Chronic Hepatitis B e Antigen PositiveNCT01581554
Withdrawal of Therapy After Long-Term Antiviral Treatment for Chronic Hepatitis B
An observational study of Chronic Hepatitis B e Antigen Positive and Chronic Hepatitis B e Antigen Negative, run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at 1 site in United States.
Trial summary
Background: Chronic infection with the hepatitis B virus may lead to cirrhosis, liver disease, and cancer of the liver. There is no cure for the infection, but several drugs have been approved to treat it. These drugs can keep the virus levels low. They seem to be safe for short-term use. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Hepatitis B e Antigen Positive, Chronic Hepatitis B e Antigen Negative
- Type of treatment
- Pill or oral medicine
- How many people
- 15 participants
- Where
- 1 siteUnited States
- Study dates
- 18 May 2011to not given
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Liver clinic population and community
Who may be able to join
- Age greater than 18 years and older, male or female
- HBsAg positive for greater than 6 months
- For HBeAg positive subjects, HBeAg loss with or without anti-HBe with a minimum period of antiviral therapy for 48 weeks after HBeAg loss was first detected.
- HBV DNA less than or equal to 500 IU/mL tested on at least 2 occasions over the last 6 months
- Antiviral therapy for a minimum of 4 years
- Baseline ALT or AST within the upper limit of normal.
- Willing and able to provide written, informed consent.
- Subjects must be eligible to enter protocol 07-DK-0207 or be willing to be treated by their local physician should relapse or a hepatitis flare occur.
Who cannot join
- Presence of cirrhosis (Ishak fibrosis score 5 or 6) on any liver biopsy performed within the last 4 years. In the absence of a liver biopsy then any three of the following five variables: platelet count less than or equal to 100,000/mm(3), reversal of ALT/AST ratio, total bilirubin greater than 2.0 mg/dL, splenomegaly on ultrasound and presence of esophageal or gastric varices or portal hypertensive gastropathy on endoscopy
- Any history of decompensated liver disease
- Prior or current therapy with tenofovir or tenofovir plus emtricitabine
- Renal insufficiency defined as a serum creatinine greater than 1.5 mg/dL or an estimated glomerular filtration rate less than or equal to 50 mls/minute using the Cockroft and Gault formula.
- Anti-hepatitis C virus positivity
- Anti-hepatitis D virus positivity
- Anti-human immunodeficiency virus positivity
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
About this study
Official title: Withdrawal of Therapy After Long-Term Oral Nucleos(t)Ide Analogue Treatment in Patients With Chronic Hepatitis B
Background:
- Chronic infection with the hepatitis B virus may lead to cirrhosis, liver disease, and cancer of the liver. There is no cure for the infection, but several drugs have been approved to treat it. These drugs can keep the virus levels low. They seem to be safe for short-term use. But the drugs have not yet been approved for long-term use because some of them can have serious side effects. However, stopping treatment too soon can make the infection worse and may lead to more serious forms of liver disease. Researchers have not been able to determine a when to stop treatment. They want to study people with chronic hepatitis B infection to find out the best time to stop treatment and prevent the disease from causing further liver damage.
Read more
Objectives:
- To study the safety and effectiveness of withdrawing antiviral treatment for chronic hepatitis B after at least 4 years of treatment.
- To determine whether stopping long-term antiviral treatment for chronic hepatitis B makes the infection worse.
Eligibility:
- People who are at least 18 years of age; have been taking antiviral drugs to treat chronic hepatitis B for at least 4 years; and are being evaluated to stop treatment.
Design:
- Those in the study will be screened with a physical exam, medical history, questionnaire, and blood tests. They will remain under the care of their regular doctor during the study.
- They will have an abdominal ultrasound to study scarring in the liver, if they have not had one in the past year.
- Those without detectable levels of the hepatitis B virus in their blood will stop antiviral treatment. They will have monthly blood tests for the first 6 months to check virus levels, and then every 3 months afterward.
- Those whose blood tests show an increase in virus levels will restart antiviral treatment as directed by the study doctors and their personal doctor.
- All those in the study will be monitored until the end of the study.
Read the detailed description
Chronic hepatitis B affects at least 1.5 million Americans and is a major cause of cirrhosis, end-stage liver disease and hepatocellular carcinoma. Five oral antiviral agents have been licensed for use in chronic hepatitis B in the United States. These agents are effective at suppressing viral replication, improving liver disease and reversing cirrhosis. The standard indications for starting antiviral therapy have been developed and widely accepted. Less clear is how long therapy should continue and when and under what conditions should therapy be stopped. Withdrawal after one year of therapy is commonly followed by relapse that in rare instances is severe and can be fatal. With longer courses of therapy, withdrawal of antiviral therapy has been associated with fewer and less severe relapses, but the criteria for stopping treatment are still unclear.
