Clinical and Basic Research of ETV Plus GM-CSF in Chronic Hepatitis B Patients

Study Overview
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Brief Summary
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Previous studies indicated that Granulocyte Macrophage-colony Stimulating Factor (GM-CSF) could improve survival rate in patients with acute liver failure and obtain higher HBsAg seroconversion rate when in combination with peg-interferon for chronic hepatitis B (CHB) patients. In this study, investigators will study the clinical effect of entecavir (ETV) plus GM-CSF in patients with CHB compared to ETV monotherapy.

Detailed Description
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Antiviral treatment plays critical role in treatment of chronic HBV infection. Entecavir, an nucleos(t)ide analogs (NA) targeting the viral polymerase, is widely used in China as the first line drug in antiviral treatment for CHB patients. The sustained suppression of serum HBV DNA to undetectable level has been proven to be associated with the prevention of progression of liver disease and inhibition of the development of hepatocellular carcinoma. According to data published, a rate about 70% HBVDNA undetectable could be reached after 1 year therapy. However, the rate of HBsAg loss is very low about 0% to 1%. Granulocyte-macrophage colony-stimulating factor(GM-CSF) is an important cytokine for the generation and propagation of antigen-presenting cells and for priming a cellular immune response. It increases the production of macrophage precursors and, in turn,enhances the T-helper cell (Th cell)-mediated cytotoxicity and regulates the tumoricidal cytokines. Previous studies indicated that when combined with IFN in patients with chronic HBV infection, it increased the therapeutic efficacy of the latter. Recent studies showed that GM-CSF benefit patients with acute liver failure. In this study, entecavir (ETV) plus GM-CSF would be used in patients with CHB compared to ETV monotherapy. Primary objective of the study is to see if there is significant improvement in HBsAg loss, rates of HBeAg loss and HBV undetectable are also to be observed. Function of NK cell from the patients enrolled will be measured during the therapy.

Official Title
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Clinical and Basic Research of Relationship Between Hepatitis B Virus Quasi-Species Evolution and Function of Natural Killer Cells With Antiviral Therapy Response in Chronic Hepatitis B Patients

Conditions
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Hepatitis B, Chronic

Intervention / Treatment
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* Drug: Granulocyte Macrophage-colony Stimulating Factor
* Drug: Entecavir


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: HBsAg positive for more than 6 months HBeAg positive ALT≥80U/L or inflammation score ≥2 of histological examination Exclusion Criteria: History of drug allergy to GM-CSF coinfection with HCV, HIV, HAV, HEV liver cirrhosis or CHILD score >7 diagnosis of hepatocellular carcinoma or AFP>100ng/ml Allergic thrombocytopenic purpura

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ETV+GM-CSF<br>Entecavir (ETV) plus Granulocyte Macrophage-colony Stimulating Factor (GM-CSF). ETV was given 0.5mg/d, oral; GM-CSF was given 100ug, the 3th, 4th, 5th day at week1, 4, 12, 24, 48, subcutaneous injection. | Drug: Granulocyte Macrophage-colony Stimulating Factor<br>* The intervention drug was used as an immunomodulator in order to improve rates of HBsAg loss and HBeAg loss.<br>* Other names: GM-CSF;Drug: Entecavir<br>* Antiviral drug for hepatitis b virus (HBV)<br>* Other names: ETV;|
| Active Comparator: ETV monotherapy<br>As standard antiviral therapy, Entecavir was given 0.5mg/d, oral. | Drug: Entecavir<br>* Antiviral drug for hepatitis b virus (HBV)<br>* Other names: ETV;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of HBsAg loss |  | 48 weeks after therapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of HBeAg loss |  | 48 weeks after therapy | 
| HBVDNA undetectable rate |  | 48 weeks after therapy | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic hepatitis B, antiviral treatment