Tan E.X.X.Lee J.W.J.Jumat N.H.Chan W.K.Treeprasertsuk S.Goh G.B.B.Fan J.G.Song M.J.Charatcharoenwitthaya P.Duseja A.Imajo K.Nakajima A.Seki Y.Kasama K.Kakizaki S.Lesmana L.A.Zheng K.I.Zheng M.H.Koh C.J.Ho K.Y.Goh K.L.Wong V.W.S.Dan Y.Y.Mahidol University2023-06-182023-06-182022-01-01Metabolism: Clinical and Experimental Vol.126 (2022)00260495https://repository.li.mahidol.ac.th/handle/20.500.14594/83944Background: A significant proportion of the non-alcoholic fatty liver disease (NAFLD) population is non-obese. Prior studies reporting the severity of NAFLD amongst non-obese patients were heterogenous. Our study, using data from the largest biopsy-proven NAFLD international registry within Asia, aims to characterize the demographic, metabolic and histological differences between non-obese and obese NAFLD patients. Methods: 1812 biopsy-proven NAFLD patients across nine countries in Asia assessed between 2006 and 2019 were pooled into a curated clinical registry. Demographic, metabolic and histological differences between non-obese and obese NAFLD patients were evaluated. The performance of Fibrosis-4 index for liver fibrosis (FIB-4) and NAFLD fibrosis score (NFS) to identify advanced liver disease across the varying obesity subgroups was compared. A random forest analysis was performed to identify novel predictors of fibrosis and steatohepatitis in non-obese patients. Findings: One-fifth (21.6%) of NAFLD patients were non-obese. Non-obese NAFLD patients had lower proportions of NASH (50.5% vs 56.5%, p = 0.033) and advanced fibrosis (14.0% vs 18.7%, p = 0.033). Metabolic syndrome in non-obese individuals was associated with NASH (OR 1.59, 95% CI 1.01–2.54, p = 0.047) and advanced fibrosis (OR 1.88, 95% CI 0.99–3.54, p = 0.051). FIB-4 performed better than the NFS score (AUROC 81.5% vs 73.7%, p < 0.001) when classifying patients with F2–4 fibrosis amongst non-obese NAFLD patients. Haemoglobin, GGT, waist circumference and cholesterol are additional variables found on random forest analysis useful for identifying non-obese NAFLD patients with advanced liver disease. Conclusion: A substantial proportion of non-obese NAFLD patients has NASH or advanced fibrosis. FIB-4, compared to NFS better identifies non-obese NAFLD patients with advanced liver disease. Serum GGT, cholesterol, haemoglobin and waist circumference, which are neither components of NFS nor FIB-4, are important biomarkers for advanced liver disease in non-obese patients.Biochemistry, Genetics and Molecular BiologyArticleSCOPUS10.1016/j.metabol.2021.1549112-s2.0-851186266941532860034648769