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Levels of insulin-like growth factor-I, inflammatory markers can indicate NAFLD severity

Reduced circulating levels of insulin-like growth factor-I were associated with increased severity of nonalcoholic fatty liver disease, according to recent results.

In a cross-sectional study, researchers evaluated 221 patients with nonalcoholic fatty liver disease (NAFLD) diagnosed via ultrasonography (group 1) and 50 patients with biopsy-proven NAFLD (group 2). Kleiner and NAFLD fibrosis scores were calculated, and concentrations of insulin-like growth factor-I (IGF-I) and inflammatory biomarkers were determined. mRNA expression levels of acute-phase reactants also were assessed via in vitro experiments with hepatoma HepG2 cells.

Among group 1 patients, when stratified by fibrosis score, an inverse association existed with the presence of inflammatory biomarkers, with those with the highest IGF-I levels at the lowest risk for fibrosis before (P=.03) and after adjusting for age, sex, diabetes, glucose-lowering therapy, statin use and other factors (P=.01). Stratification according to Kleiner score indicated a similar association between levels of IGF-I mRNA (P=.01) and score after adjustment for age and sex.

Investigators noted inverse correlations between IGF-I levels and fibrinogen (P=.01), high-sensitivity C-reactive protein (CRP; P=.05) and erythrocyte sedimentation rate (P=.02), along with a positive correlation with albumin levels (P=.05) when adjusted for age, sex, diabetes medication, metabolic syndrome and dyslipidemia.

Researchers incubated HepG2 cells with interleukin-6 (IL-6) either with or without IGF-I in the in vitro experiments. IL-6 increased fibrinogen mRNA and CRP and decreased albumin mRNA, while IGF-I reversed these effects, increasing albumin mRNA and decreasing CRP and fibrinogen mRNA.

“We consider our results important in attempting to understand the pathophysiological interaction between inflammation an IGF-I activity during progression from simple steatosis to the necroinflammatory form of [nonalcoholic steatohepatitis],” the researchers concluded, noting that all study patients were Caucasian and results could not be applied to other ethnicities. “Furthermore, our data suggest that the evaluation of IGF-I circulating levels may represent a noninvasive prognostic marker that may help to achieve a comprehensive assessment of the severity of the disease in individuals with NAFLD.”