Cardiovascular and Mortality Outcomes in Lean Versus Non-lean Steatotic Liver Disease: A Systematic Review and...

Steatotic liver disease occurring at a normal body mass index is increasingly recognized, yet whether this phenotype carries a different prognosis from the non-lean phenotype remains contested. We aimed to compare cardiovascular events and mortality between lean and non-lean steatotic liver disease. PubMed, Scopus, and the Cochrane Library were searched from database inception to July 2026. Eligible studies were longitudinal cohorts reporting cardiovascular or mortality outcomes stratified by lean versus non-lean status. Because most contributing cohorts predate the 2023 nomenclature change, studies defined by nonalcoholic fatty liver disease (NAFLD) or metabolic dysfunction-associated fatty liver disease (MAFLD) criteria were retained without retrospective reclassification, and this was treated as a source of indirectness. Records were screened and data extracted in duplicate, and risk of bias was appraised using the Risk Of Bias In Non-randomized Studies of Interventions (ROBINS-I) with exposure-specific adaptation of its domains. Adjusted time-to-event estimates were preferred, transformed to the logarithmic scale, harmonized to a lean-versus-non-lean direction, and combined using random-effects inverse-variance meta-analysis with the DerSimonian-Laird estimator. Of 395 records identified, 265 were screened, 15 could not be retrieved, and 15 observational cohort studies were included, of which six contributed to at least one pooled analysis. Lean steatotic liver disease was associated with higher all-cause mortality (five studies; pooled hazard ratio (HR), 1.66; 95% CI, 1.48-1.86; P<0.001; I²=63.8%; τ²=0.009), a finding that persisted when restricted to the three studies providing a direct lean-versus-non-lean comparison (HR, 1.64; 95% CI, 1.42-1.90; P<0.001; I²=78.2%; τ²=0.011). Composite cardiovascular outcomes and major adverse cardiovascular events did not differ significantly (five studies; pooled HR/subdistribution hazard ratio (sHR), 0.92; 95% CI, 0.70-1.19; P=0.52; I²=90.7%; τ²=0.077); an HR-only sensitivity analysis excluding the single sHR was similarly null (four studies; HR, 0.96; 95% CI, 0.70-1.30; P=0.77; I²=88.1%; τ²=0.080). Heterogeneity was substantial, and these estimates are inconclusive rather than evidence of equivalence. Cardiovascular mortality was reported by two studies using non-identical effect measures and was not pooled: one study reported an HR of 1.40 (95% CI, 1.12-1.76), and the other reported an sHR of 0.94 (95% CI, 0.47-1.89). No study was rated as having low overall risk of bias; 10 were rated moderate and five serious. Lean steatotic liver disease appears to carry excess all-cause mortality, whereas evidence for cardiovascular event risk and cardiovascular mortality remains insufficient and heterogeneous. Applicability to contemporary MASLD should be interpreted cautiously because included cohorts used heterogeneous disease definitions and body mass index thresholds. The review was prospectively registered.