Hepatitis B Research Network Pediatric Cohort Study (HBRN)

Study Overview
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Brief Summary
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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.

Detailed Description
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•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).

Official Title
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Cohort Hepatitis B Virus (HBV) Pediatric Protocol

Conditions
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Hepatitis B

Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 6 Months
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pediatric, Hepatitis B, HBV