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 Ho; Khean-Lee Goh; Vincent Wai-Sun Wong; Yock-Young Dan

doi:10.1016/j.metabol.2021.154911

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

Metabolism. 2022 Jan:126:154911. doi: 10.1016/j.metabol.2021.154911. Epub 2021 Oct 12.

Authors

Eunice Xiang-Xuan Tan¹, Jonathan Wei-Jie Lee¹, Nur Halisah Jumat², Wah-Kheong Chan³, Sombat Treeprasertsuk⁴, George Boon-Bee Goh⁵, Jian-Gao Fan⁶, Myeong Jun Song⁷, Phunchai Charatcharoenwitthaya⁸, Ajay Duseja⁹, Kento Imajo¹⁰, Atsushi Nakajima¹⁰, Yosuke Seki¹¹, Kazunori Kasama¹¹, Satoru Kakizaki¹², Laurentius A Lesmana¹³, Kenneth I Zheng¹⁴, Ming-Hua Zheng¹⁴, Calvin J Koh¹, Khek-Yu Ho¹, Khean-Lee Goh³, Vincent Wai-Sun Wong¹⁵, Yock-Young Dan¹⁶

Affiliations

¹ Division of Gastroenterology and Hepatology, National University Health System, Singapore; Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
² Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
³ University of Malaya, Kuala Lumpur, Malaysia.
⁴ Chulalongkorn University, Bangkok, Thailand.
⁵ Singapore General Hospital, Singapore.
⁶ Shanghai Jiaotong University School of Medicine, Shanghai, China.
⁷ The Catholic University Korea, Republic of Korea.
⁸ Mahidol University, Bangkok, Thailand.
⁹ Post Graduate Institute of Medical Education and Research, Chandigarh, India.
¹⁰ Yokohama City University Graduate School of Medicine, Yokohama, Japan.
¹¹ Yotsuya Medical Cube, Tokyo, Japan.
¹² Department of Gastroenterology and Hepatology, Gunma University Graduate School of Medicine, Japan.
¹³ Medistra Hospital, Jakarta, Indonesia.
¹⁴ NAFLD Research Center, Department of Hepatology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
¹⁵ The Chinese University of Hong Kong, Hong Kong.
¹⁶ Division of Gastroenterology and Hepatology, National University Health System, Singapore; Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore. Electronic address: mdcdyy@nus.edu.sg.

PMID: 34648769
DOI: 10.1016/j.metabol.2021.154911

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.

Keywords: Asian; Fatty liver; Fibrosis; NAFLD; Obesity.

MeSH terms

Adult
Asia
Cross-Sectional Studies
Female
Humans
Liver / pathology*
Liver Cirrhosis / pathology*
Male
Metabolic Syndrome / pathology*
Middle Aged
Non-alcoholic Fatty Liver Disease / pathology*
Obesity / pathology*
Registries
Retrospective Studies