Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
The Pharmacogenomics Laboratory, Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
Clin Mol Hepatol. 2021 Jul;27(3):486-498. doi: 10.3350/cmh.2020.0162. Epub 2021 Feb 23.
BACKGROUND/AIMS: 17β-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.
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.
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.
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.
背景/目的：17β-羟甾类脱氢酶 13（HSD17B13）变体被报道与非酒精性脂肪性肝病（NAFLD）的可能性显著降低有关。这是一项两部分的研究，旨在评估 HSD17B13 变体与 NAFLD 及其组织学严重程度的相关性，并确定变体与经活检证实的 NAFLD 患者队列中的临床结局的相关性。
本研究于 2009 年至 2014 年期间连续招募经活检证实的 NAFLD 患者和无脂肪肝的对照组。使用 rhAmp 测定法对 HSD17B13 变体进行基因分型。共有 165 名 NAFLD 患者接受监测，直至 2019 年 8 月。记录临床结局。
HSD17B13 rs72613567 TA 等位基因和 rs6834314 G 等位基因与总体队列和华裔人群中非酒精性脂肪性肝炎（NASH）的可能性降低相关，但在马来裔或印度裔人群中不相关（P<0.05）。在平均 89 个月的随访中，32 名患者（19.4%）经历了至少一次临床结局（心血管事件，n=22；肝脏相关并发症，n=6；肝外恶性肿瘤，n=5；和死亡，n=6）。rs72613567 纯合 TA 等位基因和 rs6834314 纯合 G 等位基因与较低的肝脏相关并发症发生率独立相关（风险比[HR]，0.004；95%置信区间[CI]，0.00-0.64；P=0.033 和 HR，0.01；95% CI，0.00-0.97；P=0.048，分别），并且与华裔人群中肝细胞气球样变的较低程度相关。
HSD17B13 rs72613567 和 rs6834314 变体与 NAFLD 和 NASH 呈负相关，并与多民族亚洲 NAFLD 患者队列中不良肝脏结局的发生率降低相关。
