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

Study Overview
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Brief Summary
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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
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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.

Official Title
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The Changes of Plasmacytoid Dendritic Cells Frequency and Function During Pegylated Interferon α-2a and Entecavir(ETV) Treatment in Patients With Chronic Hepatitis B.

Conditions
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Chronic Hepatitis B Infection

Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| experimental group<br>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. | |
| control group<br>patients who were untreated ever in immune-active phase took entecavir(ETV) for maintenance treatment. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the change of pDC% | 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. | after treatment 24 weeks | 
| the change of CD86+pDC% | CD86+pDC% will be measured by flow cytometry after Pegylated Interferon α-2a and entecavir(ETV) Treatment 24 weeks. | after treatment 24 weeks | 
| the change of mean fluorescence intensity of costimulatory molecules CD86(CD86-MFI) | 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. | after treatment 24 weeks | 
| the change of absolute molecular counting of costimulatory molecules CD86 | 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. | after treatment 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the change of HBVDNA levels (IU/ML) | the curative effect of antiviral therapy will be evaluated by HBV DNA levels | after treatment 48 weeks | 
| the change of ALT levels(U/L) | the curative effect of antiviral therapy will be evaluated by ALT levels | after treatment 48 weeks | 
| the change of AST levels(U/L) | the curative effect of antiviral therapy will be evaluated by AST levels | after treatment 48 weeks | 
| the change of HBsAg levels (IU/ML) | the curative effect of antiviral therapy will be evaluated by HBsAg levels | after treatment 48 weeks | 
| the change of HBeAg levels (IU/ML) | the curative effect of antiviral therapy will be evaluated by HBeAg levels | after treatment 48 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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chronic hepatitis B, hepatitis B virus, Pegylated Interferon α-2a, entecavir, Plasmacytoid Dendritic Cells