Sustained Virologic Response Predicts Fibrosis Regression Measured by FibroTest in HCV-infected Patients

Abstract

Introduction: Sustained virologic response (SVR) after treatment of chronic hepatitis C virus (HCV) reduces the risk for fibrosis progression. The 3 direct-acting antiviral regimen of ombitasvir (OBV), paritaprevir (identified by AbbVie and Enanta, co-dosed with ritonavir [PTV/r]), and dasabuvir (DSV) with or without ribavirin (RBV) has shown high SVR rates in HCV genotype (GT) 1 infected patients with or without cirrhosis. We assessed factors predictive of improvements in fibrosis from baseline as measured by FibroTest. Methods: TURQUOISE-II (GT1 with compensated cirrhosis) and TOPAZ-II (GT1 with or without compensated cirrhosis) patients treated with OBV/PTV/r + DSV ± RBV for 12 or 24 weeks,with FibroTest scores at baseline and at least one post-treatment week (PTW) visit were included. Stepwise logistic regression assessed the relative contribution of baseline factors, including fibrosis stage, sex, age, BMI, achievement of SVR, prior HCV treatment status, platelet count, ALT, and albumin on improvement from baseline in FibroTest score. FibroTest-derived fibrosis stage change from baseline was evaluated. The upper thresholds for METAVIR F0-1, F2, and F3 were 0.48, 0.58, and 0.72, respectively. Results: FibroTest scores at baseline and at one post-treatment visit were available for 882 patients, of whom 413 (47%) had F4 baseline METAVIR scores. For patients with PTW12 data, fibrosis stage regression occurred in 197/396 (50%) F4 patients, 73/114 (64%) F3 patients, 59/86 (69%) F2 patients, and was stable in 250/260 (96%) F0-1 patients (Table). In patients achieving SVR subgrouped by baseline METAVIR score, FibroTest least square mean changes from baseline were significantly different from no change. These changes were statistically different from those in patients that did not achieve SVR (F4: -0.17 vs -0.11; F3: -0.15 vs +0.05; F2: -0.13 vs +0.23; F0-1: -0.05 vs +0.07 for SVRs vs non-SVRs respectively). Achievement of SVR was strongly associated with FibroTest score improvement and patients with BL F4 fibrosis were more likely to have improvement than patients with F0-1, though not compared to patients with F2 or F3 fibrosis. Conclusion: Improvements in mean FibroTest score were observed in patients treated with OBV/PTV/r + DSV ± RBV and achieving SVR, irrespective of baseline score. Achievement of SVR was a predictor of improvement in FibroTest score and led to FibroTest-derived fibrosis stage regression for the majority with baseline F2 - F4 fibrosis.Table 1: Cross-Tabulation of Number and Proportion of Patients by Baseline and PTW12 FibroTest-Derived METAVIR Scores, n (%)