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.

Eligibility Criteria:
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.