Collagen proportionate area is an independent predictor of long-term outcome in patients with non-alcoholic fatty liver disease

Aliment Pharmacol Ther. 2019 May;49(9):1214-1222. doi: 10.1111/apt.15219. Epub 2019 Mar 18.

Abstract

Background: Collagen proportionate area (CPA) measurement is a technique that quantifies fibrous tissue in liver biopsies by measuring the amount of collagen deposition as a proportion of the total biopsy area. CPA predicts clinical outcomes in patients with HCV and can sub-classify cirrhosis.

Aim: To test the ability of CPA to quantify fibrosis and predict clinical outcomes in patients with NAFLD.

Methods: We assessed consecutive patients with biopsy-proven NAFLD from three European centres. Clinical and laboratory data were collected at baseline and at the time of the last clinical follow-up or death. CPA was performed at two different objective magnifications, whole biopsy macro and ×4 objective magnification, named standard (SM) and high (HM) magnification respectively. The correlation between CPA and liver stiffness was assessed in a sub-group of patients.

Results: Of 437 patients, 32 (7.3%) decompensated and/or died from liver-related causes during a median follow-up of 103 months. CPA correlated with liver stiffness and liver fibrosis stage across the whole spectrum of fibrosis. HM CPA was significantly higher than SM CPA in stages F0-F3 but similar in cirrhosis, reflecting a higher ability to capture pericellular/perisinusoidal fibrosis at early stages. Age at baseline (HR: 1.04, 95% CI: 1.01-1.08), HM CPA (HR: 1.04 per 1% increase, 95% CI: 1.01-1.08) and presence of advanced fibrosis (HR: 15.4, 95% CI: 5.02-47.84) were independent predictors of liver-related clinical outcomes at standard and competing risk multivariate Cox-regression analysis.

Conclusions: CPA accurately measures fibrosis and is an independent predictor of clinical outcomes in NAFLD; hence it merits further evaluation as a surrogate endpoint in clinical trials.

Keywords: decompensation; fibroscan; fibrosis; prognosis; steatohepatitis.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers / analysis
  • Biomarkers / metabolism
  • Biopsy
  • Collagen / analysis
  • Collagen / metabolism*
  • Female
  • Follow-Up Studies
  • Greece / epidemiology
  • Humans
  • Liver / chemistry
  • Liver / metabolism*
  • Liver / pathology
  • Liver Cirrhosis / diagnosis
  • Liver Cirrhosis / metabolism
  • Liver Cirrhosis / mortality
  • Liver Cirrhosis / therapy
  • Liver Transplantation
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Non-alcoholic Fatty Liver Disease / diagnosis*
  • Non-alcoholic Fatty Liver Disease / metabolism
  • Non-alcoholic Fatty Liver Disease / mortality
  • Non-alcoholic Fatty Liver Disease / therapy
  • Prognosis
  • Retrospective Studies
  • Sweden / epidemiology
  • Treatment Outcome
  • United Kingdom / epidemiology

Substances

  • Biomarkers
  • Collagen