Impact of Non-Alcoholic Fatty Liver Disease Severity on the Incidence of Major Adverse Cardiovascular Events: A Meta-Analysis of Longitudinal Cohort Studies

Background: Non-alcoholic fatty liver disease (NAFLD) is increasingly recognized not only as a hepatic disorder but also as a significant contributor to cardiovascular morbidity. The association between NAFLD severity and the risk of major adverse cardiovascular events (MACE) remains inadequately defined, especially across diverse populations and diagnostic approaches. Objective: To evaluate the impact of NAFLD severity on the incidence of MACE by synthesizing evidence from longitudinal cohort studies. Methods: A systematic literature search was conducted across PubMed, Embase, Web of Science, and the Cochrane Library, identifying longitudinal cohort studies that assessed the relationship between NAFLD severity and MACE outcomes. Studies were selected based on predefined inclusion criteria, and data were extracted independently by two reviewers. Risk ratios (RR) with 95% confidence intervals (Cis) were pooled using a random-effects model. Heterogeneity and publication bias were assessed via the I² statistic and funnel plots, respectively. Results: Three studies with a combined sample of over 136,000 participants were included. Subgroup analysis comparing severe vs. Mild NAFLD showed a non-significant increased risk of MACE (RR: 1.50; 95% CI: 0.97–2.32). When comparing NAFLD to non-NAFLD populations, the pooled RR was 1.19 (95% CI: 0.80–1.79). Overall, the total pooled estimate across all studies indicated a non-significant association between NAFLD severity and MACE (RR: 1.26; 95% CI: 0.92–1.73), with substantial heterogeneity (I² = 88%). Conclusion: Although not statistically significant, the findings suggest a trend toward increased cardiovascular risk with greater NAFLD severity. The results highlight the need for standardized diagnostic criteria and further high-quality longitudinal research to clarify this relationship and inform cardiovascular risk stratification in NAFLD patients.