Serum biomarkers in type 2 diabetic patients with non-alcoholic steatohepatitis and advanced fibrosis

Hepatol Res. 2013 May;43(5):508-15. doi: 10.1111/j.1872-034X.2012.01106.x. Epub 2012 Oct 16.

Abstract

Aim: Advanced stages of non-alcoholic fatty liver disease (NAFLD) are highly prevalent in type 2 diabetes (T2DM), however, no diabetes-related or biochemical variable seems to be predictive of severity of NAFLD. The aim of this study was to investigate the association of several serum biomarkers with the more severe histopathological stages of NAFLD in T2DM.

Methods: In a cross-sectional design, 84 T2DM patients with biopsy-proven NAFLD had adiponectin, tumor necrosis factor-α, transforming growth factor (TGF)-β1, interleukin (IL)-6, -8 and -10, and C-reactive protein measured. NAFLD severity was evaluated by two hepatopathologists according to the non-alcoholic steatohepatitis (NASH) Clinical Research Network scoring system. Independent associations of cytokines with NASH and advanced fibrosis were evaluated by multivariate logistic regressions.

Results: Sixty-six patients (78.6%) had NASH, and 52 patients (61.9%) had advanced fibrosis considering the highest score between the two pathologists. Patients with NASH or with advanced fibrosis had equal cytokine levels to those without NASH or with absent/light fibrosis, except for a lower serum adiponectin (8.59 vs 12.77 μg/mL; P = 0.015) in patients with NASH and a lower TGF-β1 (170 vs 180 pg/mL; P = 0.026) in patients with advanced fibrosis. In multivariate analysis, lower adiponectin was independently associated with NASH (odds ratio = 7.7, 95% confidence interval = 1.5-39.9, P = 0.014, for the subgroup with adiponectin below the median value), whereas both lower adiponectin and lower TGF-β1 levels were associated with advanced fibrosis.

Conclusion: Low adiponectin and low TGF-β1 are associated with severest NAFLD stages in T2DM and may be a valuable tool to support liver biopsy indication in this setting.