Non-Alcoholic Fatty Liver DiseaseNCT02985450
A Prospective Study of HBV Immunity and HBV Vaccination in Patients With NAFLD in Canada
An observational study of Non-Alcoholic Fatty Liver Disease and Hepatitis B, run by University of Calgary at 1 site in Canada.
Trial summary
(1) Due to missed childhood vaccination programs, the majority of adult patients with NAFLD in Canada do not have immunity to hepatitis B. (2) Adults with NAFLD who receive the HBV vaccine have reduced immunogenic responses in the setting of obesity (i.e., protective anti-HBs titres). Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Non-Alcoholic Fatty Liver Disease, Hepatitis B, Vaccine Reaction
- What is being tested?
- Engerix-B
- Type of treatment
- Vaccines
- How many people
- 82 participants
- Where
- 1 siteCanada
- Study dates
- Aug 2016to Jan 2021
- Phase
- Observational
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 to 60 years
- All sexes
- No healthy volunteers
- Adult
Study population: NAFLD patients will be recruited from large tertiary liver clinics in Canada
Who may be able to join
- Subjects 18-60 years of age, who provide signed informed consent
- Diagnosis of NAFLD/NASH according to expert assessment (by imaging, TE, abnormal lab tests and/or liver biopsy)
- No evidence of prior infection or immunity to hepatitis B (negative HBsAg, anti-HBs, anti-HBc).
Who cannot join
- Subjects < 18 years of age,
- Subjects who refused vaccination
- Have documented immunity / prior exposure to hepatitis B (i.e., positive for ant-HBs, anti-HBc, HBsAg)
- Pregnancy
- HIV-positive
- Decompensated cirrhosis (i.e., Child-Pugh Class B or C) due to impact on immune response.
- Subjects >60 y will be excluded, due to effect of age and reduced response to HBV vaccination.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Prospective Study of Hepatitis B Virus (HBV) Immunity and Hepatitis B Vaccination in Patients With Non Alcoholic Fatty Liver Disease (NAFLD) in Canada
(1) Due to missed childhood vaccination programs, the majority of adult patients with NAFLD in Canada do not have immunity to hepatitis B. (2) Adults with NAFLD who receive the HBV vaccine have reduced immunogenic responses in the setting of obesity (i.e., protective anti-HBs titres). Aims: (1) To determine the sero-prevalence of immunity against hepatitis B in a cohort of prospectively evaluated adult NAFLD patients. (2) To prospectively determine HBV vaccine responses (anti-HBs titres) in adult NAFLD patients.
Read the detailed description
The hepatitis B virus (HBV) is truly a global human pathogen that affects at least 2 billion people worldwide including ~240 million chronic hepatitis B (CHB) carriers that are at risk for end-stage liver disease. The diagnosis of CHB is confirmed by the persistence of the HBV surface antigen (HBsAg) in serum for >6 months. However, a latent form of HBV infection known as occult hepatitis B infection (OBI) characterized by low-level viremia (i.e., HBV DNA < 200 IU/ml) despite undetectable serum HBsAg has been described with unclear clinical consequences.
A safe and effective HBV vaccine has been available for ~3 decades and consists of recombinant HBsAg which contains the major viral antigenic epitopes and induces a protective neutralizing antibody to HBsAg (anti-HBs) response in >85% of children vaccinated. Canada is a low HBV-endemic region and in Alberta, and Ontario, public health uses maternal screening for HBsAg to identify babies at-risk for CHB. Thus, all infants born to HBsAg (+) mothers are given passive-active immunoprophylaxis with hepatitis B immune globulin (HBIG) and the HBV vaccine within 12 hours of birth, as well as 2 doses at ~2 and ~6 months of age. Testing of the infants for anti-HBs is recommended at 9 months to ensure immunity. In the late 1990's, a universal HBV childhood vaccination program was initiated in all Canadian provinces and jurisdictions. In Alberta and in Ontario, school-age children are scheduled to receive the 3-dose HBV vaccine series in grade 5. However there remain a significant proportion of adult Canadians (i.e., born before 1985) who missed childhood vaccination programs. Although current guidelines recommend that certain high-risk populations receive hepatitis B immunization, appropriate identification and compliance is generally much lower in adults compared to children.
According to the most recent Canadian Association for the Study of Liver Disease guidelines, all adults with diabetes, as well as all patients with chronic liver disease should receive the hepatitis B vaccine. The basis for these recommendations are two-fold, (1) diabetics may be at risk of blood-borne virus (BBV) exposure through contact with contaminated blood glucose monitoring devices and (2) diabetic patients are at increased risk of the metabolic syndrome and the development of non-alcoholic fatty liver disease (NAFLD). The improvement in blood glucose monitoring devices, and increased knowledge has reduced the risk of HBV exposure in patients with diabetes. Further, the investigators' initial seroepidemiological survey of acute HBV outbreaks in Alberta revealed a decreasing prevalence in diabetic patients. Therefore the main incentive for HBV vaccination in diabetics is due to the concomitant risk of the metabolic syndrome and advanced liver disease due to NAFLD. There is limited data on HBV vaccination in NAFLD patients. Further studies are required in a North American adult (Canadian population).
