Longitudinal Outcomes Associated with Metabolic Dysfunction-Associated Steatotic Liver Disease. A Meta Analysis of 129 Studies

Background and aims The progression of MASLD has been found to manifest in a series of hepatic and extra-hepatic complications. A comprehensive meta-analysis of the longitudinal outcomes associated with MASLD has yet to be conducted. Methods To investigate the longitudinal outcomes associated with MASLD, Medline and Embase databases were searched to identify original studies which evaluated the longitudinal risks of incident clinical outcomes among MASLD patients compared with non-MASLD individuals. DerSimonian Laird random effects meta-analysis was performed. Pooled effect estimates were calculated, and heterogeneity among studies was evaluated. Results 129 studies were included in the meta-analysis. Meta-analysis revealed a significant increase in the risk of cardiovascular outcomes (HR: 1.43, 95%Cl: 1.27 to 1.60, p<0.01), various metabolic outcomes such as incident hypertension (HR: 1.75, 95%Cl: 1.46 to 2.08, p<0.01), diabetes (HR: 2.56, 95%Cl: 2.10 to 3.13, p<0.01), pre-diabetes (HR: 1.69, 95%Cl: 1.22 to 2.35, p<0.01), metabolic syndrome (HR: 2.57, 95%Cl: 1.13 to 5.85, p=0.02), chronic kidney disease (HR: 1.38, 95%Cl: 1.27 to 1.50, p<0.01) as well as all cancers (HR: 1.54, 95%Cl: 1.35 to 1.76, p<0.01) among MASLD patients compared to non-MASLD individuals. By subgroup analysis, MASLD patients with advanced liver disease (HR: 3.60, CI: 2.10 to 6.18, p<0.01) were also found to be associated with a significantly greater risk (p=0.02) of incident diabetes than those with less severe MASLD (HR: 1.63, CI: 1.08 to 2.45, p=0.02) when compared to non-MASLD. Conclusions The present study emphasizes the association between MASLD and its clinical outcomes including cardiovascular, metabolic, oncological, and other outcomes. The multisystemic nature of MASLD found in this analysis requires treatment targets to reduce systemic events and end organ complications.