Non-obese non-alcoholic fatty liver disease (NAFLD) in Asia: an international registry study

Eunice Xiang Xuan Tan, Jonathan Wei Jie Lee, Nur Halisah Jumat, Wah Kheong Chan, Sombat Treeprasertsuk, George Boon Bee Goh, Jian Gao Fan, Myeong Jun Song, Phunchai Charatcharoenwitthaya, Ajay Duseja, Kento Imajo, Atsushi Nakajima, Yosuke Seki, Kazunori Kasama, Satoru Kakizaki, Laurentius A. Lesmana, Kenneth I. Zheng, Ming Hua Zheng, Calvin J. Koh, Khek Yu HoKhean Lee Goh, Vincent Wai Sun Wong, Yock Young Dan

Research output: Contribution to journalArticlepeer-review

Abstract

Background: 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.

Original languageEnglish
Article number154911
JournalMetabolism: Clinical and Experimental
Volume126
DOIs
Publication statusPublished - Jan 2022

Keywords

  • Asian
  • Fatty liver
  • Fibrosis
  • NAFLD
  • Obesity

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