738409, rs58542926, and rs72613567 have been associated with an increased risk of liver-related events (LREs) in patients with metabolic dysfunction–associated steatotic liver disease (MASLD). In this study, we investigated the combined effects of these variants on LREs. The longitudinal multicenter cohort study enrolled 1178 patients with biopsy-proven MASLD. We calculated the genetic risk of hepatic fibrosis and LRE according to the impact of these variants. Patients with genetic fibrosis scores of 2, 3, and 4 or 5 were at greater risk than patients with scores of 0 or 1, with odds ratios of 2.45 (95% CI, 1.27–4.74), 2.14 (95% CI, 1.17–3.94), and 2.54 (95% CI, 1.35–4.77), respectively. Multivariate analysis revealed that and , but not , were associated significantly with LRE development. The hazard ratio of the genetic high-risk group for LRE was 1.91 (95% CI, 1.20–3.04). The higher risk of LRE development in the genetic high-risk group also was seen in patients with F ≥ 3 or Fibrosis-4 index > 2.67. The hazard ratios of the genetic high-risk group for LRE were greater in patients without obesity, without diabetes, and of younger age compared with patients with obesity, with diabetes, or of older age, respectively. This combination of MASLD-related genetic variants is useful for predicting LREs in Japanese patients with MASLD. The genetic risk according to these variants is useful for LRE risk assessment, especially in patients without metabolic risk factors or in younger patients in Japan.

中文翻译：

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遗传多态性对代谢功能障碍相关脂肪肝病合并症的不同影响

738409、rs58542926 和 rs72613567 与代谢功能障碍相关脂肪肝病 (MASLD) 患者的肝脏相关事件 (LRE) 风险增加相关。在这项研究中，我们研究了这些变异对 LRE 的综合影响。这项纵向多中心队列研究招募了 1178 名经活检证实患有 MASLD 的患者。我们根据这些变异的影响计算了肝纤维化和LRE的遗传风险。遗传性纤维化评分为 2、3、4 或 5 分的患者比评分为 0 或 1 分的患者面临更大的风险，比值比为 2.45 (95% CI, 1.27–4.74)、2.14 (95% CI, 1.17–分别为 3.94）和 2.54（95% CI，1.35-4.77）。多变量分析显示 和 与 LRE 的发展显着相关，但与 LRE 的发展无关。 LRE 遗传高危组的风险比为 1.91（95% CI，1.20-3.04）。在 F ≥ 3 或纤维化 4 指数 > 2.67 的患者中，遗传高危组中发生 LRE 的风险也较高。与肥胖患者、糖尿病患者和老年患者相比，无肥胖患者、无糖尿病患者和年轻患者的 LRE 遗传高风险组的风险比更高。这种 MASLD 相关遗传变异的组合可用于预测日本 MASLD 患者的 LRE。根据这些变异的遗传风险对于 LRE 风险评估很有用，特别是对于没有代谢危险因素的患者或日本的年轻患者。