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العنوان
The Status of Fas and Fas Ligand Expression
on Peripheral Blood Mononuclear Cells in
Chronic Hepatitis C Virus Infection and
Hepatocellular Carcinoma
المؤلف
Darwish,Manal Mostafa
هيئة الاعداد
باحث / منال مصطفى درويش
مشرف / نرجس محمد إسماعيل عليش
مشرف / مرفت عبد الحميد محمد
مشرف / عبد الرحمن محمد الزيادى
مشرف / شيرين فوزى حافظ
الموضوع
Hepatocellular Carcinoma Fas and Fas Ligand Expression Chronic Hepatitis C Virus
تاريخ النشر
2004
عدد الصفحات
253P.
اللغة
الإنجليزية
الدرجة
الدكتوراه
التخصص
علم المناعة والحساسية
تاريخ الإجازة
1/1/2000
مكان الإجازة
جامعة عين شمس - كلية الطب - قسم علم الكائنات الدقيقة و المناعة
الفهرس
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Abstract

Hepatitis C is a complex disease and significant
public health problem. The long term outcome of HCV
infection is difficult to predict, as the virus may be
eliminated or may persist to establish chronic infection.
The majority of hepatitis C virus infection progress
to chronic infection, which can lead to liver fibrosis and
subsequent occurrence of cirrhosis, liver failure, and
hepatocellular carcinoma.
Combination therapy with interferon-α and ribavirin
is the treatment of choice for chronic HCV but only
modesty effective. No vaccine is currently available. In
addition, recurrence of HCV infection post liver transplant
is universal, and high level of viremia characterizes the post
liver transplant course.
Hepatocellular carcinoma is one of the most common
tumors worldwide with an estimated 1 million new cases
diagnosed per year. It is estimated that 60-90% of HCC
cases occur in cirrhotic livers.
Apoptosis is a fundamental biological process that is
important in many physiological and pathophysiological
processes in the liver, although dysregulation of apoptosis
may contribute to a wide range diseases. It has been
suggested that apoptosis plays an important role in HCV
associated liver injury.
Hepatitis C virus has the ability to infect the PBMCs
and enhance the expression of Fas on their surfaces. This
indirectly may reduce the number of PBMCs due to Fasmediated
apoptosis leading to the persistence of the
-----------------------------------* Summary *--------------------------------
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infection inside the hepatocytes due to immune
suppression.
The aim of the present work was to evaluate the
possible role of Fas-mediated apoptosis of peripheral blood
mononuclear cells in the persistence of hepatitis C
infection, development of chronic HCV infection, its
relationship to histological and pathological changes in
liver tissues and finally its relation to the development of
hepatocellular carcinoma. To achieve this aim, blood
samples were collected from 55 cases suffering from signs
and symptoms of chronic hepatitis and viral markers
revealed to be hepatitis C.
They were divided into 2 groups. Group I included
20 patients who were complicated by hepatocellular
carcinoma. Group II were further subdivided into 3
subgroups: Group IIa comprised 13 patients who were
under combined interferon and ribavirin treatment. Group
IIb were 12 patients recently diagnosed by liver biopsy and
pathological examination, group IIc included 10 patients
complicated by ascites, esophageal varices, and edema of
lower limbs. This study included also 15 apparently healthy
persons as a control subjects (Group III). The percentage of
Fas and Fas-ligand expression on PBMCs was measured by
flow cytometery technique using whole blood method.
The present study showed that:
 The percentage of Fas expressing PBMCs was low in
patients with HCC in comparison to the patients with
chronic hepatitis C. Although non significant
difference was found between all the studied groups
as regards the percentage of Fas expressing PBMCs.
 A high significant difference was found between all
the studied groups as regards the percentage of Fas-----------------------------------*
Summary *--------------------------------
-------------------------------------* *------------------------------------176 -
ligand expressing PBMCs, where its level in patients
complicated by HCC was very low in comparison to
the rest of the patients and the controls.
 No significant difference was found between group
II and group III as regards the percentage of Fasligand
expressing PBMCs.
 A high significant positive correlation was found
between the percentage of Fas expressing PBMCs
and Fas-ligand expressing PBMCs in patients
complicated by hepatocellular carcinoma and in the
control group.
 The percentage of Fas and Fas-ligand expressing
PBMCs showed no significant correlation with
either smoking or age in all groups.
 As regards group I, a significant correlation was
found between the percentage of Fas expressing
PBMCs and the prothrombin time and direct
bilirubin. Also, the percentage of Fas-ligand
expressing PBMCs showed a significant correlation
with ALT and total bilirubin.
 In group II, there was a highly significant correlation
between the percentage of Fas expressing PBMCs
and direct bilirubin, ALT, AST. As well as a
significant correlation was found between the
percentage of Fas expressing PBMCs and total
bilirubin. A significant correlation was found
between the percentage of Fas-ligand expressing
PBMCs and hemoglobin level.
-----------------------------------* Summary *--------------------------------
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 The percentage of Fas and Fas-ligand expressing
PBMCs showed no significant correlation with
neither the grade nor the stage of liver biopsy in
group IIa and IIb patients.
 The study also revealed so that group I showed a
significant increase in the level of total bilirubin,
direct bilirubin in comparison to group IIa, IIb and
IIc, a significant decrease in the level of platelets
count in comparison to group IIa and IIb. And a
highly significant increase in the level of alkaline
phosphatase and a highly significant decrease in the
level of albumin in comparison to group IIa, IIb and
IIc.