الفهرس 
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Abstract
Chronic hepatitis C (CHC) is the persistence of hepatitis C virus (HCV) RNA for more than six months. CHC is recognized as a global health concern. In Egypt, the CHC infection has become widespread, leading to a rise in the number of individuals suffering from liver cirrhosis, portal hypertension, and HCC in recent years. Cirrhosis is a long-term liver disease characterized by the transformation of typical liver structure into aberrant nodules. Compensated liver cirrhosis often presents with no symptoms or only a few mild symptoms and can persist for an uncertain amount of time. This is then followed by decompensated liver cirrhosis
MDSCs are a diverse population of myeloid progenitors produced from bone marrow that do not develop into mature myeloid cells. MDSCs are identified in the peripheral blood by expressing CD33 and CD11b myeloid markers but lack mature myeloid cell markers such as HLA-DR. The incidence of MDSCs is closely related to disease progression and clinical stage. The key feature used to define MDSCs is their immunosuppressive nature.
In this study, the main aim was to investigate the relationship between circulatory MDSCs frequency and the progression of cirrhosis in CHC virus patients with different stages of cirrhosis in comparison to a control group using flow cytometry to detect MDSCs cells in the peripheral blood of the subjects.
The present study included 55 individuals: group (A): twenty patients diagnosed with chronic HCV without cirrhosis with a fibrosis index (FIB-4) score less than 1.45. group (B): twenty patients diagnosed with chronic HCV with cirrhosis (group B), with a FIB-4 score of more than 3.25, and fifteen age and sex-matched healthy individuals as the negative control group. Twenty patients diagnosed with chronic HCV with cirrhosis (group B), with FIB-4 scores more than 3.25, and fifteen age and sex-matched healthy individuals as a negative control group.
Patients were recruited from the Tropical Medicine outpatient clinic, Alexandria University. All patients were asked to volunteer freely for the study and informed written consents were gathered before their inclusion in the study protocol, according to the ethical guidelines of the Medical Research Institute (MRI), Alexandria University.
All participants in this study were subjected to thorough history taking, clinical diagnosis, ultrasonography, laboratory investigations (complete blood count, liver enzymes, albumin, bilirubin, INR, blood urea, and serum creatinine and AFP), and immunological investigations (MDSCs CD33+ CD11b+ HLA-DR-). Peripheral blood samples were collected from all subjects under study. Flow cytometry was used to measure frequencies of MDSCs (CD33+ CD11b+and HLA-DR-) cells, and results were expressed as a percentage of cells (%), using appropriate mouse Anti-Human monoclonal Abs (anti-CD33, anti-CD11b, and anti-HLA-DR).
The study results between the total patients and control showed a statistically significant difference (p=0.001*).In the case of the three groups, the results of MDSCs showed statistically significant differences (p<0.001*). from the present study results, we can conclude that CHC patients have increased frequencies of MDSCs cells compared to the control group, which indicates that HCV can regulate MDSCs differentiation due to the cellular activation in chronic inflammation.
Also, our results showed that MDSCs frequency was affected by cirrhosis, MDSCs were measured in subgroups, and results of MDSCs showed statistically significant differences (p<0.001*). MDSCs frequencies were higher in group (A) than in group (B) and controls. So, the frequency of MDSCs among treated cirrhotic patients could be considered partially recovered but not completely normalized after achieving DAA.
Conclusions and Recommendations
- The association between MDSCs and progression of liver cirrhosis is evidenced
- Further studies should be conducted the type of MDSCs as possible predictive marker for response to HCV treatment.
- Longer follow-up periods are needed to elucidate the relation between MDSCs and DAA’s treatment.
- Studying host, immunological, and viral factors contributing to their persistence and their postulated contribution to HCC is crucial.
- Studying this issue among patients with advanced fibrosis and cirrhosis is recommended.