1 John Hopkins University, Baltimore, MD, United States.
2 University of Pittsburgh, Pittsburgh, PA, United States.
3 Saint Louis University, Saint Louis, MO, United States.
4 University of Washington, Seattle, WA, United States.
5 University of California, San Francisco, CA, United States.
6 University of Toronto, Toronto, ON, Canada.
7 University of Texas Southwestern Medical Center, Dallas, TX, United States.
8 University of Minnesota, Minneapolis, MN, United States.
9 National Institute of Diabetes and Digestive Diseases, National Institutes of Health, Bethesda, MD, United States.
Define chronic HBV phenotypes in a large, cohort of US and Canadian children utilizing recently published population-based upper limit of normal alanine aminotransferase levels (ULN ALT), compared to local laboratory ULN; identify relationships with host and viral factors.
Chronic hepatitis B virus (HBV) infection has been characterized by phases or phenotypes, possibly associated with prognosis and indications for therapy.
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.
371 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.
Among children with chronic HBV infection living in North America, the immune tolerant phenotype is uncommon and HBeAg positivity decreases with age.