Serum markers of type III and IV procollagen processing predict recurrence of fibrosis in liver transplanted patients

Following liver transplantation (LT), 10-30% of patients develop recurrent cirrhosis (RC). There is an urgent need for predictive non-invasive markers for improved monitoring of these patients. Here we studied extracellular matrix biomarkers as predictors of RC after LT. Forty-seven LT patients were divided into groups of fast, intermediate or non-progressors towards RC (<1 year, 3-5 years or no advanced fibrosis >5 years after LT), assessed by follow-up liver biopsies. Markers of interstitial matrix type III and V collagen formation (PRO-C3 and PRO-C5), basement membrane type IV collagen formation (PRO-C4) and degradation (C4M) were assessed in serum samples collected 3,6 and 12 months post-LT using specific ELISAs. PRO-C3, PRO-C4, and C4M were elevated in fast progressors compared to non-progressors 3 months after LT. C4M and PRO-C4 additionally differentiated between intermediate and fast progressors at 3 months. PRO-C3 was best predictor of survival, with LT patients in the highest PRO-C3 tertile having significantly shorter survival time. This shows that interstitial matrix and basement membrane remodeling in RC may be distinguishable. Markers originating from different sites in the extracellular matrix could be valuable tools for a more dynamic monitoring of patients at risk of RC. However, this needs validation in larger cohorts.