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.

Regression of liver stiffness after sustained hepatitis C virus (HCV) virological responses among HIV/HCV-coinfected patients

“…In addition, a reduction in elastometry values does not necessarily signify fibrosis regression, although the effect of SVR on liver stiffness persisted in adjusted analyses and also in sensitivity analyses, one of which used a more stringent definition of liver stiffness regression (two consecutive values showing at least a 30% improvement). Furthermore, in robustness analyses using FIB4 as a different noninvasive marker or liver fibrosis, we identified again an independent effect of SVR on regression in FIB4 values, which is in accordance with recent findings in HCV-monoinfected patients successfully treated with telaprevir-based regimens [32].…”

Current drugs in early development for treating hepatitis C virus-related hepatic fibrosis

“…Although the use of those first-generation HCV protease inhibitors is currently limited by their toxicities, first data of fibrosis improvement were presented. Haseltine et al [56] polled data from Phase II and Phase III clinical trials with telaprevir assessing the effect of SVR on serum fibrosis markers (FibroTest, APRI, FIB-4 and Forns' Score). Among 1208 patients who reached SVR, all exhibited significant improvements in each of these noninvasive markers after treatment.…”

Serum Biomarkers Indicate Long-term Reduction in Liver Fibrosis in Patients With Sustained Virological Response to Treatment for HCV Infection

“…However, many recent studies indeed have shown that improvement in serum markers correlates with decreasing fibrosis stage. 10,12,16 …”

“…Aminotransferase levels and platelet counts measured during antiviral therapy were excluded because therapy can influence these parameters. 16 The FIB4 score and APRI were summarized using a median smoother for every 90-day interval. Because of non-normality, data were log-transformed.…”

“…We have further validated these markers in the Chronic Hepatitis Cohort Study (CHeCS) HCV population; the validated area under the receiver operator characteristic curve was 0.83 to 0.85 for FIB4 and 0.80 to 0.81 for APRI. 9,22 Changes in FIB4 have been shown to correlate with changes in liver fibrosis stage over time in HCV patients, 10,16 and have been used to compare progression of liver fibrosis between HCV-positive and HCV-negative patients in the Veterans’ Affairs health care system. 11,12 Likewise, FIB4 and APRI have been used as end points for post-treatment and post-SVR outcomes in HCV and human immunodeficiency virus (HIV)/HCV co-infected patients.…”