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العنوان
Monocyte-derived Dendritic Cells in Children with Chronic Hepatitis C Correlation with Interferon and Ribavirin Therapy /
المؤلف
Nage, Salma Abd El Megeed.
هيئة الاعداد
باحث / سلمى عبدالمجيد ناجى
مشرف / بحيرى السيد بحيرى
مشرف / محسن حسن حسين
مشرف / محمد أحمد خضر
مشرف / أيمن محمد مرعى
الموضوع
Liver- Diseases. Pediatric gastroenterology.
تاريخ النشر
2013.
عدد الصفحات
125 p. :
اللغة
الإنجليزية
الدرجة
ماجستير
التخصص
الكبد
الناشر
تاريخ الإجازة
23/2/2014
مكان الإجازة
جامعة المنوفية - معهد الكبد - طب كبد الأطفال
الفهرس
Only 14 pages are availabe for public view

from 125

from 125

Abstract

Hepatitis C virus (HCV) infection is a major health problem worldwide and is a leading cause of chronic liver disease, associated with
significant morbidity and mortality. Globally, it is estimated that roughly
170 million people (3% of the population) are infected with HCV. Over
80% of acutely infected individuals are unable to clear the virus, resulting
in chronic infection and increased potential to develop cirrhosis, endstage
liver disease and hepatocellular carcinoma. Therapy for HCVrelated
chronic hepatitis is limited, and a vaccine protecting against HCV
infection is currently unavailable.
The study aims to evaluate the Dendritic Cells functions in
chronic infected HCV patients (who were treated with Interferon and
Ribavirin) and in healthy control.
The study participants included two groups of patients. The first
group ( treated HCV patients) included 30 patients , 10 females and 20
males, aged 4 - 17 years , with chronic HCV infection who were defined
on the basis of standard diagnostic criteria [positive for both anti-HCV
antibody and HCV RNA for more than 6 months, and the serum ALT
level greater than the upper limit of normal (40 U/L) and received
weekly pegylated-INF-α2b at a dosage of 60 µg/m2 once a week
subcutaneously, plus oral ribavirin (RBV) at a dosage of 15 mg/kg/day
depending on the pretreatment body weight for 48 weeks .
Fourteen out of 30 had failed IFN-based therapy as evidenced by
persistent or inadequate reduction in HCV RNA during therapy(They
are called non responders) while 16 out of 30 achieved sustained
Summary
88
virologic response as evidenced by undetectable serum HCV RNA 6
months after treatment (They are called responders).
The second (control group) included 30 healthy patients aged 5 -
16 years. The second group included 9 females and 21 males.
The two groups divided according to age to a group from (4-10)
years old and from (11-17) years old.
All cases were subjected to measurement of IL 10 and INF γ level.
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. Both patients and controls were age and sex matched
(P>0.05 for both).
2. The majority of HCV patients were asymptomatic.
3. Sex, age, viral load, CBC, liver enzymes, PC%,
histopathological grade or stage, and bilirubin level do not
affect dendritic cells production of IL10and IFN γ.
4. There was significant positive correlation between ALT and
IL-10 level (P-value < 0.05). While there was no significant
correlation as regards other patient’s laboratory and
histopathological parameters.
5. IL10 found to increase in chronic HCV patients than control
group therefore contribute to the high propensity of HCV to
cause chronic infection.
Summary
89
6. IFN γ found to decreases in treated chronic HCV patients
than control group.
7. We found that IL-10 of DC origin plays a central role in the
regulation of T-cell responses, with predominant
suppressive effects that counteract the action. Increased
production of IL-10 during HCV infection may therefore
contribute to the high propensity of HCV to cause chronic
infection, this last associated with weak HCV-specific Tcell
responses. So, impaired dendritic cell (DC) function
resulting in ineffective T cell priming leading to HCV
persistence. Thus, re-activation of DC may be an important
tool in fighting HCV infection. So, dendritic cells carry the
potential to be a candidate antiviral therapy in HCV
infection. This worth future in vitro (HCV replicon) and in
vivo (animal) studies to prove this notion.
We reached a conclusion that increased production of IL-10 during
HCV infection may contribute to the high propensity of HCV to
cause chronic infection. This finding represents the first step to
prove the pivotal role of IL-10 suppression in treatment of HCV
infection.
We recommend that IL10 increase in chronic HCV patients than
control group therefore contribute to the high propensity of HCV to
cause chronic infection. So, we recommend a wide study to confirm
this effect and the availability of using IL-10 inhibitors to restore DC
function in chronic HCV infected patients. Thus, re-activation of DC
may be an important tool in fighting HCV infection and vaccination.