Association between serum homocysteine levels and advanced hepatic fibrosis in alcohol-related liver disease: A cross-sectional study of NHANES.

Homocysteine (Hcy) can induce liver cell damage, but its relationship with alcohol-related liver disease (ALD) has rarely been reported. This study aimed to investigate the association between serum Hcy levels and advanced hepatic fibrosis in patients with ALD. We included 10,033 participants from the 1999 to 2006 National Health and Nutrition Examination Survey. Four hundred ninety six individuals with excessive alcohol consumption, elevated liver enzymes, and no other chronic liver disease were identified as ALD. Fibrosis-4 index, aspartate aminotransferase to platelet ratio index, and Frons index were used as noninvasive indicators for assessing the extent of liver fibrosis. Weighted multivariate logistic regression was used to analyze the correlation between serum Hcy levels and advanced hepatic fibrosis in ALD participants. Compared to non-alcoholic liver disease, ALD participants had higher serum Hcy levels (P < .001). In weighted multivariable-adjusted logistic regression models, we observed a positive correlation between serum Hcy levels and the risk of advanced hepatic fibrosis in ALD (odds ratio [OR] = 1.07, 95% confidence interval [CI], 1.01-1.12, P < .05), and the highest tertile of Hcy was significantly associated with an increased risk of advanced hepatic fibrosis (OR = 3.36, 95% CI, 1.34-8.43, P < .05). In subgroup analyses stratified by gender, physical activity, and body mass index, this association remained significant in men (OR = 1.07, 95% CI, 1.01-1.13, P = .026), vigorously physically active (OR = 1.46, 95% CI, 1.06-2.01, P = .027), and obese participants (OR = 1.36, 95% CI, 1.10-1.67, P = .008). In ALD participants, the area under the working characteristic curve of Hcy for advanced hepatic fibrosis was 0.686 (95% CI, 0.639-0.733). Serum Hcy levels were independently associated with an increased risk of advanced hepatic fibrosis in ALD, especially among men, vigorously physically active, and obese populations. This study supports the predictive value of Hcy for advanced hepatic fibrosis and suggests that Hcy may become a therapeutic entry point for ALD.