Association between the lymphocyte-to-high-density lipoprotein ratio and metabolic dysfunction-associated steatotic liver disease among US adults: a cross-sectional study from NHANES 2017 to 2020.

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a liver disease that is strongly associated with chronic low-grade inflammation. Stage 3 of MASLD is characterized by excessive formation of connective tissues, commonly referred to as liver fibrosis. Although numerous inflammatory markers have been identified and extensively studied, including the tumor necrosis factor-α and interleukin-6 have been studied [Byrne CD, Targher G. NAFLD: a multisystem disease. J Hepatol. 2015;62(1 Suppl):S47-64], the lymphocyte-to-high-density lipoprotein ratio (LHR) as a new biomarker that has not been sufficiently studied. This study aims to investigate the relationship between LHR levels and MASLD, determine its potential as a predictive marker for steatosis and fibrosis stages.

Methods: This was a population-based study using data from 15,560 participants in the 2017-2020 National Health and Nutrition Examination Survey (NHANES) database. The study aimed to explore the relationship between LHR and MASLD. The disease progression was tracked by continuously measuring CAP and liver stiffness measurements. Participants who exhibited a median Controlled Attenuation Parameter (CAP) of 248 dB/m or higher were deemed to have hepatic steatosis. The LHR was calculated by dividing the lymphocyte count by the high-density lipoprotein cholesterol (HDL-C) level. Multivariate linear regression models were employed to explore the linear association between LHR and MASLD. Fitted smoothing curves and threshold effect analysis were employed to display nonlinear relationships. A two-part linear regression model was employed to estimate threshold effects. Subgroup analyses were conducted to determine the consistency of this association across various demographic groups.

Results: A total of 6,950 adults aged 18 years and older were enrolled in the study, with an average age of 48.15 ± 17.10 years (49.14% male, 50.86% female). The adjusted multiple logistic regression analysis revealed a significant positive correlation between LHR and MASLD (OR: 1.64, 95% CI: 1.40-1.92). Using the complex two-piece linear regression model, we observed an inverted L-shaped association between LHR and CAP, suggesting a critical inflection point at -2.58. Subgroup analyses indicated a pronounced association of the LHR index with obese individuals (OR: 1.96, 95% CI: 1.66-2.32) and females (OR: 1.76, 95% CI: 1.25-2.46). There was no significant association between LHR and clinically significant fibrosis.

Conclusion: The LHR index is positively correlated with MASLD among US adults. Therefore, LHR may be a robust marker for early screening, diagnosis, and monitoring of treatment efficacy in clinical practice.