Hepatitis B Research Network Adult Cohort Study

NCT01263587 | Completed DMC

• 21 other identifiers: DK082864U01DK082864U01DK082843U01DK082866U01DK082863U01DK082867U01DK082871U01DK082872U01DK082874U01DK082919U01DK082923U01DK082927U01DK082943U01DK082944P30DK050306A-DK-3002-001M01RR000040UL1TR000058UL1TR000004UL1RR024986UL1TR001111
• Study Type: observational
• Target: 2,051
• Locations: 2 countries
• Sites: 21

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.

Conditions

Hepatitis B

Keywords

Hepatitis B; HBV; Cohort Study

Outcome Measures

Primary Outcomes (7)

• 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.

  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.

  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.

  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.

  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.

  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.

  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.

  up to 288 weeks

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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).

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Pittsburgh: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator
• National Center for Research Resources (NCRR): collaborator

Study Sites (21)

Cedars Sinai Medical Center

Los Angeles, California, 90048, United States

Location

University of California Los Angeles

Los Angeles, California, 90095, United States

Location

California Pacific Medical Center

San Francisco, California, 94115, United States

Location

University of California San Francisco

San Francisco, California, 94143, United States

Location

The Queen's Medial Center

Honolulu, Hawaii, 96813, United States

Location

NIH Clinical Center

Bethesda, Maryland, 20892, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

University of Michigan Health System

Ann Arbor, Michigan, 48109, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Saint Louis University

St Louis, Missouri, 63104, United States

Location

Washington University

St Louis, Missouri, 63108, United States

Location

University of North Carolina

Chapel Hill, North Carolina, 27599, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Baylor University Medical Center

Dallas, Texas, 75246, United States

Location

University of Texas Southwestern

Dallas, Texas, 75390, United States

Location

Virginia Commonwealth University Medical Center

Richmond, Virginia, 23298, United States

Location

Virginia Mason Medical Center

Seattle, Washington, 98101, United States

Location

Harborview Medical Center

Seattle, Washington, 98104, United States

Location

Toronto Western Hospital Liver Centre

Toronto, Ontario, Canada

Location

Related Publications (7)

• 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.

  PMID: 37278302 DERIVED

• 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.

  PMID: 36116752 DERIVED

• 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.

  PMID: 33840726 DERIVED

• 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.

  PMID: 31943262 DERIVED

• 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.

  PMID: 30974509 DERIVED

• 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.

  PMID: 29599296 DERIVED

• 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.

  PMID: 27917600 DERIVED

Related Links

• The Hepatitis B Research Network study web site

Biospecimen

Retention: SAMPLES WITH DNA

Liver biopsy tissue, blood (serum, plasma, and DNA)

MeSH Terms

Conditions

Hepatitis B

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis; Liver Diseases; Digestive System Diseases

Study Officials

• Steven Belle, PhD

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Study Chair

Study Record Dates

• First Submitted: December 14, 2010
• First Posted: December 20, 2010
• Study Start: December 1, 2010
• Primary Completion: June 9, 2021
• Study Completion: June 9, 2021
• Last Updated: May 31, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (20); CA (1)