الفهرس 
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Abstract
Hepatitis C Virus is an important global health problem that causes acute and chronic hepatitis. The virus was discovered in the USA in 1989 and about three to four million people are infected every year worldwide. Humans are the natural hosts of HCV and the virus can eventually lead to permanent liver damage and HCC. HCV is a single-stranded RNA virus of positive polarity belonging to the Flaviviridae family that encodes a single polypeptide chain that is cleaved into both structural (core, E1, E2, p7) and non-structural (NS2, NS3, NS4A, NS4B, NS5A, NS5B) proteins. Oxidative stress refers to the imbalance between the pro-oxidant and antioxidant levels in favor of pro-oxidants in cells and tissues. This scenario leads to modification of lipids, proteins, and DNA. Such modifications or damage to these molecules are called oxidative damage. Pro-oxidant is a species that causes or promotes oxidation. Antioxidant is a molecule inhibits formation of pro-oxidants and inhibits oxidation. Antioxidants are usually present at a low concentration and yet inhibit oxidation of an oxidizable substrate. Eukaryotic cells possess a special system of defense against OS. It is comprised of low molecular weight compounds (GSH and other antioxidants) and “phase II defense enzymes” capable of scavenging ROS. The delicate balance between beneficial and harmful effects of free radicals is a very important aspect of living organisms and is achieved by mechanisms called “redox regulation. Cellular redox is controlled by the Trx and GSH systems that scavenge harmful intracellular ROS. OS also evokes many
intracellular events including apoptosis. There are two major
pathways through which apoptosis are induced; one involves death
receptors and is exemplified by Fas-mediated caspase-8 activation,
and another is the stress- or mitochondria-mediated caspase-9
activation pathway. Both pathways converge on caspase-3 activation,
resulting in nuclear degradation and cellular morphological change.
Occurrence of oxidative stress during CHC was detected as
early as in the middle of 1990s. So, far ROS induction by HCV has
been put into evidence by various different approaches, including
measurement of i) ROS, ii) antioxidants, iii) expression levels and
activities of antioxidant defense enzymes, iv) products of interaction
of ROS with biological molecules. Detection of these compounds has
been performed in liver biopsies of CHC patients, suggesting a direct
influence of HCV, as well as in blood samples or blood cells of CHC
patients with special emphasis given to potential correlation between
concentration of these compounds/enzymes and course of the disease
in the liver.
Cellular GPX is a member of a family of GPX enzyme whose
function is to detoxify peroxides in the cell. Because peroxides can
decompose to form highly reactive radicals, the GPX enzymes play a
critical role in protecting the cell from free radical damage,
particularly lipid peroxidation. The GPX enzymes catalyze the
reduction of H2O2 to water and organic peroxides (R-O-O-H) to the
corresponding stable alcohols (R-O-H) using GSH as a source of
reducing equivalents:
GPX
R-O-O-H + 2 GSH R-O-H +GSSG +H2O
Malondialdehyde is a naturally occurring product of lipid
peroxidation and prostaglandin biosynthesis that is mutagenic and
carcinogenic.
The aim of this study is to assess OS factors, GPX and MDA in
children with CHC before and after combined IFN and ribavirin
therapy (responders and non-responders).
One hundred twenty-five children were enrolled in this study,
100 patients with chronic HCV infection, underwent full history
taking and thorough clinical examination and all diagnostic tools
including HCV antibody, HCV-RNA and liver biopsy and 25
apparently healthy children, with no history or clinical evidence of
liver disease or any other disease, served as controls. All cases were
subjected to measurement of plasma MDA and erythrocyte GPX
levels. They divided into the following groups:
Group I: Fifty naïve CHC children.
Group II: Twenty-five children responders to HCV treatment.
Group III: Twenty-five children non-responders to HCV treatment.
Group IV: Twenty-five control group matched in age and sex.
Data were collected, coded and processed by statistical analysis
(SPSS) statistical package version 18 on IBM compatible computer,
and the results were put in tables and graphs.
Our results showed that:
Both patients and controls were age and sex matched (P>0.05
for both).
1. The risk factor of HCV infection was mostly due to history of
operations (38%) followed by dental care (29%) then blood
transfusion (18%) yet, a considerable percentage (9%) was due
to unknown factors.
2. The majority of HCV patients were asymptomatic.
3. Echogenic liver was the main finding, normal spleen was found
in the majority of the patients and none of the patients had
ascites.
4. The majority of patients who underwent liver biopsy (69
patients) had minimal (44.9%), mild (50.7%) and moderate
(4.3%) activity and mild (87%), moderate (13%) fibrosis in
histopathological examination.
5. Fifty-three patients of one hundred patients (53%) had elevated
ALT and thirty-four patients (34%) had elevated AST while
forty-seven patients had normal ALT (47%) and/or normal AST
(66%).
6. Average GPX activity in erythrocytes of naïve CHC patients
was 29.2±10.3 mU\ml. It was significantly statistically lower (p
< 0.05) than average activity of GPX in erythrocytes of healthy
control group.
7. Average GPX activity in erythrocytes of patients with CHC
who responded to treatment (responder group) was 34.93±3.17
mU\ml. It was significantly statistically higher than average
activity of GPX in erythrocytes of patients with CHC who did
not respond to treatment.
8. Plasma MDA is significantly increased in naïve CHC patients
(n: 50), before PEG-IFN-α-2b, and ribavirin treatment when
compared with healthy subjects (n:25) (9.7±3.7 nmol/ml vs.
3±1.1 nmol/ml, (p <0.0001)
9. Plasma MDA concentration significantly decreased in patients
who responded to treatment with PEG-IFN-α-2b, and ribavirin
treatment (responder group) (5.36±0.7 nmol/ml) while still
elevated in patients who did not respond to treatment with PEGSummary
- 95 -
IFN-α-2b, and ribavirin treatment (non-responder) (16.05±2.9
nmol/ml).
10. There were negative correlations between levels of GPX and
MDA in all studied groups.
11. There was statistically significant difference between levels of
GPX and MDA between chronic naïve HCV patients and
responders groups.
12. There was statistically significant difference between levels of
GPX and MDA between chronic naïve HCV patients and nonresponders
groups.
13. There was statistically significant difference between levels of
GPX and MDA between chronic naïve HCV patients and
control groups.
14. There was statistically significant difference between levels of
GPX and MDA between responders and non-responders
groups.
As a conclusion, lower pretreatment levels of GPX and higher
level MDA level might be probable marker of the OS. Reversal
change of these levels with completion of the treatment may indicate a
correlation between the OS and the viral pathogenesis.
So antioxidant supplement can be added in these patients during
their clinical survey. However, further investigations to highlight this
issue will be recommended.