Peg-IFN and ribavirin treatment for recurrence of genotype 2 and 3 hepatitis C after liver transplantation

Abstract

Background: Relapse of hepatitis C virus (HCV) infection after liver transplantation (LT) is universal. Tolerance for treatment with pegylated-interferon (peg-IFN) and ribavirin (RBV) is suboptimal and withdrawals due to adverse events frequent. We sought to improve tolerance for treatment to improve outcome. Methods: We used concentration-guided RBV dosing to achieve an intended 10 μmol/L concentration with darbepoetin support in combination with peg-IFN alfa-2a, 180 μg for genotype 1 and 135 μg for genotype 2/3 to improve tolerance. Results: A total of 51/54 patients (94%) completed a full treatment course. In the per-protocol analysis 43% of patients (22/51) achieved sustained virological response (SVR), 82% with HCV genotype 2/3 and 22% with genotype 1, p = 0.0001. Patients with IL28B CC achieved SVR in 73% (8/11) and patients with non-CC in 33% (14/43), p = 0.016. Patients with mild fibrosis (fibrosis stage 1–2) achieved SVR in 56% (15/27), and patients with advanced fibrosis (fibrosis stage 3–4) in only 26% (7/27), p = 0.0267. Conclusions: Concentration-guided RBV dosing with darbepoetin support substantially improves tolerance and offers high adherence to a full peg-IFN and RBV treatment course in patients with post-transplant HCV relapse. With this approach genotype 2 and 3 infections can be treated cost-effectively post-transplant. Genotype 1, IL28B non-CC genotype, and advanced fibrosis predicted a low SVR rate.