The investigators propose that adults with NAFLD should undergo comprehensive screening for hepatitis B immunogenicity, in addition to screening for infection, and catch up or booster vaccinations should be administered to non-immunized patients with confirmatory immunity testing thereafter.
- Being tested
- Engerix-B
- Medical subject headings
- Non-alcoholic Fatty Liver Disease, Hepatitis B
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Engerix-BBiological
Also called Twinrix
Hepatitis B Vaccine
What is being measured
The primary outcome is the main question the study is designed to answer.
Anti-HBs Titres (IU/L)
to determine how NAFLD-associated metabolic risk factors and liver inflammation / fibrosis affects vaccine response
Measured: 1 month after completion of the vaccine series
Assessment of Memory T Cells and HBsAg-specific-proliferation of CD3 + CD4+ TH Cells
to determine how NAFLD-associated metabolic risk factors and liver inflammation / fibrosis affects vaccine response. Fresh (or cryopreserved in 4 patients) PBMC (~106) were labeled with 1 μM carboxyfluorescein-diacetate-succinimidyl-ester. Labeled PBMC were stimulated with 5 μg HBsAg) in RPMI 1640 with 10% FBS and 2mmol/L glutamine. Anti-CD3 (1 μg/mL) and anti-CD28 (5 μg/mL) stimulated cells served as a positive control.
Unstimulated DMSO-treated cells were used as negative controls. Cells were cultured in triplicates and plates incubated at 37 °C with 5% CO2 for ~8 days. Cell proliferation was assessed on day 8. SI was calculated as % CFSE low cells in stimulated cells / % CFSE low cells in the unstimulated control46. SI> 3 was considered positive for HBsAg-specific proliferation. Cells were stained using the memory T-cell panel and analyzed by flow-cytometry
Measured: 1 month after completion of the vaccine series
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Dec 2016 (estimated)
- Study startAug 2016
- Primary completionJan 2021
- Study completionJan 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Non-Alcoholic Fatty Liver DiseaseStudies of the same condition, open and under way.
- More trials run by University of CalgaryThe 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
- 82 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Calgary
- Sponsor type
- University, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR), GlaxoSmithKline
- Responsible party
- Sponsor
- Investigators
- Carla Coffin, Principal investigator, University of Calgary
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02985450
- Sponsor's protocol ID
- REB16-0274
- Status last verified
- Jun 2018
- First submitted
- 1 Dec 2016
- Last updated
- 3 Nov 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective Study of Hepatitis B Virus (HBV) Immunity and Hepatitis B Vaccination in Patients With Non Alcoholic Fatty Liver Disease (NAFLD) in Canada
- ClinicalTrials.gov ID
- NCT02985450
- Acronym / sponsor ID
- REB16-0274
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 82 participants (actual)
- Lead sponsor
- University of CalgaryUniversity, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR), GlaxoSmithKline
- Study start
- Aug 2016
- Primary completion
- Jan 2021 (actual)
- Study completion
- Jan 2021 (actual)
- First posted
- 7 Dec 2016 (estimated)
- Results
- Posted 3 Nov 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
(1) Due to missed childhood vaccination programs, the majority of adult patients with NAFLD in Canada do not have immunity to hepatitis B. (2) Adults with NAFLD who receive the HBV vaccine have reduced immunogenic responses in the setting of obesity (i.e., protective anti-HBs titres). Aims: (1) To determine the sero-prevalence of immunity against hepatitis B in a cohort of prospectively evaluated adult NAFLD patients. (2) To prospectively determine HBV vaccine responses (anti-HBs titres) in adult NAFLD patients.
Detailed description
The hepatitis B virus (HBV) is truly a global human pathogen that affects at least 2 billion people worldwide including ~240 million chronic hepatitis B (CHB) carriers that are at risk for end-stage liver disease. The diagnosis of CHB is confirmed by the persistence of the HBV surface antigen (HBsAg) in serum for >6 months. However, a latent form of HBV infection known as occult hepatitis B infection (OBI) characterized by low-level viremia (i.e., HBV DNA < 200 IU/ml) despite undetectable serum HBsAg has been described with unclear clinical consequences.
