الفهرس 
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Abstract
HCV infects an estimated 170 million individuals worldwide.
Egypt has amongst the highest prevalence of HCV infections in the Arab
world, and indeed in the world. For example, for HCV, it is estimated that
10-20% of Egyptians are infected with the virus, more than 3 times the
global rate. Most individuals with acute HCV infection will progress to
chronicity and over time will develop liver fibrosis. Progressive liver
fibrosis can lead to cirrhosis and decompensated liver disease in due
course. A total of 25% of all cirrhotic patients will also develop HCC.
Today, HCV is the primary cause of liver transplantation in the world.
Type I IFNs were initially used to treat HCV successfully.
Subsequently, RBV, an antiviral agent, was added to improve cure rate.
IFN- -2a is administered as subcutaneous injection while RBV is
administered orally. Several steps of HCV life cycle are blocked in vitro
by IFN and their products, as well as by RBV. Recently, DAAs that target
various stages of the HCV life cycle have been developed. SOF, the first
polymerase inhibitor, is effective in all HCV genotypes and affects
directly the viral replication through targeting the high conserved active
site of the HCV specific NS5B polymerase. The current study aimed to:
1- evaluate the efficacy of SOF-based combination therapy (SOF plus
RBV regimen for 24 weeks or SOF plus RBV and peg-IFN- -2a
regimen for 12 weeks).
2- record the adverse events and hematologic abnormalities during and
after the treatment.
3- monitor immune cells status after SOF-based combination therapy
regimen from chronically infected HCV Egyptian patients For the first and second purpose: three hundred and five patients
were assigned to receive either SOF, RBV and peg-IFN- -2a or SOF plus
RBV for either 12 or 24 weeks, respectively. SOF was orally
administered at 400 mg once daily and RBV dose was administrated at
1000 or 1200 mg according to the patient’s weight. Peg-IFN- -2a was
Subjects were
divided into two groups:-
Group-I: One hundred and fifty five patients with HCV infection
received SOF plus RBV therapy regimen for 24 weeks.
Group-II: One hundred and fifty patients with HCV infection,
received SOF plus RBV and peg-IFN- -2a therapy regimen for 12 weeks.
Patients were followed up after the end of the course of treatment to
detect possible complications of treatment.
Some laboratory investigations were done after the last dose of
treatment, including (creatinine, liver enzyme and T- Bile); CBC (WBCs,
Hb and PLT) and PCR after 12 week (SVR12) to evaluate the treatment
regimen and detect cure rates. SVR12 was higher in the group received
SOF plus RBV and peg-IFN- -2a therapy (91.33%) than in patients
received SOF plus RBV therapy (85.81%). The most common adverse
events were fatigue, headache, insomnia, nausea, anemia, leukopenia and
thrombocytopenia.
For the third purpose: subgroups of fifty nine patients chronically
infected with HCV were selected and divided into 2 subgroups, in
addition to twenty healthy subjects:-
Subgroup-I: Twenty eight patients with HCV infection received
SOF plus RBV therapy regimen.
Subgroup-II: Thirty one patients with HCV infections received
SOF plus RBV and peg-IFN- -2a therapy regimen. Then biochemical,
hematological parameters, immunological phenotyping, PBMCs
proliferation and apoptosis were detected pre- and post-treatment. While
SOF-based combination therapy improved the liver function, anemia,
leucopenia and thrombocytopenia were detected especially after treatment
with SOF, RBV and peg-IFN- -2a. The current data recorded significant
reduction in the percentage of CD3+CD4+ and CD3+CD8+ cells posttreatment
with either SOF and RBV or SOF, RBV and peg-IFN- -2a as
compared to the baseline. Moreover, SOF-based combination therapy
altered the percentage of CD3-CD8+, CD14+ and CD20+ cells. The
proliferative capacity of PBMCs was significantly decreased in both
regimens, whilst the percentage of apoptotic cells was significantly
augmented. In conclusion, SOF therapy regimens are efficacious in
reducing the HCV load in the present study, with some adverse effects
that include the reduction of the mononuclear cells from the blood
periphery by apoptosis. Usage of SOF, RBV and peg-IFN- -2a regimen
in Egyptian patients with HCV may still remain the standard of care in
the current study. SOF based combination therapy resulted in a high rate
of SVR among patients with HCV in Menoufia Province, Egypt.