Hepatitis B Research Network Pediatric Cohort Study (HBRN)

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.

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.

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

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.

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 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 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.

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.