FibroTest (FT) is a biomarker of liver fibrosis initially validated in patients with chronic hepatitis C (CHC).

Patients with hepatitis C virus (HCV) infection and cirrhosis are underrepresented in clinical trials of interferon‐free regimens of direct‐acting antiviral agents, making it difficult to optimize therapy. We performed a post‐hoc analysis of data from seven clinical trials to evaluate the efficacy and safety of the fixed‐dose combination of ledipasvir (LDV) and sofosbuvir (SOF), with and without ribavirin (RBV), in 513 treatment‐naïve and previously treated patients with genotype 1 HCV and compensated cirrhosis. All patients received LDV‐SOF for 12 or 24 weeks with or without RBV. We determined the rates of sustained virological response (SVR) 12 weeks after treatment (SVR12) overall and for subgroups. Of the 513 patients analyzed, 69% were previously treated and 47% had failed previous treatment with a protease‐inhibitor regimen. Overall, 493 patients (96%; 95% confidence interval [CI]: 94%‐98%) achieved SVR12, 98% of treatment‐naïve and 95% of previously treated patients. SVR12 rates did not vary greatly by treatment duration (95% of patients receiving 12 weeks and 98% of patients receiving 24 weeks of treatment), nor by addition of RBV (95% of patients receiving LDV‐SOF alone and 97% of those who received LDV‐SOF plus RBV), although previously treated patients receiving 12 weeks of LDV‐SOF without RBV had an SVR12 rate of 90%. One patient discontinued LDV‐SOF because of an adverse event (AE). The most common AEs were headache (23%), fatigue (16%‐19%), and asthenia (14%‐16%). One patient (<1%) of those receiving LDV‐SOF alone, and 4 (2%) of those receiving LDV‐SOF plus RBV had treatment‐related serious AEs. Conclusions: This analysis suggests that 12 weeks of LDV‐SOF is safe and effective for treatment‐naïve patients with HCV genotype 1 and compensated cirrhosis. The relatively lower SVR in treatment‐experienced patients treated with 12 weeks of LDV‐SOF raises the question of whether these patients would benefit from adding RBV or extending treatment duration to 24 weeks. (Hepatology 2015;62:79‐86)

Background: In patients with chronic hepatitis C virus, liver biopsy is the gold standard for assessing liver disease stage; nevertheless, it is prone to complications, some of them serious. Non-invasive methods have been proposed as surrogate markers for liver fibrosis. It was shown that serum hyaluronic acid (HA) level increases with the development for liver fibrosis. The aim of this study was to evaluate the diagnostic value of HA as well as to determine the HA level cut-off for predicting the presence or absence of fibrosis, severe fibrosis, and cirrhosis. Results: 405 patients with chronic hepatitis C were prospectively included with biomarker measurement and liver biopsy done the same day: 151 in the training set (only biopsy lengths of 25 mm or more) and 254 in the validation set. For the discrimination of significant fibrosis, severe fibrosis, and cirrhosis in the training set, the areas under curve (AUCs) were 0.75 ± 0.03, 0.82 ± 0.02, and 0.89 ± 0.03, respectively. Absence of significant fibrosis, severe fibrosis, and cirrhosis can be predicted by HA levels of 16, 25, and 50 μg/l, respectively (with negative predictive values of 82%, 89%, and 100%, in the same order). Presence of significant fibrosis, severe fibrosis, and cirrhosis can be predicted by HA levels of 121, 160, and 237 μg/l, respectively (with positive predictive values of 94%, 100%, and 57%, in the same order). Conclusion: In the validation set, HA was accurate in predicting significant fibrosis, severe fibrosis, and cirrhosis with AUCs of 0.73, 0.77, and 0.97, respectively. Moreover, accurate HA level cut-offs were defined for predicting significant fibrosis, severe fibrosis, and cirrhosis. Thus, the study supports that HA level may be clinically useful as a non-invasive marker for liver fibrosis and/or cirrhosis.