Individualized Polygenic Risk Score Identifies NASH in the Eastern Asia Region: A Derivation and Validation Study.
Individualized Polygenic Risk Score Identifies NASH in the Eastern Asia Region: A Derivation and Validation Study.
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DOI：
10.14309/ctg.0000000000000321
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发表时间：
2021-03-10
影响因子：
3.6
通讯作者：
Zheng MH
中科院分区：
文献类型：
--
作者：
Gao F;Zheng KI;Chen SD;Lee DH;Wu XX;Wang XD;Targher G;Byrne CD;Chen YP;Kim W;Zheng MH
强有力的证据表明，多种遗传和环境危险因素在非酒精性脂肪性肝炎(NASH)的发病机制中起作用。我们的目标是开发和验证一种新的诺模图，包括遗传和临床因素，用于预测NASH。共招募了来自2个国家(中国和韩国)的1,070名经活检证实为非酒精性脂肪性肝病的亚洲人。根据NASH临床研究网络评分系统对NAFLD的组织学谱进行分类。在中文训练集(n=402)中建立诺模图，然后分别在中文内部验证集(n=136)和外部朝鲜语验证组(n=532)中进行验证。性别、代谢综合征、胰岛素抵抗、血清天冬氨酸氨基转移酶水平、PNPLA3(Rs738409)和HSD17B13(Rs72613567)基因变异与NASH密切相关。基于它们的回归系数，我们开发了一个判别能力好(受试者工作特征曲线下面积：0.81，95%可信区间0.77-0.85)和良好校准(Hosmer-Lemesshow检验，P=0.794)的NASH识别图。在2个验证队列中，诺模图显示受试者操作特征曲线下的高面积(内部验证集：0.80，95%CI为0.72~0.88；外部验证队列：0.76，95%CI为0.72~0.80)和良好的校准。我们新开发和外部验证的诺模图包含了遗传和临床风险因素，可以方便地用于预测NASH。在其他种族中的进一步验证研究是有必要的，以确认其在活检证实的NAFLD患者中识别NASH的诊断价值。
Strong evidence indicates that multiple genetic and environmental risk factors play a role in the pathogenesis of nonalcoholic steatohepatitis (NASH). We aimed to develop and validate a novel nomogram, incorporating both genetic and clinical factors, for predicting NASH. A total of 1,070 Asian individuals with biopsy-confirmed nonalcoholic fatty liver disease (NAFLD) from 2 countries (China and South Korea) were recruited. The histological spectrum of NAFLD was classified according to the NASH clinical research network scoring system. The nomogram was developed in the Chinese training set (n = 402), and then, it was validated in both the Chinese internal validation set (n = 136) and the external Korean validation cohort (n = 532), respectively. Sex, metabolic syndrome, insulin resistance, serum aspartate aminotransferase levels, and PNPLA3 (rs738409) and HSD17B13 (rs72613567) genetic variants were strongly associated with NASH. Based on their regression coefficients, we developed a nomogram with good discriminatory ability (area under the receiver operating characteristic curve: 0.81, 95% confidence interval [CI] 0.77–0.85) and good calibration (Hosmer-Lemeshow test, P = 0.794) for identifying NASH. In the 2 validation cohorts, the nomogram showed high area under the receiver operating characteristic curves (internal validation set: 0.80, 95% CI 0.72–0.88; external validation cohort: 0.76, 95% CI 0.72–0.80) and good calibration. Our newly developed and externally validated nomogram, incorporating both genetic and clinical risk factors, may be conveniently used to predict NASH. Further validation studies in other ethnic groups are warranted to confirm its diagnostic utility to identify NASH, among patients with biopsy-proven NAFLD.