Mutations in hepatitis C virus genotype 1b and the sensitivity of interferon-ribavirin therapy after liver transplantation

Background & Aims: The results of post-transplant antiviral therapy for recurrent hepatitis C virus (HCV) are poor, and significant pre-transplant predictors for sustained viral response (SVR) have not yet been identified. Methods: Pegylated interferon/ribavirin therapy was performed for more than 48 weeks in 50 patients who underwent liver transplantation (LT) for HCV genotype 1-related liver disease. Of these, 22 patients achieved SVR. The predictive potential of the viral mutations, including amino acids (aa) 70 and 91 in the Core region, interferon sensitivity-determining region (ISDR, aa 2209-2248) and interferon/ribavirin resistance-determining region (IRRDR, aa 2334-2379) in NS5A, was evaluated. Results: In 16 patients, the sequences in the pre- and post-transplant samples were the same, except for aa 70 in the Core of 1 patient. The SVR achievement percentage was significantly lower in the Non-double wild (DW) at aa 70 and 91, the ISDR < 2 and IRRDR < 6 groups than in the DW (30% vs. 65%, p = 0.015), the ISDR ≥ 2 (35% vs. 69%, p = 0.035) and IRRDR ≥ 6 (25% vs. 78%, p <0.001) groups, respectively. Predictive scoring with these three items provides a newly established and significant predictor for SVR after LT (p = 0.015). Conclusion: DW, ISDR ≥ 2 and IRRDR ≥ 6 were found to be significant predictors for SVR after LT. In addition, it is possible that the establishment of a new scoring system consisting of these three factors may be a useful marker to predict interferon sensitivity for recurrent HCV after LT.