Early identification of recipients with progressive histologic recurrence of hepatitis C after liver transplantation

Approximately half of patients undergoing liver transplantation (LT) for hepatitis C virus (HCV) develop histologic evidence of recurrence within the first postoperative year. Early identification of recipients at risk for more severe recurrence of HCV may be useful in selecting patients for antiviral therapy. We determined whether recipients at greatest risk for more severe recurrence of HCV can be identified by pre- and/or early post-LT HCV-RNA levels in serum or tissue. Serum and tissue samples were prospectively collected pre-LT and at 7 days, 4 months, 1 year, and at 3 years posttransplantation from patients undergoing LT for HCV. Hepatitis activity index (HAI) and fibrosis stage (FS) were assessed in all liver biopsies. Forty-seven patients (32 men) were studied. Higher HCV-RNA levels at 4 months post-LT (≥10⁹ copies/mL, n = 29) were associated with higher HAI at 1 year and at 3 years post-LT. The HAI seen on protocol biopsies at 4 months correlated significantly with fibrosis stage (FS) at 1 year (r = .56, P ≤ .001) and 3 years (r = .53, P = .002). Higher HCV-RNA levels at 7 days and 4 months post-LT were sensitive (66% and 84%, respectively) and specific (92% and 63%, respectively) in identifying recipients with an HAI greater than 3 at 3 years. Higher pre- and early post-LT HCV-RNA levels are associated with more severe recurrence of HCV. The correlation of early HAI with subsequent FS suggests that higher mean HAI will eventually translate into more advanced stages of fibrosis. Patients at risk for more severe post-LT recurrence of HCV can be identified by early posttransplant HCV-RNA levels.