Loss-of-function HSD17B13 variants, non-alcoholic steatohepatitis and adverse liver outcomes: Results from a multi-ethnic Asian cohort

Ting, Yi-Wen and Kong, Amanda Shen-Yee and Zain, Shamsul Mohd and Chan, Wah-Kheong and Tan, Hwa-Li and Mohamed, Zahurin and Pung, Yuh-Fen and Mohamed, Rosmawati (2021) Loss-of-function HSD17B13 variants, non-alcoholic steatohepatitis and adverse liver outcomes: Results from a multi-ethnic Asian cohort. Clinical and Molecular Hepatology, 27 (3). pp. 486-498. ISSN 2287-2728, DOI https://doi.org/10.3350/cmh.2020.0162.

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Background/Aims: 17 beta-hydroxysteroid dehydrogenase 13 (HSD17B13) variants were recently reported to have significantly lower odds of non-alcoholic fatty liver disease (NAFLD). This is a two-part study that aimed to evaluate the association of HSD17B13 variants with NAFLD and its histological severity, and to identify the association of the variants with clinical outcomes in a cohort of biopsy-proven NAFLD patients. Methods: Consecutive biopsy-proven NAFLD patients and controls without fatty liver were recruited for this study between 2009 and 2014. Genotyping for HSD17B13 variants was performed using rhAmp assays. A total of 165 patients with NAFLD were monitored up until August 2019. Clinical outcomes were recorded. Results: HSD17B13 rs72613567 TA allele and rs6834314 G allele were associated with lower odds of non-alcoholic steatohepatitis (NASH) in the overall cohort and among ethnic Chinese, but not among ethnic Malays or Indians (P<0.05). During a mean follow-up of 89 months, 32 patients (19.4%) experienced at least one clinical outcome (cardiovascular events, n=22; liver-related complications, n=6; extra-hepatic malignancy, n=5; and mortality, n=6). The rs72613567 homozygous TA allele and the rs6834314 homozygous G allele were independently associated with a lower incidence of liver-related complications (hazard ratio HR], 0.004; 95% confidence interval CI], 0.00-0.64; P=0.033 and HR, 0.01; 95% CI, 0.00-0.97; P=0.048, respectively) and were associated with lower grade of hepatocyte ballooning among the ethnic Chinese. Conclusion: HSD17B13 rs72613567 and rs6834314 variants were inversely associated with NAFLD and NASH, and were associated with lower incidence of adverse liver outcomes in a cohort of multi-ethnic Asian patients with NAFLD.

Item Type: Article
Funders: University Malaya Research Grant [Grant No: BK077-2016]
Uncontrolled Keywords: Polymorphism; Genetic; Genetic variation; Liver diseases; Asia; Malaysia
Subjects: R Medicine > RC Internal medicine
Divisions: Faculty of Medicine
Depositing User: Ms Zaharah Ramly
Date Deposited: 27 Jun 2022 05:33
Last Modified: 27 Jun 2022 07:08
URI: http://eprints.um.edu.my/id/eprint/34009

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