title: 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.
abstract: BACKGROUND
  Conflicting 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).
  
  
  METHODS
  An 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.
  
  
  RESULTS
  In 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.
  
  
  CONCLUSIONS
  Our 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.
authors.affiliation: The Third Central clinical college of Tianjin Medical University, Tianjin, PR China.|Department of Gastroenterology and Hepatology, Tianjin Third Central Hospital, Tianjin, PR China.|Tianjin Institute of Hepatobiliary Disease, Tianjin, PR China.|Tianjin Key Laboratory of Artificial Cells, Tianjin, PR China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Ye
authors.affiliation: The Third Central clinical college of Tianjin Medical University, Tianjin, PR China.|Department of Gastroenterology and Hepatology, Tianjin Third Central Hospital, Tianjin, PR China.|Tianjin Institute of Hepatobiliary Disease, Tianjin, PR China.|Tianjin Key Laboratory of Artificial Cells, Tianjin, PR China.
authors.forename: Bao-Xin
authors.initials: BX
authors.lastname: Qian
authors.affiliation: The Third Central clinical college of Tianjin Medical University, Tianjin, PR China.|Department of Gastroenterology and Hepatology, Tianjin Third Central Hospital, Tianjin, PR China.|Tianjin Institute of Hepatobiliary Disease, Tianjin, PR China.|Tianjin Key Laboratory of Artificial Cells, Tianjin, PR China.
authors.forename: Wei-Li
authors.initials: WL
authors.lastname: Yin
authors.affiliation: The Third Central clinical college of Tianjin Medical University, Tianjin, PR China.|Department of Gastroenterology and Hepatology, Tianjin Third Central Hospital, Tianjin, PR China.|Tianjin Institute of Hepatobiliary Disease, Tianjin, PR China.|Tianjin Key Laboratory of Artificial Cells, Tianjin, PR China.
authors.forename: Feng-Mei
authors.initials: FM
authors.lastname: Wang
authors.affiliation: The Third Central clinical college of Tianjin Medical University, Tianjin, PR China.|Department of Gastroenterology and Hepatology, Tianjin Third Central Hospital, Tianjin, PR China.|Tianjin Institute of Hepatobiliary Disease, Tianjin, PR China.|Tianjin Key Laboratory of Artificial Cells, Tianjin, PR China.
authors.forename: Tao
authors.initials: T
authors.lastname: Han