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.

Qing Ye,Wei-Li Yin,Feng-Mei Wang,Tao Han,Bao-Xin Qian,Pavel Strnad

doi:10.1371/journal.pone.0163423

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.

Highlights

Hepatocellular carcinoma (HCC) often occurs as the end-stage or more aggressive form of many progressive chronic liver diseases, such as non-alcoholic fatty liver disease (NAFLD), liver cirrhosis, and chronic viral hepatitis [1,2,3,4]
No significant difference between liver cirrhosis cases and the control group was observed for HFE C282Y and H63D
HFE Mutation and NAFLD, Liver Cirrhosis, hepatocellular carcinoma (HCC) Risks population, while H63D increased the odds of developing non-cirrhotic HCC in the African population

Summary

Introduction

Hepatocellular carcinoma (HCC) often occurs as the end-stage or more aggressive form of many progressive chronic liver diseases, such as NAFLD (non-alcoholic fatty liver disease), liver cirrhosis, and chronic viral hepatitis [1,2,3,4]. There are many types of liver cirrhosis, such as cryptogenic cirrhosis, alcoholic liver cirrhosis, viral liver cirrhosis and NAFLD-associated cirrhosis, which are considered as the key risk factors for the occurrence of HCC [3,4,5,6,7,8]. 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)

Results

Discussion

Conclusion