The role of different immunosuppression in the long-term histological outcome of HCV reinfection after liver transplantation for HCV cirrhosis

Background. The effect of the type of immunosuppression on the course of posttransplant hepatitis C virus (HCV) infection is unclear. The aim of this study was to evaluate the histological outcome of posttransplant HCV infection with respect to initial immunosuppressive therapy in a cohort of 59 of 65 HCV positive transplant patients who survived at least 12 months. Methods. Initial immunosuppressive therapy was triple (cyclosporine or tacrolimus and azathioprine and prednisolone) in 41, double (cyclosporine and prednisolone) in 5, and single (cyclosporine or tacrolimus) in 13 patients. There was blinded histological evaluation, based on necroinflammatory activity (grading score:0-18) and fibrosis (staging score:0-6). The median histological follow-up was 36 (12-72) months. Results. In the last liver biopsy, high necroinflammatory activity indicating chronic hepatitis (grading score greater than or equal to4) was found in 42 (71%) and severe fibrosis or cirrhosis (staging score greater than or equal to4) in 18 (30.5%) patients. High necroinflammatory activity was associated significantly with absence of pretransplant alcohol abuse (P=0.01) and relatively with occurrence of posttransplant acute lobular hepatitis C (P=0.055). Development of severe fibrosis or cirrhosis was significantly associated only with the type of initial immunosuppressive therapy. In particular, severe fibrosis or cirrhosis developed significantly more frequently in patients treated with triple or double (17/46 or 37%) than with single initial immunosuppressive therapy (1/13 or 7.7%) (adjusted for biopsy time: P=0.045). Conclusions. Severe fibrosis or cirrhosis appears to develop in 30% of HCV transplant patients in a median of 3 years and to be associated with heavier initial immunosuppression.