FibroTest™ Is an Independent Predictor of Early and Sustained Virologic Response in Nonresponder Patients With Chronic Hepatitis C: Results From the EPIC 3 Study

EPIC 3 , a prospective, international, multicenter, open-label study, demonstrated the efficacy and safety of PEG-2b plus weight-based ribavirin in chronic hepatitis C patients with significant fibrosis who previously failed any interferon-alfa/ribavirin combination therapy. The aim of the present study was to assess if FibroTest™, a validated noninvasive marker of fibrosis in naive patients, is also an alternative to biopsy as a predictor of early virologic (EVR) and sustained virologic response (SVR) in previously treated patients. Methods: Patients enrolled in EPIC 3 were included in this evaluation if they had available 12 weeks' virology (TW12), interpretable baseline FT, and biopsy. Univariate (UV) and multivariate (MV) analysis for SVR was performed using a complete model that included FT and biopsy. Results: Of 2312 patients enrolled, 1459 had available baseline FT, biopsy, and complete data. Baseline characteristics: 70% male, median age 51 yr; METAVIR, 28% F2, 29% F3, and 43% F4; previous relapsers, 29%; previous PEG regimen 41%; and high (>6 × 10 5 IU/mL) baseline viral load (BVL), 64%. Patients received PEG-2b 1.5 µg/kg/wk plus weight-based ribavirin (800-1400 mg/d) for 12-18 weeks; 506 (35%) had undetectable serum hepatitis C virus (HCV)-RNA at TW12 (TW12 neg); 678 (46%) were treated 48 weeks, with 24 weeks follow-up. SVR was 58% among 506 patients TW12 neg, 13% among 108 patients with detectable but ≥2 log drop in viral load and 0% among 43 patients with <2 log drop. The accuracy of FT for the diagnosis of fibrosis was similar to previous validations: area under the ROC curve for the diagnosis of F4 vs F2=0.80 (P<.00001), when standardized according to fibrosis stages' prevalences. Five baseline factors were significantly ( P<.001) associated with SVR, in UV and MV analyses (odds ratio: UV/MV): fibrosis stage estimated using FT (4.5/5.9) or biopsy (1.5/1.6), genotype 2/3 (4.5/5.1), BVL (1.5/1.3), prior relapse (1.6/1.6), and previous treatment with non-PEG (2.6/2.0). Similarly, these same factors were significantly ( P≤.001) associated with EVR: fibrosis stage estimated using FT (3.8/4.8) or biopsy (1.2/1.3), genotype 2/3 (11/9), BVL (1.6/1.3), prior relapse (6.2/6.5), and previous treatment with non-PEG (2.6/2.0). Among patients TW12 neg (n=506), only two factors remained highly predictive of SVR by MV analysis (P≤.001): genotype 2/3 (odds ratio=2.9), and fibrosis estimated with FT (4.3) or by biopsy (1.5). Conclusions: FibroTest™ is a noninvasive alternative to biopsy for the prediction of EVR at 12 weeks and for prediction of SVR, in patients with previous failures, retreated with peginterferon alfa-2b and ribavirin, both at baseline and at week 12. BackgroundAssessment of fibrosis stage is useful for predicting therapeutic outcomes in patients undergoing treatment for chronic hepatitis C.