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Influence of Immunosuppressive Therapy on the Natural History of Genotype 3 Hepatitis-E Virus Infection After Organ Transplantation

Kamar, Nassim1,2,8; Abravanel, Florence3,4; Selves, Janick5; Garrouste, Cyril1; Esposito, Laure1; Lavayssière, Laurence1; Cointault, Olivier1; Ribes, David1; Cardeau, Isabelle1; Nogier, Marie Béatrice1; Mansuy, Jean Michel3,4; Muscari, Fabrice6; Peron, Jean Marie7; Izopet, Jacques3,4; Rostaing, Lionel1,4

doi: 10.1097/TP.0b013e3181c4096c
Clinical and Translational Research

Background. Hepatitis-E virus (HEV) infection can be responsible for chronic hepatitis in solid-organ transplant patients.

Methods. We identified 33 cases of autochthonous acute HEV infection in solid-organ transplant patients.

Results. Among 27 HEV-positive patients, who had a follow-up of more than 6 months, 16 (59.25%) evolved to chronic HEV infection, defined by persisting elevated liver-enzyme levels and positive serum HEV RNA 6 months after diagnosis. Serial liver biopsies showed progression in liver activity and liver fibrosis. Three patients developed liver cirrhosis. The proportion of patients receiving tacrolimus compared with cyclosporine A was significantly higher in patients who evolved to chronic disease. Immunosuppressive therapy was reduced in patients with chronic hepatitis; however, those who had a dramatic decrease in tacrolimus trough levels were more likely to clear the virus. Four chronic liver transplant patients were cleared off the virus at 14, 16, 22, and 23 months after diagnosis. At last follow-up, their tacrolimus trough levels and daily steroid doses were significantly lower than those who remained viremic. These four patients had lower liver-enzyme levels and lower activity scores on liver biopsies, and their peripheral blood CD3- and CD4-positive cell counts were also significantly higher.

Conclusions. The rate of chronic HEV-related hepatitis is approximately 60% in solid-organ transplant patients. When possible, the reduction of immunosuppressive drugs targeting T cells should be considered as a first-line therapeutic option.

1 Department of Nephrology, Dialysis and Multi-Organ Transplantation, CHU Rangueil, Toulouse, France.

2 INSERM U858, IFR –BMT, CHU Rangueil, Toulouse, France.

3 Department of Virology, CHU Purpan, Toulouse, France.

4 INSERM U563, IFR–BMT, CHU Purpan, Toulouse, France.

5 Department of Histopathology, CHU Purpan, Toulouse, France.

6 Department of Liver Transplantation, CHU Rangueil, France.

7 Department of Hepatology, CHU Purpan, Toulouse, France.

8 Address correspondence to: Nassim Kamar, M.D., Ph.D., Department of Nephrology, Dialysis and Multi-organ Transplantation, CHU Rangueil, TSA 50032, 31059 Toulouse Cedex 9, France.


NK designed the study, did the patients' follow-up, and wrote the article. FA and JMM did the virological analysis. JS did the pathological analysis. CG collected the data. LE, LL, OC, DR, IC, MBN, and JMP did the patients' follow-up. FM performed the liver transplantations. JI reviewed the article and the virological analysis. LR participated in the patients' follow-up and reviewed the article.

Received 23 July 2009. Revision requested 17 August 2009.

Accepted 10 September 2009.

© 2010 Lippincott Williams & Wilkins, Inc.