Fibrosis activity vs. disease stage: Complementary and independent predictors of outcomes in alcohol-related liver disease

Background & Aims Excessive alcohol consumption accelerates fibrosis progression in steatotic liver disease. Disease activity may be described by fibroblast activity of which collagen formation is a central event and type III collagen formation (PRO-C3) is a biomarker of that. We aimed to evaluate if PRO-C3 predicts clinical outcomes in alcohol-related liver disease (ALD) independent of fibrosis stage. Methods Prospective cohort study of patients with prior or current excessive alcohol intake (men: ≥36 g/day, women: ≥24 g/day for >1 year) and no prior decompensation. At baseline, we performed liver biopsies, clinical investigations, and non-invasive blood tests. During follow up, we manually reviewed patients' electronic healthcare records for decompensations and all-cause mortality. Decompensation was defined per Baveno VII recommendations. Results We followed 458 patients with ALD (76% male, mean age 57±10 years) for a median of 5.9 years (IQR 4.5-7.8). Baseline fibrosis stages: F0-1 (n=260), F2 (n=107), F3-4 (n=91). During follow-up, 67 patients decompensated and 100 died. PRO-C3 added prognostic value on top of fibrosis stage as a predictor of decompensation, both for patients with no to moderate fibrosis, F0-2 (subhazard ratio, sHR PRO-C3 1.05; 95% CI 1.03-1.07, p