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 48weeks 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.

Abbreviations: HCV, hepatitis C virus, HCC, hepatocellular carcinoma, SVR, sustained viral response, PEG-IFN/RBV, pegylated interferon and ribavirin, LT, liver transplantation, FCH, fibrosing cholestatic hepatitis, ISDR, interferon sensitivity-determining region, IRRDR, interferon/ribavirin resistance-determining region, NS5A, nonstructual protein 5A gene, G-CSF, granulocyte colony-stimulating factor, EPO, erythropoietin, PCR, polymerase chain reaction, NR, non-response, VR, viral response, aa, amino acid, MELD, model for end-stage liver disease, DW, double wild, PKR, double-strand RNA-activated protein kinase, HVR-1, hypervariable region-1, EVR, early viral response

Keywords: Hepatitis C virus, Genetic mutation, Interferon, Ribavirin, Liver transplantation