Clinical trial NCT03208998: The Changes of Natural Killer Cells Frequency and Function During Antiviral Therapy
Official title: The Changes of Natural Killer Cells Frequency and Function During Pegylated Interferon α-2a and Nucleoside Analogues Treatment in Patients With Chronic Hepatitis B.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Chronic Hepatitis B Infection
Keywords: hepatitis B virus
Chronic Hepatitis B Infection
Pegylated Interferon α-2a
Nucleoside Analogues
Natural Killer Cells
Lead sponsor: Beijing Ditan Hospital
Sponsor class: OTHER
First posted: 2017-07-06
Enrollment: 100
Sex: ALL
Minimum age (years): 20
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: the changes of Natural Killer Cells
timeFrame: at baseline and at treatment week 12, 24
Secondary outcomes:
measure: the change of HBVDNA levels (IU/ML)
timeFrame: at baseline and at treatment 12, 24, 36, 48 weeks
measure: the change of ALT levels(U/L)
timeFrame: at baseline and at treatment 12, 24, 36, 48 weeks
measure: the change of AST levels(U/L)
timeFrame: at baseline and at treatment 12, 24, 36, 48 weeks
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Ditan hospital,Capital Medical University
state: Beijing
Study officials:
References:
citation: 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.