Chronic Hepatitis bNCT04431245
Stopping Antiviral Treatment in Chronic Hepatitis B
An observational study of Chronic Hepatitis b, run by The University of Hong Kong at 1 site in Hong Kong.
Trial summary
Chronic hepatitis B (CHB) infection affected 292 million individuals in the world, translating to about 3.9% of global prevalence. Up to 40% of patients with CHB will develop liver-related complications. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Hepatitis b
- What is being tested?
- Entecavir
- Type of treatment
- Pill or oral medicine
- How many people
- 54 participants
- Where
- 1 siteHong Kong
- Study dates
- 1 Jun 2021to 31 Dec 2026
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
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: HBeAg-negative non-cirrhotic CHB patients on long-term NA ≥3 years will be identified. Only those who have undetectable serum HBV DNA by the conventional assay (Cobas Taqman, Roche Diagnostics, Branchburg, NJ) which has a lower limit of detection (LLOD) of 10 IU/mL will be recruited. CHB patients were treated with potent oral NA (i.e. tenofovir or entecavir). All recruited patients will have written informed consent for participation of study. Patients with HCC, cirrhosis, history of liver transplantation, or on immunosuppressants, will be excluded.
Who may be able to join
- HBeAg-negative
- non-cirrhotic
- on long-term NA ≥3 years (entecavir or tenofovir)
- undetectable serum HBV DNA
Who cannot join
- HCC, cirrhosis, history of liver transplantation, or on immunosuppressants,
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Stopping Antiviral Treatment and Subsequent Flare in Chronic Hepatitis B Infection: Immunological and Virological Profiling
Chronic hepatitis B (CHB) infection affected 292 million individuals in the world, translating to about 3.9% of global prevalence. Up to 40% of patients with CHB will develop liver-related complications. Many patients require long-term oral antiviral therapy since off-treatment sustained virological control can only be achieved in a minority of patients. It is uncommon for patients taking long-term antivirals to be able to stop the treatment if favorable factors are not present. Those include low viral load, long enough duration of treatment, and absence of cirrhosis. Some studies have found that inducing a mild flare is beneficial for achieving functional cure in chronic hepatitis B infection. There is lack of data in the immunological and virological profile in patients who stop their long-term antiviral therapy, and in those who developed flare after treatment cessation.
Read the detailed description
Chronic hepatitis B infection (CHB) affected 292 million individuals in the world in 2016 according to the Polaris Observatory estimation, translating to about 3.9% global prevalence. Up to 40% of patients with CHB will develop liver-related complications and there were 890,000 deaths from these complications in 2015. Current antiviral therapy is aimed to achieve effective viral suppression, biochemical remission, histological improvement, and risk reductions in liver-related complications including cirrhosis and liver cancer. Many patients require long-term oral nucleos(t)ide analogues (NA) since off-treatment sustained virological control can only be achieved in a minority of patients. For HBeAg-negative CHB patients, variable rates of durable virological response were observed after cessation of NA. Only a small proportion of HBeAg-negative Asian patients (<10%) can successfully stop NA without virological breakthrough, compared to more than 60% of Caucasian patients maintaining a durable virologic response and even HBsAg seroclearance in up to 30%. Therefore, current guidelines in general recommend indefinite duration of NA therapy in HBeAg-negative patients, unless guaranteed close monitoring could be provided after cessation of NA in suitable subjects. Favourable factors predictive of partial cure include lower baseline HBV DNA, lower HBsAg titre or hepatitis B core-related antigen at NA cessation and longer duration of consolidation therapy in HBeAg-negative patients. There is lack of data in the immunological and virological profile in patients who stop their long-term NA, and in those who developed post-NA cessation flare.
The investigators aim to study the virological and immunological profile in patients who stopped long-term NA therapy, with or without post-NA cessation flare. In addition, the investigators would like to investigate the effect of mild flare after monitored NA-cessation on subsequent virological activity and HBsAg seroclearance.
