Occult Hepatitis BOBINCT04199819
Detecting Occult HBV Infection in Liver Donors Positive for Antibody to Hepatitis B Core Antigen (Anti-HBc)
A study testing entecavir in people with Occult Hepatitis B and Liver Transplant; Complications, run by The University of Hong Kong at 1 site in Hong Kong.
Trial summary
After LT, long-term immunosuppressive therapy is required to prevent organ rejection. Therefore, for organs which may harbour OBI, there is a risk of reactivation which may result in liver graft failure. As a consequence, all patients who receive an anti-HBc positive graft will receive antiviral prophylaxis. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Occult Hepatitis B, Liver Transplant; Complications
- What is being tested?
- entecavir
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 1 siteHong Kong
- Study dates
- 1 Jan 2022to 31 Dec 2023
- Phase
- Interventional
- 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
Who may be able to join
- 1. Patient age ≥18 years undergoing liver transplantation
- 2. Donor HBsAg- and anti-HBc+
Who cannot join
- 1. Recipient of multiple solid organ transplants
- 2. Patient undergoing re-transplantation
Trial locations and contacts
1 site in 1 country.
Hong Kong1 site, 1 recruiting
- Recruiting
The University of Hong Kong
Hong Kong
James Fung, MD, 22553830, jfung@gastro.hk
Man-Fung Yuen, DSc, MD, PhD, 22553989, mfyuen@hku.hk
About this study
Official title: The Use of Novel Hepatitis B Virus (HBV) Biomarkers to Detect Occult HBV Infection in Liver Donors Positive for Antibody to Hepatitis B Core Antigen (Anti-HBc) in Liver Transplantation
After LT, long-term immunosuppressive therapy is required to prevent organ rejection. Therefore, for organs which may harbour OBI, there is a risk of reactivation which may result in liver graft failure. As a consequence, all patients who receive an anti-HBc positive graft will receive antiviral prophylaxis. Currently, all such patients will be commenced on life-long entecavir, which is highly effective in preventing reactivation.2 One major disadvantage of using such a blanket approach is that a significant proportion of anti-HBc donors may not actually have underlying occult HBV infection, and recipients of such grafts may not require lifelong antiviral therapy. Current markers such as HBsAg and HBV DNA are not sensitive enough to detect the presence of OBI.
This is the first trial proposed to look at the efficacy of these novel HBV biomarkers in identifying occult HBV infection when used in combination, and to identify patients who will not need long term antiviral prophylaxis.
Read the detailed description
Liver transplantation (LT) is potential curative for those with liver failure or hepatocellular carcinoma. In Hong Kong, where HBV infection remains endemic, chronic HBV (CHB) infection remains the leading indication for LT. Due to the low rate of organ donation, hepatitis B surface antigen (HBsAg) negative donors who are anti-HBc positive are frequently used. There is potential for anti-HBc positive donors to harbor OBI, defined as the presence of liver and/or serum HBV DNA without serological evidence of chronic infection (HBsAg negative).1 Hence, there is a risk of transmitting HBV infection when these grafts are transplanted to HBsAg negative recipients (de novo HBV infection). Nonetheless, anti-HBc positive donors represent an important source of organs in HBV endemic area, including Hong Kong, with a high prevalence rate (37%) of HBsAg negative but anti-HBc positive population.
After LT, long-term immunosuppressive therapy is required to prevent organ rejection. Therefore, for organs which may harbour OBI, there is a risk of reactivation which may result in liver graft failure. As a consequence, all patients who receive an anti-HBc positive graft will receive antiviral prophylaxis. Currently, all such patients will be commenced on life-long entecavir, which is highly effective in preventing reactivation.2 One major disadvantage of using such a blanket approach is that a significant proportion of anti-HBc donors may not actually have underlying occult HBV infection, and recipients of such grafts may not require lifelong antiviral therapy. Current markers such as HBsAg and HBV DNA are not sensitive enough to detect the presence of OBI.
