الفهرس 
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Abstract
Chronic hepatitis C virus (HCV) infection is characterized by a failure of virus-specific CD8+ T cells and expansion of regulatory T cells (T regs) inhibiting antiviral immunity and promotes fibrosis.
During CHC effector T cells become progressively exhausted and exhibit reduced antiviral activity, while Tregs gradually expand and accumulate in the liver. (27)
Direct-acting antiviral agents (DAA) have revolutionized HCV therapy leading to restoration of proliferative HCV-specific CD8+ T cells, however its effect on T regs is still not known.
Methods:
Study group and design
Fifty patients with chronic HCV genotype 4 infection and thirty controls were enrolled into this study. CHC patients were divided into 2 subgroups. Twenty nine patients (group Ia) were treated with SOF (400 mg/d p.o.) plus DCV (60 mg/d p.o.) and twenty one further patients (group Ib) with SOF (400 mg/d p.o), DCV (60 mg/d p.o.) and weight-based RBV (daily dose: 600/1000 mg p.o.).
Treatment duration was 12 weeks in all regimes. Blood samples were collected at day 0 (baseline) and 24 weeks (SVR24) after EOT.
Inclusion criteria:
Inclusion criteria
Patients eligible for the study were 22–62 years old, naive patients suffering from genotype-4 CHC for 6 months or more.
Exclusion criteria
Patients were excluded if they had other forms of liver diseases such as concomitant hepatitis-B virus (HBV) infection, HIV, and schistosomal, autoimmune, or alcoholic hepatitis.
Subjects in the present study underwent:
I-Thorough history taking included personal history with special attention to name, age, sex, residence, marital status, occupation and special habits of medical importance as cigarette smoking and daily alcohol intake and current history of symptoms suggestive of hepatic decompensation
II-Thorough clinical examination included general examination with special emphasis on stigmata of chronic liver disease; careful abdominal examination with special reference to the status of the liver and spleen.
III-Investigations:
1-Laboratory investigations:
I.Complete blood count.
II.Liver function tests.
III.Hepatitis B surface antigen (HBs Ag), anti-HCV and anti-HIV by ELISA.
IV- IFN- γ : Enzyme-Linked Immunosorbent Assay was performed in duplicate according to the technical manual (DuoSet ELISA Development System; R&D Systems).
V.Flow cytometric analysis:
-Four-colour flow cytometry of whole blood was performed using Fluorescence-Activated Cell Sorting (FACS) Caliber flow cytometer (Becton Dickinson) for Flow cytometric analysis of CD4, CD4+CD25+FOXP3+ (Treg), CD8 and PD1/CD8 on peripheral blood.
2-Imaging study:
i. Abdominal ultrasonography.
ii. 2-Fibroscan (Transient elastography)
Results:
Our results show that expression of HCV-specific CD4+ T cells, CD4+CD 25+FOXP3+ (Treg), and PD1/CD8 were significantly higher in chronic HCV patients and its 2 subgroups in comparison to control (mean ±SD, 53.6±4.9, 15.3±3.4, 55.6±4.5, 50.8±4.2, vs control 42.1±1.7, respectively, p value 0.001).
When comparing the changes in the flow cytometric characters of (CD4, Treg, CD8 and PD1/CD8) and IFγ among patients study groups, pre-treatment and post-treatment (24 weeks after treatment), there was no significant changes in the frequency of CD4, with a mean ±SD (53.6±4.9 vs 52.3±4.4 for group I, 55.6±4.5 vs, 54.1±3, for group Ia, 50.8±4.2 vs 49.7±4.6 for group Ib, (with p value 0.100, 0.134 and 0.426 respectively). Percentage of decrease in CD4 was 2.1 for group I, 3.3 for group Ia, 2.1 for group Ib. A significant decrease in the frequency of CD4+CD 25+FOXP3+ (Treg) with a mean ±SD (3±0.7 vs 1.5± 1 for group I, 3±0.6 vs 1.1±0.6 for group Ia and 3.1±0.7 vs 1.9±1.1 for group Ib, p value 0.001 for each. Percentage of decrease was 60.8 for group I, 65.7 for group Ia, 53.3 for group Ib. p value 0.002.). Similarly, significant decrease in the mean of PD1/CD8 was noticed in the CHC at SVR 24 with a mean ±SD (23.2±4 vs 15.1±4.3 for group I, 22.9±4.2 vs 14.3±4.2, for group Ia , 23.5±3.8 vs 16.2±4.2 for group Ib, p value 0.001 for each. Percentage of decrease was 34.5 for group I, 35.5 for group Ia , 27.8 for group Ib. p value 0.154. However, CD8 and INF gamma showed significant increase post treatment, the mean ±SD for CD8 was (16.3±3.4 vs 29.4±3 for group I , 15.3±3.4 vs 28.7±3.3 for group Ia and 17.7±2.9 vs 30.4±2.4 for group Ib, p value 0.001 for each. Percentage of increase was 75.7 for group I, 88.2 for group Ia , 66.7 for group Ib. p value 0.070. Also interferon gamma, a mean ±SD for (218.5±52.3 vs 344.8± 91.7 for group I, 201.9±40.1 vs 316.5±73 for group Ia and 384±101.9 vs 384±101.9 for group Ib, p value 0.001 for each. Percentage of increase was 58.0 for group I, 60.4 for group Ia, 54.1for group Ib. p value 0.930.