Abstract / Summary
Abstract Introduction: Liver fibrosis is the advanced stage of metabolic dysfunction-associated steatotic liver disease (MASLD), affecting about 10% of adults with steatosis. BMI, the main anthropometric tool, does not distinguish fat mass from lean mass and does not capture central fat distribution. BMI-C (Body Morphometric Index – Corrected) is a proprietary index that corrects the dimensional error of BMI, identifies 23.7% of normal-BMI individuals at metabolic risk, and correlates fibrosis with insulin. Objective: To validate BMI-C as a predictor of advanced liver fibrosis (F2+, F3+, F4) in two NHANES cohorts (2017–18 and 2021–23), and to investigate the role of insulin as a mediator and amplifier of the BMI-C effect on fibrosis. Methods: Cross-sectional study with n = 5,014 adults (≥ 20 years) from NHANES 2017–18 and 2021–23 with valid liver elastography (FibroScan). Outcomes: F2+ (stiffness ≥ 8 kPa), F3+ (≥ 12 kPa), F4 (≥ 20 kPa). AUC with 95% CI by bootstrap (2,000 resamples). DeLong test for AUC comparison. Mediation by insulin (Baron & Kenny method, with 95% CI by bootstrap). BMI-C × insulin interaction by logistic regression. Results: Prevalence of F2+ was 10.3% (n = 514), F3+ 3.6% (n = 182), F4 1.3% (n = 64). BMI-C had AUC of 0.725 (95% CI: 0.700–0.749) for F2+, 0.746 (0.708–0.782) for F3+, and 0.709 (0.644–0.769) for F4, outperforming BMI (ΔAUC = +0.019, p < 0.0001 for F2+). Insulin mediated 21.5% (95% CI: 13.2–29.2%) of the BMI-C effect on F2+, 30.3% (20.1–41.2%) on F3+ — the stage where insulin emerges as central to fibrosis consolidation — and 43.0% on F4. BMI-C × insulin interaction was significant for F2+ (β = +0.927, p = 0.004), indicating synergy: in the highest tertile of both, F2+ prevalence was 25.1%; in the lowest tertile of both, 4.5%. In S1 (mild steatosis), BMI-C did not predict incipient fibrosis (AUC = 0.516), but AST/ALT did (AUC = 0.623). Conclusion: BMI-C is a robust predictor of advanced liver fibrosis, outperforming BMI and BARD. Insulin mediates 20%–43% of the BMI-C effect on fibrosis, with synergistic interaction in early stages. BMI-C does not predict incipient fibrosis in S1, suggesting that fibrosis depends on biochemical factors (AST/ALT) beyond structural risk. BMI-C is a viable tool for primary care screening, with near-zero cost and no laboratory tests.