Hepatitis B Research Network Pediatric Cohort Study (HBRN)

• Hepatitis exacerbation marked by alanine aminotransferase (ALT) Flare [ Time Frame: up to 288 weeks ] [ Designated as safety issue: No ]
  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.
• Cirrhosis [ Time Frame: up to 288 weeks ] [ Designated as safety issue: No ]

  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

• Hepatic Decompensation [ Time Frame: up to 288 weeks ] [ Designated as safety issue: No ]

  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.

• Hepatocellular carcinoma (HCC) [ Time Frame: up to 288 weeks ] [ Designated as safety issue: No ]
  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 ] [ Designated as safety issue: No ]
  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.
• Liver transplantation [ Time Frame: up to 288 weeks ] [ Designated as safety issue: No ]
  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.
• Reaching 18 years of Age [ Time Frame: up to 288 weeks ] [ Designated as safety issue: No ]
  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.

• Hepatitis exacerbation marked by ALT Flare [ Time Frame: up to 288 weeks ] [ Designated as safety issue: No ]
  A flare is defined as serum 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.
• Cirrhosis [ Time Frame: up to 288 weeks ] [ Designated as safety issue: No ]

  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 HCC surveillance

• Hepatic Decompensation [ Time Frame: up to 288 weeks ] [ Designated as safety issue: No ]

  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.

• Hepatocellular carcinoma (HCC) [ Time Frame: up to 288 weeks ] [ Designated as safety issue: No ]
  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 ] [ Designated as safety issue: No ]
  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.
• Liver transplantation [ Time Frame: up to 288 weeks ] [ Designated as safety issue: No ]
  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.
• Reaching 18 years of Age [ Time Frame: up to 288 weeks ] [ Designated as safety issue: No ]
  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.

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.

•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).

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

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