الفهرس 
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Abstract
Hepatitis C virus (HCV) infection is a devastating health problem and a leading cause of chronic liver disease worldwide. Hepatitis C infection causes acute symptoms which are generally mild and non-specific in only 15% of patients. About 80% of those exposed to the virus develop a chronic infection with its consequences of liver cirrhosis and hepatocellular carcinoma. It has been reported that about 700,000 persons die annually as a consequence of HCV-related complications; all of which could be avoided if proper antiviral treatment is provided at an early stage of the disease.
The pathogenesis of chronic HCV infection has not been clearly elucidated. Hepatitis C virus is RNA virus without apparent cytopathic effects, therefore in chronic infection the hepatocellular damage is generally believed to be immune-mediated.
Apoptosis or programmed cell death plays an important role in the maintenance of cellular homeostasis through removal of aged, damaged, and hyperproliferative cells. Bcl-2 family has emerged as a dominant regulator of apoptosis through the regulation of the mitochondrial-mediated pathway. Bcl-2 family includes anti-apoptotic (Bcl-2, Bcl-xl, Mcl-1) and pro-apoptotic proteins (Bax, Bad, and Bak).
Apoptosis has been implicated not only in the pathogenesis of HCV infection, but also in determining the individual susceptibility to the infection. Additionally, it has been shown that apoptosis is the cause of HCV-induced cell death. Bax, which is a pro-apoptotic member of the Bcl-2 family that induces apoptosis of the host cell through a Bax-triggered, mitochondria-mediated mechanism, is activated by HCV infection. Also, it has been suggested that the cell susceptibility to apoptosis is determined by the Bcl-2: Bax ratio. Considering the high prevalence of HCV infection in Egypt, the current study was conducted to assess the potential role of Bcl-2 and Bax in the pathogenesis of chronic hepatitis c virus related liver diseases.
The study included 70 chronic HCV patients. The study population was divided into 3 groups; group 1 (n=35) chronic HCV patients with no evidence of cirrhosis and group 2 (n=35) chronic HCV patients with cirrhosis; Child-Pugh class B/C; group 3 (n=15) age and sex matched healthy controls (HCV and HBV seronegative).
Bcl-2 serum level showed a highly significant increase in group 1 while it decreased significantly in group 2 as compared to controls (P value < 0.001). On the contrary, there was a highly significant elevation of Bax serum level in group 2 and a significant decrease in group 1 (P value < 0.001). Although, Bcl-2/Bax ratio showed a highly significant elevation in group 1, it decreased significantly in group 2 in comparison to controls (P value < 0.001).
Serum apoptotic markers (Bcl-2, Bax and Bcl-2/Bax ratio) showed statistically significant positive correlations (P value < 0.05) with total protein, albumin, ALT, AST and HCV viral load of all the studied HCV patients while significant negative correlations were found with total and direct bilirubin. Moreover, positive correlations were noticed between serum Bcl-2, Bax, Bcl-2/Bax ratio and HCV viral load of group 1 but negative correlations were reported in group 2.
These results indicate that the progression of HCV infection is explained by this dysregulation of the apoptotic process.
Conclusion
Apoptotic markers may be a useful non-invasive surrogate marker of disease activity in HCV infection; increased serum Bax level with decreased serum Bcl-2 level and Bcl-2/Bax ratio were detected with the progression of the disease that provide prognostic potential for chronic HCV infected patients.
Recommendations
• Estimation of the levels of apoptotic markers Bcl-2, Bax, Bcl-2/Bax ratio could be a good indicator for the prognosis of chronic HCV infected patients and may open new avenues in the management of the disease.
• Further studies are recommended to focus on the mechanisms by which apoptosis contributes to the immune clearance or the persistence of viral hepatitis.
• Further studies are needed to evaluate the potential role of Bcl-2 and Bax in the pathogenesis of chronic hepatitis C virus related liver diseases on a large study scale.