Lean non-alcoholic fatty liver disease (lean NAFLD): characteristics, metabolic outcomes and risk factors from a 7-year prospective, community cohort study from Sri Lanka

Introduction While patients with non-alcoholic fatty liver disease (NAFLD) are mostly overweight or obese, some are lean. Methods In a community-based follow-up study (baseline and follow-up surveys performed in 2007 and 2014), we investigated and compared the clinical characteristics, body composition, metabolic associations and outcomes, and other risk factors among individuals with lean (BMI < 23 kg/m 2 ) NAFLD, non-lean (BMI ≥ 23 kg/m 2 ) NAFLD and those without NAFLD. To investigate associations of selected genetic variants, we performed a case–control study between lean NAFLD cases and lean non-NAFLD controls. Results Of the 2985 participants in 2007, 120 (4.0%) had lean NAFLD and 816 (27.3%) had non-lean NAFLD. 1206 (40.4%) had no evidence of NAFLD (non-NAFLD). Compared to non-lean NAFLD, lean NAFLD was commoner among males ( p < 0.001), and had a lower prevalence of hypertension ( p < 0.001) and central obesity (WC < 90 cm for males, < 80 cm for females) ( p < 0.001) without prominent differences in the prevalence of other metabolic comorbidities at baseline survey. Of 2142 individuals deemed as either NAFLD or non-NAFLD in 2007, 704 NAFLD individuals [84 lean NAFLD, 620 non-lean NAFLD] and 834 individuals with non-NAFLD in 2007 presented for follow-up in 2014. There was no difference in the occurrence of incident metabolic comorbidities between lean NAFLD and non-lean NAFLD. Of 294 individuals who were non-NAFLD in 2007 and lean in both 2007 and 2014, 84 (28.6%) had developed lean NAFLD, giving an annual incidence of 4.1%. Logistic regression identified the presence of diabetes at baseline, increase in weight from baseline to follow-up and a higher educational level as independent risk factors for the development of incident lean NAFLD. NAFLD association of PNPLA3 rs738409 was more pronounced among lean individuals (one-tailed p < 0.05) compared to the whole cohort sample. Conclusion Although lean NAFLD constitutes a small proportion of NAFLD, the risk of developing incident metabolic comorbidities is similar to that of non-lean NAFLD. A PNPLA3 variant showed association with lean NAFLD in the studied population. Therefore, lean NAFLD also warrants careful evaluation and follow-up.