Effective prediction of outcome of combination therapy with pegylated interferon alpha 2b plus ribavirin in Japanese patients with genotype-1 chronic hepatitis C using early viral kinetics and new indices.

BACKGROUND: The rates of sustained virologic response (SVR) and relapse with pegylated interferon alpha 2b (peginterferon) plus ribavirin in patients with genotype-1 chronic hepatitis C (CHC) are approximately 50 and 30%, respectively. We investigated whether SVR and transient response (TR) can be differentiated during treatment using new indices calculated from early viral kinetics and the timing of when hepatitis C virus (HCV)-RNA becomes undetectable. METHODS: Peginterferon alpha 2b (1.5 microg/kg per week) plus weight-based ribavirin (600-1,000 mg/day) were administered to 141 patients with genotype-1 CHC for 48 weeks. The HCV-RNA loads were measured at baseline, 24 h, week 1, and week 2. The rebound index (RI, viral load at week 1 divided by viral load at 24 h) and the second rebound index (RI-2nd, viral load at week 2 divided by viral load at 24 h) were calculated. RESULTS: With SVR, the viral load was reduced at 24 h, did not rise during week 1 (RI < or = 1.0), and was significantly reduced at week 2 (P < 0.05). Viral loads with TR and non-response increased at week 1. The SVR rate was 90% with RI < or = 1.0, 96% with rapid viral responders, and 93% with RI-2nd < 0.7 and week 8 early viral responders. The SVR rate with these 3 groups was 90% and administration for 48 weeks was recommended. With other groups, the SVR rate was 23% and the TR rate was 77%. Administration for 72 weeks was therefore recommended. CONCLUSIONS: We distinguished SVR from TR during treatment using two indices (RI and RI-2nd) and the timing of HCV-RNA negativity.