ALT levels, alcohol use, and metabolic risk factors have prognostic relevance for liver-related outcomes in the general population.

Background & Aims: A new nomenclature and subclassification for steatotic liver disease (SLD) was recently introduced. We validated the prognostic value of SLD subclasses in a Finnish population-based cohort and explored the impact of metabolic risk factors and alcohol consumption on liver-related outcomes and death.

Methods: The study included 23,910 individuals (47% men, mean age 50.5 ± 14.0 years, BMI 27.0 ± 4.7 kg/m) from the FINRISK and Health 2000 health examination surveys with healthcare registry linkage for severe liver-related outcomes and deaths. SLD was identified by alanine aminotransferase (ALT) levels >20 U/L in women and >30 U/L in men (primary analysis) or fatty liver index (FLI) ≥60 (sensitivity analysis).

Results: The prevalence of ALT-defined SLD was 43% (n = 10,380), with subclass rates of 34.5% for metabolic dysfunction-associated steatotic liver disease (MASLD), 4.2% for coexistent MASLD and alcohol-related liver disease (ALD) (i.e., MetALD), and 1.8% for ALD. During a median 13.3-year follow-up, we observed 129 liver-related events. MetALD and ALD increased the age- and sex-adjusted liver-related outcome risk by fourfold (HR 3.83, 95% CI 2.51-5.84, <0.001) and eightfold (HR 7.90, 95% CI 5.16-12.30, <0.001), respectively, compared with patients with MASLD. ALD was also associated with the highest risk for non-liver mortality. Metabolic risk factors were present in 93% and 96% of individuals with ALT-defined SLD and ALD, respectively. Alcohol use amplified the risk of liver-related outcomes in individuals with MASLD. Sensitivity analyses by the FLI were similar.

Conclusion: SLD is a significant public health concern. Nearly all ALD cases exhibit metabolic risk factors. Among ALT-defined SLD subclasses, ALD presents the highest risk for both liver-related and non-liver-related outcomes. Alcohol use increases the risk of liver-related outcomes in individuals with MASLD.

Impact And Implications: This study provides important information for physicians, researchers, and patients, demonstrating that the new classification of steatotic liver disease (SLD) has prognostic relevance at the population level. Evaluating the SLD subclass for a patient helps in understanding the magnitude of the risk for liver- and non-liver-related outcomes. In particular, the risks are highest in those with alcohol-related liver disease (ALD), but also increased in individuals with coexisting metabolic dysfunction-associated steatotic liver disease (MASLD) and ALD (MetALD) when compared with those with MASLD. However, alcohol use increased the risk of liver-related outcomes also in individuals with MASLD, highlighting the importance of evaluating alcohol use in every patient with SLD. Nearly all individuals with ALD have metabolic risk factors, and it is important to treat these factors to improve the survival of these patients.