BACKGROUND The aim of this study was to evaluate the long-term impact of chronic hepatitis C virus (HCV) infection on the liver in renal transplant patients. METHODS We studied 78 patients for whom at least one posttransplant liver biopsy (LB) was available and for whom the duration of HCV infection was precisely defined. The LB were graded according to a histological activity index, i.e., the Knodell score, divided into the activity score and the fibrosis score. They were also classified as either normal or showing evidence of chronic persistent hepatitis, chronic active hepatitis (CAH), or cirrhosis. RESULTS The study comprised 7 HCV-positive/hepatitis B surface antigen-positive patients (group 1); 4 HCV-positive/RNA-negative patients (group 2); and 67 HCV-positive/RNA-positive patients (group 3). The three groups were comparable according to demographic data and baseline immunosuppression. The median time from transplantation to LB was 38 months (range, 10-306 months). At that time, alanine aminotransferase (ALT) levels had increased in 71.4%, 0%, and 42% of patients from groups 1, 2, and 3, respectively (P=0.07). The total Knodell score showed significantly more severe lesions in group 1 patients (6.2+/-3.2) than in group 2 (1+/-1.2) or in group 3 (4.6+/-2.4) patients (P=0.007). The Knodell score also showed that the fibrosis score was significantly higher in group 1 (2.3+/-1.6) than in group 2 (0) or in group 3 (0.9+/-1.1) patients (P=0.007). Overall, there were 28 cases of CAH (36%) and 4 cases of cirrhosis (5%). We did not observe any correlation between liver histology and characteristics of HCV infection or the type of chronic immunosuppression (double-drug versus triple-drug therapy). However, liver histology (total Knodell score) and the activity score were significantly correlated with ALT levels. Multivariate analysis did identify (i) four independent variables that could explain the degree of liver fibrosis-the sex of the patient, the number of blood units received before transplantation, increased ALT levels at the time of LB, and the occurrence of at least one acute rejection episode (thus the receipt of methylprednisolone pulses); and (ii) two independent variables associated with the occurrence of CAH-the number of blood units before transplantation and increased ALT levels at the time of LB. CONCLUSIONS This study showed that renal transplant patients infected by HCV for more than 10 years, with a mean posttransplant follow-up of more than 5 years, showed more severe liver lesions when coinfected by hepatitis B virus. Overall, we observed only four cases of cirrhosis (5%) and evidence of histological CAH lesions in 36% of the patients.