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Background: Elevated liver stiffness reflects hepatic fibrosis but can also be secondary to venous congestion. We aimed to study the association between liver stiffness and mortality in the general population, stratified for heart failure and/or coronary heart disease (CHD). Methods: We analysed individuals enrolled in the ongoing prospective population-based Rotterdam Study who attended a visit between 2009–2014 that included liver stiffness measurement. Exclusion criteria for the primary analysis were incomplete data on heart failure, unreliable liver stiffness, alcohol abuse and viral hepatitis, leaving 4.153 participants (aged 67.5 ± 8.4 years, 44.2% male) for analysis with a median follow-up of 6.0 (interquartile range: 5.1–7.0) years. Secondary analysis included participants with viral hepatitis, alcohol abuse and/or unreliable measurement. The association between liver stiffness and mortality was assessed using Cox regression. Associations between heart failure, CHD, and echocardiographic characteristics and liver stiffness were quantified with linear regression. Results: Liver stiffness ≥8.0 kPa was associated with mortality (aHR: 1.37, 95%CI: 1.00–1.89). However, this was driven by participants with heart failure (aHR: 2.48, 95%CI: 1.15–5.35), since high liver stiffness was not associated with mortality in participants without heart failure and/or CHD (aHR: 1.07, 95%CI: 0.70–1.64). Results were consistent when individuals with viral hepatitis, alcohol abuse or unreliable liver stiffness measurement were not excluded. Several cardiovascular characteristics were significantly associated with higher liver stiffness, e.g. heart failure, moderate/poor diastolic dysfunction, and right atrium diameter > 4.5 cm. Conclusion: In our cohort of community-dwelling elderly, high liver stiffness was associated with excess mortality, primarily explained by participants with heart failure. Moreover, heart failure and its indicators were associated with increased liver stiffness.

Background & Aims: The applicability of the novel metabolic dysfunction associated fatty liver disease (MAFLD) definition has been studied in numerous cohorts and compared to non-alcoholic fatty liver disease (NAFLD). No consensus has been reached on which definition is preferred. Therefore, this meta-analysis aims to compare the epidemiological and clinical features of NAFLD and MAFLD in the general and non-general population. Methods: We searched Medline, Embase and Web of Science for studies comparing MAFLD to NAFLD. Based on MAFLD and NAFLD status, the following subgroups were investigated for liver health: overlap fatty liver disease (FLD), NAFLD-only and MAFLD-only. Data were pooled using random-effects models. Results: We included 17 studies comprising 9 808 677 individuals. In the general population, MAFLD was present in 33.0% (95% CI 29.7%-36.5%) and NAFLD in 29.1% (95% CI 27.1%-31.1%). Among those with FLD, 4.0% (95% CI 2.4%-6.4%) did not meet the MAFLD criteria but had NAFLD (NAFLD-only) and 15.1% (95% CI 11.5%-19.5%) was exclusively captured by the novel MAFLD definition (MAFLD-only). Notably, this MAFLD-only group was at significantly increased risk for fibrosis (RR 4.2; 95% CI 1.3-12.9) and had higher alanine aminotransferase (mean difference: 8.0 U/L, 95% CI 2.6-13.5) and aspartate aminotransferase (mean difference: 6.4 U/L, 95% CI 3.0-9.7), compared to NAFLD-only. Similar results were obtained among the non-general population. Conclusions: Metabolic dysfunction associated fatty liver disease and NAFLD are highly prevalent in the general population, with considerable overlap between them. However, compared to NAFLD, significantly more individuals were additionally identified by MAFLD than were missed. Importantly, by using the MAFLD criteria, more individuals with liver damage were identified. Therefore, the novel MAFLD definition is superior to NAFLD on a population level.