Hepatitis BHBRNNCT01263587
Hepatitis B Research Network Adult Cohort Study
An observational study of Hepatitis B, run by University of Pittsburgh at 21 sites in 2 countries.
Trial summary
The primary purpose of this study is to describe participants with hepatitis B virus (HBV) infection and identify factors that may cause the disease to activate or worsen. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hepatitis B
- How many people
- 2,051 participants
- Where
- 21 sitesin 2 countries
- Study dates
- Dec 2010to 9 Jun 2021
- 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: The study population will be recruited from multi-site clinical centers in the United States and Canada including primary care hospitals and community centers.
Who may be able to join
- Written informed consent
- At least 18 years of age
- Hepatitis B surface antigen (HBsAg) positive and either:
- Pregnant
- Anti-Hepatitis D positive
- Diagnosed with acute Hepatitis B infection or experiencing a hepatitis flare
- Immune tolerant or immune active phenotype
- Potentially eligible for the Immune Regulation and Costimulation in Natural History of Chronic Hepatitis B ancillary study (NCT01298037).
Who cannot join
- Hepatic decompensation
- Hepatocellular carcinoma (HCC)
- Liver transplantation
- Current hepatitis B antiviral treatment (except pregnant women and patients who are anti-HDV positive)
- Known Human immunodeficiency virus (HIV) co-infection (patients with Hepatitis D (HDV) or Hepatitis C (HCV) co-infection are not excluded).
- Medical or social condition which in the opinion of the investigator will interfere with or prevent follow-up per protocol
- Unable or unwilling to return for follow-up visits
Trial locations and contacts
21 sites in 2 countries.
21 sites in 2 countries
United States20 sites
University of Michigan Health System
Ann Arbor, Michigan, 48109
NIH Clinical Center
Bethesda, Maryland, 20892
Massachusetts General Hospital
Boston, Massachusetts, 02114
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215
University of North Carolina
Chapel Hill, North Carolina, 27599
Baylor University Medical Center
Dallas, Texas, 75246
University of Texas Southwestern
Dallas, Texas, 75390
Duke University Medical Center
Durham, North Carolina, 27710
The Queen's Medial Center
Honolulu, Hawaii, 96813
Cedars Sinai Medical Center
Los Angeles, California, 90048
University of California Los Angeles
Los Angeles, California, 90095
University of Minnesota
Minneapolis, Minnesota, 55455
Virginia Commonwealth University Medical Center
Richmond, Virginia, 23298
Mayo Clinic
Rochester, Minnesota, 55905
California Pacific Medical Center
San Francisco, California, 94115
University of California San Francisco
San Francisco, California, 94143
Virginia Mason Medical Center
Seattle, Washington, 98101
Harborview Medical Center
Seattle, Washington, 98104
Saint Louis University
St Louis, Missouri, 63104
Washington University
St Louis, Missouri, 63108
About this study
Official title: Observational Study of Persons With Hepatitis B Virus Infection in North America (Cohort Study)
The primary purpose of this study is to describe participants with hepatitis B virus (HBV) infection and identify factors that may cause the disease to activate or worsen.
Read the detailed description
Aims
- Primary Aim:
- To describe participants with hepatitis B virus (HBV) infection in a prospective cohort in the United States (US) and Canada and identify predictors of disease activation and progression
- Secondary Aims:
- To describe clinical, virological, and immunological characteristics of participants with HBV in the US and Canada
- To evaluate changes in HBV infection status and quantitative hepatitis B surface antigen (HBsAg) levels and factors associated with those changes
- To verify whether a baseline HBsAg below 1,000 IU/mL and HBV DNA below 1,000 IU/mL is an accurate predictor of people who are, or who will become, inactive carriers, defined as people who are HBsAg positive, hepatitis B "e" antigen (HBeAg) negative, have normal Alanine transaminase (ALT) and HBV DNA under 1,000 IU/mL on at least two occasions over a period of at least 6 months
- To develop a bank of biospecimens (e.g., serum, plasma, DNA, lymphocytes, liver tissue) obtained from participants with HBV infection
- To identify participants with HBV infection who are potential candidates in one of the treatment studies to be conducted by the Hepatitis B Research Network (HBRN)
- To describe the natural history of hepatitis B infection in pregnancy including the frequency of, and clinical and virological characteristics associated with, hepatic flares during pregnancy and post-partum.
- Conditions
- Hepatitis B
- Keywords
- Hepatitis B, HBV, Cohort Study
- Medical subject headings
- Hepatitis B
What is being measured
The primary outcome is the main question the study is designed to answer.
Hepatitis Exacerbation marked by alanine aminotransferase (ALT) Flare
A flare is defined as serum ALT greater than or equal to 10 times the upper limit of normal which corresponds to 300 IU/L in males or 200 IU/L in females. This definition will also be applied to hepatitis B surface antigen (HBsAg) positive pregnant women whose ALT levels increase during pregnancy or postpartum. Once a flare is detected, participants will be followed more closely until its resolution.
Measured: up to 288 weeks
Antigen loss: e and s
Loss of these viral markers may be associated with appearance of corresponding antibodies in serum (anti-HBe or anti-HBs). HBsAg loss appears to represent a "cure" of HBV infection and is associated with reduction, but not necessarily elimination, of the risk of future complications, such as Hepatocellular carcinoma (HCC) which may occur, particularly in those who lose HBsAg at an older age (after 50 years) or after the development of cirrhosis. When HBeAg or HBsAg loss occurs, participants will be followed more closely initially and then return to the regular follow-up schedule.
Measured: up to 288 weeks
Cirrhosis
Once cirrhosis is diagnosed, follow-up will include hepatocellular carcinoma (HCC) surveillance. HCC surveillance will also be performed in non-cirrhotic participants who meet American Association for the Study of Liver Disease guidelines criteria.
Measured: up to 288 weeks
Hepatic decompensation
Development of hepatic decompensation will be defined by any of the following events:
- Ascites or hepatic hydrothorax
- Variceal or portal hypertensive bleeding
- Hepatic encephalopathy
- Child-Turcotte-Pugh (CTP) score of 7 or above
It is anticipated that there will be a small number of participants who will develop hepatic decompensation during follow-up.
Measured: up to 288 weeks
Hepatocellular carcinoma (HCC)
Hepatocellular carcinoma (HCC) may be detected by routine surveillance or may become clinically apparent. The diagnosis of HCC will be made using the American Association for the Study of Liver Disease criteria.
Measured: up to 288 weeks
Death
Death may occur related to liver disease (typically hepatic decompensation or Hepatocellular carcinoma) or may occur unrelated to hepatitis B or liver disease. Date and cause of death will be recorded.
Measured: up to 288 weeks
Liver transplantation
Liver transplantation will be recorded upon notification. Date of transplantation, indication for transplantation, and occurrence of incidental Hepatocellular carcinoma (HCC) will be recorded. Follow-up ends with liver transplantation.
Measured: up to 288 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Dec 2010 (estimated)
- Study startDec 2010
- Primary completion9 Jun 2021
- Study completion9 Jun 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Hepatitis BStudies of the same condition, open and under way.
- More trials run by University of PittsburghThe 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
- 2,051 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Pittsburgh
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Center for Research Resources (NCRR)
- Responsible party
- Principal investigator, Anna Lok, University of Michigan
- Investigators
- Steven Belle, PhD, Principal investigator, University of Pittsburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01263587
- Sponsor's protocol ID
- DK082864
- Other IDs
- U01DK082864, U01DK082843, U01DK082866, U01DK082863, U01DK082867, U01DK082871, U01DK082872, U01DK082874
- Acronym
- HBRN
- Status last verified
- May 2022
- First submitted
- 14 Dec 2010
- Last updated
- 31 May 2022
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Lisker-Melman M, King WC, Ghany MG, Chung RT, Hinerman AS, Cloherty GA, Khalili M, Jain MK, Sulkowski M, Sterling RK. Human immunodeficiency virus coinfection differentially impacts hepatitis B virus viral markers based on hepatitis Be antigen status in patients with suppressed viremia. J Viral Hepat. 2023 Aug;30(8):700-709. doi: 10.1111/jvh.13857. Epub 2023 Jun 6.
PubMed 37278302Sterling RK, Wahed AS, Cloherty G, Hoofnagle JH, Lee WM; Hepatitis B Research Network Investigators. Acute Hepatitis B Virus Infection in North American Adults. Clin Gastroenterol Hepatol. 2023 Jul;21(7):1881-1892.e4. doi: 10.1016/j.cgh.2022.09.004. Epub 2022 Sep 16.
PubMed 36116752Khalili M, Kleiner DE, King WC, Sterling RK, Ghany MG, Chung RT, Bhan AK, Rosenthal P, Lisker-Melman M, Ramachandran R, Lok AS; ; and the Hepatitis B Research Network (HBRN). Hepatic Steatosis and Steatohepatitis in a Large North American Cohort of Adults With Chronic Hepatitis B. Am J Gastroenterol. 2021 Aug 1;116(8):1686-1697. doi: 10.14309/ajg.0000000000001257.
PubMed 33840726Evon DM, Lin HS, Khalili M, Fontana RJ, Yim C, Wahed AS, Fried MW, Hoofnagle JH; Hepatitis B Research Network (HBRN). Patient-reported outcomes in a large North American cohort living with chronic hepatitis B virus: a cross-sectional analysis. Aliment Pharmacol Ther. 2020 Feb;51(4):457-468. doi: 10.1111/apt.15618. Epub 2020 Jan 14.
PubMed 31943262Di Bisceglie AM, King WC, Lisker-Melman M, Khalili M, Belle SH, Feld JJ, Ghany MG, Janssen HLA, Lau D, Lee WM, Ling SC, Cooper S, Rosenthal P, Schwarz KB, Sterling RK, Teckman JH, Terrault N; Hepatitis B Research Network (HBRN). Age, race and viral genotype are associated with the prevalence of hepatitis B e antigen in children and adults with chronic hepatitis B. J Viral Hepat. 2019 Jul;26(7):856-865. doi: 10.1111/jvh.13104. Epub 2019 May 2.
PubMed 30974509Khalili M, Shuhart MC, Lombardero M, Feld JJ, Kleiner DE, Chung RT, Terrault NA, Lisker-Melman M, Sanyal A, Lok AS; Hepatitis B Research Network (HBRN); Harvard Consortium. Relationship Between Metabolic Syndrome, Alanine Aminotransferase Levels, and Liver Disease Severity in a Multiethnic North American Cohort With Chronic Hepatitis B. Diabetes Care. 2018 Jun;41(6):1251-1259. doi: 10.2337/dc18-0040. Epub 2018 Mar 29.
PubMed 29599296Di Bisceglie AM, Lombardero M, Teckman J, Roberts L, Janssen HL, Belle SH, Hoofnagle JH; Hepatitis B Research Network (HBRN). Determination of hepatitis B phenotype using biochemical and serological markers. J Viral Hepat. 2017 Apr;24(4):320-329. doi: 10.1111/jvh.12643. Epub 2016 Dec 5.
PubMed 27917600
Study at a glance
From the registry record, last updated by the sponsor on 31 May 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Observational Study of Persons With Hepatitis B Virus Infection in North America (Cohort Study)
- ClinicalTrials.gov ID
- NCT01263587
- Acronym / sponsor ID
- HBRN / DK082864
- Conditions
- Hepatitis B
- Keywords
- Hepatitis B, HBV, Cohort Study
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 2,051 participants (actual)
- Lead sponsor
- University of PittsburghUniversity, hospital or other
- Collaborators
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Center for Research Resources (NCRR)
- Study start
- Dec 2010
- Primary completion
- 9 Jun 2021 (actual)
- Study completion
- 9 Jun 2021 (actual)
- First posted
- 20 Dec 2010 (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.
The primary purpose of this study is to describe participants with hepatitis B virus (HBV) infection and identify factors that may cause the disease to activate or worsen.
Detailed description
Aims
- Primary Aim:
- To describe participants with hepatitis B virus (HBV) infection in a prospective cohort in the United States (US) and Canada and identify predictors of disease activation and progression
- Secondary Aims:
- To describe clinical, virological, and immunological characteristics of participants with HBV in the US and Canada
- To evaluate changes in HBV infection status and quantitative hepatitis B surface antigen (HBsAg) levels and factors associated with those changes
- To verify whether a baseline HBsAg below 1,000 IU/mL and HBV DNA below 1,000 IU/mL is an accurate predictor of people who are, or who will become, inactive carriers, defined as people who are HBsAg positive, hepatitis B "e" antigen (HBeAg) negative, have normal Alanine transaminase (ALT) and HBV DNA under 1,000 IU/mL on at least two occasions over a period of at least 6 months
- To develop a bank of biospecimens (e.g., serum, plasma, DNA, lymphocytes, liver tissue) obtained from participants with HBV infection
- To identify participants with HBV infection who are potential candidates in one of the treatment studies to be conducted by the Hepatitis B Research Network (HBRN)
- To describe the natural history of hepatitis B infection in pregnancy including the frequency of, and clinical and virological characteristics associated with, hepatic flares during pregnancy and post-partum.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- The study population will be recruited from multi-site clinical centers in the United States and Canada including primary care hospitals and community centers.
Key inclusion criteria (8 listed)
- Written informed consent
- At least 18 years of age
- Hepatitis B surface antigen (HBsAg) positive and either:
Key exclusion criteria (7 listed)
- Hepatic decompensation
- Hepatocellular carcinoma (HCC)
- Liver transplantation
- Current hepatitis B antiviral treatment (except pregnant women and patients who are anti-HDV positive)
- Known Human immunodeficiency virus (HIV) co-infection (patients with Hepatitis D (HDV) or Hepatitis C (HCV) co-infection are not excluded).
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
Hepatitis Exacerbation marked by alanine aminotransferase (ALT) Flare
Time frame: up to 288 weeks
A flare is defined as serum ALT greater than or equal to 10 times the upper limit of normal which corresponds to 300 IU/L in males or 200 IU/L in females. This definition will also be applied to hepatitis B surface antigen (HBsAg) positive pregnant women whose ALT levels increase during pregnancy or postpartum. Once a flare is detected, participants will be followed more closely until its resolution.
Antigen loss: e and s
Time frame: up to 288 weeks
Loss of these viral markers may be associated with appearance of corresponding antibodies in serum (anti-HBe or anti-HBs). HBsAg loss appears to represent a "cure" of HBV infection and is associated with reduction, but not necessarily elimination, of the risk of future complications, such as Hepatocellular carcinoma (HCC) which may occur, particularly in those who lose HBsAg at an older age (after 50 years) or after the development of cirrhosis. When HBeAg or HBsAg loss occurs, participants will be followed more closely initially and then return to the regular follow-up schedule.
Cirrhosis
Time frame: up to 288 weeks
Once cirrhosis is diagnosed, follow-up will include hepatocellular carcinoma (HCC) surveillance. HCC surveillance will also be performed in non-cirrhotic participants who meet American Association for the Study of Liver Disease guidelines criteria.
Hepatic decompensation
Time frame: up to 288 weeks
Development of hepatic decompensation will be defined by any of the following events: * Ascites or hepatic hydrothorax * Variceal or portal hypertensive bleeding * Hepatic encephalopathy * Child-Turcotte-Pugh (CTP) score of 7 or above It is anticipated that there will be a small number of participants who will develop hepatic decompensation during follow-up.
Hepatocellular carcinoma (HCC)
Time frame: up to 288 weeks
Hepatocellular carcinoma (HCC) may be detected by routine surveillance or may become clinically apparent. The diagnosis of HCC will be made using the American Association for the Study of Liver Disease criteria.
Death
Time frame: up to 288 weeks
Death may occur related to liver disease (typically hepatic decompensation or Hepatocellular carcinoma) or may occur unrelated to hepatitis B or liver disease. Date and cause of death will be recorded.
Liver transplantation
Time frame: up to 288 weeks
Liver transplantation will be recorded upon notification. Date of transplantation, indication for transplantation, and occurrence of incidental Hepatocellular carcinoma (HCC) will be recorded. Follow-up ends with liver transplantation.
