U-shaped association between TC/HDL-C ratio and the risk of metabolic dysfunction-associated fatty liver disease in older adults.

This cross-sectional study aimed to evaluate the association between the total cholesterol to high-density lipoprotein cholesterol (TC/HDL-C) ratio and metabolic dysfunction-associated fatty liver disease (MAFLD) risk in older adults. Utilizing data from 4,844 participants aged ≥ 18 years from the 2005 to 2020 National Health and Nutrition Examination Survey (NHANES), the TC/HDL-C ratio was calculated and categorized into quartiles. MAFLD was diagnosed according to the 2020 International Expert Consensus Criteria. Multivariable logistic regression assessed the association between the TC/HDL-C ratio and MAFLD prevalence, while restricted cubic splines evaluated the potential non-linearity and threshold effects. Among the participants, 2,716 (56.1%) were diagnosed with MAFLD. A higher TC/HDL-C ratio was significantly associated with an increased prevalence of MAFLD (odds ratio [OR] 1.30; 95% confidence interval [CI] 1.09-1.55; p < 0.01). This analysis revealed a U-shaped positive association (p for non-linearity = 0.004) with an inflection point at a TC/HDL-C ratio of 3.56. Below this threshold, each unit increase in the TC/HDL-C ratio was associated with a steeper increase in MAFLD risk (adjusted OR [aOR] = 1.370, 95% CI 1.066-1.760) compared with increases above the threshold (aOR = 1.165, 95% CI 1.049-1.294; p for log-likelihood ratio = 0.01). The TC/HDL-C ratio demonstrated superior diagnostic accuracy for MAFLD (AUC = 0.682) compared with isolated TC or HDL-C measurements. Subgroup analysis indicated significant interactions with body mass index (BMI) and stroke (both p-interaction < 0.05). Sensitivity analysis confirmed the robustness of the findings. Further longitudinal studies are warranted to validate these results and inform optimal MAFLD prevention strategies.