- Conditions
- Chronic Hepatitis b
- Being tested
- Entecavir
- Keywords
- functional cure, antiviral therapy, nucleoside analogue
- Medical subject headings
- Hepatitis B, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EntecavirDrug
Also called oral nucleoside analogue
Study subjects will stop the antiviral therapy. Patients will be closely monitored every 6-8 weeks for virological flare and/or biochemical flare.
| Study group | Role | What they receive |
|---|---|---|
| Stop antiviral | HBeAg-negative non-cirrhotic CHB patients on long-term NA ≥3 years will be identified. Only those who have undetectable serum HBV DNA by the conventional assay (Cobas Taqman, Roche Diagnostics, Branchburg, NJ) which has a lower limit of detection (LLOD) of 10 IU/mL will be recruited. CHB patients were treated with potent oral NA (i.e. tenofovir or entecavir). All recruited patients will have written informed consent for participation of study. Patients with HCC, cirrhosis, history of liver transplantation, or on immunosuppressants, will be excluded. Receives: Drug: Entecavir |
What is being measured
The primary outcome is the main question the study is designed to answer.
The immunological profile in CHB patients who stopped antiviral therapy
The investigators will perform analysis for the immunological aspects for these patients
Measured: 24 months
The virological profile in CHB patients who stopped antiviral therapy
The investigators will perform analysis for the virological aspects for these patients
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jun 2020
- Study start1 Jun 2021
- Primary completion31 Aug 2025
- Study completion31 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Hepatitis bStudies of the same condition, open and under way.
- More trials run by The University of Hong KongThe 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
- Case only
- Time perspective
- Prospective
- Enrolment
- 54 participants (estimated)
Sponsor and investigators
- Lead sponsor
- The University of Hong Kong
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Professor Yuen Man Fung, The University of Hong Kong
- Investigators
- Man-Fung Yuen, DSc, MD, PhD, Principal investigator, The University of Hong Kong
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04431245
- Sponsor's protocol ID
- HKUUW20-425
- Status last verified
- Feb 2026
- First submitted
- 31 May 2020
- Last updated
- 10 Feb 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Individual participant's personal identification data will be only accessed by the PI and study team.
Study at a glance
From the registry record, last updated by the sponsor on 10 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Stopping Antiviral Treatment and Subsequent Flare in Chronic Hepatitis B Infection: Immunological and Virological Profiling
- ClinicalTrials.gov ID
- NCT04431245
- Acronym / sponsor ID
- HKUUW20-425
- Conditions
- Chronic Hepatitis b
- Keywords
- functional cure, antiviral therapy, nucleoside analogue
- Study type
- Observational
- Recruitment status
- Active, not recruiting
- Enrolment
- 54 participants (estimated)
- Lead sponsor
- The University of Hong KongUniversity, hospital or other
- Study start
- 1 Jun 2021 (actual)
- Primary completion
- 31 Aug 2025 (actual)
- Study completion
- 31 Dec 2026 (estimated)
- First posted
- 16 Jun 2020 (actual)
- 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.
Chronic hepatitis B (CHB) infection affected 292 million individuals in the world, translating to about 3.9% of global prevalence. Up to 40% of patients with CHB will develop liver-related complications. Many patients require long-term oral antiviral therapy since off-treatment sustained virological control can only be achieved in a minority of patients. It is uncommon for patients taking long-term antivirals to be able to stop the treatment if favorable factors are not present. Those include low viral load, long enough duration of treatment, and absence of cirrhosis. Some studies have found that inducing a mild flare is beneficial for achieving functional cure in chronic hepatitis B infection. There is lack of data in the immunological and virological profile in patients who stop their long-term antiviral therapy, and in those who developed flare after treatment cessation.
