Clinical trial NCT01263587: Hepatitis B Research Network Adult Cohort Study
Official title: Observational Study of Persons With Hepatitis B Virus Infection in North America (Cohort Study)
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Hepatitis B
Keywords: Hepatitis B
HBV
Cohort Study
Lead sponsor: University of Pittsburgh
Sponsor class: OTHER
Collaborators: name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
name: National Center for Research Resources (NCRR)
First posted: 2010-12-20
Enrollment: 2051
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
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.

Brief 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.

Detailed description: Aims

* Primary Aim:

  o 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.

Eligibility criteria: The study population will be recruited from multi-site clinical centers in the United States and Canada including primary care hospitals and community centers.

Inclusion criteria

* 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).

Exclusion Criteria:

* 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

Primary outcomes:
measure: Hepatitis Exacerbation marked by alanine aminotransferase (ALT) Flare
timeFrame: up to 288 weeks
measure: Antigen loss: e and s
timeFrame: up to 288 weeks
measure: Cirrhosis
timeFrame: up to 288 weeks
measure: Hepatic decompensation
timeFrame: up to 288 weeks
measure: Hepatocellular carcinoma (HCC)
timeFrame: up to 288 weeks
measure: Death
timeFrame: up to 288 weeks
measure: Liver transplantation
timeFrame: up to 288 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Cedars Sinai Medical Center
state: California
city: Los Angeles
country: United States
facility: University of California Los Angeles
state: California
city: San Francisco
country: United States
facility: California Pacific Medical Center
state: California
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
city: Honolulu
country: United States
facility: The Queen's Medial Center
state: Hawaii
city: Bethesda
country: United States
facility: NIH Clinical Center
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Health System
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Saint Louis
country: United States
facility: Saint Louis University
state: Missouri
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: Chapel Hill
country: United States
facility: University of North Carolina
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Dallas
country: United States
facility: Baylor University Medical Center
state: Texas
city: Dallas
country: United States
facility: University of Texas Southwestern
state: Texas
city: Richmond
country: United States
facility: Virginia Commonwealth University Medical Center
state: Virginia
city: Seattle
country: United States
facility: Virginia Mason Medical Center
state: Washington
city: Seattle
country: United States
facility: Harborview Medical Center
state: Washington
city: Toronto
country: Canada
facility: Toronto Western Hospital Liver Centre
state: Ontario
Study officials:
affiliation: University of Pittsburgh
name: Steven Belle, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Sterling 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.
citation: Khalili 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.
citation: Evon 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.
citation: Di 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.
citation: Khalili 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.
citation: Di 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.