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Impact of hepatitis B virus (HBV) x gene mutations on hepatocellular carcinoma development in chronic HBV infection

Authors
 Jong-Han Lee  ;  Kwang-Hyub Han  ;  Jae Myun Lee  ;  Jeon Han Park  ;  Hyon-Suk Kim 
Citation
 Clinical and Vaccine Immunology, Vol.18(6) : 914-921, 2011 
Journal Title
Clinical and Vaccine Immunology
ISSN
 1556-6811 
Issue Date
2011
MeSH
Adult ; Amino Acid Substitution/genetics ; Carcinoma, Hepatocellular/virology* ; Female ; Hepatitis B virus/genetics* ; Hepatitis B virus/isolation & purification ; Hepatitis B, Chronic/complications* ; Hepatitis B, Chronic/virology* ; Humans ; Male ; Middle Aged ; Mutation, Missense* ; NF-kappa B/biosynthesis ; Trans-Activators/genetics* ; Virulence Factors/genetics*
Abstract
The hepatitis B virus (HBV) PreS mutations C1653T, T1753V, and A1762T/G1764A were reported as a strong risk factor of hepatocellular carcinoma (HCC) in a meta-analysis. HBV core promoter overlaps partially with HBx coding sequence, so the nucleotide 1762 and 1764 mutations induce HBV X protein (HBx) 130 and 131 substitutions. We sought to elucidate the impact of HBx mutations on HCC development. Chronically HBV-infected patients were enrolled in this study: 42 chronic hepatitis B (CHB) patients, 23 liver cirrhosis (LC) patients, and 31 HCC patients. Direct sequencing showed HBx131, HBx130, HBx5, HBx94, and HBx38 amino acid mutations were common in HCC patients. Of various mutations, HBx130+HBx131 (double) mutations and HBx5+HBx130+HBx131 (triple) mutations were significantly high in HCC patients. Double and triple mutations increased the risk for HCC by 3.75-fold (95% confidence interval [CI] = 1.101 to 12.768, P = 0.033) and 5.34-fold (95% CI = 1.65 to 17.309, P = 0.005), respectively, when HCC patients were compared to CHB patients. Functionally, there were significantly higher levels of NF-κB activity in cells with the HBx5 mutant and with the double mutants than that of wild-type cells and the triple-mutant cells. The triple mutation did not increase NF-κB activity. Other regulatory pathways seem to exist for NF-κB activation. In conclusion, a specific HBx mutation may contribute to HCC development by activating NF-κB activity. The HBx5 mutation in genotype C2 HBV appears to be a risk factor for the development of HCC and may be used to predict the clinical outcomes of patients with chronic HBV infection.
Files in This Item:
T201101389.pdf Download
DOI
10.1128/CVI.00474-10
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Laboratory Medicine (진단검사의학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Microbiology (미생물학교실) > 1. Journal Papers
Yonsei Authors
Kim, Hyon Suk(김현숙) ORCID logo https://orcid.org/0000-0001-5662-7740
Park, Jeon Han(박전한) ORCID logo https://orcid.org/0000-0001-9604-3205
Lee, Jae Myun(이재면) ORCID logo https://orcid.org/0000-0002-5273-3113
Lee, Jong Han(이종한)
Han, Kwang-Hyub(한광협) ORCID logo https://orcid.org/0000-0003-3960-6539
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/93208
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