IntroductionThe melanoma antigen (MAGE) family members are tumour-specifi c antigens exclusively expressed in neoplastic cells. Therefore, the present work was designed to study the expression of MAGE-1 and MAGE-3 mRNAs in the peripheral blood and cancerous tissues of patients with hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC). Methods 30 patients with HCV-related cirrhosis (15 patients with HCC and 15 patients without HCC) and 15 healthy subjects were enrolled in the present study. Expression of MAGE-1 and MAGE-3 mRNAs in peripheral blood samples, HCC specimens and surrounding non-neoplastic liver tissues, were studied by a reverse-transcription PCR (RT-PCR) with the specifi c primers after RNA extraction. The sensitivity and specifi city of MAGE-1 and MAGE-3 mRNAs as markers for diagnosis of HCC have been assessed by plotting a receiver-operating characteristic (ROC) curve. Results In HCC patients, the positive rate of MAGE-1 and MAGE-3 mRNA expression was 53.3% and 33.3% in peripheral blood samples respectively, while the positive rate was 53.3% and 40.0% in HCC tissue samples, respectively. By contrast, MAGE-1 and MAGE-3 mRNA were not detected in the adjacent non-neoplastic liver tissues or in the peripheral blood samples of cirrhotic patients without HCC and healthy subjects. No relationship was found between MAGE-1 and

IntroductionCellular immune responses are thought to play a key role in the pathogenesis of hepatitis C virus (HCV)-related liver damage. Recently, increasing attention has been drawn towards components of the innate immune system to HCV, including natural killer (NK) cells. The present work was designed to study peripheral blood and intrahepatic NK cells in patients with chronic hepatitis C in relation to disease activity and severity of hepatic fibrosis.MethodsFifteen patients with untreated chronic hepatitis C (CHC) and 12 healthy subjects were included in the current study. The NK and NKT cells in fresh whole blood samples were identified using two-colour flow cytometry as CD3-CD56+ and CD3+CD56 cells, respectively, and the results were expressed as percentages of the total lymphocyte count. Liver biopsies were taken from all patients and the specimens were evaluated as regards the histological activity grade and fibrosis stage according to METAVIR scoring system and for the presence and grade of steatosis. Immunohistochemical staining was done using antibodies against CD56 and smooth muscle actin (SMA) for detection of intrahepatic NK cells and activated hepatic stellate cells (HSCs), respectively. A semi-quantitative method was used to score the intensity of immunostaining.ResultsThe percentages of CD3-CD56+ NK cells and CD3+CD56+ NKT cells in peripheral blood showed significant decreases in patients with CHC compared with healthy subjects (p<0.01) and was positively correlated with the intensity of intrahepatic NK cells (p=0.001). The CD56+ NK cell infiltrate was found to be absent or minimal in about 70% of the liver biopsies of patients with CHC. Patients presented with chronic fatigue showed significantly lower percentages of circulating NK and NKT cells and intensity of intrahepatic NK cells than patients who were asymptomatic (p<0.05). The percentages of peripheral blood NK cells and NKT cells and the intensity of intrahepatic NK cells showed significant inverse correlations with serum HCV RNA levels, steatosis grade, METAVIR fibrosis stage and intensity of activated HSCs (p<0.05) and statistically insignificant correlations with serum levels of aminotransferases and the histological activity grade (p>0.05).ConclusionThe deficiency of peripheral blood and intrahepatic NK cells in patients with chronic hepatitis C may provide a mechanism for immune suppression resulting in viral persistence, disease chronicity and progression of hepatic fibrosis. Restoration of the NK cell population may be one of the potential manipulations for resolution of HCV infection and for therapeutic modulation of hepatofibrogenesis.

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