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

Abstract

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.