In this study, we propose to withdraw therapy in up to 50 patients with both HBeAg positive and negative chronic hepatitis B who have received a minimum of 4 years of oral nucleoside therapy with a serum HBV DNA level less than 500 IU/ml in the 6 months prior to withdrawal. After an outpatient evaluation, consenting patients will be withdrawn from therapy and followed carefully for presence of symptoms, abnormal liver tests and HBV DNA levels monthly for 6 months and every 3 months thereafter. Patients who relapse will be offered retreatment. Patients without relapse will be followed for at least four years after stopping therapy. The primary endpoint of the study will be the proportion of patients who maintain an HBV DNA < 1,000 IU/ml, and a serum ALT or AST<1.5 times the upper limit of normal one year off therapy. Secondary endpoints will be the proportion of patients who maintain HBeAg loss and clear HBsAg one year off therapy, the number of ALT or AST flares, predictors of maintained virological suppression and HBeAg negativity and the proportion of subjects who require re-initiation of therapy.
- Keywords
- Hepatitis B, Treatment, Nucleoside/Nucleotide Analogue, Natural History
- Medical subject headings
- Hepatitis B
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Patients with HBeAg negative chronic hepatitis B | Patients with HBeAg negative chronic hepatitis B who have received a minimum of 4 years of oral nucleoside therapy with a serum HBV DNA level less than 500 IU/ml in the 6 months prior to withdrawal. | |
| Patients with HBeAG positive chronic hepatitis B | Patients with HBeAg positive chronic hepatitis B who have received a minimum of 4 years of oral nucleoside therapy with a serum HBV DNA level less than 500 IU/ml in the 6 months prior to withdrawal. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of patients who maintain an HBV DNA <1.5 X the upper limit of normal one year off therapy
Proportion of patients who maintain an HBV DNA <1,000 IU/ml, and a serum ALT or AST <1.5 X the upper limit of normal one year off therapy
Measured: One year after stopping therapy
Secondary outcomes (2)
Proportion of patients who maintain HBeAg loss and clear HBsAg one year off therapy
Proportion of patients who maintain HBeAg loss and clear HBsAg
Measured: One year after stopping therapy
Number of ALT or AST flares
Number of ALT or AST flares
Measured: One year after stopping therapy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Apr 2012 (estimated)
- Study start18 May 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Hepatitis B e Antigen PositiveStudies of the same condition, open and under way.
- More trials run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Marc G Ghany, M.D., Principal investigator, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01581554
- Sponsor's protocol ID
- 110151
- Other IDs
- 11-DK-0151
- Status last verified
- 10 Mar 2026
- First submitted
- 19 Apr 2012
- Last updated
- 28 Jul 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Withdrawal of Therapy After Long-Term Oral Nucleos(t)Ide Analogue Treatment in Patients With Chronic Hepatitis B
- ClinicalTrials.gov ID
- NCT01581554
- Acronym / sponsor ID
- 110151
- Keywords
- Hepatitis B, Treatment, Nucleoside/Nucleotide Analogue, Natural History
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)US National Institutes of Health
- Study start
- 18 May 2011 (actual)
- First posted
- 20 Apr 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Background:
- Chronic infection with the hepatitis B virus may lead to cirrhosis, liver disease, and cancer of the liver. There is no cure for the infection, but several drugs have been approved to treat it. These drugs can keep the virus levels low. They seem to be safe for short-term use. But the drugs have not yet been approved for long-term use because some of them can have serious side effects. However, stopping treatment too soon can make the infection worse and may lead to more serious forms of liver disease. Researchers have not been able to determine a when to stop treatment. They want to study people with chronic hepatitis B infection to find out the best time to stop treatment and prevent the disease from causing further liver damage.
Objectives:
- To study the safety and effectiveness of withdrawing antiviral treatment for chronic hepatitis B after at least 4 years of treatment.
- To determine whether stopping long-term antiviral treatment for chronic hepatitis B makes the infection worse.
Eligibility:
- People who are at least 18 years of age; have been taking antiviral drugs to treat chronic hepatitis B for at least 4 years; and are being evaluated to stop treatment.
Design:
- Those in the study will be screened with a physical exam, medical history, questionnaire, and blood tests. They will remain under the care of their regular doctor during the study.
- They will have an abdominal ultrasound to study scarring in the liver, if they have not had one in the past year.
