Gastroenterology · Medical Literature
[Corrections] Correction to Lancet Gastroenterol Hepatol 2025; 10: 998–1012
Abstract
Celsa C, Pennisi G, Tulone A, et al. 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. Lancet Gastroenterol Hepatol 2025; 10: 998–1012—In the Acknowledgments section, further details of the PNRR-MAD-2022–12375656 project should have been provided. The beginning of this sentence shoud read: “The project was also supported by the Italian PNRR-MAD-2022–12375656 project (funded by the European Union - Next Generation EU - NRRP M6C2 - Investment 2.1 Enhancement and strengthening of biomedical research in the NHS; title RATIONAL: Risk strAtificaTIon Of Nonalcoholic fAtty Liver – CUP: I75E22000540006),…”.
Clinical relevance
Among adults with steatotic liver disease (SLD), does MetALD (metabolic dysfunction and alcohol-associated steatotic liver disease) confer a higher risk of hepatic and extrahepatic clinical outcomes compared with MASLD (metabolic dysfunction-associated steatotic liver disease)? __SNAPSHOT__ {"studyDesign":"Systematic review and meta-analysis of observational cohort studies","setting":"International; multicenter; studies identified through PubMed, Scopus, and Cochrane databases up to March 2025","sampleSize":"n=11,575,558 adults with SLD across 24 included studies (9,801,312 with MASLD; 1,774,246 with MetALD)","population":"Adults with steatotic liver disease classified as either MASLD or MetALD per current nomenclature (Delphi consensus criteria); specific individual-level inclusion criteria varied by constituent study","intervention":"MetALD (steatotic liver disease with metabolic dysfunction and moderate-to-higher alcohol intake)","comparator":"MASLD (steatotic liver disease with metabolic dysfunction and minimal alcohol intake)","primaryOutcome":"Hepatic and extrahepatic clinical outcomes including liver-related events, hepatocellular carcinoma (HCC), all-cause mortality, cardiovascular events/mortality, and extrahepatic cancers","followUp":"Not reported (varied by constituent study)","fundingSource":"Italian Ministry of Education, University, and Research (MIUR); Italian PNRR-MAD-2022–12375656 project (funded by the European Union – Next Generation EU – NRRP M6C2, Investment 2.1; CUP: I75E22000540006)"}
Key findings
Compared with MASLD, MetALD was associated with a significantly higher risk of liver-related events (HR 1.62; p=0.0086) and HCC (HR 1.33; p=0.048). The risk of extrahepatic cancers was also higher in MetALD versus MASLD (HR 1.03; p<0.0001), though the absolute magnitude of this excess risk is modest by the point estimate. Conversely, risk of cardiovascular events or MACE was not significantly different between MetALD and MASLD (HR 0.96; p=0.48), nor was cardiovascular-related mortality (HR 0.90; p=0.053). All-cause mortality was similarly not reported as significantly different between the two groups. Confidence intervals for individual hazard ratios were not reported in available abstract/summary sources. NNT/NNH cannot be calculated from available data. No safety or adverse event data were applicable to this observational meta-analytic design.
Practice implications
This large meta-analysis (>11.5 million individuals) provides the most comprehensive evidence to date suggesting that MetALD, compared with MASLD, carries a meaningfully higher risk of hepatic decompensation and HCC, and a statistically higher risk of extrahepatic cancers—though the HR of 1.03 for extrahepatic cancers warrants scrutiny regarding clinical versus statistical significance. Cardiovascular risk appears comparable between the two conditions, which is clinically important and potentially counterintuitive given the additional alcohol exposure in MetALD. These findings apply to adults meeting Delphi consensus criteria for MASLD or MetALD; pediatric populations, lean phenotypes, and those with concurrent significant alcohol use disorder were likely not adequately represented. The study was limited to abstract-level data in this summary, which precludes full assessment of subgroup analyses, heterogeneity statistics, or methodological quality scoring across all 24 studies. The observed differences in hepatic outcomes support more intensive hepatic surveillance and liver-directed risk stratification in MetALD patients compared with MASLD patients. However, given the observational and heterogeneous nature of constituent studies, confounding by alcohol intake misclassification, fibrosis stage, and metabolic comorbidity burden cannot be excluded. Practice should be informed—but not unilaterally changed—by these data pending corroboration from prospective registries and interventional studies. __LIMITATIONS__ Observational design of constituent studies precludes causal inference; confounding by disease severity, fibrosis stage, comorbidities, and alcohol misclassification is inherent.,Alcohol intake is largely self-reported across constituent studies, and underreporting is well-documented in MetALD populations, potentially misclassifying true ALD cases as MetALD.,Significant heterogeneity across 24 studies in terms of population, follow-up duration, outcome definitions, and MetALD/MASLD classification methods is anticipated but not quantified in available summary data.,Confidence intervals for key hazard ratios were not reported in available sources, limiting assessment of precision.,The HR of 1.03 for extrahepatic cancers, while statistically significant (p<0.0001), may not be clinically meaningful without absolute risk differences and NNH calculations.,The relative prevalence of MASLD to MetALD ranged widely (median ratio 6.6), reflecting heterogeneous study populations and diagnostic thresholds.,Only abstract-level data were available for this summary; full-text methodology (e.g., GRADE assessment, publication bias analysis, sensitivity analyses) could not be independently reviewed.,Generalizability is uncertain for pediatric, lean, or ethnically diverse populations underrepresented in the constituent studies.,Funding from the Italian government and EU Next Generation EU program represents non-industry support, but this does not eliminate the possibility of investigator-level conflicts in constituent studies. __BOTTOM_LINE_CATEGORY__ potentially_practice_informing __BOTTOM_LINE__ This meta-analysis of over 11.5 million adults demonstrates that MetALD is associated with significantly higher risks of liver-related events and HCC compared with MASLD, supporting more proactive hepatic surveillance in MetALD patients. Cardiovascular risk appears similar between the two conditions, suggesting that cardiometabolic risk management should remain equally prioritized regardless of SLD subtype. These findings are hypothesis-generating and practice-informing, but do not yet constitute sufficient evidence to mandate discrete management algorithms for MetALD without prospective validation.