Global epidemiology of lean non-alcoholic fatty liver disease: A systematic review and meta-analysis

Background and Aim Lean non-alcoholic fatty liver disease (NAFLD) is a potentially metabolically unhealthy state that refers to NAFLD occurring in non-overweight/nonobese subjects. Yet its global epidemiology and metabolic characteristics are not extensively elucidated. Methods PubMed, EMBASE, Web of Science and Cochrane databases were searched for eligible studies until January 2020. Random-effects/fixed-effects models were used to estimate the global prevalence of lean NAFLD and to compare clinical characteristics among lean non-NAFLD, lean NAFLD, and overweight/obese NAFLD subjects. "Lean" NAFLD was defined by ethnic-specific body mass index measurements in the normal range. Meta-regression and subgroup analyses were performed to determine potential sources of heterogeneity. Results A total of 33 observational studies were included with 205 307 individuals from 14 countries. The global prevalence of lean NAFLD was 4.1% (95% confidence interval [CI]: 3.4-4.8%). In lean subjects, the prevalence of NAFLD was 9.7% (95% CI: 7.7-11.8%). The prevalence of lean NAFLD with diabetes, hypertension, metabolic syndrome, dyslipidemia, or central obesity was 0.6% (95% CI: 0.4-0.9%), 1.8% (95% CI: 1.2-2.5%), 1.4% (95% CI: 1.0-1.9%), 2.8% (95% CI: 1.9-3.7%), and 2.0% (95% CI: 1.6-2.4%), respectively. The prevalence of lean NAFLD showed an upward trend between 1988 and 2017. Asian individuals had the highest prevalence of lean NAFLD (4.8%, 95% CI: 4.0-5.6%). Middle-aged people (45-59 years old) had the highest prevalence of lean NAFLD (4.4%, 95% CI: 3.2-5.5%). The prevalence of metabolic complications in lean non-NAFLD, lean NAFLD, and overweight/obese NAFLD groups increased sequentially. Conclusions Lean NAFLD occurs with metabolic complications and is not an uncommon condition. The highest prevalence of lean NAFLD occurs in middle-aged individuals of Asian countries.