Assessing Mortality Disparities Among Non-Alcoholic Fatty Liver Disease Metabolic Dysfunction Fatty Liver Disease and Metabolic Dysfunction-Associated Liver Disease: A Comprehensive Meta-Analysis

Abstract

Non-alcoholic fatty liver disease (NAFLD) has emerged as a major global health concern due to its association with increased mortality. While previous studies have indicated a link between NAFLD and mortality, variations in risk factors such as age, sex, and disease severity warrant a comprehensive meta-analysis to clarify these associations. This meta-analysis aimed to evaluate the overall cardiovascular disease (CVD) mortality risk associated with NAFLD, considering various subgroups defined by age, sex, disease severity, presence of cirrhosis or fibrosis, study quality, and follow-up duration. A systematic search of eight studies was conducted to assess the hazard ratios (HRs) for all-cause and CVD mortality associated with NAFLD. Heterogeneity among studies was evaluated using the I² statistic, and subgroup analyses were performed based on participant age, sex, disease severity, presence of cirrhosis or fibrosis, study quality, and follow-up duration. NAFLD was significantly associated with an increased risk of all-cause mortality (HR = 1.34, 95% CI: 1.17-1.54, I² = 80.0%). Subgroup analyses revealed that individuals aged ≥50 years (HR = 1.50, 95% CI: 1.31-1.73) and males (HR = 1.43, 95% CI: 1.29-1.59) had a higher mortality risk. Patients with nonalcoholic steatohepatitis (NASH) showed a significant association with both overall (HR = 1.37, 95% CI: 1.14-1.65) and CVD mortality (HR = 1.56, 95% CI: 1.25-1.97). The presence of cirrhosis or fibrosis further elevated the risk of mortality (HR = 3.22, 95% CI: 2.40-4.33). However, NAFLD was not significantly associated with CVD mortality in the overall analysis (HR = 1.13, 95% CI: 0.92-1.38). Heterogeneity was high across most subgroups, indicating varying effects based on study characteristics. NAFLD is significantly associated with increased all-cause mortality, particularly in older individuals, males, and those with NASH or cirrhosis/fibrosis. The association with CVD mortality was not significant in the overall analysis but was evident in specific subgroups. These findings underscore the importance of early detection and tailored management of NAFLD to mitigate its impact on mortality. Further research is needed to elucidate the mechanisms linking NAFLD with adverse health outcomes and to develop effective interventions.

Keywords: cardiovascular disease; cirrhosis; fibrosis; meta-analysis; metabolic dysfunction-associated fatty liver disease; mortality; non-alcoholic fatty liver disease; nonalcoholic steatohepatitis.

Figure 1. Identification and depicting studies via databases using PRISMA guidelines

Figure 2. Forest plot showing mortality disparities among selected studies