Association of Alcohol and Incremental Cardiometabolic Risk Factors With Liver Disease: A National Cross-sectional Study

Abstract

Background & aims: New nomenclature allows a single cardiometabolic risk factor (CMRF) with alcohol to classify metabolic dysfunction-associated steatotic liver disease (MASLD) and with "increased alcohol intake" (MetALD), which is controversial because alcohol causes CMRFs. Studies regarding incremental CMRFs and liver-related outcomes among alcohol users would be informative.

Methods: Using the National Health and Nutrition Examination Survey (NHANES) (1/2001-3/2020), we included participants aged ≥20 years with complete alcohol and CMRF status. CMRFs were defined by the National Cholesterol Education Program's Adult Treatment Panel III. Increased alcohol use corresponded to ≥140 g/week (women)/≥210 g/week (men). The primary outcome was Fibrosis-4 (FIB-4) >2.67.

Results: Among 40,898 participants, 2282 had increased vs 38,616 without increased alcohol use. Prevalence of high FIB-4 among increased vs without increased alcohol use was higher at each quantity of CMRFs, and with each incremental CMRF: 0 (2.3%; 95% confidence interval [CI], 1.0%-5.0% vs 0.7%; 95% CI, 0.5%-0.9%), 1 (3.0%; 95% CI, 1.6%-5.6% vs 1.7%; 95% CI, 1.4%-2.1%), 2 (3.3%; 95% CI, 2.1%-5.1% vs 2.1%; 95% CI, 1.8%-2.4%), 3 (5.9%; 95% CI, 3.5%-9.6% vs 2.5%; 95% CI, 2.1%-2.9%), and 4 or 5 (6.1%; 95% CI, 3.3%-9.7% vs 4.0%; 95% CI, 3.5%-4.5%) CMRFs. Among increased alcohol users, in multivariable logistic regression, 3 (adjusted odds ratio [aOR], 2.57; 95% CI, 0.93-7.08), 4 or 5 (aOR, 2.64; 95% CI, 1.05-6.67) CMRFs were associated with 2-fold higher odds of high FIB-4 (vs 0 CMRFs), but not 1 (aOR, 1.24; 95% CI, 0.41-3.69) or 2 (aOR, 1.39; 95% CI, 0.56-3.50) CMRFs. Among individuals with increased alcohol use, sensitivity/specificity-based Euclidean distance suggested an optimal cutoff of ≥3 CMRFs to differentiate higher probability of high FIB-4.

Conclusions: Stratifying MetALD as ≥3 CMRFs, rather than 1 CMRF, may provide more optimal fibrosis stratification. Diabetes, high waist circumference, and hypertension are associated with significant liver fibrosis among individuals with increased alcohol use, but not dyslipidemia.

Keywords: ALD; Fatty Liver; MASLD; MetALD; SLD.