Novel association between serum pentraxin-2 levels and advanced fibrosis in well-characterised patients with non-alcoholic fatty liver disease

Aliment Pharmacol Ther. 2015 Sep;42(5):582-90. doi: 10.1111/apt.13292. Epub 2015 Jun 29.

Abstract

Background: Pentraxin-2 (PTX-2), a serum protein, inhibits inflammation and fibrosis, and recombinant PTX-2 is being tested as an anti-fibrotic agent.

Aim: To evaluate the association between serum PTX-2 levels and fibrosis stage in patients with non-alcoholic fatty liver disease (NAFLD).

Methods: Serum pentraxin-2 levels were compared between four groups of well-characterised patients including NAFLD with no fibrosis, NAFLD with mild-moderate fibrosis (stage 1-2), NAFLD with advanced fibrosis (stage 3-4), and age-sex matched non-NAFLD controls.

Results: Sixty subjects were included in the study. The mean age was 58.9 years, 68% were male and 58% were Caucasian. In univariate analysis, serum PTX-2 levels significantly decreased from non-NAFLD controls to mild NAFLD with no fibrosis, to NAFLD with mild-moderate fibrosis and were lowest in patients with NAFLD and advanced fibrosis, in a dose-dependent manner (P < 0.0001). In multivariable-adjusted analyses controlling for age, sex, albumin, and CRP, the results remained consistent and statistically significant. Serum PTX-2 level had an AUROC of 0.84 (95% CI: 0.71-0.97) for the diagnosis of NAFLD, and an AUROC of 0.77 (95% CI: 0.65-0.90) for the diagnosis of advanced fibrosis in NAFLD. Serum PTX-2 levels also decreased with increasing liver stiffness as estimated by magnetic resonance elastography (r = -0.31, P = 0.02).

Conclusions: PTX-2 levels are significantly lower in patients with NAFLD compared to non-NAFLD controls, and decline further in patients with advanced fibrosis. PTX-2 may therefore be both a biomarker of disease and a potential target for anti-fibrotic therapy with the recombinant pentraxin-2.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Biomarkers
  • Blood Proteins / metabolism*
  • Cross-Sectional Studies
  • Female
  • Humans
  • Liver Cirrhosis / blood*
  • Liver Cirrhosis / complications*
  • Male
  • Middle Aged
  • Non-alcoholic Fatty Liver Disease / blood*
  • Non-alcoholic Fatty Liver Disease / complications*
  • Severity of Illness Index

Substances

  • Biomarkers
  • Blood Proteins