Introduction

Metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction with alcohol-related steatotic liver disease (MetALD) are two separate entities within the spectrum of steatotic liver disease (SLD).

Aims & Methods

This meta-analysis aims to compare the risks of hepatic and extrahepatic outcomes between MASLD and MetALD. We systematically searched for observational cohort studies published up to March 1, 2025, comparing clinical outcomes between individuals with MASLD and MetALD. The primary outcome was liver-related events, while secondary outcomes included hepatocellular carcinoma (HCC), liver-related mortality, cardiovascular events, extrahepatic cancers, and all-cause mortality. We used random-effect models to calculate pooled hazard ratios (HRs) with 95% confidence intervals (95% CI).

Results

Twenty-four studies involving 11,396,962 individuals were analyzed (9,622,716 with MASLD and 1,774,246 with MetALD). Individuals with MetALD had significantly higher risks of liver-related events (HR 1.62, 95% CI 1.16-2.25, p=0.02) and HCC (HR 1.33, 95%CI 1.00-1.77, p=0.04) than those with MASLD. The risk of extrahepatic cancers was also increased in MetALD (HR 1.03, 95% CI 1.01-1.06, p<0.001), while the rates of cardiovascular events (HR 0.96, 95% CI 0.85-1.09, p=0.48), extrahepatic cancer-related mortality (HR 1.44, 95% CI 0.97-2.15, p=0.07), and all-cause mortality (HR 1.08, 95% CI 0.97-1.19, p=0.14) did not differ between these two conditions.

Conclusion

MetALD confers a higher risk of liver-related outcomes, HCC, and extrahepatic cancers than MASLD, while all-cause mortality and cardiovascular risk are similar between the two conditions. These findings emphasize the need for distinct clinical strategies for these related yet different entities within the SLD spectrum and highlight the importance of conducting pharmacological clinical trials in this context.

Disclosure

Nothing to disclose