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Abstract Total of 60 subjects were included in this study, 50 hepatic patients and10 healthy volunteers with age and sex matched were taken as controls.. Patients selected were classified into the following groups:group I: 10 patients suffering from bilharzial hepatic fibrosis and they were seronegative for HCV.group II:10 patients suffering from chronic hepatitis C without bilharziasis. group III: 10 patients suffering from chronic hepatitis C on top of bilharziasis. group IV:10 patients suffering from hepatocellular carcinoma without HCV infections.group V: 10 patients suffering from hepatocellular carcinoma on top of chronic hepatitis C.Fasting 10 ml EDTA anticoagulated blood sample was collected from every subject in our study and divided into two parts:One ml was stored as whole blood at 30oC until DNA extraction and utilized for genetic study of cytochromeP4502D6*4 gene by conventional PCR followed by restriction enzyme analysis by Mva1enzyme.The rest of the sample was centrifuged at 3000 rpm for 10 minutes and the separated plasma was divided into aliquots for the biochemical assays: soluble Intercellular Adhesion Molecules1(sICAM1)and Malondialdehyde .Results: Cytochrome P4502D6*4 gene was amplified in all groups of liver diseases as well as in the control group.Restriction enzyme analysis by Mva1enzyme revealed that: Subjects of the normal control group have wild type determination of CYP2D6*4 gene. Patients with pure bilharzial hepatic fibrosis have homozygous mutation of CYP 2D6*4. Patients with pure chronic hepatitis C without bilharziasis have homogenous mutation of CYP2D6*4 gene. While, patients suffering from chronic hepatitis C on top of bilharziasis have wild type determination of CYP2D6*4 gene. Patients with hepatocellular carcinoma not associated with HCV have wild type determination of CYP2D6*4 gene. While, those patients suffering from hepatocellular carcinoma on top of chronic hepatitis C have heterozygous mutation of CYP2D6*4. There is statistically significant increase in the plasma levels of sICAM1 in all patients as compared to control group. There is statistically significant increase in the plasma levels of MDA in all patients compared to the controls.Conclusion: CYP2D6*4gene showed no mutation in normal individuals and appeared as wild type determination. On the other hand, there are different forms of mutations in cases of patients with pure bilharzial hepatic fibrosis, patients with HCV with no bilharziasis (homozygous mutation) and patients with HCC on top of chronic hepatitis C infection (heterozygous mutation).Detection of mutation of cytochrome P4502D6*4 in patients with pure bilharzial hepatic fibrosis alone or patients with pure HCV may be used as an early marker for predisposition to hepatocellular carcinoma. Also further genetic study needed as regard genetic implication in families and wide range of population to reach a decisive result.sICAM1 plays an important role in the pathogenesis and prognosis of liver diseases as it had shown an association of increased level in the different studied groups of liver diseases. Malondialdehyde also increased significantly in different forms of liver diseases and indicated that reactive oxygen species may have a role in the pathogenesis of liver diseases and its possible progression to hepatocellular carcinoma. |