Non-alcoholic fatty liver disease and risk of new-onset heart failure: an updated meta-analysis of about 11 million individuals

Objective Recent studies reported an association between non-alcoholic fatty liver disease (NAFLD) and increased risk of new-onset heart failure (HF). However, the magnitude of the risk and whether this risk changes with severity of liver disease remains uncertain. We performed a meta-analysis of observational studies to quantify the magnitude of the association between NAFLD and risk of new-onset HF. Design We systematically searched Scopus, Web of Science and PubMed from database inception to March 2022 to identify eligible observational studies, in which NAFLD was diagnosed by serum biomarkers/scores, International Classification of Diseases (ICD) codes, imaging techniques or liver histology. The primary outcome was new-onset HF, as assessed mainly by ICD codes. Data from selected studies were extracted, and meta-analysis was performed using random-effects models to obtain summary hazard ratios (HRs) with 95% CIs. Results We identified 11 longitudinal cohort studies with aggregate data on 11 242 231 middle-aged individuals from different countries and 97 716 cases of incident HF over a median of 10 years. NAFLD was associated with a moderately higher risk of new-onset HF (pooled random-effects hazard ratio 1.50, 95% CI 1.34 to 1.67, pI (2)=94.8%). This risk was independent of age, sex, ethnicity, adiposity measures, diabetes, hypertension and other common cardiovascular risk factors. Sensitivity analyses did not change these results. The funnel plot did not show any significant publication bias. Conclusion NAFLD is associated with a 1.5-fold higher long-term risk of new-onset HF, regardless of the presence of diabetes, hypertension and other common cardiovascular risk factors. However, the observational design of the studies does not allow for proving causality.