A Polygenic Risk Score to Refine Risk Stratification and Prediction for Severe Liver Disease by Clinical Fibrosis Scores.

Abstract

BACKGROUND & AIMS:

A polygenic risk score based on well-known genetic variants in PNPLA3, TM6SF2, MBOAT7, and GCKR predicts hepatic fat content (polygenic risk score-hepatic fat content [PRS-HFC]). Here, we hypothesized that the addition of PRS-HFC to clinical fibrosis scores may improve risk stratification and prediction of severe liver disease (SLD).

METHODS:

We used data from 266,687 individuals in the UK Biobank, evaluating the incidence of cirrhosis, decompensated liver disease, hepatocellular carcinoma, and/or liver transplantation during a median follow-up period of 9 years. Nonalcoholic fatty liver disease fibrosis score, Fibrosis-4, aspartate aminotransferase-to-platelet ratio, BARD, and Forns scores, and PRS-HFC, were computed. All analyses were stratified according to the presence of diabetes, obesity, and a positive fatty liver index (≥60).

RESULTS:

Unfavorable genetics (PRS-HFC, ≥0.396) further stratified the risk of SLD in subjects in intermediate-/high-risk classes of fibrosis scores, with a higher effect in those with metabolic risk factors, and the prediction was improved by integrating PRS-HFC (areas under the receiver operating characteristic increased for all scores with a P value of approximately 10-2 to 10-4, except for the aspartate aminotransferase-to-platelet ratio in the overall population and in subjects with obesity). PRS-HFC improved diagnostic accuracies and positive predictive values for SLD in intermediate-high clinical score risk classes. Risk stratification and prediction were not affected or were poorly affected by unfavorable genetics in subjects without metabolic risk factors.

CONCLUSIONS:

Integration of genetics with clinical fibrosis scores refines individual risk and prediction for SLD, mainly in individuals at risk for nonalcoholic fatty liver disease. These data provide evidence from a prospective cohort that common genetic variants capture additional prognostic insights not conveyed by validated clinical/biochemical parameters.

• Authors: Antonio De Vincentis, Federica Tavaglione, Oveis Jamialahmadi, Antonio Picardi, Raffaele Antonelli Incalzi, Luca Valenti, Stefano Romeo, Umberto Vespasiani-Gentilucci
• Journal: Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association (Clin Gastroenterol Hepatol) Vol. 20 Issue 3 Pg. 658-673 (03 2022) ISSN: 1542-7714 [Electronic] United States
• PMID: 34091049 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.

Topics

• Fibrosis
• Humans
• Liver (pathology)
• Liver Cirrhosis (diagnosis)
• Liver Neoplasms (pathology)
• Non-alcoholic Fatty Liver Disease (epidemiology)
• Prospective Studies
• Risk Assessment
• Risk Factors