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Synergistic Effects of A1896, T1653 and T1762/A1764 Mutations in Genotype C2 Hepatitis B Virus on Development of Hepatocellular Carcinoma
Author(s) -
Lyu H.,
Lee D.,
Chung Y.H.,
Kim J. A.,
Lee J.H.,
Jin Y.J.,
Park W.,
Mathews P.,
Jaffee E.,
Zheng L.,
Yu E.,
Lee Y. J.
Publication year - 2013
Publication title -
journal of viral hepatitis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.329
H-Index - 100
eISSN - 1365-2893
pISSN - 1352-0504
DOI - 10.1111/j.1365-2893.2012.01654.x
Subject(s) - hepatocellular carcinoma , hepatitis b virus , genotype , medicine , virology , mutation , hepatitis b , chronic hepatitis , virus , gastroenterology , biology , gene , genetics
Summary The effects of genomic changes in hepatitis B virus ( HBV ) on the occurrence of hepatocellular carcinoma ( HCC ) are still unclear, especially in relation to the genotype of HBV . In this study, we examined the effects of genomic changes in HBV of genotype C 2 on the development of HCC . A total of 318 patients with HBV ‐associated HCC and 234 patients with chronic hepatitis B ( CHB ) were studied. All of HCC cases were diagnosed histologically and treated with surgical resection. The whole of the X, S, basal core promoter ( BCP ) and precore regions of the viral genome from sera or liver tissues were sequenced. All subjects had HBV of genotype C2. The prevalence of the T1653 mutation in the X region and the A1896 mutation in the precore region of HBV was significantly higher in the HCC group than in the control CHB group (22% vs 11%, P = 0.003; 50% vs 23%, P < 0.001, respectively). Moreover, the T1762/A1764 mutations in the BCP region in combination with either T1653 or A1896 were more common in the HCC compared with the CHB group ( BCP +X1653: 18% vs 11%, P = 0.05; BCP + PC , 40% vs 15%, P < 0.001, respectively). In multivariate analysis, T1653 and A1896 were revealed to be independent risk factors for HCC development. G1896A in the precore region and C1653T mutation in the X region of genotype C2 HBV are important risk factors for HCC development. Also, the A1762T/G1764A double mutation may act in synergy with C1653T to increase the risk of HCC in patients chronically infected with HBV genotype C2.