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 po sttransplant hepatitis C virus (HCV) infection is unclear. The aim of this study was to evaluate the histological outcome of posttransplant HCV infect ion 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 tacr olimus and azathioprine and prednisolone) in 41, double (cyclosporine and p rednisolone) in 5, and single (cyclosporine or tacrolimus) in 13 patients. There was blinded histological evaluation, based on necroinflammatory activ ity (grading score:0-18) and fibrosis (staging score:0-6). The median histo logical follow-up was 36 (12-72) months. Results. In the last liver biopsy, high necroinflammatory activity indicati ng chronic hepatitis (grading score greater than or equal to4) was found in 42 (71%) and severe fibrosis or cirrhosis (staging score greater than or e qual to4) in 18 (30.5%) patients. High necroinflammatory activity was assoc iated significantly with absence of pretransplant alcohol abuse (P=0.01) an d relatively with occurrence of posttransplant acute lobular hepatitis C (P =0.055). Development of severe fibrosis or cirrhosis was significantly asso ciated only with the type of initial immunosuppressive therapy. In particul ar, severe fibrosis or cirrhosis developed significantly more frequently in patients treated with triple or double (17/46 or 37%) than with single ini tial 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 heavie r initial immunosuppression.