ArticleJournal of hepatology2021
Non-invasive stratification of hepatocellular carcinoma risk in non-alcoholic fatty liver using polygenic risk scores.
Article in Journal of hepatology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 195 papers, 6 of them syntheses that pooled it.
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Who cites it
195 citing papers in PubMed, 6 syntheses or guidelines pooled it, 346 citations in OpenAlex.
- AGA Clinical Practice Update on Risk Stratification and Emerging Surveillance Strategies for Hepatocellular Carcinoma: Expert Review.Gastroenterology · 2026Guideline
- Global incidence of adverse clinical events in non-alcoholic fatty liver disease: A systematic review and meta-analysis.Clinical and molecular hepatology · 2024Pooled it
- EASL-EASD-EASO Clinical Practice Guidelines on the Management of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD).Obesity facts · 2024Guideline
- MGAT5/TMEM163 variant is associated with prognosis in ursodeoxycholic acid-treated patients with primary biliary cholangitis.Journal of gastroenterology · 2024Pooled it
- Genome-wide association meta-analysis identifies 17 loci associated with nonalcoholic fatty liver disease.Nature genetics · 2023Pooled it
- AGA Clinical Practice Update: Diagnosis and Management of Nonalcoholic Fatty Liver Disease in Lean Individuals: Expert Review.Gastroenterology · 2022Guideline
- Long-term hepatic safety of lomitapide in homozygous familial hypercholesterolaemia.Liver international : official journal of the International Association for the Study of the Liver · 2023Trial
- Genetics of MASLD: a diabetes perspective.Diabetologia · 2026Review
- Association Between Allostatic Load, Genetic Susceptibility, and Liver Cancer Incidence: A Large-Scale Prospective Cohort Study.International journal of cancer · 2026Article
- Age-Specific Associations of Polygenic Risk Scores With Advanced Fibrosis and Histological Activity in Biopsy-Proven MASLD.Liver international : official journal of the International Association for the Study of the Liver · 2026Article
- Long-term ambient benzene exposure increases incident NAFLD risk through accelerated biological aging.iScience · 2026Article
- Evaluating a Polygenic Risk Score for Hepatocellular Carcinoma in Multiethnic Cirrhosis Patients in Texas.Cancer medicine · 2026Article
- Large-Scale Plasma Proteomics Enhances Prediction of Liver-Related Events Among Individuals With Prediabetes and Type 2 Diabetes: A Prospective Cohort Study in the UK Biobank.Diabetes, obesity & metabolism · 2026Article
- Subtyping metabolic dysfunction-associated steatotic liver disease using electronic health record-linked genomic cohorts reveals diverse etiologies and progression.Nature communications · 2026Article
- Molecular mechanisms and pathogenesis of MASH.Nature · 2026Review
- Genetic and genomic insights across the steatotic liver disease spectrum.Clinical and molecular hepatology · 2026Review
- Review
- The Emerging Challenge of Non-Cirrhotic MASLD-Related Hepatocellular Carcinoma: Etiology, Immunopathology, and Precision Oncology.Liver cancer · 2026Review
- Prophylactic Effects of Dietary Patterns and Indexes, Nutrition and Lifestyle on Hepatocellular Carcinoma.Annals of surgical oncology · 2026Review
- HFpEF and MASLD: converging mechanisms and clinical implications.Nature reviews. Cardiology · 2026Review
135 more citing papers are in PubMed but not listed here.
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Authors and funding
30 authors at 14 institutions in 5 countries.
Funding
Abstract
BACKGROUND &
aimsHepatocellular carcinoma (HCC) risk stratification in individuals with dysmetabolism is a major unmet need. Genetic predisposition contributes to non-alcoholic fatty liver disease (NAFLD). We aimed to exploit robust polygenic risk scores (PRS) that can be evaluated in the clinic to gain insight into the causal relationship between NAFLD and HCC, and to improve HCC risk stratification.
methodsWe examined at-risk individuals (NAFLD cohort, n = 2,566; 226 with HCC; and a replication cohort of 427 German patients with NAFLD) and the general population (UK Biobank [UKBB] cohort, n = 364,048; 202 with HCC). Variants in PNPLA3-TM6SF2-GCKR-MBOAT7 were combined in a hepatic fat PRS (PRS-HFC), and then adjusted for HSD17B13 (PRS-5).
resultsIn the NAFLD cohort, the adjusted impact of genetic risk variants on HCC was proportional to the predisposition to fatty liver (p = 0.002) with some heterogeneity in the effect. PRS predicted HCC more robustly than single variants (p <10
conclusionsOur results are consistent with a causal relationship between hepatic fat and HCC. PRS improved the accuracy of HCC detection and may help stratify HCC risk in individuals with dysmetabolism, including those without severe liver fibrosis. Further studies are needed to validate our findings. LAY SUMMARY: By analyzing variations in genes that contribute to fatty liver disease, we developed two risk scores to help predict liver cancer in individuals with obesity-related metabolic complications. These risk scores can be easily tested in the clinic. We showed that the risk scores helped to identify the risk of liver cancer both in high-risk individuals and in the general population.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.