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.