title: Successful treatment with telaprevir-based regimens for chronic hepatitis C results in significant improvements to serum markers of liver fibrosis.
abstract: Patients infected with hepatitis C virus (HCV) have differing levels of liver health when they initiate treatment. We sought to quantify whether liver health improves following successful treatment with telaprevir-based antiviral regimens. We performed a retrospective analysis of data generated from one Phase 2 and two Phase 3 telaprevir clinical studies. 1208 patients treated with a telaprevir-based regimen were included in the analysis. Patients were grouped according to their baseline Metavir score (F0-F1, F2 and F3-F4) and whether or not they attained sustained virologic response (SVR). Scores from four biomarker tests, FibroTest, APRI, FIB-4 and Forns' Score, were monitored both before and after HCV treatment. All four of these tests differentiated the fibrosis stage as determined by Metavir score at baseline. Consistent with previous studies, patients who attained SVR exhibited significant improvements in scores from each of these tests after treatment. These improvements remained significant even when patients were grouped according to their baseline Metavir score. On average, the scores from different tests exhibited differential improvements following SVR. Improvements in APRI scores corresponded to complete fibrosis regression (i.e. a Metavir stage of F0-F1). In contrast, improvements in scores from Forns' Score, FIB-4 and FibroTest were more modest (i.e. fibrosis regression of less than a Metavir stage). Overall, these results demonstrated that attaining SVR with a telaprevir-based regimen led to significant improvements in liver health as determined by four biomarker tests. However, not all correlations observed between noninvasive markers and fibrosis stage at baseline hold after SVR is attained.
authors.affiliation: Vertex Pharmaceuticals Incorporated, Boston, MA, USA.
authors.forename: E L
authors.initials: EL
authors.lastname: Haseltine
authors.affiliation: Vertex Pharmaceuticals Incorporated, Boston, MA, USA.
authors.forename: M S
authors.initials: MS
authors.lastname: Penney
authors.affiliation: Vertex Pharmaceuticals Incorporated, Boston, MA, USA.
authors.forename: S
authors.initials: S
authors.lastname: George
authors.affiliation: Vertex Pharmaceuticals Incorporated, Boston, MA, USA.
authors.forename: T L
authors.initials: TL
authors.lastname: Kieffer
mesh_terms: D000998:Antiviral Agents / Q000627:therapeutic use*; D015415:Biomarkers; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D005260:Female; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000188:drug therapy*; D006801:Humans; D008103:Liver Cirrhosis / Q000473:pathology*; D008297:Male; D009842:Oligopeptides / Q000627:therapeutic use*; D012189:Retrospective Studies; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D015415:Biomarkers; D009842:Oligopeptides; C486464:telaprevir
keywords: fibrosis regression; hepatitis C viral infection; surrogate markers; sustained virologic response; telaprevir