IGFBP-1 and IGF-I as markers for advanced fibrosis in NAFLD – a pilot study

Abstract

Background and aims: Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease globally. Advanced fibrosis (stage 3–4) is the most robust marker for future mortality, but diagnosis requires liver biopsy. Current non-invasive scoring systems aimed to identify advanced fibrosis are imperfect. Insulin-like growth factor I (IGF-I) and its binding protein IGFBP-1 are liver derived proteins, that are involved in various liver disorders. The aim of this study was to examine the possible association between advanced fibrosis and IGF-I and IGFBP-1 in NAFLD.Methods: Fasting blood samples were obtained from 52 patients diagnosed with NAFLD by liver biopsy. Total IGF-I and IGFBP-1 concentrations were determined in serum by in-house radio-immuno-assays. IGF-I levels were age-standardized (IGF-SD). A logistic regression model was used to investigate the association of IGF-SD and IGFBP-1 with advanced fibrosis (stage 3–4).Results: Patients with advanced fibrosis (stage 3–4 vs. 0–2) had lower IGF-SD (−1.17 vs. 0.11, p = .01) and higher mean levels of IGFBP-1 (29.9 vs. 18.8 µg/l, p = .02). IGFBP-1 was associated with presence of advanced fibrosis (OR 1.04 per unit increase, 95%CI 1.0–1.07, p = .05), while IGF-1 was negatively associated with advanced fibrosis (OR 0.63 per standard deviation, 95%CI 0.44–0.92, p = .02).Conclusions: This pilot study suggests an association between serum IGFBP-1 and IGF-I levels with advanced fibrosis in NAFLD patients. IGFBP1 and IGF-1 could be of interest as future biomarkers. Similar studies in larger cohorts are needed.