Chronic Hepatitis Is Common and Often Untreated Among Children with Hepatitis B Infection in the United States and Canada

Hepatitis B Research Network (HBRN)

doi:10.1016/j.jpeds.2021.05.035

Chronic Hepatitis Is Common and Often Untreated Among Children with Hepatitis B Infection in the United States and Canada

Hepatitis B Research Network (HBRN)

Pediatric Gastroenterology, Hepatology & Nutrition

Research output: Contribution to journal › Article › peer-review

12 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	24-33.e12
Journal	Journal of Pediatrics
Volume	237
Early online date	May 20 2021
DOIs	https://doi.org/10.1016/j.jpeds.2021.05.035
State	Published - Oct 2021

Bibliographical note

Funding 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.

Funding Information:
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.

Publisher Copyright:
© 2021 Elsevier Inc.

Keywords

alanine aminotransferase
clinical outcomes
entecavir
interferon
lamivudine
phenotype
platelet count
vertical transmission

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.jpeds.2021.05.035

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@article{a23eafd81cef40e2ba05c4b30b2382a6,

title = "Chronic Hepatitis Is Common and Often Untreated Among Children with Hepatitis B Infection in the United States and Canada",

abstract = "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.",

keywords = "alanine aminotransferase, clinical outcomes, entecavir, interferon, lamivudine, phenotype, platelet count, vertical transmission",

author = "{Hepatitis B Research Network (HBRN)} and Ling, {Simon C.} and Lin, {Hsing Hua S.} and Murray, {Karen F.} and Philip Rosenthal and Douglas Mogul and Norberto Rodriguez-Baez and Schwarzenberg, {Sarah Jane} and Jeffrey Teckman and Schwarz, {Kathleen B.} and Hongxia Li and Robert Anders and Hejab Imteyaz and Peter Lee and Kiyoko Oshima and Kim Kafka and Naureen Islam and Riggs, {Shannon M.} and Nagy, {Rosemary A.} and Jacki Cerkoski and Athena Hau and Daniel Cui and Rodgers-Augustyniak, {Laurie A.} and Shirley Montanye and Natasha Feier and Joel Feier and Camille Langlois and Cooper, {Kara L.} and Hoofnagle, {Jay H.} and Sherker, {Averell H.} and Edward Doo and Torrance, {Rebecca J.} and Hall, {Sherry R.} and Frani Averbach and Tamara Haller and Regina Hardison and Stephanie Kelley and Lalama, {Christina M.} and Sharon Lawlor and Manuel Lombardero and Andrew Pelesko and Donna Stoliker and Melissa Weiner and Ella Zadorozny and Qian Zhao",

note = "Funding 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. Funding Information: 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. Publisher Copyright: {\textcopyright} 2021 Elsevier Inc.",

year = "2021",

month = oct,

doi = "10.1016/j.jpeds.2021.05.035",

language = "English (US)",

volume = "237",

pages = "24--33.e12",

journal = "Journal of Pediatrics",

issn = "0022-3476",

publisher = "Mosby Inc.",

}

TY - JOUR

T1 - Chronic Hepatitis Is Common and Often Untreated Among Children with Hepatitis B Infection in the United States and Canada

AU - Hepatitis B Research Network (HBRN)

AU - Ling, Simon C.

AU - Lin, Hsing Hua S.

AU - Murray, Karen F.

AU - Rosenthal, Philip

AU - Mogul, Douglas

AU - Rodriguez-Baez, Norberto

AU - Schwarzenberg, Sarah Jane

AU - Teckman, Jeffrey

AU - Schwarz, Kathleen B.

AU - Li, Hongxia

AU - Anders, Robert

AU - Imteyaz, Hejab

AU - Lee, Peter

AU - Oshima, Kiyoko

AU - Kafka, Kim

AU - Islam, Naureen

AU - Riggs, Shannon M.

AU - Nagy, Rosemary A.

AU - Cerkoski, Jacki

AU - Hau, Athena

AU - Cui, Daniel

AU - Rodgers-Augustyniak, Laurie A.

AU - Montanye, Shirley

AU - Feier, Natasha

AU - Feier, Joel

AU - Langlois, Camille

AU - Cooper, Kara L.

AU - Hoofnagle, Jay H.

AU - Sherker, Averell H.

AU - Doo, Edward

AU - Torrance, Rebecca J.

AU - Hall, Sherry R.

AU - Averbach, Frani

AU - Haller, Tamara

AU - Hardison, Regina

AU - Kelley, Stephanie

AU - Lalama, Christina M.

AU - Lawlor, Sharon

AU - Lombardero, Manuel

AU - Pelesko, Andrew

AU - Stoliker, Donna

AU - Weiner, Melissa

AU - Zadorozny, Ella

AU - Zhao, Qian

N1 - Funding 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. Funding Information: 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. Publisher Copyright: © 2021 Elsevier Inc.

PY - 2021/10

Y1 - 2021/10

N2 - 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.

AB - 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.

KW - alanine aminotransferase

KW - clinical outcomes

KW - entecavir

KW - interferon

KW - lamivudine

KW - phenotype

KW - platelet count

KW - vertical transmission

UR - http://www.scopus.com/inward/record.url?scp=85109002240&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85109002240&partnerID=8YFLogxK

U2 - 10.1016/j.jpeds.2021.05.035

DO - 10.1016/j.jpeds.2021.05.035

M3 - Article

C2 - 34022250

AN - SCOPUS:85109002240

SN - 0022-3476

VL - 237

SP - 24-33.e12

JO - Journal of Pediatrics

JF - Journal of Pediatrics

ER -

Chronic Hepatitis Is Common and Often Untreated Among Children with Hepatitis B Infection in the United States and Canada

Abstract

Bibliographical note

Keywords

UN SDGs

Publisher link

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