Objective: To determine the outcomes of chronic hepatitis B virus (HBV) infection in a large, prospectively studied cohort of children in the US and Canada. Study design: This was a prospective, observational study of children with chronic HBV enrolled in 7 clinical centers and evaluated at baseline, weeks 24 and 48, and annually thereafter, with analysis of demographic, clinical, physical examination, and blood test data. Results: Among 362 children followed for a median of 4.2 years, elevated alanine aminotransferase (ALT) levels (>1 upper limit of normal) were present in 72% at last evaluation, including in 60% of children with loss of hepatitis B e antigen during follow-up and 70% of those who were hepatitis B e antigen negative at baseline. Significant ALT flares (male patients ≥400 U/L, female patients ≥350 U/L) occurred in 13 children. Of 129 children who fulfilled the American Association for the Study of Liver Diseases treatment criteria during follow-up, anti-HBV treatment was initiated in only 25. One child died (unrelated to liver disease), 1 developed cirrhosis, but no episodes of cirrhotic decompensation or hepatocellular carcinoma were observed. Decline in platelet count was inversely associated with ALT elevations. Conclusions: In a cohort of children with chronic HBV infection in the US and Canada, many children remained at risk of progressive liver disease due to active hepatitis, but major clinical outcomes such as cirrhosis, cancer, and death were rare. Many children who met criteria for treatment remained untreated.
Bibliographical noteFunding Information:
The HBRN and the enrollment criteria for its pediatric cohort study have been previously described in detail. 6 To summarize, the HBRN was established and is funded by the National Institute of Diabetes and Digestive and Kidney Diseases to conduct clinical, scientific, epidemiologic, and therapeutic research in acute and chronic HBV infection in children and adults.
The HBRN was funded as a Cooperative Agreement between the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and the following investigators: Kathleen B. Schwarz, MD (U01-DK082916), Steven H. Belle, PhD, MScHyg (U01-DK082864), Harry L. A. Janssen, MD, PhD (U01-DK082874), Mandana Khalili, MD (U01-DK082944), Lewis R. Roberts, MB, ChB, PhD (U01-DK082843), and Adrian M. Di Bisceglie, MD (U01-DK082871) and an interagency agreement with NIDDK: Lilia Milkova Ganova-Raeva, PhD (A-DK-3002-001). Additional funding to support this study was provided to Kathleen B. Schwarz, MD (CTSA UL1TR000423) and Norah A. Terrault, MD, MPH (CTSA UL1TR000004). Additional support was provided by Roche Molecular Systems via a CRADA through the NIDDK. S.L. receives research support from AbbVie and Gilead. K.M. serves as a consultant for Gilead and Albireo. P.R. receives research support from AbbVie, Gilead, Bristol Myers Squibb, Roche/Genentech, Merck, and Travere Therapeutics and consults for Gilead, AbbVie, Intercept, Travere Therapeutics, Albireo, Audentes, Dicerna, and Mirum. N.R-B. receives research support from Gilead. S.S. receives research support from the Cystic Fibrosis Therapeutic Disease Network, the Cystic Fibrosis Foundation, and Gilead and serves as a consultant for UpToDate. J.T. receives research support from Gilead, Alnylam Inc, Arrowhead Pharmaceuticals, and Dicerna, Inc, and serves as a consultant for BioMarin, Editas, Proteostasis, and Retrophin. K.S. receives research support from Gilead, Bristol-Myers Squibb, and Roche/Genentech and serves as a consultant for Gilead, Roche/Genentech, and UptoDate. The other authors declare no conflicts of interest.
© 2021 Elsevier Inc.
- alanine aminotransferase
- clinical outcomes
- platelet count
- vertical transmission