Hepatitis B Research Network Pediatric Cohort Study (HBRN)

Cohort Hepatitis B Virus (HBV) Pediatric Protocol

The purpose of this study is to describe participants 6 months to <18 years of age 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.

Study Overview

• Status: Completed
• Conditions: Hepatitis B

Detailed Description

•Primary Aim:

o To describe participants 6 months to <18 years of age 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 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 aminotransferase (ALT) and HBV DNA under 1,000 IU/mL on at least two occasions over a period of at least 6 months with HBV DNA under 1,000 IU/mL.
• To assess the health related quality of life (HRQOL) of treatment naïve hepatitis B surface antigen (HBsAg) positive children and adolescents
• To develop a bank of biospecimens (e.g., serum, plasma, DNA, liver tissue) obtained from participants with HBV infection.
• To identify pediatric participants from 2 years to <18 years of age with chronic HBV infection for potential participation in treatment study to be conducted by the Hepatitis B Research Network (HBRN).

• Study Type: Observational
• Enrollment (Actual): 462

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G1X8
      • Hospital for Sick Children
• United States
  • California
    • San Francisco, California, United States, 94143
      • University of California San Francisco Medical Center
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins University
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota
  • Missouri
    • Saint Louis, Missouri, United States, 63104
      • Cardinal Glennon Children's Medical Center
  • Texas
    • Dallas, Texas, United States, 75235
      • University of Texas Southwestern
  • Washington
    • Seattle, Washington, United States, 98015
      • Seattle Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 months to 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Pediatric patients from Children's Hospitals and university medical centers in the United States and Canada

Description

Inclusion Criteria:

• Written informed consent/assent as appropriate
• At least 6 months to <18 years of age
• Hepatitis B surface antigen (HBsAg) positive

Exclusion Criteria:

• Hepatic decompensation
• Hepatocellular carcinoma (HCC)
• Liver transplantation
• Current Hepatitis B antiviral treatment (except pregnant females)
• Known coinfection with HIV (patients with hepatitis D or hepatitis C coinfection are not excluded)
• Medical or social condition which in the opinion of the principal investigator would interfere with or prevent regular follow up.
• Unable or unwilling to return for regular follow-up

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hepatitis exacerbation marked by alanine aminotransferase (ALT) Flare	A flare is defined as serum alanine aminotransferase (ALT) greater than or equal to 10 times the upper limit of normal which corresponds to (1 550 IU/L in females and 600 IU/L in males for 6 months - 18 months of age and 2) 350 IU/L in females and 400 IU/L in males for >18 months - < 18 years of age (12). Once a flare is detected, participants will be followed more closely until its resolution.	up to 288 weeks
Cirrhosis	The diagnosis of cirrhosis will be made by (1) liver histology, when available or In the absence of histological diagnosis, cirrhosis is defined as any one of the following; Presence of ascites or hepatic hydrothorax; Variceal or portal hypertensive bleeding; Hepatic encephalopathy; Child-Turcotte-Pugh (CTP) score of 7 or above or in the absence of hepatic decompensation (any two of the following): Splenomegaly; Nodular liver; Platelet count below 120,000/mm3 Once cirrhosis is diagnosed, patient follow-up should include Hepatocellular carcinoma(HCC)surveillance	up to 288 weeks
Hepatic Decompensation	It is likely that the development of cirrhosis and subsequent hepatic decompensation will be preceded and foreseen by the progression of fibrosis. Development of hepatic decompensation will be defined by any of the following events: Ascites or hepatic hydrothorax; Variceal bleeding 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 patients that will develop decompensation during the follow-up.	up to 288 weeks
Hepatocellular carcinoma (HCC)	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 HCC) 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 HCC will be recorded. Follow-up ends with liver transplantation.	up to 288 weeks
Reaching 18 years of Age	Patients who reach 18 years of age and are within an adult HBRN clinical center will be offered participation in the adult cohort study and re-consented for the adult protocol.	up to 288 weeks

Collaborators and Investigators

• Sponsor: University of Pittsburgh
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Publications and helpful links

General Publications

• 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.

Helpful Links

• The Hepatitis B Research Network study web site

Study record dates

Study Major Dates

• Study Start: December 1, 2010
• Primary Completion (Actual): June 9, 2021
• Study Completion (Actual): June 9, 2021

Study Registration Dates

• First Submitted: December 14, 2010
• First Submitted That Met QC Criteria: December 17, 2010
• First Posted (Estimate): December 20, 2010

Study Record Updates

• Last Update Posted (Actual): May 31, 2022
• Last Update Submitted That Met QC Criteria: May 26, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: Pediatric; Hepatitis B; HBV
• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Enterovirus Infections; Picornaviridae Infections; Hepatitis B; Hepatitis; Hepatitis A
• Other Study ID Numbers: DK082864Pediatric; U01DK082916 (U.S. NIH Grant/Contract); U01DK082864 (U.S. NIH Grant/Contract); U01DK082874 (U.S. NIH Grant/Contract); U01DK082944 (U.S. NIH Grant/Contract); U01DK082843 (U.S. NIH Grant/Contract); U01DK082871 (U.S. NIH Grant/Contract); UL1TR000423 (U.S. NIH Grant/Contract); UL1TR000004 (U.S. NIH Grant/Contract); A-DK-3002-001 (Other Grant/Funding Number: Interagency agreement with NIDDK)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO