Lean non-alcoholic fatty liver disease and the risk of all-cause mortality: An updated meta-analysis

Abstract

Introduction and Objectives: Cohort studies reported controversial results regarding the long-term prognosis of patients with lean non-alcoholic fatty liver disease (NAFLD) compared to non-lean NAFLD patients. This updated meta-analysis aimed to estimate the magnitude of the association between lean body mass index and all-cause mortality risk in NAFLD patients. Materials and Methods: We systematically searched the EMBASE and MEDLINE databases from inception to March 2023 to identify observational studies that reported hazard ratio (HR) for all-cause mortality of patients with lean NAFLD versus those with non-lean, overweight, or obese NAFLD. Multivariable-adjusted hazard ratios (HRs) for all-cause mortality were pooled using a random effects model. Results: Fourteen studies with 94,181 NAFLD patients (11.3 % with lean NAFLD) and 7,443 fatal events over a median follow-up of 8.4 years (IQR, 6.6–17.4 years) were included. Patients with lean NAFLD had a higher risk of all-cause mortality than those with non-lean NAFLD (random-effects HR 1.61, 95 % CI 1.37–1.89; I2=77 %). The magnitude of this risk remained unchanged even after stratified analysis by measures of NAFLD diagnosis, study country, cohort setting, length of follow-up, adjustment with fibrosis stage/cirrhosis, and the Newcastle-Ottawa Scale. The risk was independent of age, sex, and cardiometabolic risk factors. Sensitivity analyses did not alter these findings. The funnel plot and Egger's test revealed no significant publication bias. Conclusions: This meta-analysis revealed that lean NAFLD is associated with an approximately 1.6-fold increased mortality risk. Further studies are needed to unravel the existing but complex link between lean NAFLD and an increased risk of death.

Keywords

• Nonalcoholic fatty liver disease
• Lean
• Overweight
• Obesity
• Mortality
• Meta-analysis