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. 2025 Jul 1;25(1):467.
doi: 10.1186/s12876-025-04057-w.

Association of serum lactate dehydrogenase levels with non-alcoholic fatty liver disease and advanced hepatic fibrosis in the United States: a cross-sectional study using NHANES data from 2007 to 2018

Xiaotong Zhang  1   2   3 , Min Liu  2   3 , Junjun Huang  4 , Ya Zheng  5   6 , Yuping Wang  2   3 , Yongning Zhou  7   8
Affiliations

Association of serum lactate dehydrogenase levels with non-alcoholic fatty liver disease and advanced hepatic fibrosis in the United States: a cross-sectional study using NHANES data from 2007 to 2018

Xiaotong Zhang et al. BMC Gastroenterol. .

Abstract

Background: The associations between LDH and non-alcoholic fatty liver disease (NAFLD), as well as advanced hepatic fibrosis (AHF), have not been explored. This study aims to investigate the association between log-transformed LDH levels and the prevalence of NAFLD and AHF.

Methods: In this cross-sectional study, after applying specific criteria for inclusion and exclusion, a total of 7,316 individuals were chosen from the 59,842 participants for the final analysis. LDH levels were measured using an enzymatic rate method. A fatty liver index (FLI) greater than or equal to 60 and an NAFLD fibrosis score (NFS) higher than 0.676 were found to be indicative of hepatic steatosis and advanced hepatic fibrosis. Both weighted multivariable linear and logistic regression analyses were used to finish the study. Moreover, additional analyses were performed utilizing weighted stratified analysis and weighted smoothed curve fitting using the generalized additive model (GAM).

Results: Following data analysis, the multivariable regression model 3 showed a significant association between the elevated log-transformed LDH levels and AHF (OR: 3.087, 95% CI: 1.378-6.915, P = 0.007). Furthermore, a modest association was observed between log-transformed LDH tertiles and FLI (βQ2 vs. Q1 = 0.965, 95% CI: 0.014-1.916, P = 0.047). However, there was no evidence to prove that there was an association between log-transformed LDH levels and NAFLD in model 3. The weighted smoothed curve fitting using the GAM suggested a linear dose-response effect between log-transformed LDH levels and an increased risk of NAFLD, as well as a non-linear relationship between log-transformed LDH levels with AHF risk. Moreover, the weighted stratified analysis further suggested that the associations of log-transformed LDH with NAFLD and AHF could differ in different population groups.

Conclusions: This study indicates that elevated log-transformed LDH levels are associated with an increased prevalence of AHF in our study population. However, the cross-sectional study analysis cannot prove causality, which requires further cohort studies or mechanistic studies to elucidate the precise mechanisms and root causes.

Keywords: Biomarker; Cross-sectional analysis; Lactate dehydrogenase; NAFLD; NHANES.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The study was approved by the NCHS Research Ethics Review Board ( https://www.cdc.gov/nchs/nhanes/irba98.htm ; accessed on August 24, 2022). NHANES was approved by the National Center for Health Statistics research ethics review board. Informed consent was obtained from all individual participants included in the study. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Flow chart of the participants in NHANES from 2007 to 2017. Abbreviations: NHANES, the National Health and Nutrition Examination Survey; LDH, lactate dehydrogenase; FLI, fatty liver index; NFS, NAFLD fibrosis score
Fig. 2
Fig. 2
Association between LDH and NAFLD (a) as well as AHF (b) Weighted smoothed curve fitting using the GAM was conducted in model 3, which was adjusted for age, gender, race, PIR, educational level, marital status, BMI, ALT, AST, TC, TG, GGT, liver condition, dietary quality, physical activity, hypertension, diabetes, and smoking status. The fitted line was shown as solid black lines, and the corresponding 95 percent CIs were shown as short black dashed lines. Abbreviations: LDH, lactate dehydrogenase; NAFLD, non-alcoholic fatty liver disease; AHF, advanced hepatic fibrosis; GAM, Generalized additive model. ORs, odds ratios; CIs, confidence intervals; BMI, body mass index; PIR, poverty-income ratio; AST, aspartate transaminase; ALT, alanine transaminase; TC, total cholesterol; TG, triglycerides; GGT, gamma-glutamyl transferase
Fig. 3
Fig. 3
The weighted stratified and interaction analysis of relationship between LDH and NAFLD (shown in the left half of the figure) as well as AHF (shown in the right half of the figure) was conducted in model 3, which was adjusted for age, gender, race, PIR, educational level, marital status, BMI, ALT, AST, TC, TG, GGT, liver condition, dietary quality, physical activity, hypertension, diabetes, and smoking status by removing the applied categorical variables at the time of their respective strata. Abbreviations: ORs, odds ratios; CIs, confidence intervals; NAFLD, non-alcoholic fatty liver disease; AHF, advanced hepatic fibrosis; BMI, body mass index; PIR, poverty-income ratio
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