الفهرس 
Acknowledgment
Aim of the workOnly 14 pages are availabe for public view
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Abstract
There are strong evidences that Treg cells and their cytokines may play an important role in the induction of tolerance in the liver and progression of HCV infection. The aim of this work was to quantify percentages of circulating regulatory T (Treg) cells in human peripheral blood in different stages of hepatitis C chronically infected patients, HCV patients received DAA therapy showing SVR (sustained viral response) and healthy controls and to estimate IL35 level in serum samples of all research groups to declare if there is a possible relationship between Tregs percentage & IL35 serum level and various patterns of HCV viral persistence, complications with cirrhosis and HCC and treatment responses with DAA . Our study included 88 subjects in total, 70 of them were chronic HCV patients presented to outpatient clinic of Tropical Medicine Department in Assiut University Hospital from December 2017 to September 2018. The other 18 subjects were healthy controls. They were divided into 5 groups: group I included 18 healthy controls, group II included 18 patients with sustained viral response (SVR), group III included 16 chronic HCV-infected patients naïve to treatment (Naïve CHC), group IV included 18 HCV-infected patients complicated with cirrhosis, group V included 18 HCV-infected patients complicated with cirrhosis and HCC. The control subjects were attending blood bank of Assiut University Hospital during the study period. They were negative for known serologic markers of hepatitis (B & C) including hepatitis B surface antigen and antibodies to Hepatitis C virus. All patients were subjected to history taking, clinical examination, liver function tests and abdominal ultrasonography. Blood samples were obtained from patients and controls to quantify the percentages of 1st day circulating Treg cells by Flowcytometry. Blood samples were centrifuged at 5000 r.p.m. and the supernatant was stored at -20°c used for measurement of serum IL-35 level by ELISA. This study showed that the highest percentage of Treg cells in the CD4+CD25high cell population was seen in peripheral blood of HCV HCC patients (Mean value ± SD , 96.96 ± 4.22%) followed by HCV LC patients (90.9 ± 5.49%) followed by Naïve CHC patients (88.36 ± 3.81) then patients with SVR (82.91 ± 7.61%) and lastly controls (73.53 ± 20.68%).There was a high significant difference in the percentage of circulating Treg cells between HCV HCC and HCV LC patients (P < 0.001**), HCV HCC and Naïve CHC patients (P < 0.001**) and between HCV HCC patients and controls (P < 0.001**) but there was no significant difference between Naïve CHC and patients with SVR (P= 0.095). serum IL-35 concentration was the highest in HCV HCC patients (Mean ± SD : 64.86 ± 30.84) followed by HCV LC patients (52.5 ± 15.14) followed by Naïve CHC patients (40.25 ± 24.77) then patients with SVR (29.11± 9.27) with the least mean value detected in Controls (19.11± 4.62)but no correlation was found between Treg cells and IL-35 level in all research groups Conclusion Patients with chronic HCV infection have a higher percentage of Tregs in their peripheral blood compared with healthy controls that may contribute to viral persistence. However, it was not possible to say that Tregs were definitely the cause of immune suppression in CHC patients. In addition, CD4⁺CD25⁺highFoxp3⁺ T cells may have close relation with the course and progression of the disease as was evidenced by their highest level in HCV HCC and lowest level in controls and patients with SVR. Serum IL-35 concentration was the highest in HCV HCC patients compared to other groups which may link this novel cytokine to the progression of the disease either alone or linked to the activity of Tregs. Taken all together, the higher percentage of Tregs and IL35 level in peripheral blood of HCV LC or HCC compared with those of healthy controls and patients with SVR may contribute to viral persistence and progression of HCV infection.