Clinical and Basic Research of ETV Plus GM-CSF in Chronic Hepatitis B Patients
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
N/A |
Detailed Description
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: ETV+GM-CSF 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
The intervention drug was used as an immunomodulator in order to improve rates of HBsAg loss and HBeAg loss.
Other Names:
Drug: Entecavir
Antiviral drug for hepatitis b virus (HBV)
Other Names:
|
| Active Comparator: ETV monotherapy As standard antiviral therapy, Entecavir was given 0.5mg/d, oral. |
Drug: Entecavir
Antiviral drug for hepatitis b virus (HBV)
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Rate of HBsAg loss [48 weeks after therapy]
Secondary Outcome Measures
- Rate of HBeAg loss [48 weeks after therapy]
- HBVDNA undetectable rate [48 weeks after therapy]
Eligibility Criteria
Criteria
Inclusion Criteria:
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HBsAg positive for more than 6 months
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HBeAg positive
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ALT≥80U/L or inflammation score ≥2 of histological examination
Exclusion Criteria:
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History of drug allergy to GM-CSF
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coinfection with HCV, HIV, HAV, HEV
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liver cirrhosis or CHILD score >7
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diagnosis of hepatocellular carcinoma or AFP>100ng/ml
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Allergic thrombocytopenic purpura
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | 302 Military Hospital | Beijing | Beijing | China | 100039 |
Sponsors and Collaborators
- Beijing 302 Hospital
Investigators
- Study Director: Ping Zhao, Director, 302 Military Hospital, Beijing, China
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 首发2014-2-5033