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个新的列线图,结合遗传和临床因素,用于预测NASH。
共招募了来自2个国家(中国和韩国)的1,070名患有活检确诊的非酒精性脂肪性肝病(NAFLD)的亚洲个体。根据NASH临床研究网络评分系统对NAFLD的组织学谱进行分类。列线图是在中文训练集中开发的(n=402),然后,它在中国内部验证集(n=136)和外部韩国验证队列(n=532)中进行了验证,分别。
性,代谢综合征,胰岛素抵抗,血清天冬氨酸转氨酶水平,PNPLA3(rs738409)和HSD17B13(rs72613567)遗传变异与NASH密切相关。根据它们的回归系数,我们开发了一个具有良好判别能力的列线图(接收器工作特征曲线下面积:0.81,95%置信区间[CI]0.77-0.85)和良好的校准(Hosmer-Lemeshow检验,P=0.794)用于鉴定NASH。在2个验证队列中,列线图显示受试者工作特征曲线下面积较高(内部验证集:0.80,95%CI0.72-0.88;外部验证队列:0.76,95%CI0.72-0.80),校准效果良好.
我们新开发和外部验证的列线图,结合遗传和临床风险因素,可以方便地用于预测NASH。其他种族的进一步验证研究是必要的,以确认其诊断效用,以确定NASH,在活检证实NAFLD的患者中。
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.