Low Serum Insulin-Like Growth Factor-1 as a Predictor of Fibrosis Burden in Metabolic-Associated Fatty Liver Disease.

OBJECTIVES

To examine the association between circulating insulin-like growth factor-1 (IGF-1) levels and liver fibrosis burden in adults with metabolic dysfunction-associated fatty liver disease (MAFLD).

METHODS

We conducted a cross-sectional analysis of 1473 U S. adults with MAFLD from the National Health and Nutrition Examination Survey III (1988-1994) to examine the association between serum IGF-1 levels and liver fibrosis severity, assessed by 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 subsequently applied to identify potential threshold effects, and likelihood ratio tests were used to compare linear and segmented models. Stratified analyses and multiplicative interaction tests were performed to assess potential effect modification by sex, age, diabetes status, obesity, and hypertension.

RESULTS

Higher serum IGF-1 levels were independently associated with lower log-transformed FIB-4 scores after adjustment for demographic, metabolic, and lifestyle factors (β = -0.0013; 95% CI: -0.0016 to -0.0010). A nonlinear threshold effect was observed, with the inverse association being more pronounced at lower IGF-1 concentrations (threshold: 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 observed across clinically relevant subgroups, with a significant interaction for diabetes status (P for interaction = 0.004).

CONCLUSIONS

Circulating IGF-1 levels are inversely associated with liver fibrosis risk in adults with MAFLD, exhibiting a nonlinear relationship characterized by a threshold effect. IGF-1 may serve as a biomarker for fibrosis risk stratification and warrants further investigation regarding its potential biological relevance in metabolic liver disease.