Endotrophin Measured by
PRO
‐
C6
as a Prognostic Biomarker for Liver‐Related Events in Patients With Advanced Chronic Liver Disease
Thomas Wiggers, Emilie Toft Skovgaard, Morten Karsdal, Jens Juul Holst, Frederik Christiansen, Andressa de Zawadzki, Diana Julie Leeming, Keyur Patel ABSTRACT
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.