A safe and effective HBV vaccine has been available for ~3 decades and consists of recombinant HBsAg which contains the major viral antigenic epitopes and induces a protective neutralizing antibody to HBsAg (anti-HBs) response in >85% of children vaccinated. Canada is a low HBV-endemic region and in Alberta, and Ontario, public health uses maternal screening for HBsAg to identify babies at-risk for CHB. Thus, all infants born to HBsAg (+) mothers are given passive-active immunoprophylaxis with hepatitis B immune globulin (HBIG) and the HBV vaccine within 12 hours of birth, as well as 2 doses at ~2 and ~6 months of age. Testing of the infants for anti-HBs is recommended at 9 months to ensure immunity. In the late 1990's, a universal HBV childhood vaccination program was initiated in all Canadian provinces and jurisdictions. In Alberta and in Ontario, school-age children are scheduled to receive the 3-dose HBV vaccine series in grade 5. However there remain a significant proportion of adult Canadians (i.e., born before 1985) who missed childhood vaccination programs. Although current guidelines recommend that certain high-risk populations receive hepatitis B immunization, appropriate identification and compliance is generally much lower in adults compared to children.
According to the most recent Canadian Association for the Study of Liver Disease guidelines, all adults with diabetes, as well as all patients with chronic liver disease should receive the hepatitis B vaccine. The basis for these recommendations are two-fold, (1) diabetics may be at risk of blood-borne virus (BBV) exposure through contact with contaminated blood glucose monitoring devices and (2) diabetic patients are at increased risk of the metabolic syndrome and the development of non-alcoholic fatty liver disease (NAFLD). The improvement in blood glucose monitoring devices, and increased knowledge has reduced the risk of HBV exposure in patients with diabetes. Further, the investigators' initial seroepidemiological survey of acute HBV outbreaks in Alberta revealed a decreasing prevalence in diabetic patients. Therefore the main incentive for HBV vaccination in diabetics is due to the concomitant risk of the metabolic syndrome and advanced liver disease due to NAFLD. There is limited data on HBV vaccination in NAFLD patients. Further studies are required in a North American adult (Canadian population).
The investigators propose that adults with NAFLD should undergo comprehensive screening for hepatitis B immunogenicity, in addition to screening for infection, and catch up or booster vaccinations should be administered to non-immunized patients with confirmatory immunity testing thereafter.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
- Study population
- NAFLD patients will be recruited from large tertiary liver clinics in Canada
Key inclusion criteria (3 listed)
- Subjects 18-60 years of age, who provide signed informed consent
- Diagnosis of NAFLD/NASH according to expert assessment (by imaging, TE, abnormal lab tests and/or liver biopsy)
- No evidence of prior infection or immunity to hepatitis B (negative HBsAg, anti-HBs, anti-HBc).
Key exclusion criteria (7 listed)
- Subjects < 18 years of age,
- Subjects who refused vaccination
- Have documented immunity / prior exposure to hepatitis B (i.e., positive for ant-HBs, anti-HBc, HBsAg)
- Pregnancy
- HIV-positive
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 |
|---|---|---|
| Engerix-BAlso: TwinrixHepatitis B Vaccine | Biological | – |
Primary outcome
Anti-HBs Titres (IU/L)
Time frame: 1 month after completion of the vaccine series
to determine how NAFLD-associated metabolic risk factors and liver inflammation / fibrosis affects vaccine response
Assessment of Memory T Cells and HBsAg-specific-proliferation of CD3 + CD4+ TH Cells
Time frame: 1 month after completion of the vaccine series
to determine how NAFLD-associated metabolic risk factors and liver inflammation / fibrosis affects vaccine response. Fresh (or cryopreserved in 4 patients) PBMC (~106) were labeled with 1 μM carboxyfluorescein-diacetate-succinimidyl-ester. Labeled PBMC were stimulated with 5 μg HBsAg) in RPMI 1640 with 10% FBS and 2mmol/L glutamine. Anti-CD3 (1 μg/mL) and anti-CD28 (5 μg/mL) stimulated cells served as a positive control. Unstimulated DMSO-treated cells were used as negative controls. Cells were cultured in triplicates and plates incubated at 37 °C with 5% CO2 for ~8 days. Cell proliferation was assessed on day 8. SI was calculated as % CFSE low cells in stimulated cells / % CFSE low cells in the unstimulated control46. SI> 3 was considered positive for HBsAg-specific proliferation. Cells were stained using the memory T-cell panel and analyzed by flow-cytometry
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Nov 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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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.
Carla Coffin principal investigator
University of Calgary
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 Non-Alcoholic Fatty Liver Disease and Hepatitis B, run by University of Calgary at 1 site in Canada.
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 3 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 3 Nov 2021. 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 Canada. 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?
Yes. Results are posted in the registry (first posted 3 Nov 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Anti-HBs Titres (IU/L) (time frame: 1 month after completion of the vaccine series). 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 3 Nov 2021.