Expression of apoptotic markers BCL-2 and bax chronic hepatitis C virus patients

ABSTRACT

Despite advances in the knowledge of the molecular virology of hepatitis C virus [HCV], the mechanisms of hepatocellular injury in HCV infection are not completely understood. The available reports are in favor of a destructive mechanism mediated by the host immune system rather than a direct cytopathic effect of the virus. Some viral infections influence the susceptibility of peripheral blood mononuclear cells [PBMC] to apoprosis. This could lead to insufficient antiviral immune response, persistent viral infection and disease progression. To evaluate the expression of apoptotic markers Bcl-2 and Bax in PBMC in chronic HCV patients. The study included three groups; group 1. Fifteen chronic HCV patients with biopsy-proven liver cirrhosis and ascites; among this group, five patients had cryoglobulinemia [group la] and the remaining ten patients had no cryoglobulinemia; group lb. Group 2 Ffteen chronic HCV patients without any suspected evidence of liver cirrhosis and group 3 Fifteen healthy subjects as a control group. All groups were age and sex matched and subjected to physical examination, abdominal ultrasound, laboratory investigations including Complete blood cell count, liver and renal functions, Hepatitis B suiface antigen, anti-HCV antibodies, serum cryoglobulins, detection of apoptotic markers Bcl-2 and Box in peripheral blood lymphocytes, other necessary tests and in addition serum HCV RNA levels in the patient groups, by quantitative polymerase chain reaction [PCR] assay, and peritonealfluid analysis in group 1 patients. Group 1 chronic HCV patients [with cirrhosis and ascites] had a statistically significantly low Bcl-2 percentage expression in peripheral blood lymphocytes, a significantly high Bax expression and a significantly decreased Bcl-2/Bax ratio compared than healthy controls, with a statistically significant difference between group la [cryoglobulinemic] and group lb [non-cryoglobulinemic]. Group 2 patients had a statistically significantly increased Bcl-2 percentage expression, a signcantly decreased Bax expression and a significantly increased Bcl-2/Bax ratio than controls. In chronic hepatitis C virus patients [group 1 and 2] Bcl-2 expression showed a statistically significant positive correlation with S. albumin, prothrombin activity, ALT and the Bcl-2/Bax ratio and a significantly negative correlation with S. total blirubin, blood urea and the Bax expression. Bax expression showed a statistically significant positive correlation with S. total blirubin, blood urea and S. creatinine and a significantly negative correlation with S. albumin, prothromhin activity, ALT and the Bcl-2/Bcvc ratio. Bcl-2/Bax ratio showed a statistically significant positive correlation with S. albumin, prothrombin activity and ALT and a significantly negative correlation with S. total blirubin, blood urea and S. creatinine. Chronic HCV patients exhibit a dysregulation of apoptosis, in the form of a down regulation of Bcl-2 expression together with an increasd Bax expression and, a decreased Bcl-2/Bax ratio in peripheral blood lymphocytes, with the disease pro gression. This provides an insight into the pathogenesis of chronic HCV infection and may open new avenues in the management of the disease