More recently a panel of novel HBV biomarkers have emerged.3,4 These include quantification of anti-HBc, HBV RNA, hepatitis B core-related antigen (HBcrAg), and intrahepatic covalently closed circular DNA (cccDNA) levels. Some of these markers have been associated with OBI, and may predict HBV reactivation for immunosuppressed patients.5,6
This is the first trial proposed to look at the efficacy of these novel HBV biomarkers in identifying occult HBV infection when used in combination, and to identify patients who will not need long term antiviral prophylaxis
- Being tested
- entecavir
- Keywords
- occult hepatitis b, liver transplantation, novel biomarkers
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
entecavirDrug
Also called antiviral therapy
Patients with evidence of OBI, as characterized by any one positive biomarker (serum HBV DNA, serum HBV RNA, serum HBcrAg, intrahepatic HBV DNA, intrahepatic cccDNA) in either the donor or recipient, will be commenced on life-long oral nucleos(t)ide analog therapy as part of their routine antiviral prophylaxis.
| Study group | Role | What they receive |
|---|---|---|
| HBsAg-negative recipients | Other | Recipients who are HBsAg-negative will undergo a panel of test to detect HBV viral markers. In addition, real-time PCR will be used to determine the presence of intrahepatic HBV DNA and cccDNA on the explant histology. Patients with evidence of OBI, as characterized by any one positive biomarker (serum HBV DNA, serum HBV RNA, serum HBcrAg, intrahepatic HBV DNA, intrahepatic cccDNA) in either the donor or recipient, will be commenced on life-long oral nucleos(t)ide analog therapy as part of their routine antiviral prophylaxis. For those without evidence of OBI, that is, negative for all biomarkers, no antiviral prophylaxis will be given. Receives: Drug: entecavir |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of HBsAg-negative recipients of an anti-HBc+ graft needing antiviral therapy
Proportion of HBsAg-negative recipients of an anti-HBc+ graft needing antiviral therapy
Measured: 2 years
Secondary outcomes (1)
Prevalence of occult hepatitis B infection in HBsAg-/anti-HBc+ donors
Prevalence of occult hepatitis B infection in HBsAg-/anti-HBc+ donors
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Dec 2019
- Study start1 Jan 2022
- Primary completion31 Dec 2023 (estimated)
- Study completion31 Dec 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Occult 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- The University of Hong Kong
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, James Yan Yue Fung, The University of Hong Kong
- Investigators
- James Fung, MD, Principal investigator, The University of Hong Kong
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04199819
- Sponsor's protocol ID
- occult HBV infection 01
- Acronym
- OBI
- Status last verified
- May 2022
- First submitted
- 3 Dec 2019
- Last updated
- 23 May 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 May 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Use of Novel Hepatitis B Virus (HBV) Biomarkers to Detect Occult HBV Infection in Liver Donors Positive for Antibody to Hepatitis B Core Antigen (Anti-HBc) in Liver Transplantation
- ClinicalTrials.gov ID
- NCT04199819
- Acronym / sponsor ID
- OBI / occult HBV infection 01
- Keywords
- occult hepatitis b, liver transplantation, novel biomarkers
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- The University of Hong KongUniversity, hospital or other
- Study start
- 1 Jan 2022 (actual)
- Primary completion
- 31 Dec 2023 (estimated)
- Study completion
- 31 Dec 2023 (estimated)
- First posted
- 16 Dec 2019 (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.
After LT, long-term immunosuppressive therapy is required to prevent organ rejection. Therefore, for organs which may harbour OBI, there is a risk of reactivation which may result in liver graft failure. As a consequence, all patients who receive an anti-HBc positive graft will receive antiviral prophylaxis. Currently, all such patients will be commenced on life-long entecavir, which is highly effective in preventing reactivation.2 One major disadvantage of using such a blanket approach is that a significant proportion of anti-HBc donors may not actually have underlying occult HBV infection, and recipients of such grafts may not require lifelong antiviral therapy. Current markers such as HBsAg and HBV DNA are not sensitive enough to detect the presence of OBI.
This is the first trial proposed to look at the efficacy of these novel HBV biomarkers in identifying occult HBV infection when used in combination, and to identify patients who will not need long term antiviral prophylaxis.
