Very Early Viral Kinetics on Interferon Treatment in Chronic Hepatitis C virus Genotype 4 Infection

Abstract

Background

Interferon (IFN)-resistant hepatitis C virus strains limit efficacy of antiviral combination therapy in patients infected with genotypes 1 and 4. A single test dose of IFN was useful to identify non-responders to IFN-α2b/ribavirin (RBV) or likely non-responders to pegylated (PEG)-IFN-α2a/RBV therapy in genotype 1 patients. Our aim was to investigate this approach in genotype 4 patients.

Methods

Viral load was measured in 46 patients before and 24 h after 10 megaunits (MU) IFN-α2b, and before and during 2 weeks of daily 5 MU IFN-α2b administration. Thereafter, patients received 48 weeks combination therapy with either 180 μg PEG-IFN-α2a/week (n=33), 1.5 μg/kg PEG-IFN-α2b/week (n=7) or 5 MU IFN-α2b/2 days (n=6), along with 1–1.2g RBV/day. For prediction analysis the largest group (PEG-IFN-α2a) was evaluated only.

Results

Median 24 h log₁₀ change after 10 MU IFN-α2b was 1.15 (range 0.08–2.48) and after 5 MU IFN-α2b was 0.81 (-0.12–2.22; P<0.0001). Log₁₀ changes after 2 weeks on 5 MU IFN-α2b daily and 24 h after 10 MU were the best predictors of early virological response (defined by negativity of a standard qualitative PCR) to PEG-IFN-α2a/RBV combination therapy (area under curve [AUC]=0.97; P<0.001, receiver operating characteristics), 24 h log₁₀ change after 10 MU was the best predictor of sustained virological response (SVR; AUC=0.91, P=0.001).

Conclusion

As in genotype 1 patients, there is large variation in IFN responsiveness, including the presence of resistant strains, in genotype 4 patients. A 24 h log₁₀ change after 10 MU IFN-α2b is an excellent predictor of SVR on PEG-IFNα2a/RBV combination therapy. This test may be useful to obtain homogeneous groups for clinical studies and could help in clinical decision making.