Nonalcoholic fatty liver disease and mortality from all causes, cardiovascular disease, and cancer: a meta-analysis

Whether nonalcoholic fatty liver disease (NAFLD) is associated with an increased risk of mortality remains controversial. The present study aimed to clarify this issue. A systematic search of PubMed and Embase was conducted through October 2018. Studies providing risk estimates of NAFLD and mortality were included. A random-effects model was employed to calculate summary risk estimates. Subgroup analyses were performed to identify potential effect modifiers. Fourteen studies, involving 498501 subjects and 24234 deaths, were included. Patients with NAFLD were found to be at an elevated risk of all-cause mortality compared with those without [hazard ratio (HR) = 1.34; 95% confidence interval (CI) 1.17-1.54)]. The significantly positive association between NAFLD and all-cause mortality could not be modified by age, sex, follow-up duration, and adjustment for body mass index, diabetes, smoking or hypertension (all P_interaction > 0.05), and remained in sensitivity analyses. No significant associations of NAFLD with CVD (HR = 1.13; 95% CI 0.92-1.38) and cancer (HR = 1.05; 95% CI 0.89-1.25) mortality were found. In conclusion, NAFLD is a predictor of increased all-cause mortality but not CVD and cancer mortality. These findings have important implications for decision making in public health and clinical practice, and highlight the urgency of developing effective treatments for NAFLD.