الفهرس 
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Abstract
HCV is a major public health problem in Egypt as 7.8 million people have chronic HCV infection. The overall prevalence rate is 15% with 500,000 newly infected individuals each year. The majority of acute HCV infected patients develop chronic hepatitis which then progress to severe fibrosis, cirrhosis and hepatocellular carcinoma. The mortality rate from HCV infection is high as a result of end stage liver disease complications. Therefore, the understanding of chronic hepatitis C related liver disease progression mechanisms could help in designing more efficient therapies to control the HCV disease complications.
The host immune response in HCV infected patients plays a key role in not only determining the HCV infection outcome but also causing liver injury, fibrosis and hepatocellular. A strong and effective immune response will clear the virus infection while weak and ineffective immune response will allow continuous viral replication and release of many inflammatory cytokines in the liver such as IL-2, IL-10, tumor necrosis factor (TNFα), IFNγ and hepatocyte Fas. Also, HCV infection triggers apoptosis and down regulates antioxidant protective mediators which increase the liver damage.
Several studies showed that intrahepatic TGF and TNFα cause chronic liver inflammation, hepatocyte stellate cell proliferation and extracellular matrix deposition which finally lead to fibrosis. During liver damage it was reported that continuous expressions of TGF and TNFα induced the synthesis of matrix protein and inhibited apoptosis of the activated HSC, therefore the liver fibrosis can be maintained.
Different polymorphisms in TGFβ gene were probably related to differences in TGFβ synthesis and expression. Some TGFβ polymorphisms at positions -509 (C/T), +869 (C/T, codon 10), and +915 (C/G, codon 25) were showed to affect the TGFβ level. TGFβ -509 C/T polymorphism is associated with portal vein thrombosis, lymph node metastasis, which finally leads to tumor invasiveness. It was reported that the presence of the T allele at -509 was associated with higher TGFβ serum level and the concentration was higher in homozygote TT genotype than in heterozygote GT genotype. Moreover, HCC patients had a higher frequency of TT genotype and lower frequency of than CC genotype at TGFβ-509 polymorphism.
Therefore, in this study we aimed to evaluate the role of TNFα -308G/A and TGFβ -509C/T polymorphism in liver fibrosis progression in Egyptian patients (72) with HCV genotype 4 with different fibrosis grades (F0-F4) in comparesion to controls.
The results of the present study showed that:
The distribution & Frequency of GG genotype of TNFα gene was higher in control group compared with HCV patients, in contrast AA genotypes was higher in HCV patients than control group
The frequency of GG genotype was higher in early fibrosis patients (F0-F1),while AA genotype was higher in late fibrosis patients (F2-F4)
The distribution and frequency of CC genotype of TGFβ gene was higher in in control group compared with HCV patients, in contrast TT genotypes was higher in HCV patients than control group
The frequency of CC genotype was higher in early fibrosis patients (F0-F1), while TT genotype was higher in late fibrosis patients (F2-F4)
Serum levels of TNF & TGF was higher in HCV patients compared with Control group. Also serum levels of both TNF & TGF was higher in late fibrosis patients in comparison with early fibrosis patients
TNF & TGF polymorphisms showed negative impact on hepatic fibrosis progression status and which leads to increase serum levels of TNF & TGF in HCV patients rather than control , and in Late fibrosis rather than early fibrosis
Patients who had both GG genotype of TNF with CC genotype of TGF together was found predominantly in early stage of fibrosis group than late fibrosis group
patients who had both AA genotype of TNF with TT genotype of TGF together was found predominantly in late stage of fibrosis than early fibrosis group which was confirmed by significant alteration in liver function tests
Conclusion & Recommendation:
Chronic HCV patients who have AA genotype of TNF gene or Have TT genotype of TGF gene or have combination of both of them (AA+ TT) will develop liver fibrosis and disease progression so they have to follow up regularly and to start treatment to delay the disease progression.