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个体多基因风险评分可识别东亚地区的 NASH:一项推导和验证研究。

Individualized Polygenic Risk Score Identifies NASH in the Eastern Asia Region: A Derivation and Validation Study.

机构信息

Department of Gastroenterology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.

NAFLD Research Center, Department of Hepatology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.

出版信息

Clin Transl Gastroenterol. 2021 Mar 10;12(3):e00321. doi: 10.14309/ctg.0000000000000321.

DOI:10.14309/ctg.0000000000000321
PMID:33704100
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7954375/
Abstract

INTRODUCTION

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.

METHODS

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.

RESULTS

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.

DISCUSSION

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.

摘要

简介

大量证据表明,多种遗传和环境风险因素在非酒精性脂肪性肝炎(NASH)的发病机制中起作用。我们旨在开发和验证一种新的列线图,该列线图结合了遗传和临床因素,用于预测 NASH。

方法

共招募了来自 2 个国家(中国和韩国)的 1070 名经肝活检证实的非酒精性脂肪性肝病(NAFLD)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。列线图在来自中国的训练集(n = 402)中开发,然后分别在中国内部验证集(n = 136)和外部韩国验证队列(n = 532)中进行验证。

结果

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以及 PNPLA3(rs738409)和 HSD17B13(rs72613567)遗传变异与 NASH 密切相关。基于其回归系数,我们开发了一个具有良好判别能力(受试者工作特征曲线下面积:0.81,95%置信区间 [CI] 0.77-0.85)和良好校准(Hosmer-Lemeshow 检验,P = 0.794)的列线图,用于识别 NASH。在 2 个验证队列中,该列线图显示出较高的受试者工作特征曲线下面积(内部验证集:0.80,95%CI 0.72-0.88;外部验证队列:0.76,95%CI 0.72-0.80)和良好的校准。

讨论

我们新开发的和经过外部验证的列线图,结合了遗传和临床危险因素,可方便地用于预测 NASH。需要在其他种族群体中进行进一步的验证研究,以确认其在经活检证实的 NAFLD 患者中识别 NASH 的诊断效用。

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