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Abstract Hepatitis C virus (HCV) is a single stranded ribo nucleic acid (RNA) virus classified as a separate genus within the flaviviridae family, with marked genetic heterogeneity. It has eleven major genotypes and numerous subtypes and quasispecies which permit the virus to escape host immune surveillance. Genotype variation might partially explain the difference in clinical course and response to treatment. About 4 million people in the United States and 200 million people worldwide are estimated to be infected with HCV. In children, worldwide seroprevalence of HCV is 0.2% in those < 11years of age and 0.4% in those >11 years of age. In Egypt the main (90%) HCV genotype is type 4. The magnitude of HCV infection in Egyptians revealed an overall prevalence of 8.7% in Upper Egypt and 24.3% in Lower Egypt and in those under 19 years of age it was 3% in Upper Egypt and 9% in Lower Egypt. Liver fibrosis has been shown to be an independent predictor of liverrelated mortality. Liver biopsy followed by conventional histological analysis is the gold-standard to evaluate liver fibrosis; however, liver biopsy can have lifethreatening complications in both adults and children. In addition to the classical serum proteins, the serum also contains all tissue proteins as leakage markers. Since the liver makes many serum proteins, it is logical to expect that the serum proteome may reflect liver disease. Inter-alpha-trypsin inhibitor heavy chain 4 (ITIH4) is a plasma glycoprotein that is expressed mainly in liver. It acts as type II acute-phase protein involved in inflammation. Also it may play a role in liver development or regeneration. Inter alpha trypsin inhibitor heavy chain 4 was increased in the serum samples of HCV patients with moderate fibrosis and cirrhosis compared with healthy controls; So ITIH4 was found to be a sensitive marker for liver fibrosis. The aim of this study is to assess serum level of ITIH4 and its relation to liver fibrosis in children with chronic HCV infection. Sixty individuals were enrolled in this study, 30 patients with chronic HCV infection, underwent full history taking and thorough clinical examination and all diagnostic tools including HCV antibody, HCV-PCR and liver biopsy, and 30 age and sex matched healthy children, with no history or clinical evidence of liver disease or any other disease, served as a control group. All controls underwent liver function tests, and HCV antibody testing. All cases were subjected to measurement of serum ITIH4 level by ELISA. Patients with associated liver diseases other than HCV or with other systemic diseases e.g., pulmonary, cardiac or renal diseases were all excluded from the study. Data were collected, coded and processed by statistical analysis (SPSS) statistical package version 13 on IBM compatible computer, and the results were put in tables and graphs. Our results showed that: 1- The possible risk factors were family history (63.3%) followed by circumcision (60.0%), history of operations (43.4%), blood transfusion (30.0%) and dental procedures (16.7%). 2- The majority of patients were asymptomatic. There were 4 cases with hepatomegaly, one case with splenomegaly and none had jaundice, hematemesis, melena, encephalopathy or ascites. 3- Normal liver (66.7%) and normal spleen (86.7) were the main ultrasonography finding, echogenic liver was found in (33.3%), enlarged spleen in (13.3%) and none of the patients had coarse liver or ascites. 4- Alanine aminotransferase was significantly higher in patients than in the controls (P = 0.034) while there was no significant statistical difference as regards AST (P>0.05). 5- All patients, except one with F0, had mild (40.0 %) to moderate (56.7%) fibrosis and all of them had mild (70.0%) to moderate (30.0%) activity while (23.3%) had steatosis. 6- The majority of patients had elevated ALT (60.0%) and (26.7%) had elevated AST; nonetheless, all the patients (except one with F0) had either mild or moderate activity or fibrosis. 7- There was no significant statistical difference in ITIH4 levels between patients and control group (P > 0.05). 8- There was no significant statistical difference in the mean ITIH4 levels according different grades of activity, different stages of fibrosis or in those with or without steatosis. Nonetheless, ITIH4 was in its lowest value in F0 and increases as fibrosis progress with its highest level in F3. 9- Inter-alpha-trypsin inhibitor heavy chain 4 did not correlate with any of CBC parameters or histopathological scores of liver biopsy except for AST which directly correlated with ITIH4 levels (P = 0.024). 10- Inter-alpha-trypsin inhibitor heavy chain 4 did not correlate with HCV viral load (P = 0.843). Nonetheless, ITIH4 was in its highest value with low viremia and decreases as viremia progress with its lowest level with high viremia. Conclusion from the study results, we can conclude that 1- Inter-alpha-trypsin inhibitor heavy chain 4 correlates significantly with AST which is a marker of liver cell injury and disease activity. 2- The higher levels ITIH4 were associated with higher stages of fibrosis and with lower levels of HCV viremia, implicating possible antiviral properties of ITIH4 against HCV, as one of protease inhibitors. 3- Contact with HCV- infected family and circumcision still a major risk factors for HCV infection in childrens. 4- The lack of significant statistical difference in fibrosis and activity between patients with different disease duration suggests the slow nature of disease progression in children. |