The Changes of CD4+T Cells Frequency and Function During Antiviral Therapy

Study Overview
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Brief Summary
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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, CD4+T Cells are the main effector cells in adaptive immune response. This study was aimed at investigating the changes of CD4+T Cells frequency and function, and the expression of costimulatory molecules during Peg-IFN-αand nucleoside analog(ue) therapy.Meanwhile, the investigators want to verify whether Peg IFN - alpha suppressed the virus and the reduction of virus led to the recovery of CD4+T Cells function, or Peg IFN - alpha enhanced CD4+T Cells function which gave rise to the decline of the virus.

Detailed Description
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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, CD4+T Cells are the main effector cells in adaptive 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 CD4+T Cells in the case of hepatitis and the function enhancement of CD4+T Cells during Peg-IFN-α therapy. This study was aimed at investigating the changes of CD4+T Cells frequency and function, and the expression of costimulatory molecules during Peg-IFN-αand nucleoside analog(ue) therapy.Meanwhile, the investigators want to explore whether the decline of HBsAg and HBeAg resulted in recovery of CD4+T cells function, or recovery of CD4+T Cells function led to the decrease of HBsAg and HBeAg. Several studies demonstrated that HBsAg and HBeAg could damage CD4+T cells function, and the loss of HBsAg and HBeAg led to recovery of CD4+T cells function.

Official Title
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The Changes of CD4+T Cells Frequency and Function During Pegylated Interferon α-2a and Nucleoside Analogues Treatment in Patients With Chronic Hepatitis B

Conditions
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Chronic Hepatitis B Infection

Intervention / Treatment
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* Drug: Peginterferon Alfa-2a


Participation Criteria
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Eligibility Criteria
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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

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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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 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. | Drug: Peginterferon Alfa-2a<br>* patients untreated in immune-active phase were given subcutaneous injection of Peginterferon Alfa-2a with starting dose of 180 mg/weekly in experiment group.<br>* Other names: Peg-IFN-α;|
| No Intervention: control group<br>patients who were untreated ever in immune-active phase took Nucleoside Analogues for maintenance treatment. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the changes of CD4+T Cells | the changes of CD4+T cells%, CD62L+T cells%, CD62L-T cells%, CD62L+/ CD62L-, CD69+CD4+T cells%, CD69MFI, CD69ABC, IFN-AR2+CD4+T cells%, IFNAR2MFI, IFNAR2ABC will be measured by flow cytometry during Pegylated Interferon α-2a and Nucleoside Analogues treatment every 3 months. | at baseline and at treatment week 12, 24. | 

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 markers | at baseline and at treatment 12, 24, 36, 48 weeks | 
| the change of ALT levels(U/L) | the curative effect of antiviral therapy will be evaluated by ALT levels | at baseline and at treatment 12, 24, 36, 48 weeks | 
| the change of AST levels(U/L) | the curative effect of antiviral therapy will be evaluated by AST levels | at baseline and at treatment 12, 24, 36, 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, CD4+T Cells, Pegylated Interferon α-2a, Nucleoside Analogues