Detailed description
Chronic hepatitis B infection (CHB) affected 292 million individuals in the world in 2016 according to the Polaris Observatory estimation, translating to about 3.9% global prevalence. Up to 40% of patients with CHB will develop liver-related complications and there were 890,000 deaths from these complications in 2015. Current antiviral therapy is aimed to achieve effective viral suppression, biochemical remission, histological improvement, and risk reductions in liver-related complications including cirrhosis and liver cancer. Many patients require long-term oral nucleos(t)ide analogues (NA) since off-treatment sustained virological control can only be achieved in a minority of patients. For HBeAg-negative CHB patients, variable rates of durable virological response were observed after cessation of NA. Only a small proportion of HBeAg-negative Asian patients (<10%) can successfully stop NA without virological breakthrough, compared to more than 60% of Caucasian patients maintaining a durable virologic response and even HBsAg seroclearance in up to 30%. Therefore, current guidelines in general recommend indefinite duration of NA therapy in HBeAg-negative patients, unless guaranteed close monitoring could be provided after cessation of NA in suitable subjects. Favourable factors predictive of partial cure include lower baseline HBV DNA, lower HBsAg titre or hepatitis B core-related antigen at NA cessation and longer duration of consolidation therapy in HBeAg-negative patients. There is lack of data in the immunological and virological profile in patients who stop their long-term NA, and in those who developed post-NA cessation flare.
The investigators aim to study the virological and immunological profile in patients who stopped long-term NA therapy, with or without post-NA cessation flare. In addition, the investigators would like to investigate the effect of mild flare after monitored NA-cessation on subsequent virological activity and HBsAg seroclearance.
Study design
- Observational model
- Case only
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Stop antiviral | – | Drug: EntecavirHBeAg-negative non-cirrhotic CHB patients on long-term NA ≥3 years will be identified. Only those who have undetectable serum HBV DNA by the conventional assay (Cobas Taqman, Roche Diagnostics, Branchburg, NJ) which has a lower limit of detection (LLOD) of 10 IU/mL will be recruited. CHB patients were treated with potent oral NA (i.e. tenofovir or entecavir). All recruited patients will have written informed consent for participation of study. Patients with HCC, cirrhosis, history of liver transplantation, or on immunosuppressants, will be excluded. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- HBeAg-negative non-cirrhotic CHB patients on long-term NA ≥3 years will be identified. Only those who have undetectable serum HBV DNA by the conventional assay (Cobas Taqman, Roche Diagnostics, Branchburg, NJ) which has a lower limit of detection (LLOD) of 10 IU/mL will be recruited. CHB patients were treated with potent oral NA (i.e. tenofovir or entecavir). All recruited patients will have written informed consent for participation of study. Patients with HCC, cirrhosis, history of liver transplantation, or on immunosuppressants, will be excluded.
Key inclusion criteria (4 listed)
- HBeAg-negative
- non-cirrhotic
- on long-term NA ≥3 years (entecavir or tenofovir)
- undetectable serum HBV DNA
Key exclusion criteria (1 listed)
- HCC, cirrhosis, history of liver transplantation, or on immunosuppressants,
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EntecavirAlso: oral nucleoside analogueStudy subjects will stop the antiviral therapy. Patients will be closely monitored every 6-8 weeks for virological flare and/or biochemical flare. | Drug | Stop antiviral |
Primary outcome
The immunological profile in CHB patients who stopped antiviral therapy
Time frame: 24 months
The investigators will perform analysis for the immunological aspects for these patients
The virological profile in CHB patients who stopped antiviral therapy
Time frame: 24 months
The investigators will perform analysis for the virological aspects for these patients
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Feb 2026.
- Individual participant dataSharing planned: No. Individual participant's personal identification data will be only accessed by the PI and study team.
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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.
Man-Fung Yuen, DSc, MD, PhD principal investigator
The University of Hong Kong
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, run by The University of Hong Kong at 1 site in Hong Kong.
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 4 inclusion and 1 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: under way, not looking for participants, as of the sponsor's last update on 10 Feb 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 Hong Kong. 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?
This study is still under way. Results are not available in the source record yet.
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?
The immunological profile in CHB patients who stopped antiviral therapy (time frame: 24 months). The study lists 2 primary outcomes in all. 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 10 Feb 2026.