Detailed description
Liver transplantation (LT) is potential curative for those with liver failure or hepatocellular carcinoma. In Hong Kong, where HBV infection remains endemic, chronic HBV (CHB) infection remains the leading indication for LT. Due to the low rate of organ donation, hepatitis B surface antigen (HBsAg) negative donors who are anti-HBc positive are frequently used. There is potential for anti-HBc positive donors to harbor OBI, defined as the presence of liver and/or serum HBV DNA without serological evidence of chronic infection (HBsAg negative).1 Hence, there is a risk of transmitting HBV infection when these grafts are transplanted to HBsAg negative recipients (de novo HBV infection). Nonetheless, anti-HBc positive donors represent an important source of organs in HBV endemic area, including Hong Kong, with a high prevalence rate (37%) of HBsAg negative but anti-HBc positive population.
After LT, long-term immunosuppressive therapy is required to prevent organ rejection. Therefore, for organs which may harbour OBI, there is a risk of reactivation which may result in liver graft failure. As a consequence, all patients who receive an anti-HBc positive graft will receive antiviral prophylaxis. Currently, all such patients will be commenced on life-long entecavir, which is highly effective in preventing reactivation.2 One major disadvantage of using such a blanket approach is that a significant proportion of anti-HBc donors may not actually have underlying occult HBV infection, and recipients of such grafts may not require lifelong antiviral therapy. Current markers such as HBsAg and HBV DNA are not sensitive enough to detect the presence of OBI.
More recently a panel of novel HBV biomarkers have emerged.3,4 These include quantification of anti-HBc, HBV RNA, hepatitis B core-related antigen (HBcrAg), and intrahepatic covalently closed circular DNA (cccDNA) levels. Some of these markers have been associated with OBI, and may predict HBV reactivation for immunosuppressed patients.5,6
This is the first trial proposed to look at the efficacy of these novel HBV biomarkers in identifying occult HBV infection when used in combination, and to identify patients who will not need long term antiviral prophylaxis
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| HBsAg-negative recipients | Other | Drug: entecavirRecipients who are HBsAg-negative will undergo a panel of test to detect HBV viral markers. In addition, real-time PCR will be used to determine the presence of intrahepatic HBV DNA and cccDNA on the explant histology. Patients with evidence of OBI, as characterized by any one positive biomarker (serum HBV DNA, serum HBV RNA, serum HBcrAg, intrahepatic HBV DNA, intrahepatic cccDNA) in either the donor or recipient, will be commenced on life-long oral nucleos(t)ide analog therapy as part of their routine antiviral prophylaxis. For those without evidence of OBI, that is, negative for all biomarkers, no antiviral prophylaxis will be given. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- 1. Patient age ≥18 years undergoing liver transplantation
- 2. Donor HBsAg- and anti-HBc+
Key exclusion criteria (2 listed)
- 1. Recipient of multiple solid organ transplants
- 2. Patient undergoing re-transplantation
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: antiviral therapyPatients with evidence of OBI, as characterized by any one positive biomarker (serum HBV DNA, serum HBV RNA, serum HBcrAg, intrahepatic HBV DNA, intrahepatic cccDNA) in either the donor or recipient, will be commenced on life-long oral nucleos(t)ide analog therapy as part of their routine antiviral prophylaxis. | Drug | HBsAg-negative recipients |
Primary outcome
Proportion of HBsAg-negative recipients of an anti-HBc+ graft needing antiviral therapy
Time frame: 2 years
Proportion of HBsAg-negative recipients of an anti-HBc+ graft needing antiviral therapy
1 secondary outcome
Prevalence of occult hepatitis B infection in HBsAg-/anti-HBc+ donors
Time frame: 2 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 May 2022.
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Occult Hepatitis B Virus Infection and HBV Reactivation After Switching to Long Acting Therapy in Patients With HIV-1
HBV (Hepatitis B Virus), HIV Infection
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.
James Fung, MD 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?
A study testing entecavir in people with Occult Hepatitis B and Liver Transplant; Complications, 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 2 inclusion and 2 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: status not confirmed, as of the sponsor's last update on 23 May 2022. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact James Fung, MD (+852 22553830, jfung@gastro.hk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of HBsAg-negative recipients of an anti-HBc+ graft needing antiviral therapy (time frame: 2 years). 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 23 May 2022.