HCV does not kill the cells it infects but triggers
HCV does not kill the cholesterol absorption inhibitor it infects, but triggers an immune-mediated inflammatory response (hepatitis) that either rapidly clears the infection or slowly destroys the liver, causing the development of HCC and cirrhosis. The outcome is largely determined by the efficiency of the antiviral immune response. So the innate immune response might be expected to influence the outcome of infection. Apoptosis is an active, genetically programmed phenomenon of cell death characterized by a unique sequence of events, with morphological features distinct from necrosis. Three pathomorphologic features are suggestive of increased apoptosis in the liver of patients with chronic hepatitis C: (1) the presence of shrinkage and fragmentation of nucleus/cytoplasm in areas of piecemeal necrosis; (2) the presence of acidophilic bodies; and (3) focal cell drop out in the liver lobule. Increased expression of Fas, one of the most important members of the tumor necrosis factor family receptors and able to act as a transducer for the apoptotic signal to complete programmed cell death, has been described in chronic hepatitis C. Hepatic up-regulation of Fas was found to correlate with more severe inflammation and ongoing HCV infection. Fas expressing cells are potential targets of cytotoxic T lymphocytes bearing Fas ligand. The interaction between Fas ligand and its receptor, Fas, induces apoptosis in the target cell. Hepatocyte expression of Fas has been shown to be common in chronic HCV infection suggesting that apoptosis is a frequent occurrence in this disease. Active inflammation was observed in chronic hepatitis C patients who had high levels of serum sFas, suggesting that sFas may serve as a serological indicator of active inflammation in chronic hepatitis C. Serum sFas levels may be correlated with the degree of inflammation in the liver and Fas expression on hepatocytes. Because apoptosis of hepatocytes is determined not only by Fas/sFas expression but also by expression of FasL/soluble form of FasL, the inducing effect of FasL on CTL might have exceeded the inhibitory effect of sFas. Nevertheless, correlation between Fas genotype and histopathological activity grade is consistent with a body of data indicating that Fas-mediated hepatocyte apoptosis contributes significantly to the pathology of chronic hepatitis C. In particular, activity grade in hepatitis C patients has been correlated with both the level of Fas expression and the extent of apoptosis in hepatocytes. Genetic polymorphyisms that change the level of Fas expression in hepatocytes could therefore alter hepatocyte apoptosis, and hence affect the activity grade of HCV patients. Genetic polymorphyism in the Fas gene may account for some of the histopathological variability in chronic hepatitis. Hepatitis C is a viral infection with a highly variable disease course; approximately 20% of infections are resolved spontaneously, and progressive fibrosis eventually leads to cirrhosis in 20–30% of chronically infected patients. In contrast, the role of cytokine gene polymorphyisms in HCV infection is less clear. Of some importance is that the correlation between Fas -1377G, −690C, −670A haplotype and lower activity grade was stronger in McIlroy\'s study. These results were similar to our results in that the genotypes of Fas-1377 G/G and Fas-670 A/A have the lower risk for HCV infected cirrhosis. The data suggests that the SNPs in the Fas promoter regions strongly correlate to the severity of cirrhosis caused by HCV infection. The Fas/FasL system plays an important role in tumor outgrowth and metastasis.FasL expressed in colorectal carcinoma cells may kill the Fas-positive immune effect of TILs and had a poor prognosis. The expression of FasL on HCC tumor cells is thought to be a mechanism that tumors employ to escape immune surveillance and may induce apoptosis of activated T lymphocytes and had a worse prognosis. The SNPs of FasL have not been well-studied regarding cancer progression, nor have issues of survival and disease-free survival been addressed. In our study, the genotype of FasL844 C/C had a higher rate in the early CLIP score cancer stage and a lower AFP level. It means that the genotype of FasL844 C/C is related to the progression of HCC. Then, we analyzed the overall survival rate. Although there was no significant difference between patients with genotype FasL844 C/C and that of T/C + T/T, but tended to have longer survival time. We could not determine these patients\' survival rates or DFS by using SNP, but they may play an important role in this study and require additional review and comprehension.