The Assesment of MMP-1 Genotypes Polymorphism as a Risk Factor for HCC in Chronic HCV Patients With LC
The Assesment of MMP-1 Genotypes Polymorphism as a Risk Factor for HCC in Chronic HCV Patients With LC
Egypt is an endemic area of HCV.Cirrhosis and HCC are the most serious complications of
 chronic HCV infection.Some studies noted that the risk of HCC increased 17-fold among
 HCV-infected patients compared with anti-HCV negative controls.

 Many studies demonstrate that direct antiviral therapy seems to accelerate the development of
 HCC, soon after the end of treatment, in those patients at higher risk of HCC occurrence or
 recurrence; and preliminary reports seem to indicate that HCC developed after direct
 antiviral therapy has more aggressive features. These findings clearly indicate the need for
 aggressive and close monitoring of cirrhotic patients during and after antiviral treatment,
 to detect and treat HCC at their earliest occurrence.

 Genetic variation plays a key role in HCC susceptibility and development of the
 disease.Genotype distribution frequency data can be used to map single nucleotide
 polymorphism (SNP) diversity in a population and to examine the risk and development of
 specific diseases.Many reports indicate an association between SNPs in certain genes and the
 susceptibility and clinicopathological status of HCC.

 MMP-1 is an endogenous peptide enzyme that is most widely expressed in interstitial
 collagenase,which can degrade the extracellular matrix surrounding tumor cells. It is
 involved in many stages of tumorigenesis, in angiogenesis, and in suppression of tumor cell
 apoptosis .

 MMP-1 - 1607 1G/2G (rs1799750) contains a guanine insertion/deletion polymorphism at position
 - 1607 and is a functional (SNP) that can upregulate MMP expression. The association between
 the MMP-1 - 1607 1G/2G polymorphism and the emergence of several diseases including the risk
 for many cancers has been reported.

 There are results suggest that MMP-1 is overexpressed in a large proportion of patients with
 HCC which correlated with the disease progression and poor clinical outcome. Furthermore,
 MMP-1 high expression proved to be a risk factor for tumor recurrence and independent
 molecular marker of prognosis in HCC and may become a novel target in the strategies for the
 prediction of tumor progression and prognosis of this disease.

 Aim:

 Is to asses:

 The contribution of MMP-1-1607 genotype polymorphism to the risk of HCC on top of HCV.

 The relationship between MMP-1-1607 gene polymorphism with HCC in patients who received
 antiviral treatment to HCV.
This study is a case-control observational study to be done at Clinical pathology department,
 Assiut University hospital, Assiut University, Egypt. The control population comprised 20
 healthy individuals with no liver infection. Patients will be subjected to a full history and
 thorough physical examination.The liver will be examined in all patients by local physical
 examination to detect possible abnormalities.The diagnosis of HCC cases include a combination
 of history, clinical examination ,radiological examination including ultrasound and triphasic
 computed tomography, Child-Pugh classification, and laboratory investigations including
 hepatitis C marker, irrespective of alpha-fetoprotein as it is positive in 30% of cases.

 Neither patients nor controls had a history of other malignancy.The diagnosis of liver
 cirrhosis is based on clinical features, laboratory tests, abdominal ultrasound.

 3-Exclusion criteria Exclude patients who had chronic hepatitis B virus infection by
 detecting HBsAg and core total, alcoholism, primary biliary cirrhosis, or autoimmune liver
 disease, decompensated liver cirrhosis on top of HCV .

 4- Participants All individuals are subjected to the following:-

 1. Full history taking including the history of taking antiviral drug,clinical examination,
 abdominal ultrasound.

 2. Laboratory tests including:

 -  Routine investigations: CBC,PT &PC,liver function tests.

 -  Specific investigations: AFP level, serum level of MMP-1,Determination of MMP-1
 gene polymorphism By PCR amplification followed by restriction Fragment length
 polymorphism (RFLP) and gel electrophoresis.
Inclusion Criteria:

 -  The control popula¬tion comprised 20 healthy individuals with no liver infection.
 Patients will be subjected to a full history and thorough physical examination.

 -  The liver will be examined in all patients by local physical examination to detect
 possible abnormalities.

 -  The diagnosis of HCC cases include a combination of history, clinical examination
 ,radiological examination including ultrasound and triphasic computed tomography,
 Child-Pugh classification, and laboratory investigations including hepatitis C marker.

 Exclusion Criteria:

 -  Exclude patients who had chronic hepatitis B virus infection by detecting HBsAg and
 core total IgG, alcoholism, primary biliary cirrhosis, or autoimmune liver disease,
 decompensated liver cirrhosis on top of HCV will be excluded.