Significant Liver Fibrosis in Pre-Metabolic Dysfunction-Associated Alcohol-Relate Liver Disease Population: A Nationally Representative Analysis of Moderate Drinkers With Cardiometabolic Risk Factors.

BACKGROUND/AIMS: Metabolic dysfunction-associated alcohol-related liver disease (MetALD), a recently defined entity, represents the combination of metabolic dysfunction-associated steatotic liver disease (MASLD) and moderate to heavy alcohol consumption. While these thresholds mark the transition from MASLD to MetALD, the prevalence of significant liver fibrosis in individuals with metabolic dysfunction who consume alcohol below these levels, a "pre-MetALD" population, remains unknown. In this study, we estimated the burden of significant liver fibrosis within this pre-MetALD population using a nationally representative sample. METHODS: We analyzed National Health and Nutrition Examination Survey 2021-2023 data. Adults aged ≥18 years with a body mass index ≥25 kg/m2 (≥23 for Asian participants), consuming 7-14 drinks per week with valid liver stiffness measurement (LSM) (interquartile range/median ≤0.30) and available Fibrosis-4 index (FIB-4) scores were included (N = 193). Cardiometabolic risk factor (CMRF) burden was scored using overweight/obesity, dysglycemia, and hypertension. Participants were categorized as having 1, 2, or 3 CMRFs. The primary outcome was an LSM ≥8 kPa; the secondary outcome was an LSM ≥12 kPa. Alcohol was categorized as low-moderate (7-10 drinks per week) or high-moderate (11-14 drinks per week). All analyses used survey weights. RESULTS: The cohort had a mean age of 55.2 years (standard deviation: 15.4); 56.5% had hypertension and 30.1% had dysglycemia. Weighted prevalence of significant fibrosis was 15.8% (95% confidence interval [CI]: 9.2-22.4%), affecting approximately 1 in 6 participants. Fibrosis prevalence was similar across CMRF burden (15.0%, 16.4%, and 15.4% for 1, 2, and 3 CMRFs, respectively). A dose-response relationship was observed with alcohol intake, with significant fibrosis prevalence rising from 13.2% among those consuming 7-10 drinks per week to 18.0% among those consuming 11-14 drinks per week. Advanced fibrosis was present in 4.5% overall (95% CI: 1.9-7.1%). Notably, 40.9% of participants with significant fibrosis had a normal FIB-4 score (≤1.3). In the sensitivity analysis restricted to obese participants (n = 84), the prevalence rose to 23.2% (95% CI: 11.9-34.4%). CONCLUSION: Significant liver fibrosis affects approximately 1 in 6 adults with CMRFs who consume alcohol below the MetALD threshold. Nearly 41% of those with confirmed fibrosis had a normal FIB-4 score, underscoring the limitations of serum-based screening in this group. These findings support prospective evaluation of elastography-based screening strategies in the pre-MetALD population.