الفهرس 
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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.