الفهرس 
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Abstract
Hepatitis B infection affects 300 million people and is one of the most common causes of chronic liver disease and hepatocellular carcinoma (HCC) worldwide. Egypt is considered one of the moderate HBV-infected arenas worldwide, with a 2-8% viremic prevalence and about 3.3 million chronically infected people.
Chronic HBV infection is associated with immune dysregulation, particularly impaired T-cell responses. However, the factors and mechanisms determining dysfunctional immune response and viral persistence in chronic HBV remain obscure.
Moreover, several studies documented the ability of HBV to evade immunity by several immune alteration mechanisms. One of these suggested mechanisms is the accumulation of undifferentiated immature myeloid cells known as myeloid derived suppressor cells (MDSCs) which have been extensively studied in the field of cancer research as potent immunosuppressant cells that play a major role in cancer immune evasion. However, little is known about the significance of MDSCs in chronic HBV patients.
The European Association for the Study of the Liver (EASL) and the American association for the study of liver diseases (AASLD-IDSA) approved the use of interferon alpha and nucleos(t)ide analogs (NAs) as two treatment options for chronic HBV-infected patients. Interferon alpha is an immunomodulator drug given by injection and includes pegylated interferon (Pegasys) and interferon alfa-2b (intron A). Nucleos(t)ide analogues (NAs) are antiviral agents administrated orally and can be divided into first and second-line treatments. First-line NAs treatments include tenofovir disoproxil (Viread300 mg), tenofovir alafenamide (Vemlidy 25 mg), and entecavir (Baraclude 0.5 - 1mg). Second-line NAs treatments include telbivudine (Tyzeka or Sebivo 600mg), adefovir dipivoxil (Hepsera 10mg), and lamivudine (Zeffix 100mg). These antiviral treatments have been shown to delay the progression of cirrhosis, improve survival and reduce the need for liver transplantation. However, they face many problems, including viral resistance, relapse, and the need for lifelong administration. They also can not eliminate all forms of HBV or the risk of hepatocellular carcinoma in most chronic hepatitis B-infected patients. These obstacles facing current HBV control have increased the demand for further investigation into the disease environment and host immunity that allows the persistence of the chronic infection.
In the present study, we aimed at investigating the role of MDSCs in chronic HBV infection and the impact of entecavir treatment on HBV eradication and MDSCs accumulation. We included twenty untreated chronic HBV patients, twenty patients treated with entecavir (0.5 mg/day), and fifteen healthy controls. We observed a statistically significant increase in the frequency of total MDSCs and M-MDSCs in treated and untreated chronic HBV patients compared to healthy individuals (P<0.001). In contrast, no significant difference was found between the three groups regarding G-MDSC (p=0.612). We also recognized a significant increase in M-MDSCs frequency in HBeAg-positive patients compared to that in HBeAg-negative patients in both treated and untreated chronic HBV patient groups (p=0.039, p=0.041, respectively), which positively correlated with the level of HBeAg. Moreover, we found a significant decrease in serum IFN-γ concentration in untreated patients compared with treated patients and healthy individuals (P<0.001). No statistical difference was found between treated patients and healthy controls regarding IFN-γ concentration (p=0.493). A significant positive correlation also was obtained between alanine transaminase, aspartate transaminase, HBeAg, HBsAg, HBV-DNA, and the frequency of MDSCs and M-MDSCs in both treated and untreated chronic HBV patient groups. We also found a significant negative correlation between MDSC frequency and IFN-ɣ in both groups of chronic HBV patients.