Low Serum IGF-1 Predicts Higher Liver Fibrosis Burden in MAFLD Adults

Metabolic dysfunction-associated fatty liver disease (MAFLD), also known as MASLD, is a growing global health concern that can progress to advanced liver fibrosis, cirrhosis, and liver failure. Early identification of fibrosis burden is crucial for risk stratification and intervention, but current diagnostic methods often involve invasive biopsies. Insulin-like growth factor-1 (IGF-1) is a key hormone involved in growth and metabolism, and its levels are known to be altered in various metabolic conditions. Understanding IGF-1's role in MAFLD fibrosis could provide a non-invasive biomarker for disease progression.

Researchers conducted a cross-sectional analysis of 1473 U.S. adults with MAFLD from the National Health and Nutrition Examination Survey III (1988-1994). The study examined the association between serum IGF-1 levels and liver fibrosis severity, which was assessed using the fibrosis-4 (FIB-4) index. Nonlinear associations between serum IGF-1 levels and the log-transformed FIB-4 index were explored using generalized additive models with smoothing splines. A segmented linear regression model was applied to identify potential threshold effects, and stratified analyses were performed for various demographic and metabolic subgroups.

Higher serum IGF-1 levels were independently associated with lower log-transformed FIB-4 scores after adjusting for demographic, metabolic, and lifestyle factors (β = -0.0013; 95% CI: -0.0016 to -0.0010). A significant nonlinear threshold effect was observed, indicating that the inverse association was more pronounced at lower IGF-1 concentrations. This threshold was identified at 283.4 ng/mL. Below this threshold, IGF-1 was more strongly inversely associated with log-transformed FIB-4 (β = -0.0024; P < .001). Similar inverse associations were consistently observed across clinically relevant subgroups, including those stratified by sex, age, obesity, and hypertension. A significant interaction was noted for diabetes status (P for interaction = 0.004), suggesting that the relationship between IGF-1 and fibrosis might differ in individuals with diabetes.