The Changes of Natural Killer Cells Frequency and Function During Antiviral Therapy

The Changes of Natural Killer Cells Frequency and Function During Pegylated Interferon α-2a and Nucleoside Analogues Treatment in Patients With Chronic Hepatitis B.

Pegylated interferon α-2a(Peg-IFN-α) not only inhibit viral replication, but also play an important role in immune regulation, while Nucleoside analog(ue) drugs only inhibit viral replication. In hepatitis B infection, NKs are the main effector cells in early antiviral innate immune response. This study was aimed at investigating the changes of NKs frequency and function, and the expression of costimulatory molecules during Peg-IFN-αand nucleoside analog(ue) therapy.Meanwhile, investigators want to verify whether Peg IFN - alpha suppressed the virus and the reduction of virus led to the recovery of NKs function, or Peg IFN - alpha enhanced NKs function which gave rise to the decline of the virus.

Pegylated interferon α-2a(Peg-IFN-α)and Nucleoside analog(ue) drugs can inhibit viral replication , but Peg-IFN-α also play an important role in immune regulation . In hepatitis B infection, NKs are the main effector cells in early antiviral innate immune response.Peg-IFN-α recommended as the first-line treatment has a higher chance to achieve HBeAg seroconversion and even HBsAg disappearance than nucleoside analog(ue) drugs, which may be related to the functional activation of pDCs in the case of hepatitis and the function enhancement of NKs during Peg-IFN-α therapy. This study was aimed at investigating the changes of NKs frequency and function, and the expression of costimulatory molecules during Peg-IFN-αand nucleoside analog(ue) therapy.Meanwhile, investigators want to explore whether the decline of HBsAg and HBeAg resulted in recovery of NKs function, or recovery of NKs function led to the decrease of HBsAg and HBeAg. Several studies demonstrated that HBsAg and HBeAg could damage NKs function, and the loss of HBsAg and HBeAg led to recovery of NKs function.

hepatitis B virus, Chronic Hepatitis B Infection, Pegylated Interferon α-2a, Nucleoside Analogues, Natural Killer Cells

patients who were untreated ever in immune-active phase were given subcutaneous injection of Peginterferon Alfa-2a with starting dose of 180 mg/weekly till 48 weeks.

patients who were untreated ever in immune-active phase took Nucleoside Analogues for maintenance treatment.

patients untreated in immune-active phase were given subcutaneous injection of Peginterferon Alfa-2a with starting dose of 180 mg/weekly in experiment group.

the changes of NK%,CD56bri/NK%,CD56dim/NK%,IFNAR2+NK%,IFNAR2MFI,NKp46+/NK%,NKp46dim/NK%,NKp46high/NK%, NKp46MFI,and NKp46ABC will be measured by flow cytometry during Pegylated Interferon α-2a and Nucleoside Analogues Treatment

the curative effect of antiviral therapy will be evaluated by HBV markers and HBV DNA levels and liver function

the curative effect of antiviral therapy will be evaluated by HBV markers and HBV DNA levels and liver function

the curative effect of antiviral therapy will be evaluated by HBV markers and HBV DNA levels and liver function

Inclusion Criteria: HBsAg and HBeAg positive for more than 6 months, HBV DNA detectable with ALT level abnormal lasted for three months and at least time190 IU/L or liver puncture biopsy demonstrated apparent inflammation, never treated before enrolled. Exclusion Criteria: Active consumption of alcohol and/or drugs Co-infection with human immunodeficiency virus, hepatitis C virus, or hepatitis D virus History of autoimmune hepatitis Psychiatric disease Evidence of neoplastic diseases of the liver

Cao W, Li M, Zhang L, Lu Y, Wu S, Shen G, Chang M, Liu R, Gao Y, Hao H, Hu L, Yi W, Pan CQ, Xie Y. The Characteristics of Natural Killer Cells in Chronic Hepatitis B Patients Who Received PEGylated-Interferon versus Entecavir Therapy. Biomed Res Int. 2021 Jan 25;2021:2178143. doi: 10.1155/2021/2178143. eCollection 2021.