Phenotypes of Chronic Hepatitis B in Children From a Large North American Cohort

Hepatitis B Research Network (HBRN)

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)588-594
Number of pages7
JournalJournal of pediatric gastroenterology and nutrition
Volume69
Issue number5
DOIs
StatePublished - Nov 1 2019

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Hepatitis B e Antigens
Chronic Hepatitis B
Hepatitis B virus
Phenotype
DNA
Virus Diseases
Alanine Transaminase
North America
Hepatitis B

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Phenotypes of Chronic Hepatitis B in Children From a Large North American Cohort. / Hepatitis B Research Network (HBRN).

In: Journal of pediatric gastroenterology and nutrition, Vol. 69, No. 5, 01.11.2019, p. 588-594.

Research output: Contribution to journalArticle

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title = "Phenotypes of Chronic Hepatitis B in Children From a Large North American Cohort",
abstract = "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.",
author = "{Hepatitis B Research Network (HBRN)} and Schwarz, {Kathleen B.} and Manuel Lombardero and {Di Bisceglie}, {Adrian M.} and Murray, {Karen F.} and Philip Rosenthal and Ling, {Simon C.} and Cloonan, {Yona Keich} and Norberto Rodriguez-Baez and Schwarzenberg, {Sarah Jane} and Hoofnagle, {Jay H.} and Jeffrey Teckman",
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T1 - Phenotypes of Chronic Hepatitis B in Children From a Large North American Cohort

AU - Hepatitis B Research Network (HBRN)

AU - Schwarz, Kathleen B.

AU - Lombardero, Manuel

AU - Di Bisceglie, Adrian M.

AU - Murray, Karen F.

AU - Rosenthal, Philip

AU - Ling, Simon C.

AU - Cloonan, Yona Keich

AU - Rodriguez-Baez, Norberto

AU - Schwarzenberg, Sarah Jane

AU - Hoofnagle, Jay H.

AU - Teckman, Jeffrey

PY - 2019/11/1

Y1 - 2019/11/1

N2 - 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.

AB - 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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