This research systematically analyzed 24 cohort studies encompassing more than 11.5 million adults throughout the globe. Of these, approximately 9.8 million had MASLD, while 1.7 million had MetALD. The participants with MASLD were on average older (57 years vs. 49 years) and included a larger proportion of women (38% vs. 18%) when compared to the individuals with MetALD, where men predominated.
This study assessed risks for a range of outcomes, including liver-related events, hepatocellular carcinoma (HCC), extrahepatic cancers, cardiovascular disease, and overall mortality. Advanced statistical models were used to account for confounding factors such as age, sex, and comorbidities.
The patients with MetALD were 62% more likely to develop severe liver complications when compared to those with MASLD. The risk of primary liver cancer was 33% higher in the MetALD group. The individuals with MetALD carried a modest but statistically significant 3% increased risk of cancers outside the liver. Also, the outcomes like cardiovascular events, all-cause mortality, and mortality from extrahepatic cancers did not show meaningful differences between MASLD and MetALD.
The results indicated clear disparities in liver-specific outcomes, while broader health risks like heart disease and overall survival appeared comparable across the two groups. For example, cardiovascular events occurred at nearly identical rates in both conditions (hazard ratio close to 1.0). Similarly, while there was a trend toward higher extrahepatic cancer-related mortality in MetALD, this did not reach statistical significance.
Overall, these findings support the view that MetALD is a more aggressive disease phenotype, particularly in terms of liver progression and cancer development. However, since overall mortality and cardiovascular risks remain similar to MASLD, the results suggest that prevention and management strategies should not be one-size-fits-all.
Source:
Celsa, C., Pennisi, G., Tulone, A., Ciancimino, G., Vaccaro, M., Pecorella, F., Di Maria, G., Enea, M., Midiri, F., Mantovani, A., Targher, G., Krag, A., Rinella, M. E., Cammà, C., & Petta, S. (2025). Risk of hepatic and extrahepatic outcomes associated with metabolic dysfunction-associated steatotic liver disease and metabolic dysfunction and alcohol-associated steatotic liver disease: a systematic review and meta-analysis. The Lancet. Gastroenterology & Hepatology. https://doi.org/10.1016/S2468-1253(25)00188-8
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