Non-invasive hepatic biomarkers (ELF and CK18) in people with type 2 diabetes: the Edinburgh type 2 diabetes study

Liver Int. 2014 Sep;34(8):1267-77. doi: 10.1111/liv.12385. Epub 2013 Dec 3.

Abstract

Background & aims: Type 2 diabetes is an established risk factor for the presence and progression of fatty liver. Little is known about the distributions and correlates of hepatic non-invasive biomarkers in community-based populations with diabetes, unselected for liver disease. We aimed to identify the distribution of, and metabolic risk factors associated with serum cytokeratin-18 (CK18) and the Enhanced Liver Fibrosis score (ELF), in a large, representative cohort of people with type 2 diabetes (the Edinburgh Type 2 Diabetes Study, ET2DS).

Methods: Nine hundred and thirty-nine ET2DS participants, aged 60-74 years underwent physical examination including ultrasound for assessment of liver fat. Representative subgroups were assessed for markers of chronic liver disease (CK18 and ELF).

Results: CK18 values ranged from 29-993 U/L (median 102, IQR 76-137 U/L) and ELF scores ranged from 6.9-11.6 (mean 8.9, SD 0.8). Statistically significant associations were found between both biomarkers and a number of metabolic risk factors. Neither CK18 nor ELF was consistently or strongly associated with established hepatic risk factors (alcohol excess, hepatotoxic medication use and positive immunology titres).

Conclusions: We identified the distribution of CK18 and ELF in a large cohort of older people with type 2 diabetes and showed that these markers are associated with an adverse metabolic risk factor profile, although much of the variation in biomarkers remained unexplained. Prospective studies are required to determine the extent to which CK18 and/or ELF predict the development of symptomatic liver disease and to identify additional risk factors which may influence the development of advanced liver disease in people with type 2 diabetes.

Keywords: cytokeratin-18; enhanced liver fibrosis score; fatty liver disease; non-invasive hepatic biomarkers; type 2 diabetes mellitus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biomarkers / blood*
  • Cohort Studies
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / epidemiology*
  • Fatty Liver / blood
  • Fatty Liver / diagnosis*
  • Fatty Liver / epidemiology*
  • Fatty Liver / etiology
  • Humans
  • Keratin-18 / blood
  • Liver Cirrhosis / pathology
  • Middle Aged
  • Risk Factors
  • Scotland / epidemiology

Substances

  • Biomarkers
  • Keratin-18