Influence of immunosuppressive therapy on the natural history of genotype 3 hepatitis-E virus infection after organ transplantation.
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.
Department of Nephrology, Dialysis and Multi-Organ Transplantation, CHU Rangueil, Toulouse, France. kamar.n@chu-toulouse.fr
Nassim
N
Kamar
Florence
F
Abravanel
Janick
J
Selves
Cyril
C
Garrouste
Laure
L
Esposito
Laurence
L
Lavayssière
Olivier
O
Cointault
David
D
Ribes
Isabelle
I
Cardeau
Marie Béatrice
MB
Nogier
Jean Michel
JM
Mansuy
Fabrice
F
Muscari
Jean Marie
JM
Peron
Jacques
J
Izopet
Lionel
L
Rostaing
D000410:Alanine Transaminase / Q000097:blood; D001219:Aspartate Aminotransferases / Q000097:blood; D001663:Bilirubin / Q000097:blood; D005260:Female; D005838:Genotype; D016751:Hepatitis E / Q000097:blood / Q000601:surgery; D016752:Hepatitis E virus / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008103:Liver Cirrhosis / Q000601:surgery / Q000821:virology; D016031:Liver Transplantation / Q000276:immunology*; D008297:Male; D016896:Treatment Outcome; D019562:Viral Load
D007166:Immunosuppressive Agents; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D001663:Bilirubin