Insulin-like growth factor-I, inflammatory proteins, and fibrosis in subjects with nonalcoholic fatty liver disease

J Clin Endocrinol Metab. 2013 Feb;98(2):E304-8. doi: 10.1210/jc.2012-3290. Epub 2013 Jan 11. Insulin-like growth factor-I, inflammatory proteins, and fibrosis in subjects with nonalcoholic fatty liver disease. Hribal ML, Procopio T, Petta S, Sciacqua A, Grimaudo S, Pipitone RM, Perticone F, Sesti G. SourceDepartment of Medical and Surgical Sciences, University Magna-Graecia of Catanzaro, 88100 Catanzaro, Italy. Abstract CONTEXT: Inflammation may have a pathogenic role in the progression of nonalcoholic fatty liver disease (NAFLD); by contrast, the role of anti-inflammatory molecules has not been addressed. Low circulating levels of the anti-inflammatory molecule IGF-I have been described in subjects with NAFLD. OBJECTIVE: The aim of the study was to elucidate the clinical significance of IGF-I in NAFLD and its relationship with inflammatory biomarkers and fibrosis. DESIGN AND SETTING: We conducted a cross-sectional study and in vitro experiments on hepatic HepG2 cells at the Internal Medicine and Gastrointestinal and Liver Units of the Universities of Catanzaro and Palermo. SUBJECTS: A total of 221 individuals with NAFLD diagnosed on ultrasonography (cohort 1) and 50 subjects with biopsy-proven NAFLD (cohort 2) participated in the study. Intervention: Liver ultrasonography was performed on cohort 1, and hepatic biopsies were obtained from cohort 2. MAIN OUTCOME MEASURES: NAFLD fibrosis and Kleiner scores were calculated. IGF-I and inflammatory biomarker plasma concentrations were assessed with specific assays. In the in vitro study, real-time RT-PCR was used to assess the mRNA expression levels of acute-phase reactants. RESULTS: In the first cohort, circulating IGF-I levels showed an inverse correlation with NAFLD fibrosis score and inflammatory biomarkers; similarly in the second cohort, liver IGF-I mRNA levels and the fibrosis score showed a negative relationship. Finally, we showed that IGF-I was able to directly modulate the expression of acute-phase reactants, decreasing C-reactive protein and fibrinogen levels and up-regulating albumin expression in HepG2 cells. CONCLUSIONS: The present data suggest that evaluation of circulating IGF-I and proinflammatory markers might be useful to assess comprehensively the severity of the disease in individuals with NAFLD.