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

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.

• Authors: Feng Gao, Kenneth I Zheng, Sui-Dan Chen, Dong Hyeon Lee, Xi-Xi Wu, Xiao-Dong Wang, Giovanni Targher, Christopher D Byrne, Yong-Ping Chen, Won Kim, Ming-Hua Zheng
• Journal: Clinical and translational gastroenterology (Clin Transl Gastroenterol) Vol. 12 Issue 3 Pg. e00321 (03 10 2021) ISSN: 2155-384X [Electronic] United States
• PMID: 33704100 (Publication Type: Journal Article, Multicenter Study, Observational Study, Research Support, Non-U.S. Gov't, Validation Study)
• Copyright: Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.

Chemical References

• Membrane Proteins
• 17-Hydroxysteroid Dehydrogenases
• HSD17B13 protein, human
• Lipase
• adiponutrin, human

Topics

• 17-Hydroxysteroid Dehydrogenases (genetics)
• Adult
• Biopsy
• China (epidemiology)
• Cross-Sectional Studies
• Female
• Genetic Predisposition to Disease
• Humans
• Insulin Resistance (genetics)
• Lipase (genetics)
• Liver (pathology)
• Male
• Membrane Proteins (genetics)
• Metabolic Syndrome (epidemiology, genetics)
• Middle Aged
• Nomograms
• Non-alcoholic Fatty Liver Disease (diagnosis, epidemiology, genetics, pathology)
• Polymorphism, Single Nucleotide
• ROC Curve
• Republic of Korea (epidemiology)
• Risk Assessment (methods)
• Risk Factors