الفهرس 
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Abstract
Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide, and the death rate attributed to this tumour is increasing. It has been shown that chronic hepatitis C virus (HCV) infection is a strong and independent risk factor associated with the likelihood of HCC, but the precise mechanism(s) of hepatocarcinogenesis during chronic viral hepatitis in humans are still largely unknown. Recently, there has been an increasing body of evidence suggesting that oxidative stress may play a pathogenic role in chronic hepatitis C.
In the present study we included 69 HCV patients and 29 healthy controls sero-nagative for HCV. Patients were divided into 3 groups representing the different stages of the clinical course of HCV infection; 14 sero-positive patients without evidence of cirrhosis, 28 cirrhotic patients and 27 patients who developed HCC on top of cirrhosis. Since lymphocytes represent an accessible biological substrate, the degree of DNA damage was assessed in peripheral blood lymphocytes using the alkaline comet assay; a genotoxic assay that has an ability to detect various types of DNA damage with high sensitivity in eukaryotic cells.
In the present study the comet scores in peripheral blood lymphocytes, representing oxidative DNA damage, were significantly different between the 4 group subjects (p=0.000). Comet scores were significantly higher in HCC and cirrhotic groups compared to non-cirrhotic HCV patients and controls upon multiple comparisons. HCV patients collectively showed a higher comet score than healthy controls. These findings suggest considerable oxidative DNA damage in lymphocytes of HCC and cirrhotic patients.
Whether the oxidative stress could be a cause or consequence of liver cell injury, is not clear from the present results of increased comet scores in HCC and cirrhotic patients, whichever is correct, hepatic DNA damage could be the cause of hepatocarcinogenesis which is frequently observed during chronic HCV.
The above observations point to a potential role of antioxidants in the treatment of HCV-related chronic liver damage. Therefore, it is conceivable that the treatment of chronic liver disease to suppress hepatic inflammation may have a preventive benefit for HCC development in chronic hepatitis patients. Also, interferon may promote long-term inhibition of oxidative stress with concomitant improvement of activity and fibrosis in chronic hepatitis.
We can conclude ongoing DNA damage in peripheral blood lymphocytes in cirrhotic and HCC patients by alkaline comet assay. A follow up study for cirrhotic patient with higher comet scores would be of benefit to detect progression to HCC.