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. 2025 Jul 1;15(1):21292.
doi: 10.1038/s41598-025-06171-x.

Utility of the serum alanine aminotransferase to high density lipoprotein cholesterol ratio in evaluating nonalcoholic fatty liver disease and liver fibrosis

Affiliations

Utility of the serum alanine aminotransferase to high density lipoprotein cholesterol ratio in evaluating nonalcoholic fatty liver disease and liver fibrosis

Yanyan Xuan et al. Sci Rep. .

Abstract

The association of the serum alanine aminotransferase to high-density lipoprotein cholesterol ratio(ALT/HDL-C) with NAFLD remains unclear. This study aimed to examine the association of the ALT/HDL-C ratio with the prevalence of NAFLD and liver fibrosis in the U.S. general population. 4764 participants from the 2017-2018 National Health and Nutrition Examination Survey were included in our cross-sectional study. The association of ALT/HDL-C with NAFLD was examined using a general additive model. Furthermore, we conducted subgroup analyses to evaluate the relationship between liver fibrosis, NAFLD risk, and the ALT/HDL-C ratio. Of the 4764 participants, 1513 (31.76%) were diagnosed with NAFLD. All three logistic regression models showed positive associations between NAFLD risk and ALT/HDL-C. Furthermore, in stratified analyses by body mass index (BMI), gender, and age, ALT/HDL-C was positively associated with NAFLD. Hepatic steatosis and fibrosis severity were strongly linked with the ALT/HDL-C. The ALT/HDL-C and the incidence of NAFLD exhibited a nonlinear distribution that was particularly noticeable in women with an inverted U distribution with an inflection point of 0.528. NAFLD was more accurately predicted by ALT/HDL-C than by ALT or HDL-C alone, according to receiver operating characteristic (ROC) analysis. A higher ALT/HDL-C ratio in the U.S. population is independently associated with a significantly higher risk of NAFLD and liver fibrosis. The ALT/HDL-C ratio is a useful noninvasive diagnostic tool to quickly and accurately identify those at high risk of developing NAFLD and liver fibrosis.

Keywords: Alanine aminotransferase; Fibrosis; High-density lipoprotein cholesterol; NAFLD; NHANES; Steatosis.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: The National Center for Health Statistics ethics review board approved all NHANES protocols. The participants provided written informed consent to participate in this study. This study uses publicly available secondary data. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Flowchart of the study participants.
Fig. 2
Fig. 2
Associations between alanine aminotransferase to high-density lipoprotein cholesterol ratio and CAP values or prevalence of NAFLD. (A) and (B): Associations between ALT/HDL-C ratio and CAP values. (C) and (D): Associations between ALT/HDL-C ratio and prevalence of NAFLD. Each black point represents a sample. The solid red line represents the smooth curve fit between variables. Blue bands represent the 95% confidence interval from the fit. They were adjusted for age, gender, race, hypertension, BMI, T2DM, smoke, W.C., LSM, DBP, SBP, CRP, fast glucose, fast insulin, HbA1c, TBIL, ALP, GGT, AST, T.G., and SUA.
Fig. 3
Fig. 3
Associations between alanine aminotransferase to high-density lipoprotein cholesterol ratio and the prevalence of NAFLD by gender (A), age (B), BMI (C), and race (D). They were adjusted for age, gender, race, hypertension, BMI, T2DM, smoke, W.C., LSM, DBP, SBP, CRP, fast glucose, fast insulin, HbA1c, TBIL, ALP, GGT, AST, T.G., and SUA. In subgroup analyses, the model was not adjusted for the classified variables.
Fig. 4
Fig. 4
ROC curves for ALT/AST, compared to ALT, AST, GGT, and T.G. for NAFLD onset in various age groups: AGE < 20 years (A), AGE ≥ 20, < 40 years (B), AGE ≥ 40, < 60 years (C), and AGE ≥ 60 years (D). As determined by AUC, the predictive value for ALT/AST is more significant than other factors.

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