PDF(Pubmed)
Abstract：
Genetic factors contribute to the risk and severity of metabolic dysfunction-associated steatotic liver disease (MASLD). However, the utility of genetic testing in risk stratification remains poorly characterised.
To examine the influence of genetic risk on advanced fibrosis and cirrhosis in patients with type 2 diabetes mellitus (T2DM) and the utility of a polygenic risk score (PRS) in screening guidelines.
We prospectively enrolled adults aged ≥50 years with T2DM recruited from clinics. PRS was the sum of risk alleles in PNPLA3, TM6SF2 and SERPINA1 minus the protective variant in HSD17B13. We performed magnetic resonance elastography and vibration-controlled transient elastography to assess for advanced fibrosis and cirrhosis.
Of 382 included patients, the mean age and BMI were 64.8 (±8.4) years and 31.7 (±6.2) kg/m2 respectively. The prevalence of advanced fibrosis and cirrhosis were 12.3% and 5.2% respectively; higher PRS was associated with increased risk of cirrhosis (2.7% vs. 7.5%, p = 0.037). High PRS was associated with increased risk of advanced fibrosis among those with fibrosis-4 index (FIB-4) index <1.3 (9.6% vs. 2.3%, p = 0.036) but was not significantly different in other FIB-4 categories. Incorporating PRS determination into the American Gastroenterological Association and American Association for the Study of Liver Diseases screening guidelines prevented approximately 20% of all participants with advanced fibrosis from being inappropriately classified as low risk.
Utilising a well-phenotyped, prospective cohort of adults with T2DM, we found that adding an assessment of genetic risk to recommendations to screen at-risk populations may improve risk prediction.
To examine the influence of genetic risk on advanced fibrosis and cirrhosis in patients with type 2 diabetes mellitus (T2DM) and the utility of a polygenic risk score (PRS) in screening guidelines.
We prospectively enrolled adults aged ≥50 years with T2DM recruited from clinics. PRS was the sum of risk alleles in PNPLA3, TM6SF2 and SERPINA1 minus the protective variant in HSD17B13. We performed magnetic resonance elastography and vibration-controlled transient elastography to assess for advanced fibrosis and cirrhosis.
Of 382 included patients, the mean age and BMI were 64.8 (±8.4) years and 31.7 (±6.2) kg/m2 respectively. The prevalence of advanced fibrosis and cirrhosis were 12.3% and 5.2% respectively; higher PRS was associated with increased risk of cirrhosis (2.7% vs. 7.5%, p = 0.037). High PRS was associated with increased risk of advanced fibrosis among those with fibrosis-4 index (FIB-4) index <1.3 (9.6% vs. 2.3%, p = 0.036) but was not significantly different in other FIB-4 categories. Incorporating PRS determination into the American Gastroenterological Association and American Association for the Study of Liver Diseases screening guidelines prevented approximately 20% of all participants with advanced fibrosis from being inappropriately classified as low risk.
Utilising a well-phenotyped, prospective cohort of adults with T2DM, we found that adding an assessment of genetic risk to recommendations to screen at-risk populations may improve risk prediction.
摘要：
背景：遗传因素有助于代谢功能障碍相关脂肪变性肝病（MASLD）的风险和严重程度。然而,基因检测在风险分层中的应用特征仍然不明确.
目的：研究遗传风险对2型糖尿病（T2DM）患者晚期纤维化和肝硬化的影响，以及多基因风险评分（PRS）在筛查指南中的应用。
方法：我们前瞻性招募了从诊所招募的≥50岁T2DM成年人。PRS是PNPLA3、TM6SF2和SERPINA1中的风险等位基因减去HSD17B13中的保护性变体的总和。我们进行了磁共振弹性成像和振动控制瞬时弹性成像，以评估晚期纤维化和肝硬化。
结果：在382名患者中，平均年龄和BMI分别为64.8（±8.4）岁和31.7（±6.2）kg/m2。晚期纤维化和肝硬化的患病率分别为12.3%和5.2%;较高的PRS与肝硬化风险增加相关(2.7%vs.7.5%,p=0.037)。在纤维化-4指数（FIB-4）指数<1.3的患者中，高PRS与晚期纤维化风险增加相关（9.6％vs.2.3%,p=0.036），但在其他FIB-4类别中没有显着差异。将PRS测定纳入美国胃肠病协会和美国肝病研究协会筛查指南，可防止约20％的晚期纤维化参与者被不适当地归类为低风险。
结论：利用良好的表型，成人T2DM前瞻性队列,我们发现,在筛选高危人群的建议中加入遗传风险评估可能会改善风险预测.
目的：研究遗传风险对2型糖尿病（T2DM）患者晚期纤维化和肝硬化的影响，以及多基因风险评分（PRS）在筛查指南中的应用。
方法：我们前瞻性招募了从诊所招募的≥50岁T2DM成年人。PRS是PNPLA3、TM6SF2和SERPINA1中的风险等位基因减去HSD17B13中的保护性变体的总和。我们进行了磁共振弹性成像和振动控制瞬时弹性成像，以评估晚期纤维化和肝硬化。
结果：在382名患者中，平均年龄和BMI分别为64.8（±8.4）岁和31.7（±6.2）kg/m2。晚期纤维化和肝硬化的患病率分别为12.3%和5.2%;较高的PRS与肝硬化风险增加相关(2.7%vs.7.5%,p=0.037)。在纤维化-4指数（FIB-4）指数<1.3的患者中，高PRS与晚期纤维化风险增加相关（9.6％vs.2.3%,p=0.036），但在其他FIB-4类别中没有显着差异。将PRS测定纳入美国胃肠病协会和美国肝病研究协会筛查指南，可防止约20％的晚期纤维化参与者被不适当地归类为低风险。
结论：利用良好的表型，成人T2DM前瞻性队列,我们发现,在筛选高危人群的建议中加入遗传风险评估可能会改善风险预测.
