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Purpose: Advanced liver fibrosis is a negative predictor of virologic response in genotype 1 chronic hepatitis C (CHC) patients. Biopsy, however, is invasive, costly, and carries some risk of complications. Methods: Using data from the prospective, international cohort study PROPHESYS, we assessed two alternative noninvasive measures of fibrosis, the FIB-4 and AST-to-platelet ratio index (APRI), to predict virologic response in CHC patients. Results: CHC genotype 1, monoinfected, treatment-naive patients prescribed peginterferon alfa-2a (40 KD)/ribavirin in accordance with country-specific legal and regulatory requirements and who had baseline METAVIR, FIB-4, and APRI scores ( N = 1,592) were included in this analysis. Patients were stratified according to the baseline METAVIR, FIB-4, or APRI score to assess virologic response [hepatitis C virus (HCV) RNA <50 IU/mL] by week 4 of treatment (rapid virologic response) and 24 weeks after untreated follow-up ]sustained virologic response (SVR)]. Baseline predictors of SVR were explored by multiple logistic regression, and the strength of the association between each fibrosis measure and SVR was evaluated. Both FIB-4 and APRI scores increased with increasing levels of biopsy-assessed fibrosis. The association between FIB-4 and SVR ( p < 0.1 × 10) was stronger than that between METAVIR ( p = 3.86 × 10) or APRI ( p = 5.48 × 10) and SVR. Baseline factors significantly associated with SVR included male gender, lower HCV RNA, lower FIB-4 score, no steatosis, and higher alanine aminotransferase ratio. Conclusion: The FIB-4 index provides a valuable, noninvasive measure of fibrosis and can be used to predict virologic response in patients treated with peginterferon alfa-2a (40 KD)/ribavirin. [ABSTRACT FROM AUTHOR]

The 2 reported trials investigated the effectiveness of treatment with peginterferon alfa-2a in Asian patients with chronic hepatitis B (CHB). Patients with HBeAg-positive ( n = 708) or HBeAg-negative ( n = 332) CHB were enrolled in 2 randomized, double blind, placebo-controlled studies. Patients received peginterferon alfa-2a 180 μg once weekly, peginterferon plus lamivudine 100 mg per day, or lamivudine alone for 48 weeks. Patients were followed up at 6 and 12 months posttreatment. Peginterferon alfa-2a provided significantly higher rates of HBeAg seroconversion (31%) in HBeAg-positive patients than did lamivudine (19%, P = 0.005) 6 months posttreatment, irrespective of genotype. Of these, 83% achieving seroconversion during treatment or early posttreatment sustained their response at 12 months posttreatment. In patients who seroconverted, 69% maintained HBV DNA suppression at <10,000 copies/ml and alanine aminotrasferase (ALT) normalization. In HBeAg-negative patients, peginterferon produced a significantly higher combined response of HBV DNA at <20,000 copies/ml and ALT normalization (45%) than lamivudine (31%, P = 0.032), irrespective of genotype. Almost 80% of these patients sustained their response at 12 months posttreatment. In conclusion, a finite course of peginterferon alfa-2a provides significant and sustained treatment benefit in Asian CHB patients, who have traditionally been regarded as difficult to treat. [ABSTRACT FROM AUTHOR]