Impact of amino acid substitutions in the core region of HCV on multistep hepatocarcinogenesis.
OBJECTIVE
The core protein of hepatitis C virus (HCV) has multiple functions for not only viral replication but also hepatocellular carcinogenesis. A significant association of the substitutions in the core region with hepatocarcinogenesis has recently been reported. In this report, we evaluated the association of the substitutions in the core region with multistep hepatocarcinogenesis.


METHODS
Sixty-nine non-cancerous and cancerous liver tissues were obtained from the patients with primary developed hepatocellular carcinoma (HCC) due to HCV and 17 cirrhotic liver tissues were obtained from the patients without HCC. A sequence analysis of the core protein of HCV was performed and the association between the substitution rates in the core gene and the degree of fibrosis or steatosis during the primary development of HCC and tumor differentiation was analyzed.


RESULTS
The substitution rates of amino acid 70, 75, 91 and 147 exceeded 25% (amino acid 70, 51%; 75, 45%; 91, 36%; 147, 30%). All substitution rates were comparable among cancerous and non-cancerous region of patients with HCC and non-cancerous region without HCC. The substitution rates of these four amino acids were not associated with the degree of fibrosis, steatosis or tumor differentiation during the primary development of HCC. In addition, the substitution rates were comparable between the patients with or without HCC. The cumulative substitution numbers in the core region were also not associated with the degree of fibrosis and steatosis.


CONCLUSIONS
It is possible that the substitutions in the core region are not associated with HCV-related multistep hepatocarcinogenesis.
Fukuhara
Takasuke
T
Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Takeishi
Kazuki
K
Toshima
Takeo
T
Morita
Kazutoyo
K
Ueda
Shigeru
S
Iguchi
Tomohiro
T
Nagata
Shigeyuki
S
Sugimachi
Keishi
K
Ikegami
Toru
T
Gion
Tomonobu
T
Soejima
Yuji
Y
Taketomi
Akinobu
A
Maehara
Yoshihiko
Y