Discontinuation of Antiviral Therapy as a Strategy to Cure Hepatitis B

Study Overview
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Brief Summary
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Cirrhosis or cancer of the liver caused by hepatitis B virus (HBV) are major global health problems. Chronic HBV infection has become more common in Sweden with immigration. The risk of cancer and the availability of effective antivirals has led to more and more people receiving long-term treatment with antiviral drugs. The disadvantages of this treatment are that it does not have a defined duration and that it very rarely leads to the cure. Several published studies suggest that a large proportion of patients who discontinue antiviral therapy after at least three years may achieve lasting cure of the infection or at least do not need to resume treatment. The mechanism of this effect is not known, but it is thought to be due to the fact that the immune response, which is activated when the amount of virus increases after the end of treatment, becomes more effective in eradicating infected liver cells than it was before starting treatment. As a consequence of these findings updated guidelines for treatment of hepatitis B state that for patients that have received nucleoside analogue treatment for > 3 years, discontinuation is an accepted therapeutic alternative. The purpose of the planned study is to investigate the results of discontinued treatment, in terms of clinical outcome as well as immunological and virological mechanisms. The aim is to include 120 patients at four regional infectious diseases clinics (in Gothenburg, Borås, Skövde and Trollhättan), of which 90 will be randomized to discontinue and 30 to continue antiviral treatment. Blood samples will be taken regularly to monitor the outcome and for detailed studies of viral antigens and nucleic acid in the blood and for specific analyzes of the cells of the immune system. The goal is to understand why the discontinued treatment in some patients activates an effective immune response and how such an effect can be predicted even before or early after the treatment is stopped.

Official Title
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Discontinuation of Antiviral Therapy as a Strategy to Cure Hepatitis B

Conditions
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Hepatitis B, Chronic

Intervention / Treatment
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* Other: Stopping


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Nucleoside analogue treatment for HBeAg-negative chronic hepatitis B for at least 36 months. Exclusion Criteria: Liver cirrhosis or liver cancer. Co-infection with HCV, HDV or HIV. Inability to understand study information and give informed consent

Ages Eligible for Study
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Minimum Age: 18 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: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Stopping<br>Discontinuation of nucleoside analogue treatment | Other: Stopping<br>* Discontinuation of nucleoside analogue<br>|
| No Intervention: Continue<br>Treatment with nucleoside analogue continued | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HBsAg seronegativisation | Serum HBsAg becoming negative | 1 year | 
| HBsAg seronegativisation | Serum HBsAg becoming negative | 2 years | 
| HBsAg reduction | HBsAg reduction by > 1 log IU/mL | 1 year | 
| HBsAg reduction | HBsAg reduction by > 1 log IU/mL | 2 years | 
| Clinical responder | Sustained HBV DNA < 2000 IU/mL and normal ALT | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HBV-specific T cell activation | Activation of HBV-specific T-cell responses, induced by incubating whole blood with HBV-core and HBsAg derived peptides for 48 hours, and investigated by measuring gamma interferon, chemokine and cytokine levels in plasma after centrifugation of the stimulated whole blood. | After 16 weeks |