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Phenotypes of Chronic Hepatitis B in Children From a Large North American Cohort
Kathleen B Schwarz1, Manuel Lombardero2, Adrian M Di Bisceglie3
1John Hopkins University, Baltimore, MD.
Insights
Defining chronic hepatitis B virus (HBV) infection phenotypes in children using updated alanine aminotransferase (ALT) levels reveals the immune-tolerant phenotype is uncommon. HBeAg positivity also decreases with age in pediatric HBV patients.
Area of Science:
- Pediatric Hepatology
- Virology
- Immunology
Background:
- Chronic hepatitis B virus (HBV) infection is classified into distinct phases or phenotypes.
- These phenotypes may influence prognosis and treatment decisions.
- Accurate phenotyping is crucial for managing pediatric HBV cases.
Purpose of the Study:
- To define chronic HBV phenotypes in a large cohort of North American children.
- To compare phenotype definitions using updated population-based upper limits of normal (ULN) for alanine aminotransferase (ALT) versus local laboratory standards.
- To identify associations between HBV phenotypes and host or viral factors.
Main Methods:
- Analysis of baseline enrollment data from the Hepatitis B Research Network cohort of children.
- Phenotype classification based on hepatitis B e-antigen (HBeAg) status, HBV DNA levels, and ALT levels (using both local and updated ULN ALT).
- Statistical examination of relationships between phenotypes and demographic/viral factors.
Main Results:
- Using updated ULN ALT, only 12% of children were classified as immune-tolerant, compared to 35% with local ULN ALT.
- 82% of children were classified as having chronic hepatitis B when using updated ULN ALT.
- HBeAg positivity and higher HBV DNA levels were more common in younger children, decreasing with age.
- A significant proportion of HBeAg-negative children had an indeterminate phenotype (abnormal ALT with low HBV DNA).
Conclusions:
- The immune-tolerant phenotype is infrequent in North American children with chronic HBV infection.
- HBeAg positivity declines with increasing age in this pediatric population.
- Updated ULN ALT levels significantly alter phenotype classification, highlighting the importance of standardized criteria.
Objective:
The aim of the study was to define chronic HBV phenotypes in a large, cohort of United States and Canadian children utilizing recently published population-based upper limit of normal alanine aminotransferase levels (ULN ALT), compared with local laboratory ULN; identify relationships with host and viral factors.
Background:
Chronic hepatitis B virus (HBV) infection has been characterized by phases or phenotypes, possibly associated with prognosis and indications for therapy.
Methods:
Baseline enrollment data of children in the Hepatitis B Research Network were examined. Phenotype definitions were inactive carrier: HBeAg-negative with low HBV DNA and normal ALT levels; immune-tolerant: HBeAg-positive with high HBV DNA but normal ALT levels; or chronic hepatitis B: HBeAg-positive or -negative with high HBV DNA and abnormal ALT levels.
Results:
Three hundred seventy-one participants were analyzed of whom 274 were HBeAg-positive (74%). Younger participants were more likely be HBeAg-positive with higher HBV DNA levels. If local laboratory ULN ALT levels were used, 35% were assigned the immune tolerant phenotype, but if updated ULN were applied, only 12% could be so defined, and the remaining 82% would be considered to have chronic hepatitis B. Among HBeAg-negative participants, only 21 (22%) were defined as inactive carriers and 14 (14%) as HBeAg-negative chronic hepatitis B; the majority (61%) had abnormal ALT and low levels of HBV DNA, thus having an indeterminant phenotype. Increasing age was associated with smaller proportions of HBeAg-positive infection.
Conclusions:
Among children with chronic HBV infection living in North America, the immune tolerant phenotype is uncommon and HBeAg positivity decreases with age.
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