Introduction Cellular 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.
Methods Fifteen 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.
Results The 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).
Conclusion The 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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