The Changes of Plasmacytoid Dendritic Cells Frequency and Function During Antiviral Therapy

• Conditions: Chronic Hepatitis B Infection

• Registration Number: NCT03210467
• Lead Sponsor: Beijing Ditan Hospital

Brief Summary

Pegylated interferon(IFN) α-2a(Peg-IFN-α) not only inhibit viral replication, but also play an important role in immune regulation, while entecavir(ETV) drugs only inhibit viral replication. In hepatitis B infection, Plasmacytoid Dendritic Cells（pDCs） are the main effector cells in early antiviral innate immune response. This study was aimed at investigating the changes of pDCs frequency and function, and the expression of costimulatory molecules CD86(Cluster of Differentiation antigen 86) during Peg-IFN-αand entecavir(ETV) therapy.Meanwhile, investigators want to verify whether Peg-IFN-α suppressed the virus and the reduction of virus led to the recovery of pDCs function, or Peg-IFN-α enhanced pDCs function which gave rise to the decline of the virus.

Detailed Description

Pegylated interferon α-2a(Peg-IFN-α)and entecavir(ETV) drugs can inhibit viral replication , but Peg-IFN-α also play an important role in immune regulation . In hepatitis B infection, Plasmacytoid Dendritic Cells (pDCs) 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 entecavir(ETV) drugs, which may be related to the functional activation of pDCs in the case of hepatitis and the function enhancement of pDCs during Peg-IFN-α therapy. This study was aimed at investigating the changes of pDCs frequency and function, and the expression of costimulatory molecules CD86 during Peg-IFN-αandentecavir(ETV) therapy.Meanwhile,investigators want to explore whether the decline of HBsAg and HBeAg resulted in recovery of CD86+pDC function, or recovery of CD86 + pDC function led to the decrease of HBsAg and HBeAg. Several studies demonstrated that HBsAg and HBeAg could damage pDC function, and the loss of HBsAg and HBeAg led to recovery of CD86+pDC function.

Study Timeline

• Study Start: 2016-01
• Study First Submitted: 2017-06-30
• Status Verified: 2017-07
• Study First Submitted QC: 2017-07-04
• Last Update Submitted: 2017-07-04
• Study First Posted: 2017-07-07
• Last Update Posted: 2017-07-07
• Primary Completion: 2017-12
• Study Completion: 2017-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 120

Inclusion Criteria

• HBsAg and HBeAg positive for more than 6 months, HBVDNA detectable with ALT(alanine aminotransferase) 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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
the change of pDC%	after treatment 24 weeks	The host immune function will be evaluated by pDC. pDC% will be measured by flow cytometry after Pegylated Interferon α-2a and entecavir(ETV) Treatment 24 weeks.
the change of mean fluorescence intensity of costimulatory molecules CD86(CD86-MFI)	after treatment 24 weeks	mean fluorescence intensity of costimulatory molecules CD86(CD86-MFI) will be measured by flow cytometry after Pegylated Interferon α-2a and entecavir(ETV) Treatment 24 weeks.
the change of absolute molecular counting of costimulatory molecules CD86	after treatment 24 weeks	absolute molecular counting of costimulatory molecules CD86 (CD86-ABC) will be measured by flow cytometry after Pegylated Interferon α-2a and entecavir(ETV) Treatment 24 weeks.
the change of CD86+pDC%	after treatment 24 weeks	CD86+pDC% will be measured by flow cytometry after Pegylated Interferon α-2a and entecavir(ETV) Treatment 24 weeks.

Secondary Outcome Measures

Name	Time	Method
the change of HBsAg levels (IU/ML)	after treatment 48 weeks	the curative effect of antiviral therapy will be evaluated by HBsAg levels
the change of HBVDNA levels (IU/ML)	after treatment 48 weeks	the curative effect of antiviral therapy will be evaluated by HBV DNA levels
the change of ALT levels(U/L)	after treatment 48 weeks	the curative effect of antiviral therapy will be evaluated by ALT levels
the change of HBeAg levels (IU/ML)	after treatment 48 weeks	the curative effect of antiviral therapy will be evaluated by HBeAg levels
the change of AST levels(U/L)	after treatment 48 weeks	the curative effect of antiviral therapy will be evaluated by AST levels

Trial Locations

Locations (1)

Beijing Ditan hospital,Capital Medical University; 🇨🇳 Beijing, Beijing, China