Accumulation of 8-nitroguanine in the liver of patients with chronic hepatitis C.
OBJECTIVE
Nucleic acid damage by reactive nitrogen and oxygen species may contribute to inflammation-related carcinogenesis. To investigate the extent of nucleic acid damage in hepatitis C virus infection and its change after interferon treatment, we measured 8-nitroguanine and 8-hydroxy-2'-deoxyguanosine (8-OHdG) in the liver of patients with chronic hepatitis C (CHC) before and after interferon therapy.


METHODS
Hepatic accumulation of 8-nitroguanine and 8-OHdG was immunohistochemically evaluated in 20 CHC patients and 7 control patients with non-alcoholic fatty liver.


RESULTS
Immunoreactivities of 8-nitroguanine and 8-OHdG were strongly detected in the liver from patients with CHC, but not in control livers. 8-Nitroguanine accumulation was found not only in infiltrating inflammatory cells, but also hepatocytes particularly in the periportal area. The accumulation of 8-nitroguanine and 8-OHdG increased with inflammatory grade (8-nitroguanine; P = 0.0019, 8-OHdG; P = 0.0009). In the sustained virological responder group after interferon therapy, 8-nitroguanine and 8-OHdG accumulation were markedly decreased in the liver (8-nitroguanine; P = 0.018, 8-OHdG; P = 0.018).


CONCLUSIONS
In this study, we demonstrated for the first time that 8-nitroguanine accumulated in the liver of patients with CHC. 8-Nitroguanine is a useful biomarker to evaluate the severity of HCV-induced chronic inflammation in relation to hepatocellular carcinoma.
Horiike
Shinichiro
S
Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mie University School of Medicine, Tsu, Mie 514-8507, Japan.
Kawanishi
Shosuke
S
Kaito
Masahiko
M
Ma
Ning
N
Tanaka
Hideaki
H
Fujita
Naoki
N
Iwasa
Motoh
M
Kobayashi
Yoshinao
Y
Hiraku
Yusuke
Y
Oikawa
Shinji
S
Murata
Mariko
M
Wang
Jinyan
J
Semba
Reiji
R
Watanabe
Shozo
S
Adachi
Yukihiko
Y
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000328:Adult; D000368:Aged; D015415:Biomarkers; D006528:Carcinoma, Hepatocellular / Q000453:epidemiology; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D005260:Female; D006147:Guanine / Q000031:analogs & derivatives* / Q000378:metabolism; D019698:Hepatitis C, Chronic / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008113:Liver Neoplasms / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D017382:Reactive Oxygen Species
C095838:8-nitroguanine; D015415:Biomarkers; D017382:Reactive Oxygen Species; D006147:Guanine; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine