Hepatitis C is the most common indication for
liver transplantation (LT) in the United States. Recurrence of hepatitis C virus (HCV)
infection post-LT remains a problem for which there is no completely satisfactory treatment. The aim of the present study is to evaluate
mycophenolate mofetil (MMF), which has both immunosuppressive and
antiviral properties, to determine whether it is associated with a difference in the rate of HCV recurrence and also examine its impact on patient and graft survival. Between August 1995 and May 1998, a total of 106 patients who were HCV positive before LT were randomized to
tacrolimus (TAC) and
prednisone versus TAC,
prednisone, and MMF
therapy. The rate of recurrence of HCV, patient and graft survival, incidences of rejection, and histological findings were examined. Fifty six patients were randomized to TAC and
steroid therapy (double [D] drug; group D), and 50 patients were randomized to TAC,
steroid, and MMF
therapy (triple [T] drug; group T). Liver biopsies were performed when liver function was abnormal; protocol liver biopsies were not performed. Mean follow-up was 4.3 +/- 0.8 years. Actuarial patient survivals at 4 years were 72.6% in group D and 73.8% in group T (P = not significant). Actuarial graft survivals at 4 years were 65.6% in group D and 65.4% in group T. One patient in group D and 2 patients in group T underwent a second LT for recurrent HCV. One patient in each group died of recurrent HCV without re-LT. Twenty-six patients in group D (46.4%) and 23 patients in group T (46.0%) showed signs of recurrent HCV. Mean
hepatitis activity index (HAI) scores were 7.4 +/- 2.7 in group D and 7.0 +/- 3.4 in group T, and mean
fibrosis scores were 2.9 +/- 1.7 in group D and 2.6 +/- 1.1 in group T. The rate of rejection was 0.57/patient in each group for the entire follow-up period. None of these values reached statistical significance. Rates of HCV recurrence, graft loss or death from recurrent HCV, and 4-year actuarial patient and graft survival were not different between the groups. In
liver transplant recipients with HCV, MMF has no impact on patient survival, graft survival, rejection, or rate of HCV recurrence based on biochemical changes and histological findings. In addition, there was no difference in HAI or
fibrosis score between the two groups. Either MMF has no anti-HCV effect or its immunosuppressive properties overwhelm its
antiviral effect in the clinical setting.