Epidemiology of nonalcoholic fatty liver disease in non‐obese populations: Meta‐analytic assessment of its prevalence, genetic, metabolic, and histological profiles

Objective As a subgroup of nonalcoholic fatty liver disease (NAFLD), patients with non‐obese NAFLD may also have an increased risk of adverse hepatic and metabolic outcomes. We aimed to estimate the prevalence and incidence of non‐obese NAFLD and to describe its clinical characteristics in this systematic review and meta‐analysis. Methods We performed a systematic search of 1235 citations published up to Mar 2020. Meta‐analyses, stratified analyses and meta‐regression were all performed. Results Of the 46 studies included, 28 cross‐sectional and longitudinal studies of 155 846 non‐obese participants reported a pooled NAFLD prevalence of 14.5% (95% confidence interval [CI] 12.3%‐17.1%). A multivariate meta‐regression analysis showed the trend that the prevalence varied by their geographical location. Further stratified analyses showed that NAFLD was relatively prevalent among people aged ≥45 years (16.2%; 95% CI 10.8‐23.4) and those in South America (25.7%; 95% CI 24.4‐27.0). The PNPLA3 rs738409 gene polymorphism was more frequently observed in non‐obese NAFLD than in both obese NAFLD and non‐obese controls, while the metabolic profiles of non‐obese NAFLD were less severe than those of the obese NAFLD group. Patients with non‐obese NAFLD had 4.81‐fold and 5.43‐fold higher risk of diabetes mellitus and metabolic syndrome, respectively, than the non‐obese controls. Conclusions Non‐obese NAFLD is common, particularly in South America and among people aged ≥45 years. Metabolic diseases and PNPLA3 rs738409 gene polymorphism are more frequent in the non‐obese NAFLD group than in non‐obese controls.