8-nitroguanine and Hepatitis-C--Chronic

Topics: Antiviral Agents; Guanine; Hepatitis C, Chronic; Hepatocytes; Humans; Interferon alpha-2; Interferon-alpha; Liver; Recombinant Proteins; Treatment Outcome

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

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Aged; Biomarkers; Carcinoma, Hepatocellular; Deoxyguanosine; DNA Damage; Female; Guanine; Hepatitis C, Chronic; Humans; Inflammation; Liver; Liver Neoplasms; Male; Middle Aged; Reactive Oxygen Species