- Those without detectable levels of the hepatitis B virus in their blood will stop antiviral treatment. They will have monthly blood tests for the first 6 months to check virus levels, and then every 3 months afterward.
- Those whose blood tests show an increase in virus levels will restart antiviral treatment as directed by the study doctors and their personal doctor.
- All those in the study will be monitored until the end of the study.
Detailed description
Chronic hepatitis B affects at least 1.5 million Americans and is a major cause of cirrhosis, end-stage liver disease and hepatocellular carcinoma. Five oral antiviral agents have been licensed for use in chronic hepatitis B in the United States. These agents are effective at suppressing viral replication, improving liver disease and reversing cirrhosis. The standard indications for starting antiviral therapy have been developed and widely accepted. Less clear is how long therapy should continue and when and under what conditions should therapy be stopped. Withdrawal after one year of therapy is commonly followed by relapse that in rare instances is severe and can be fatal. With longer courses of therapy, withdrawal of antiviral therapy has been associated with fewer and less severe relapses, but the criteria for stopping treatment are still unclear.
In this study, we propose to withdraw therapy in up to 50 patients with both HBeAg positive and negative chronic hepatitis B who have received a minimum of 4 years of oral nucleoside therapy with a serum HBV DNA level less than 500 IU/ml in the 6 months prior to withdrawal. After an outpatient evaluation, consenting patients will be withdrawn from therapy and followed carefully for presence of symptoms, abnormal liver tests and HBV DNA levels monthly for 6 months and every 3 months thereafter. Patients who relapse will be offered retreatment. Patients without relapse will be followed for at least four years after stopping therapy. The primary endpoint of the study will be the proportion of patients who maintain an HBV DNA < 1,000 IU/ml, and a serum ALT or AST<1.5 times the upper limit of normal one year off therapy. Secondary endpoints will be the proportion of patients who maintain HBeAg loss and clear HBsAg one year off therapy, the number of ALT or AST flares, predictors of maintained virological suppression and HBeAg negativity and the proportion of subjects who require re-initiation of therapy.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Patients with HBeAg negative chronic hepatitis B | – | –Patients with HBeAg negative chronic hepatitis B who have received a minimum of 4 years of oral nucleoside therapy with a serum HBV DNA level less than 500 IU/ml in the 6 months prior to withdrawal. |
| Patients with HBeAG positive chronic hepatitis B | – | –Patients with HBeAg positive chronic hepatitis B who have received a minimum of 4 years of oral nucleoside therapy with a serum HBV DNA level less than 500 IU/ml in the 6 months prior to withdrawal. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Liver clinic population and community
Key inclusion criteria (8 listed)
- Age greater than 18 years and older, male or female
- HBsAg positive for greater than 6 months
- For HBeAg positive subjects, HBeAg loss with or without anti-HBe with a minimum period of antiviral therapy for 48 weeks after HBeAg loss was first detected.
- HBV DNA less than or equal to 500 IU/mL tested on at least 2 occasions over the last 6 months
- Antiviral therapy for a minimum of 4 years
Key exclusion criteria (7 listed)
- Presence of cirrhosis (Ishak fibrosis score 5 or 6) on any liver biopsy performed within the last 4 years. In the absence of a liver biopsy then any three of the following five variables: platelet count less than or equal to 100,000/mm(3), reversal of ALT/AST ratio, total bilirubin greater than 2.0 mg/dL, splenomegaly on ultrasound and presence of esophageal or gastric varices or portal hypertensive gastropathy on endoscopy
- Any history of decompensated liver disease
- Prior or current therapy with tenofovir or tenofovir plus emtricitabine
- Renal insufficiency defined as a serum creatinine greater than 1.5 mg/dL or an estimated glomerular filtration rate less than or equal to 50 mls/minute using the Cockroft and Gault formula.
- Anti-hepatitis C virus positivity
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Proportion of patients who maintain an HBV DNA <1.5 X the upper limit of normal one year off therapy
Time frame: One year after stopping therapy
Proportion of patients who maintain an HBV DNA <1,000 IU/ml, and a serum ALT or AST <1.5 X the upper limit of normal one year off therapy
2 secondary outcomes
Proportion of patients who maintain HBeAg loss and clear HBsAg one year off therapy
Time frame: One year after stopping therapy
Number of ALT or AST flares
Time frame: One year after stopping therapy
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jul 2026.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: No
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Marc G Ghany, M.D. principal investigator
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Chronic Hepatitis B e Antigen Positive and Chronic Hepatitis B e Antigen Negative, run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of patients who maintain an HBV DNA <1.5 X the upper limit of normal one year off therapy (time frame: One year after stopping therapy). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jul 2026.