High Incidence of Allograft Cirrhosis in Hepatitis C Virus Genotype 1B Infection Following Transplantation: Relationship With Rejection Episodes

Abstract

The natural history of hepatitis C virus (HCV) infection following liver transplantation and predictors of disease severity remain controversial. The aims of the study were to assess in a homogeneous population of 81 cyclosporine–based HCV–infected liver transplant recipients mostly infected with genotype 1b and undergoing strict protocol annual biopsies: 1) the histological progression of posttransplantation HCV disease and, in particular, the incidence of HCV–related graft cirrhosis within the first 5 years after surgery; and 2) the relationship between progression to cirrhosis and i) rejection episodes and ii) first–year liver biopsy findings. We studied 81 consecutive HCV–RNA-positive patients (96% genotype 1b) undergoing liver transplantation between 1991 and 1996 with a minimum histological follow–up of 1 year. All patients received cyclosporine–based immunosuppression and underwent protocol yearly liver biopsies for the first 5 years. The mean histological follow–up was 32 months (range, 12–60 months). Biopsies were scored according to the histological activity index (HAI), with separate evaluation of grade (activity) and stage (fibrosis). Histological hepatitis, present in 97% of patients in the most recent biopsy, was moderate or severe in 64%. Twelve patients developed HCV–related cirrhosis at a median time of 24 months (range, 12–48 months), with an actuarial rate of HCV–cirrhosis of 3.7%, 8.5%, 16%, 28%, and 28% at 1, 2, 3, 4, and 5 years, respectively. Rejection was significantly more common among patients with cirrhosis versus those without (83% vs. 48%; P = .02), with an association between the incidence of cirrhosis and the number of rejection episodes: 5%, 15%, and 50% in patients without rejection, one and two episodes, respectively (P = .001). The degree of activity and fibrosis score in the first–year biopsy were higher in patients who developed cirrhosis than in those who did not (P = .008 and .18, respectively). In conclusion, HCV genotype 1b-infected liver recipients are at a high risk of developing graft cirrhosis in the first 4 to 5 years following transplantation, especially those with previous rejection episodes. First–year liver biopsies may help to sooner identify patients at the highest risk, improving further patient management.