High Prevalence of Protective HSD17B13 Variant in Taiwan: An Analysis in Morbidly Obese Individuals and Liver Donors

We aimed to investigate the prevalence of HSD17B13 polymorphisms while evaluating the correlation between HSD17B13 gene variants and NASH prevalence in the Taiwanese population. Furthermore, we tried to identify the diagnostic value of liver enzymes as non-invasive biomarkers for NASH in morbidly obese patients.

Severely obese patients with non-alcoholic fatty liver disease (NAFLD) who received liver biopsy during bariatric surgery and controls of liver donors who underwent donor hepatectomy were enrolled from 2016 to 2021. Genotyping was utilized in TaqMan PCR assays. For comparison of NAFLD severity, patients were divided into no NASH (NAFLD activity score, NAS 0-2), borderline NASH (NAS 3-4), and NASH (NAS 5-8).

The proportion of HSD17B13 rs72613567 TA allele carriers (T/TA and TA/TA genotypes) was 96% in both groups, corresponding to an estimated TA allele frequency of approximately 50% based on a standard allele-counting method. Among morbidly obese patients, T/TA and TA/TA genotypes were associated with lower odds of NASH prevalence compared with T/T genotype. For the non-invasive predictive factors of NASH, NASH group had significantly higher level of liver enzymes compared to "no NASH" and "borderline NASH" groups. Receiver operating characteristic curve analysis revealed there were moderate predictive values for NASH in AST (AUC = 0.71, p = 0.014) and ALT (AUC = 0.73, p = 0.007).

Our study revealed a relatively high prevalence of the loss-of-function TA variant of HSD17B13 in this southern Taiwanese cohort, irrespective of body weight. This variant may contribute to the comparatively lower prevalence of NASH in the region. Additionally, AST and ALT may have potential predictive value for NASH prevalence. Given the single-center design, further larger, population-representative studies are warranted.