To examine the association between the lymphocyte-to-high-density lipoprotein cholesterol ratio (LHR) and metabolic dysfunction-associated steatotic liver disease (MASLD).

This study used data from the National Health and Nutrition Examination Survey (NHANES) database, including 3,863 adult participants. MASLD was diagnosed using current common criteria. We used multivariable logistic regression models to examine the association between LHR and MASLD risk, while restricted cubic spline (RCS) regression was used to look for nonlinear relationships. We found threshold effects using segmented linear regression, and subgroup differences were checked.

Multivariable logistic regression analysis showed that for each unit rise in LHR, the risk of MASLD went up 33% (OR=1.33, 95%CI: 1.18-1.50, P<0.001) after considering age, sex, race, socioeconomic factors, lifestyle, comorbidities, anthropometric indices, and liver enzyme/lipid profiles. RCS analysis showed a clear nonlinear link between LHR and MASLD risk (P=0.02), with the lowest risk seen at LHR=1.62. Threshold analysis found an inflection point at LHR=2.554. When LHR <2.554, each unit rise in LHR pushed up MASLD risk by 53.5% (OR=1.535, 95%CI: 1.270-1.856, P<0.001); but when LHR≥2.554, the link was not significant (OR=1.105, 95%CI: 0.718-1.700, P=0.650). Subgroup analysis showed that the link weakened and became non-significant in people with obesity (BMI≥30 kg/m²) or diabetes.

LHR has a nonlinear link with MASLD risk, which means it might work as a biomarker for checking MASLD risk, especially for people without severe metabolic dysfunction.