Association between HOMA-IR and metabolic dysfunction-associated steatohepatitis in U.S. adults with MASLD.

Background: MASH is a critical point in metabolic dysfunction-associated steatotic liver disease (MASLD). Understanding its association with the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) is essential, as HOMA-IR is a marker for insulin resistance. Methods: This study analyzed 700 adults from the NHANES 2017-2020, using the FAST score (with thresholds of ≥0.35 and ≥ 0.67) to identify individuals at high MASH risk. Logistic regression assessed HOMA-IR's association with MASH risk, while linear regression evaluated its link to liver stiffness measurement (LSM) and controlled attenuation parameter (CAP). Nonlinear associations were explored using restricted cubic splines (RCS), and BMI's mediation effects were examined through causal mediation analysis. Results: MASH risk was significantly higher in the highest HOMA-IR quartile compared to the lowest (OR = 5.942, 95 %CI = 2.117-16.679, P = 0.001). RCS revealed nonlinear associations between HOMA-IR and both MASH risk (P = 0.007) and liver metrics (LSM: P = 0.045; CAP: P < 0.001). HOMA-IR correlated with increased hepatic steatosis and fibrosis severity. BMI mediated 34.26 % and 19.62 % of the associations for LSM and CAP, respectively. Conclusion: Monitoring HOMA-IR is vital for early MASH risk detection and intervention. Targeting insulin resistance and BMI may reduce MASH risk and severity, highlighting the need for integrated therapeutic strategies.