Treatment of Children With Chronic Hepatitis B Virus... : Hepatology (original) (raw)

Meeting Report

Treatment of Children With Chronic Hepatitis B Virus Infection in the United States

Patient Selection and Therapeutic Options

Jonas, Maureen M.1; Block, Joan M.2; Haber, Barbara A.3; Karpen, Saul J.4; London, W. Thomas5; Murray, Karen F.6; Narkewicz, Michael R.7; Rosenthal, Philip8; Schwarz, Kathleen B.9; McMahon, Brian J.10

1Division of Gastroenterology, Children’s Hospital Boston, Boston, MA

2Hepatitis B Foundation, Doylestown, PA

3Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, Children’s Hospital of Philadelphia, Philadelphia, PA

4Department of Pediatrics/Gastroenterology, Hepatology and Nutrition, Baylor College of Medicine, Houston, TX

5Fox Chase Cancer Center, Philadelphia, PA

6Division of Gastroenterology and Hepatology, Seattle Children’s and University of Washington School of Medicine, Seattle, WA

7Department of Pediatrics, Section of Pediatric Gastroenterology, Hepatology and Nutrition and The Pediatric Liver Center, University of Colorado Denver School of Medicine and The Children’s Hospital, Aurora, CO

8Pediatric Hepatology, University of California San Francisco, San Francisco, CA

9Department of Pediatrics, Division of Pediatric Gastroenterology and Nutrition, The Pediatric Liver Center, Johns Hopkins University School of Medicine, Baltimore, MD

10Liver Disease and Hepatitis Program, Alaska Native Tribal Health Consortium, Alaska Native Medical Center, Anchorage, AK

Received February 11, 2010; accepted April 8, 2010.

The workshop was convened and funded by the Hepatitis B Foundation (http://www.hepb.org) from its general operating funds.

The Hepatitis B Foundation is supported primarily by federal, state and private foundation grants as well as individual charitable donations. The Foundation also has small, unrestricted educational grants from Bristol-Myers Squibb, Gilead Sciences, Idenix, Merck, and Novartis, but no commercial support was provided for this August 11, 2009, workshop. Barbara A. Haber, research support from Bristol-Myers Squibb, Gilead, and Roche; Joan Block, no disclosures; Maureen M. Jonas, research support from Bristol-Myers Squibb, Gilead, and consulting agreement with Gilead, Novartis, and Roche; Saul J. Karpen, no disclosures; W. Thomas London, no disclosures; Brian McMahon, spouse has 100 shares of GlaxoSmithKline in her IRA; Karen F. Murray, research funding from Gilead and Roche; Michael R. Narkewicz, research funding from GlaxoSmithKline; Philip Rosenthal, research support from Bristol-Myers Squibb, Roche, and speakers bureau with GlaxoSmithKline and Merck; and Kathleen B. Schwarz, research support from Bristol-Myers Squibb, Gilead, Roche, and consulting agreement with Novartis.

View this article online at wileyonlinelibrary.com.

DOI 10.1002/hep.23934

Abbreviations: AFP, alpha-fetoprotein; ALT, alanine aminotransferase; AST, aspartate aminotransferase; HBeAg, hepatitis B e antigen; HBsAg, hepatitis B surface antigen; HBV, hepatitis B virus; HCC, hepatocellular carcinoma; HIV, human immunodeﬁciency virus; IFN, interferon; PCR, polymerase chain reaction; peginterferon, peg-IFN; ULN, upper limit of normal.

Potential conflict of interest: Dr. Jonas is a consultant for, and received grants from Novartis. He is a consultant for Roche. He also received grants from Bristol-Myers Squibb and Gilead. Dr. Haber received grants from Bristol-Myers Squibb, Gilead, and Roche. Dr. Murray received grants from Gilead and owns stock in Merck. Dr. Narkewics received grants from Novartis. Dr. Rosenthal advises and received grants from Roche. He is on the speakers’ bureau of GlaxoSmithKline and received grants from Bristol-Myers Squibb.

Address reprint requests to: Maureen M. Jonas, MD, Children’s Hospital Boston, 300 Longwood Avenue, Boston, MA 02115. E-mail: [email protected]; fax: 617-730-0716.

Online date: October 1, 2010

Abstract

Chronic hepatitis B virus (HBV) infection in children presents a therapeutic challenge for the practitioner. Decisions regarding selection of patients who may beneﬁt from treatment, appropriate timing of treatment, and the choice of antiviral therapy are complex and are compounded by the limited number of drugs that have been studied in children. An expert panel of nationally recognized pediatric liver specialists was convened by the Hepatitis B Foundation on August 11, 2009, to consider clinical practice relative to the therapeutic options available for children. A detailed account of these discussions is provided, and the opinions expressed are based on consensus of the experts, as well as on published evidence when available. The panel concludes that, at this time, there is no established beneﬁt of treatment of children in the immune tolerant phase, and there is a very high risk of devel-opment of drug resistance. In addition, there is no indication for treatment of children in the inactive carrier state. For children in the immune active or reactivation phases, liver histology can help guide treatment decisions, and family history of liver disease, especially hepatocellular carcinoma, may argue for early treatment in some cases. Outside of clinical trials, interferon is the agent of choice in most cases. Nucleos(t)ide analogues are secondary therapies, and children who receive these agents require careful monitoring for development of resistance. There are a few situations when treatment is indicated regardless of HBV DNA or alanine aminotransferase levels. There is still much to be elucidated about the appropriate use of HBV therapy in children. Until more clinical data and therapeutic options are avail-able, a conservative approach is warranted. (HEPATOLOGY 2010;52:2192-2205)