科研之友
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摘要
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-alpha 2b/ribavirin (RBV) or likely non-responders to pegylated (PE(3)-IFN-alpha 2a/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-alpha 2b, and before and during 2 weeks of daily 5 MU IFN-alpha 2b administration. Thereafter, patients received 48 weeks combination therapy with either 180 mu g IPEGIFN-alpha 2a/week (n=33), 1.5 mu g/kg PEG-IFN-alpha 2b/week (n=7) or 5 MU IFN-alpha 2b/2 days (n=6), along with 1-1.2g RBV/day. For prediction analysis the largest group (PEG-IFN-alpha 2a) was evaluated only.
Results: Median 24 In log(10) change after 10 MU IFN-alpha 2b was 1.15 (range 0.08-2.48) and after 5 MU IFN-alpha 2b was 0.81 (-0.12-2.22; P<0.0001). Log(10) changes after 2 weeks on 5 MU IFN-alpha 2b daily and 24 h after 10 MU were the best predictors of early virological response (defined by negativity of a standard qualitative PCR) to PIEGIFN-alpha 2a/RBV combination therapy (area under curve [AUC]=0.97; P<0.001, receiver operating characteristics), 24 In log(10) change after 10 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 log,, change after 10 MU IFN-alpha 2b is an excellent predictor of SVR on PEG-IFN alpha 2a/RBV combination therapy. This test may be useful to obtain homogeneous groups for clinical studies and could help in clinical decision making.
- 出版日期2008
