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Combinations of eight key mutations in the X /pre C region and genomic activity of hepatitis B virus are associated with hepatocellular carcinoma
Author(s) -
Park Y. M.,
Jang J. W.,
Yoo S. H.,
Kim S. H.,
Oh I. M.,
Park S. J.,
Jang Y. S.,
Lee S. J.
Publication year - 2014
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/jvh.12134
Subject(s) - hepatocellular carcinoma , hepatitis b virus , mutation , genotype , mutant , hepatitis b , biology , virology , cancer research , medicine , virus , gene , genetics
Summary Accumulation of eight key mutations located in the X /pre C regions of the hepatitis B virus ( HBV ) genome ( G 1613 A , C 1653 T , T 1753 V , A 1762 T , G 1764 A , A 1846 T , G 1896 A and G 1899 A ) is a risk marker for the development of hepatocellular carcinoma ( HCC ). In this study, we analysed the 8 key mutations in 442 serum samples collected from 310 non‐ HCC and 132 HCC patients to identify the combinations linked to HCC . After the patients were stratified according to the age groups and mutation combinations, clinical parameters were compared between the HCC and the non‐ HCC groups. Analyses were focused on patient ≥40 years of age infected by HBV genotype C with A 1762T and G 1764 A mutations in the basal core promoter region ( BCP double mutation). In patients with ≥6 mutations, the combination of [G1613A + C1653T + A1846T + G1896A] mutations was closely linked to HCC , whereas no specific single or double mutation combination was associated with HCC . In patients with ≤5 mutations, HB eAg and HBV DNA serum titres were lower in the HCC group than those in the non‐ HCC group. Unlike the number of mutations, no specific combination correlated with advanced clinical stage in HCC . Of the BCP double mutation–based HBV mutant types, combinations of ≥6 mutations that include G1613A + C1653T + A1846T + G1896A, and combinations of ≤5 mutations with reduced HB eAg production, may be more specific indicators of HCC risk than only the number of mutations or any specific combination(s).