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 31 May 2022.
- Derived from this study: PubMed 37278302Lisker-Melman M, King WC, Ghany MG, Chung RT, Hinerman AS, Cloherty GA, Khalili M, Jain MK, Sulkowski M, Sterling RK. Human immunodeficiency virus coinfection differentially impacts hepatitis B virus viral markers based on hepatitis Be antigen status in patients with suppressed viremia. J Viral Hepat. 2023 Aug;30(8):700-709. doi: 10.1111/jvh.13857. Epub 2023 Jun 6.
- Derived from this study: PubMed 36116752Sterling RK, Wahed AS, Cloherty G, Hoofnagle JH, Lee WM; Hepatitis B Research Network Investigators. Acute Hepatitis B Virus Infection in North American Adults. Clin Gastroenterol Hepatol. 2023 Jul;21(7):1881-1892.e4. doi: 10.1016/j.cgh.2022.09.004. Epub 2022 Sep 16.
- Derived from this study: PubMed 33840726Khalili M, Kleiner DE, King WC, Sterling RK, Ghany MG, Chung RT, Bhan AK, Rosenthal P, Lisker-Melman M, Ramachandran R, Lok AS; ; and the Hepatitis B Research Network (HBRN). Hepatic Steatosis and Steatohepatitis in a Large North American Cohort of Adults With Chronic Hepatitis B. Am J Gastroenterol. 2021 Aug 1;116(8):1686-1697. doi: 10.14309/ajg.0000000000001257.
- Derived from this study: PubMed 31943262Evon DM, Lin HS, Khalili M, Fontana RJ, Yim C, Wahed AS, Fried MW, Hoofnagle JH; Hepatitis B Research Network (HBRN). Patient-reported outcomes in a large North American cohort living with chronic hepatitis B virus: a cross-sectional analysis. Aliment Pharmacol Ther. 2020 Feb;51(4):457-468. doi: 10.1111/apt.15618. Epub 2020 Jan 14.
- Derived from this study: PubMed 30974509Di Bisceglie AM, King WC, Lisker-Melman M, Khalili M, Belle SH, Feld JJ, Ghany MG, Janssen HLA, Lau D, Lee WM, Ling SC, Cooper S, Rosenthal P, Schwarz KB, Sterling RK, Teckman JH, Terrault N; Hepatitis B Research Network (HBRN). Age, race and viral genotype are associated with the prevalence of hepatitis B e antigen in children and adults with chronic hepatitis B. J Viral Hepat. 2019 Jul;26(7):856-865. doi: 10.1111/jvh.13104. Epub 2019 May 2.
- Derived from this study: PubMed 29599296Khalili M, Shuhart MC, Lombardero M, Feld JJ, Kleiner DE, Chung RT, Terrault NA, Lisker-Melman M, Sanyal A, Lok AS; Hepatitis B Research Network (HBRN); Harvard Consortium. Relationship Between Metabolic Syndrome, Alanine Aminotransferase Levels, and Liver Disease Severity in a Multiethnic North American Cohort With Chronic Hepatitis B. Diabetes Care. 2018 Jun;41(6):1251-1259. doi: 10.2337/dc18-0040. Epub 2018 Mar 29.
- Derived from this study: PubMed 27917600Di Bisceglie AM, Lombardero M, Teckman J, Roberts L, Janssen HL, Belle SH, Hoofnagle JH; Hepatitis B Research Network (HBRN). Determination of hepatitis B phenotype using biochemical and serological markers. J Viral Hepat. 2017 Apr;24(4):320-329. doi: 10.1111/jvh.12643. Epub 2016 Dec 5.
- Individual participant dataSharing planned: No
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RecruitingObservational study
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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.
Steven Belle, PhD principal investigator
University of Pittsburgh
21 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Hepatitis B, run by University of Pittsburgh at 21 sites in 2 countries.
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 31 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 21 sites in United States, 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?
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?
Hepatitis Exacerbation marked by alanine aminotransferase (ALT) Flare (time frame: up to 288 weeks). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01263587, which also lists 7 linked publications.
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 31 May 2022.