الفهرس 
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Abstract
Hepatocellular carcinoma is considered the commonest primary
hepatic cancer, the fifth most frequent cancer worldwide and the third cause of
cancer related mortality. Hepatitis C virus is the etiological agent of hepatitis C
which is an infectious disease affecting the liver. It has high tendency to cause
chronic progressive hepatic damage and HCC.
Toll-like receptors (TLRs) are evolutionarily conserved
membranebound proteins. They are widely expressed on the surface of immune
cells. Toll-like receptors have an imperative role in immunity, neurogenesis and
developmental processes across the eukaryotic species.
Toll-like receptors (TLRs) stand out as significant players in the
pathogenesis of HCC. TLRs are capable of recognizing PAMPs/DAMPs and
initiating related intracellular signaling pathways. In the human immune and
non-immune cells, there are a total of 10 TLRs, which utilize different adaptor
proteins.
Toll-like receptor 4 (TLR4) can be stimulated by HCV nonstructural
protein NS5A and thereby results in the secretion of IFNs and IL6 from
hepatocyte and B cells. The activation of and TLR4 signaling in hepatocyte
leads to upregulation of pro inflammatory cytokines and chemokines and
recruitment of inflammatory cells to the liver.
Toll-like receptor 4 (TLR4) gene polymorphism was identified to be a
good prognostic predictor for the development of cirrhosis in HCV infected
patients. Also, it was shown that TLR4 SNPs are associated with protection
from liver fibrosis, possibly through conformational changes of the protein,
thereby affecting its interaction with other proteins.
This study aimed to determine the association between two single
nucleotide polymorphisms (rs2149356, rs1927914) of TLR4 gene and HCC risk in patients with HCV, evaluate the effects of two single nucleotide
polymorphisms (rs2149356, rs1927914) of TLR4 gene on liver fibrosis in
chronic hepatitis C patients and determine the frequency of alleles of TLR4 gene
in HCV patient and HCC patients as compared to healthy control.
This study was carried out during the period from September 2018 to
December 2020. Patients were randomly selected from those admitted to
National liver institute, Menoufia University. This study included 100 HCC
patients, 100 chronic HCV patients (CHC) and 100 apparently healthy
volunteers as a control group.
All participants were subjected to:
1. History taking.
2. Complete clinical examination.
3. Laboratory investigations; (Complete blood count, Prothrombin
concentration, INR, Liver function tests and Hepatitis markers; hepatitis C
virus antibody (anti HCV), Hepatitis B surface antigen (HBsAg).
4. Measurement of serum Alpha fetoprotein (AFP) level by two-step
sandwich solid phase enzyme immunoassay.
5. Detection of HCV RNA by quantitative Real Time PCR.
6. Detection of TLR4 single-nucleotide polymorphisms (rs2149356,
rs1927914) by PCR RFLP.
The results of the present study revealed that:
This cohort study included 200 patients chronically infected with HCV
and 100 healthy controls. They were categorized into three groups.
Demographic analysis of the studied subjects revealed no statistically
significant difference between the three groups.