Non-linear Association of the Alanine Aminotransferase to High-density Lipoprotein Cholesterol Ratio with Non-alcoholic Fatty Liver Disease: A Secondary Analysis of a Chinese Cohort

Xiaoqing Lin¹Yaoxuan Peng²Junjie Huang³Ziyang Huang^1*

• ¹Shantou Central Hospital, Shantou, China
• ²The First Affiliated Hospital of Shantou University Medical College, Shantou, China
• ³Joint Shantou International Eye Center of Shantou University and The Chinese University of Hong Kong, Shantou, China

Background: Non-alcoholic fatty liver disease (NAFLD) is increasingly recognized as a major public health concern, with rising prevalence worldwide. The alanine aminotransferase to high-density lipoprotein cholesterol (ALT/HDL-C) ratio has emerged as a potential marker of metabolic dysfunction, but its association with NAFLD remains underexplored, particularly in Chinese populations. This study aimed to investigate the independent and nonlinear association between the ALT/HDL-C ratio and NAFLD in Chinese adults. Methods: This was a secondary analysis of a cross-sectional dataset. A total of 1,592 Chinese adults aged 40–70 years who underwent health checkups were included. NAFLD was diagnosed via abdominal ultrasound. The ALT/HDL-C ratio was calculated and analyzed as both a continuous and categorical variable (tertiles). Multivariable logistic regression, restricted cubic spline (RCS) analysis, and receiver operating characteristic curves were used to assess the association and predictive performance of the ALT/HDL-C ratio for NAFLD. Results: The prevalence of NAFLD was 61.1%. After full adjustment, each one standard deviation increase in the ALT/HDL-C ratio was associated with a 79% higher odds of NAFLD (odds ratio [OR] = 1.79, 95% CI: 1.39–2.31, p < 0.001). A significant positive trend was observed across ALT/HDL-C tertiles (p for trend < 0.001). RCS analysis revealed a non-linear association (p for non-linearity = 0.002). Subgroup analyses showed a stronger association in females (OR = 3.89, p < 0.001) than in males (OR = 1.66, p < 0.001). However, no significant association was observed among adults aged ≥ 60 years (OR = 1.49, 95 % CI 0.90–2.48, p = 0.125). The ALT/HDL-C ratio demonstrated superior predictive performance (area under the curve = 0.710) compared to ALT or HDL-C alone. Conclusions: The ALT/HDL-C ratio is independently and nonlinearly associated with NAFLD in Chinese adults, with a particularly strong association in non-elderly individuals and women. This simple and readily available biomarker shows promise for enhancing NAFLD risk stratification in middle-aged adults, while its utility in the elderly population may be limited and requires further investigation.