Non-linear relationship between high-density lipoprotein cholesterol and metabolic dysfunction-associated steatotic liver disease: a cross-sectional study in the Japanese population.

Xiangfei Guo,Yucong Zou,Cui Yang,C. Cao,Yulong Wang,Fubing Zha

Published 2026 in Frontiers in Medicine

ABSTRACT

Background Research into the effect of high-density lipoprotein cholesterol (HDL-C) on metabolic dysfunction-associated steatotic liver disease (MASLD) remains relatively limited. This research aims to shed light on how HDL-C levels correlate with MASLD among the Japanese demographic. Methods A comprehensive review of health records from 14,280 patients at Murakami Memorial Hospital from 2004 to 2015 was undertaken. To investigate the linear association of HDL-C concentrations with MASLD occurrence, binary logistic regression was applied. Additionally, a generalized additive model (GAM) integrated with smooth curve fitting procedures was implemented to characterize potential non-linear dependencies. Results An inverse correlation was observed between HDL-C levels and MASLD prevalence (OR = 0.46; 95% CI: 0.37-0.58), holding steady after adjustments for various demographic and health variables. The consistency of these findings was confirmed through multiple sensitivity tests. The study also uncovered a non-linear correlation between HDL-C concentrations and MASLD occurrence. A detailed analysis using a two-piece logistic regression and recursive techniques pinpointed a critical HDL-C level of 1.04 mmol/L. Above this level, each unit increase in HDL-C was linked to a 61% decrease in the likelihood of MASLD (OR = 0.39; 95% CI: 0.30-0.50), a connection that dissipates below this threshold of HDL-C (OR = 1.49; 95% CI: 0.66-3.35). Conclusion The investigation revealed an inverse, non-linear relationship between HDL-C and MASLD within the Japanese community, emphasizing a pivotal threshold effect. Elevated HDL-C levels beyond 1.04 mmol/L significantly diminish MASLD risk.

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