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Multicenter Study
. 2019 Nov;69(5):588-594.
doi: 10.1097/MPG.0000000000002467.

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

Kathleen B Schwarz  1 , Manuel Lombardero  2 , Adrian M Di Bisceglie  3 , Karen F Murray  4 , Philip Rosenthal  5 , Simon C Ling  6 , Yona Keich Cloonan  2 , Norberto Rodriguez-Baez  7 , Sarah Jane Schwarzenberg  8 , Jay H Hoofnagle  9 , Jeffrey Teckman  3 ; Hepatitis B Research Network (HBRN)
Affiliations
Multicenter Study

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

Kathleen B Schwarz et al. J Pediatr Gastroenterol Nutr. 2019 Nov.

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.

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Conflict of interest statement

Disclosures:

KB Schwarz has research grants from Gilead, Bristol-Myers Squibb, Roche/Genentech and consults for Gilead, Roche/Genentech and Up to Date

Adrian M Di Bisceglie has research grants from Gilead and serves on advisory boards to Gilead and Bristol-Myers Squibb.

Karen F Murray has research grants supported by Gilead, Merck, Shire, and owns stock in Merck

Philip Rosenthal has research grants from Abbvie, Gilead, Bristol-Myers Squibb, Roche/Genentech and consults for Gilead, Abbvie, Intercept, Alexion, Retrophil, Albireo, Audentes and Mirum.

Simon C Ling receives research funding from Abbvie and Bristol-Myers Squibb.

Norberto Rodriguez-Baez has research grants supported by Gilead.

Jeffrey Teckman has research grants from Gilead, Alnylam Inc., Arrowhead Pharmaceuticals and Dicerna Inc., and consultant relationships with BioMarin, Editas, Proteostasis and Retrophin.

Yona Keich Cloonan, Manuel Lombardero, Sarah Jane Schwarzenberg and Jay H Hoofnagle have no duality or conflicts of interest.

Figures

Figure 1.
Figure 1.
Scatterplots of serum HBV DNA vs ALT levels for each subject. The horizontal line shows the cut point for normal vs. raised ALT, and the vertical line the cut points for high vs low HBV DNA. a. ALT and HBV levels for 274 HBeAg-positive children, classifying those with chronic HBeAg-positive hepatitis B, immune tolerant or indeterminant HBV infection. b. ALT and HBV DNA levels for 97 HBeAg-negative children, classifying those with chronic HBeAg-negative hepatitis B, inactive carriers and indeterminants.
Figure 1.
Figure 1.
Scatterplots of serum HBV DNA vs ALT levels for each subject. The horizontal line shows the cut point for normal vs. raised ALT, and the vertical line the cut points for high vs low HBV DNA. a. ALT and HBV levels for 274 HBeAg-positive children, classifying those with chronic HBeAg-positive hepatitis B, immune tolerant or indeterminant HBV infection. b. ALT and HBV DNA levels for 97 HBeAg-negative children, classifying those with chronic HBeAg-negative hepatitis B, inactive carriers and indeterminants.
Figure 2
Figure 2
a. Distribution of HBV phenotypes by age groups b. Distribution of HBV phenotypes by genotype
Figure 2
Figure 2
a. Distribution of HBV phenotypes by age groups b. Distribution of HBV phenotypes by genotype
Figure 3.
Figure 3.
Distribution of HBV phenotypes using two different reference standards for upper limits of the normal range.
See this image and copyright information in PMC

References

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