| Title: | A Polygenic Risk Score to Refine Risk Stratification and Prediction for Severe Liver Disease by Clinical Fibrosis Scores |
| Journal: | Clinical Gastroenterology and Hepatology |
| Published: | 4 Jun 2021 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/34091049/ |
| DOI: | https://doi.org/10.1016/j.cgh.2021.05.056 |
| URL: | http://www.cghjournal.org/article/S1542356521005954/pdf |
Publication 13790
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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).</p>
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).</p>
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.</p>
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.</p>
9 Keywords
- Fibrosis
- Humans
- Liver
- Liver Cirrhosis
- Liver Neoplasms
- Non-alcoholic Fatty Liver Disease
- Prospective Studies
- Risk Assessment
- Risk Factors
8 Authors
- Antonio De Vincentis
- Federica Tavaglione
- Oveis Jamialahmadi
- Antonio Picardi
- Raffaele Antonelli Incalzi
- Luca Valenti
- Stefano Romeo
- Umberto Vespasiani-Gentilucci
1 Application
| Application ID | Title |
|---|---|
| 37142 | UNDERSTANDING THE GENETIC ARCHITECTURE OF CHRONIC LIVER DISEASE |
Enabling scientific discoveries that improve human health