection in German blood donors , 2014, Transfusion.

[2]  N. Schmitz,et al.  Fatal course of an autochthonous hepatitis E virus infection in a patient with leukemia in Germany , 2012, Infection.

[3]  S. Nick,et al.  Occurrence of hepatitis E virus RNA in plasma donations from Sweden, Germany and the United States , 2012, Vox sanguinis.

[4]  J. Izopet,et al.  Low risk of hepatitis E virus reactivation after haematopoietic stem cell transplantation. , 2012, Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology.

[5]  M. Koopmans,et al.  Hepatitis E Virus Infection among Solid Organ Transplant Recipients, the Netherlands , 2012, Emerging infectious diseases.

[6]  A. Ganser,et al.  Chronic hepatitis E in hematopoietic stem cell transplant patients in a low‐endemic country? , 2012, Transplant infectious disease : an official journal of the Transplantation Society.

[7]  B. van der Holt,et al.  Insufficient recovery of thymopoiesis predicts for opportunistic infections in allogeneic hematopoietic stem cell transplant recipients , 2011, Haematologica.

[8]  J. Dumortier,et al.  Factors associated with chronic hepatitis in patients with hepatitis E virus infection who have received solid organ transplants. , 2011, Gastroenterology.

[9]  R. Tedder,et al.  Is there evidence of recent hepatitis E virus infection in English and North Welsh blood donors? , 2011, Vox sanguinis.

[10]  L. Rostaing,et al.  Hepatitis E Virus Infection without Reactivation in Solid-Organ Transplant Recipients, France , 2011, Emerging infectious diseases.

[11]  L. Rostaing,et al.  Ribavirin therapy inhibits viral replication on patients with chronic hepatitis e virus infection. , 2010, Gastroenterology.

[12]  O. Wichmann,et al.  Transmission routes and risk factors for autochthonous hepatitis E virus infection in Europe: a systematic review , 2009, Epidemiology and Infection.

[13]  B. Dörken,et al.  Reactivation of hepatitis E infection in a patient with acute lymphoblastic leukaemia after allogeneic stem cell transplantation , 2009, Gut.

[14]  H. Dalton,et al.  Hepatitis E: an emerging infection in developed countries. , 2008, The Lancet. Infectious diseases.

[15]  Jonathan K. Mitchell,et al.  Autochthonous hepatitis E in Southwest England: natural history, complications and seasonal variation, and hepatitis E virus IgG seroprevalence in blood donors, the elderly and patients with chronic liver disease , 2008, European journal of gastroenterology & hepatology.

[16]  Harry Vennema,et al.  Chronic hepatitis E virus infection in liver transplant recipients , 2008, Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society.

[17]  L. Rostaing,et al.  Hepatitis E virus and chronic hepatitis in organ-transplant recipients. , 2008, The New England journal of medicine.

[18]  M. Bouwknegt,et al.  Hepatitis E virus RNA in commercial porcine livers in The Netherlands. , 2007, Journal of food protection.

[19]  H. Dalton,et al.  The role of hepatitis E virus testing in drug‐induced liver injury , 2007, Alimentary pharmacology & therapeutics.

[20]  B. van der Holt,et al.  A comparison of postengraftment infectious morbidity and mortality after allogeneic partially T cell-depleted peripheral blood progenitor cell transplantation versus T cell-depleted bone marrow transplantation. , 2005, Experimental hematology.

[21]  E. Wils,et al.  Thymopoiesis following allogeneic stem cell transplantation: new possibilities for improvement. , 2005, Blood reviews.

[22]  F. Miedema,et al.  Impaired recovery of Epstein-Barr virus (EBV)--specific CD8+ T lymphocytes after partially T-depleted allogeneic stem cell transplantation may identify patients at very high risk for progressive EBV reactivation and lymphoproliferative disease. , 2003, Blood.

[23]  K. Sullivan,et al.  Infectious morbidity in long‐term survivors of allogeneic marrow transplantation is associated with low CD4 T cell counts , 1997, American journal of hematology.

[24]  F. T. ten Kate,et al.  Clinical implications of chronic hepatitis E virus infection in heart transplant recipients. , 2013, The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation.