Endotrophin Measured by <scp>PRO</scp> ‐ <scp>C6</scp> as a Prognostic Biomarker for Liver‐Related Events in Patients With Advanced Chronic Liver Disease

BACKGROUND & AIMS: Prognostic non-invasive tests for liver-related events in compensated cirrhosis are needed. Endotrophin, a fragment of type VI alpha 3 collagen involved in fibrosis and inflammation, has been associated with adverse outcomes in several chronic diseases. This study examined the association between baseline endotrophin levels, measured by nordicPRO-C6 (PRO-C6), and liver-related events in advanced hepatitis C virus (HCV)-related liver disease. METHODS: nordicPRO-C6 was assessed in baseline serum from 339 patients with advanced liver fibrosis from the Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis (HALT-C) trial. The prognostic value of PRO-C6 was evaluated. RESULTS: Baseline serum levels of PRO-C6 were significantly higher in patients with cirrhosis and PRO-C6 was an independent prognostic marker for liver-related events. Each doubling of PRO-C6 was associated with increased hazard of liver-related events in all patients (hazard ratio (HR) = 2.22, 95% confidence interval (CI) 1.57-3.14, p < 0.0001), and in patients with cirrhosis (HR = 1.71, 95% CI 1.14-2.58, p = 0.01). CONCLUSION: Endotrophin assessed by PRO-C6 is an independent prognostic marker for liver-related events in patients with advanced liver fibrosis and ongoing inflammation due to HCV, particularly in those with cirrhosis, from the HALT-C trial. PRO-C6 may be useful for risk stratification in end-stage liver disease. However, validation in non-interferon-treated cohorts and across chronic liver diseases of varying etiologies is required to confirm its prognostic value for liver-related events.