Enhanced liver fibrosis test predicts transplant-free survival in primary sclerosing cholangitis, a multi-centre study

Liver Int. 2017 Oct;37(10):1554-1561. doi: 10.1111/liv.13402. Epub 2017 Apr 13.

Abstract

Background & aims: Biomarkers reflecting disease activity and prognosis in primary sclerosing cholangitis (PSC) have not been firmly established. Enhanced liver fibrosis (ELF) test was previously reported to predict outcome in PSC. We aimed to validate the prognostic utility of ELF test in an independent, multi-centre, retrospective PSC study population.

Methods: We collected serum samples from PSC patients from seven countries. We estimated rates of transplant-free survival by the Kaplan-Meier method, used Cox proportional hazards regression to explore the association between ELF test and clinical outcome and determined prognostic performance of ELF test by computing the area under the receiver operating characteristic (AUC-ROC) curve.

Results: The final analysis included 534 PSC patients (61% males). Features of autoimmune hepatitis or concomitant inflammatory bowel disease affected 44 (8%) and 379 (71%) patients respectively. ELF test levels were higher in patients reaching the combined endpoint liver transplantation or death (median 10.9 [Interquartile range (IQR): 9.8-12.1]; n=24 deaths, 79 liver transplantations) compared to those censored (8.8 [IQR: 8.0-9.8]); P<.001. ELF test expressed as mild, moderate and severe fibrosis was significantly associated with the risk of reaching the endpoint (P<.001). ELF test independently predicted clinical outcome (Hazard ratio 1.31; 95% confidence interval [1.05-1.65]; P=.018), and enabled good discrimination between PSC patients with and without endpoint (AUC-ROC: 0.79).

Conclusion: Our retrospective data validates the predictive utility of ELF test for clinical outcomes in PSC. The clinical utility of biomarkers for fibrosis in patients with PSC should be assessed in prospective patient cohorts.

Keywords: biomarker; enhanced liver fibrosis test; primary sclerosing cholangitis; risk stratification; surrogate endpoint.

Publication types

  • Multicenter Study
  • Validation Study

MeSH terms

  • Adult
  • Area Under Curve
  • Biomarkers / blood
  • Canada
  • Cholangitis, Sclerosing / blood
  • Cholangitis, Sclerosing / diagnosis*
  • Cholangitis, Sclerosing / mortality
  • Cholangitis, Sclerosing / surgery
  • Disease Progression
  • Disease-Free Survival
  • Europe
  • Female
  • Humans
  • Hyaluronic Acid / blood*
  • Kaplan-Meier Estimate
  • Liver Cirrhosis / blood
  • Liver Cirrhosis / diagnosis*
  • Liver Cirrhosis / mortality
  • Liver Cirrhosis / surgery
  • Liver Transplantation
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Peptide Fragments / blood*
  • Phenotype
  • Predictive Value of Tests
  • Procollagen / blood*
  • Proportional Hazards Models
  • ROC Curve
  • Reproducibility of Results
  • Retrospective Studies
  • Risk Factors
  • Time Factors
  • Tissue Inhibitor of Metalloproteinase-1 / blood*
  • Young Adult

Substances

  • Biomarkers
  • Peptide Fragments
  • Procollagen
  • TIMP1 protein, human
  • Tissue Inhibitor of Metalloproteinase-1
  • procollagen Type III-N-terminal peptide
  • Hyaluronic Acid