الفهرس 
Epidemiology-prevalence and incidence of hepatitis C virus (HCV)Only 14 pages are availabe for public view
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Abstract
A great progress has been done in understanding chronic hepatitis C virus (HCV) infection and its association with the development of hepatocellular carcinoma (HCC). It is widely accepted that host immunity plays an important role in HCV pathogenesis. On the other hand, HCV proteins can exert direct effects on cellular growth, metabolism, signal transduction and genome integrity. In this context, key factors that are influential in HCV-related HCC include chronic inflammation, steatosis, fibrosis, cirrhosis, oxidative stress, genome instability, and viral interference with cellular growth control.
The present study aimed to :
1- Study the sequence of hepatitis C virus RNA extracted non-structural 5A region (NS5A) from patients with hepatocellular carcinoma (HCC) on top of hepatitis C virus and compare these sequences with sequences of hepatitis C virus RNA extracted non-structural 5A region (NS5A) from patients with chronic active hepatitis C virus to find out the similarity and/or differences between the two groups, and if this comparative structural of NS5A region improve any role in the pathogenesis of hepatocellular carcinoma together with the expression of Nuclear Factor Kappa B (NFkB).
2- To investigate the usefulness of biomarkers :
• Alpha fetoprotein (AFP).
• Tumor necrosis factor (TNF-α).
• Transforming growth factor B1 (TGF-B1) in predicting and prognosis of hepatocellular carcinoma.
The current study was performed on 20 Egyptian male patients their age ranged from 43-74 with hepatitis C virus – related hepatocellular carcinoma (HCV-related HCC) (groupI).
All patients group were diagnosed as having HCV-related HCC with no evidence of extrahepatic metastasis and they all negative for hepatitis B surface antigen (HBsAg).
All patients were HCV 4-a subtype which is the most prevalence subtype in Egypt.
Also 10 Egyptian patients 9 males and one female with chronic active hepatitis C virus infection. Their age ranged from 25-60 with chronic active hepatitis C (subtype 4-a) were included in this study as a reference control (group II).
The results obtained in this study showed an increased prevalence of wild type NS5A region in HCV-related HCC patients with a sequence identities (100%) while all reference group with chronic HCV harboured mutations in NS5A region with sequence identities (88.9%). A significant increase in the mean number of mutations in the reference group compared to the patients group. Also there was a significant increase in the mean number of mutations in ISDR region and PKR-bd in the reference group compared to the patients group. There was a significant fixed mutation at codon 2212 in ISDR region of patients group where glutamine changed to lysine (QK) in 8 cases (88%), also there was a significant fixed mutation at codon 2260 in 7 cases (77%) in PKRbd region of patients group where Aspargine changed to Aspartate (N D), on the other hand there was a fixed mutation at codon 2212 in ISDR region of reference control group where glutamine changed to lysine (QK) in 8 cases (80%) and also another significant fixed mutation at codon 2260 in PKR-bd region in 8 cases (80%) where Aspargine changed to Aspartate (N D). No significant differences in HCV-RNA titre was founded between the two groups. A highly significant increased in NFkB expression was founded in patients group compared to the reference control group.
There was a highly significant increase in TGF-B1 levels in patients group compared to the reference control group. Also there was a highly significant increase in AFP levels in patients group compared to the reference group. High significant increase in TNF-α levels was reported in patients group compared to the reference control group. There was a significant decrease in serum albumin in patients group compared to the reference control group. On the other hand no significant differences was reported in case of alaninaminotransferase (ALT) activity, prothrombin time (PT) prothrombin concentration (PT conc) and international normalized ratio (INR) in both two groups.
In Conclusion :
• The wild type NS5A region is significant in HCV-related HCC patients and the amino acid substitutions in ISDR/PKR domains could be significant factor associated with the development of HCC in long standing patients with chronic active hepatitis.
• Determination of ISDR/PKR substitutions in HCV carriers may aid in the identification of patients at high risk for developing HCC. The finding of a fixed mutation need more address in the future.
• NFkB is a significant variable for the diagnosis of patients with hepatitis C virus related hepatocellular carcinoma.
• TGF-B1 is a significant serological marker for the diagnosis of patients with hepatitis C virus related hepatocellular carcinoma.
• TNF-α is a significant variable reflecting inflammation in both chronic active hepatitis C and patients with hepatitis C virus related hepatocellular carcinoma.