Mortality and Cardiovascular Outcomes in Patients with MAFLD Compared with Patients with MASLD: A Systematic Review and Meta-Analysis

Abstract

Background/Aims: Although metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated fatty liver disease (MAFLD) represent the updated nomenclature and diagnostic criteria for nonalcoholic fatty liver disease, studies comparing the prognostic implications of these conditions remain limited. This meta-analysis aimed to quantify the associations among MAFLD, MASLD, and long-term clinical outcomes. Methods: A comprehensive literature search was performed to identify cohort studies that assessed the association of MASLD and MAFLD with all-cause mortality, cause-specific (cardiovascular and cancer-related) mortality, and the incidence of cardiovascular disease in the PubMed, Embase, Web of Science, CINAHL, and CENTRAL databases from inception through October 31, 2024. Pooled hazard ratios (HRs) were calculated for relevant outcomes. Results: We identified 18 cohort studies, comprising 10,653,666 patients with MAFLD from 13 studies and 3,202,447 patients with MASLD from nine studies. MAFLD was significantly associated with an increased risk of overall mortality (pooled HR [95% confidence interval], 1.30 [1.16 to 1.47]) and cardiovascular mortality (1.31 [1.08 to 1.60]; both p<0.01), but not with cancer-related mortality (1.10 [0.97 to 1.24]; p=0.130). Conversely, MASLD was associated with a higher risk for all mortality outcomes: overall mortality (1.34 [1.12 to 1.61]), cardiovascular mortality (1.17 [1.07 to 1.27]), and cancer-related mortality (1.24 [1.19 to 1.29]; all p<0.01). The risk of cardiovascular disease was increased in patients with both MAFLD (1.48 [1.31 to 1.66]) and MASLD (1.33 [1.21 to 1.46]; both p<0.001). Conclusions: MAFLD and MASLD were both associated with increased risks of mortality and cardiovascular outcomes. Notably, a significant association with cancer-related mortality was observed for MASLD, but not for MAFLD.