Fibroblast activity kills - Circulating endotrophin (PRO-C6) is prognostic for liver-related events in cirrhotic patients with chronic hepatitis C

Abstract

Background and Aims: Patients with cirrhosis are at increased risk of developing a liver-related events, thus it is crucial to monitor such patients. Endotrophin, a potential driver of fibroblast activation and mediator of fibroinflammatory disease, may be assessed non-invasively using the PRO-C6. Non-invasive tests (NITs) of fibrosis may provide prognostic insight into which patients with cirrhosis are at higher risk of developing a liver-related event, diminishing the need for repeated liver biopsy. Here we aimed to investigate the ability of PRO-C6 to predict liver-related events in The Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis Trial (HALT-C) (ClinicalTrials.gov #NCT00006164). Method: A subgroup of 151 patients with cirrhosis and serum samples from the HALT-C cohort, were included in this study. NordicPRO-C6TM was assessed in serum using a fully validated competitive enzyme-linked immunosorbent assay. Between groups comparison of biomarker levels was performed using Mann-Whitney U test. Patients were stratified above and below a 15.0 ng/mL cut-off of baseline PRO-C6. Cox proportional hazards regression was used to analyze the prognostic value of serum PRO-C6 to identify patients at risk of developing liver-related events. Results: 69% of the included 151 patients were male. The median (Q1, Q3) age and BMI were 50 (47, 55) years and 29.3 (26.7, 32.6) kg/m2, respectively. 47 (31%) of the patients had a liver related outcome over median follow-up (Q1, Q3) of 755 days (371, 1098). PRO-C6 was significantly elevated in patients who had a liver-related event (p = < 0.001). When stratifying the patients above and below the cut-off of 15 ng/mL (high versus low level), the hazard ratio for having a liver related outcome was 3.56 times higher (SD = 0.30, 95% CI = [1.48, 5.52], p = < 0.001) in the group with high serum PRO-C6 at baseline, compared to low serum PRO-C6. Conclusion: PRO-C6, a biomarker of circulating endotrophin was associated with an increased risk of developing a liver-related event, in cirrhotic patients with chronic hepatitis C. PRO-C6 may be a potential monitoring NIT that may provide prognostic information on which cirrhosis patients, are at high risk of developing a liver-related event.