Global Prevalence, Incidence and Outcome of Non-Obese or Lean NAFLD:  A Meta-Analysis of 134 Studies and 11,947,163 Persons

Abstract

Background: While commonly associated with obesity, non-alcoholic fatty liver disease (NAFLD) is increasingly recognized in non-obese individuals, but data are limited. Using a systematic review and meta-analytic approach, we determined the global prevalence, incidence, and clinical outcomes of NAFLD in non-obese or lean persons. Methods: We searched four databases (PubMed, EMBASE, SCOPUS, and the Cochrane Library) from inception to May 1, 2019 and included relevant original research articles without language restriction. Literature search and data extraction performed independently by two investigators. Findings: We found a total of 134 studies (N=11,947,163) from 26 countries/areas: 124 (N=11,799,621) for prevalence analysis, 14 (N=110,588) for incidence analysis, and eight (N=36,954) for outcome analysis. Within the NAFLD population, non-obese (lean plus overweight) NAFLD prevalence was 40·75% varying from about ≤25% (Malaysia, Pakistan, Bangladesh) to over 50% (e.g. Mexico, Austria, Sweden); and lean (not overweight or obese) NAFLD prevalence was 19·19%. In the general population (NAFLD and non-NAFLD), non-obese NAFLD prevalence was 12·12% and also varied geographically, and lean NAFLD prevalence was 5·12%. Among people with non-obese or lean NALFD, the prevalence of metabolic disease was similar to those with obese NAFLD, 38·98% had NASH, 29·23% had significant fibrosis (stage ≥2) and, and 3·16% had cirrhosis. The incidence rate of NAFLD among non-obese people with NAFLD at baseline was 24·6 per 1000 person-years. The incidence per 1000 person-years was 12·1 for all-cause mortality, 4·1 for liver-related mortality, 4·0 for cardiovascular death, and 56·1 for hypertension development for persons with non-obese or lean NAFLD. Interpretation: Overall, close to half of the NAFLD population were not obese and one-fifth were lean, but they carried substantial long-term liver and non-liver comorbidities. Therefore, BMI should not be the sole criterion for NAFLD screening and NAFLD treatment trials should include NAFLD persons that cover the BMI spectrum. Funding Statement: No external funding to disclose. Declaration of Interests: Tetsuya Hosaka: Speaking fees and educational fund from Gilead. Ramsey Cheung: Research support from Gilead Mindie H. Nguyen: Research support: Gilead, Pfizer; Consulting/advisory board: Intercept, Gilead. All other authors have nothing to disclose. Ethics Approval Statement: The study was carried out using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standards.