ArticlePloS one
Association between the HFE C282Y, H63D Polymorphisms and the Risks of Non-Alcoholic Fatty Liver Disease, Liver Cirrhosis and Hepatocellular Carcinoma: An Updated Systematic Review and Meta-Analysis of 5,758 Cases and 14,741 Controls.
Article in PloS one. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 2 of them syntheses that pooled it.
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Who cites it
22 citing papers in PubMed, 2 syntheses or guidelines pooled it, 47 citations in OpenAlex.
- Recent Advancements in Known and Emerging Risk Factors of Hepatocellular Carcinoma.Cancer medicine · 2025Pooled it
- Long non‑coding RNA HOTTIP promotes hepatocellular carcinoma tumorigenesis and development: A comprehensive investigation based on bioinformatics, qRT‑PCR and meta‑analysis of 393 cases.International journal of oncology · 2017Pooled it
- Functional Iron-Transport Genes-International journal of molecular sciences · 2026Article
- Molecular mechanisms in MASLD/MASH-related HCC.Hepatology (Baltimore, Md.) · 2025Review
- Review
- Associations of genetically predicted iron status with 24 gastrointestinal diseases and gut microbiota: a Mendelian randomization study.Frontiers in genetics · 2024Article
- Non-alcoholic fatty liver disease in hemochromatosis probands with iron overload and HFE p.C282Y/p.C282Y.BMC gastroenterology · 2023Article
- Chronic hepatitis B complicated with secondary hemochromatosis was cured clinically: A case report.Open medicine (Warsaw, Poland) · 2023Article
- Epidemiologic, Genetic, Pathogenic, Metabolic, Epigenetic Aspects Involved in NASH-HCC: Current Therapeutic Strategies.Cancers · 2022Review
- Molecular Screening via Sanger Sequencing of the Genetic Variants in Non-Alcoholic Fatty Liver Disease Subjects in the Saudi Population: A Hospital-Based Study.Metabolites · 2022Article
- The Pathogenesis of HCC Driven by NASH and the Preventive and Therapeutic Effects of Natural Products.Frontiers in pharmacology · 2022Review
- Hepatocellular Carcinoma in Non-Alcoholic Fatty Liver Disease: From Epidemiology to Diagnostic Approach.Cancers · 2021Review
- Significance of Hereditary Hemochromatosis Gene (HFE) Mutations in Chronic Hepatitis C and Hepatocellular Carcinoma Patients in Egypt: A Pilot Study.Asian Pacific journal of cancer prevention : APJCP · 2021Article
- Revisiting hemochromatosis: geneticAnnals of translational medicine · 2021Review
- Multifocal Nodular Fatty Infiltration of the Liver: A Rare Benign Disorder That Mimics Metastatic Liver Disease.ACG case reports journal · 2021Article
- Plasma Lipidome, PNPLA3 polymorphism and hepatic steatosis in hereditary hemochromatosis.BMC gastroenterology · 2020Article
- Iron Status and Cancer Risk in UK Biobank: A Two-Sample Mendelian Randomization Study.Nutrients · 2020Article
- Abnormal CD44 activation of hepatocytes with nonalcoholic fatty accumulation in rat hepatocarcinogenesis.World journal of gastrointestinal oncology · 2020Article
- Impact of HFE variants and sex in lung cancer.PloS one · 2019Article
- Molecular Pathogenesis of Nonalcoholic Steatohepatitis- (NASH-) Related Hepatocellular Carcinoma.Canadian journal of gastroenterology & hepatology · 2018Review
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundConflicting results have been obtained for the association between two common polymorphisms (C282Y, H63D) of human HFE (hereditary hemochromatosis) gene and the risks of the liver diseases, including non-alcoholic fatty liver disease (NAFLD), liver cirrhosis and hepatocellular carcinoma (HCC).
methodsAn updated systematic review and meta-analysis was conducted to evaluate the potential role of HFE polymorphisms in the susceptibility to NAFLD, liver cirrhosis and HCC. After retrieving articles from online databases, eligible studies were enrolled according to the selection criteria. Stata/SE 12.0 software was utilized to perform the statistical analysis.
resultsIn total, 43 articles with 5,758 cases and 14,741 controls were selected. Compared with the control group, a significantly increased risk of NAFLD was observed for the C282Y polymorphism in the Caucasian population under all genetic models and for the H63D polymorphism under the allele, heterozygote and dominant models (all OR>1, Passociation<0.05). However, no significant difference between liver cirrhosis cases and the control group was observed for HFE C282Y and H63D (all Passociation>0.05). In addition, we found that HFE C282Y was statistically associated with increased HCC susceptibility in the overall population, while H63D increased the odds of developing non-cirrhotic HCC in the African population (all OR>1, Passociation<0.05). Moreover, a positive association between compound heterozygosity for C282Y/H63D and the risk of NAFLD and HCC, but not liver cirrhosis, was observed.
conclusionOur meta-analysis provides evidence that the HFE C282Y and H63D polymorphisms confer increased genetic susceptibility to NAFLD and HCC but not liver cirrhosis. Additional well-powered studies are required to confirm our conclusion.
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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.