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Complicated relationships of amino acid substitution in hepatitis C virus core region and IL28B genotype influencing hepatocarcinogenesis
Author(s) -
Akuta Norio,
Suzuki Fumitaka,
Seko Yuya,
Kawamura Yusuke,
Sezaki Hitomi,
Suzuki Yoshiyuki,
Hosaka Tetsuya,
Kobayashi Masahiro,
Hara Tasuku,
Kobayashi Mariko,
Saitoh Satoshi,
Arase Yasuji,
Ikeda Kenji,
Kumada Hiromitsu
Publication year - 2012
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.25949
Subject(s) - hepatitis c virus , medicine , genotype , gastroenterology , hepatocellular carcinoma , hepatitis c , hepatology , glutamine , hepacivirus , immunology , virus , biology , amino acid , gene , genetics
The impact of amino acid (aa) 70 substitution in the core region on hepatocarcinogenesis and survival for liver‐related death in patients of hepatitis C virus (HCV) genotype 1b (HCV‐1b), who had not received antiviral therapy, is unknown. The relationships among aa 70 substitution, IL28B genotype, and hepatocarcinogenesis are also not clear. A total of 1,181 consecutive HCV‐infected patients, who had not received antiviral therapy, were included in a follow‐up study to determine predictive factors of hepatocarcinogenesis and survival for liver‐related death. The cumulative hepatocarcinogenesis rates in HCV‐1b of Gln70(His70) (glutamine (histidine) at aa 70) were significantly higher than those in HCV‐1b of Arg70 (arginine at aa 70) and HCV‐2a/2b. The cumulative survival rates for liver‐related death in HCV‐1b of Gln70(His70) were significantly lower than those in HCV‐1b of Arg70 and HCV‐2a/2b. Multivariate analysis identified gender (male), age (≥60 years), albumin (<3.9 g/dL), platelet count (<15.0 × 10 4 /mm 3 ), aspartate aminotransferase (≥67 IU/L), and HCV subgroup (HCV‐1b of Gln70(His70)) as determinants of both hepatocarcinogenesis and survival rates for liver‐related death. In HCV‐1b patients, the cumulative change rates from Arg70 to Gln70(His70) by direct sequencing were significantly higher than those from Gln70(His70) to Arg70. In patients of Arg70 at the initial visit, the cumulative change rates from Arg70 to Gln70(His70) in IL28B rs8099917 non‐TT genotype were significantly higher than those in the TT genotype. Conclusion: Substitution of aa 70 in the core region of HCV‐1b is an important predictor of hepatocarcinogenesis and survival for liver‐related death in HCV patients who had not received antiviral therapy. The IL28B genotype might partly affect changes over time of dominant amino acid in core aa 70 of HCV‐1b. (H EPATOLOGY 2012;56:2134–2141)