Clinical Gastroenterology George Y. Wu, Series Editor
For other titles published in this series, go to www.springer.com/series/7672
Viral Hepatitis in Children Unique Features and Opportunities Edited by
Maureen M. Jonas Division of Gastroenterology, Children’s Hospital Boston, Boston, MA, USA
Editor Maureen M. Jonas Division of Gastroenterology Children’s Hospital Boston Harvard Medical School Boston, MA, USA
[email protected]
ISBN 978-1-60761-372-5 e-ISBN 978-1-60761-373-2 DOI 10.1007/978-1-60761-373-2 Springer New York Dordrecht Heidelberg London Library of Congress Control Number: 2010934591 © Springer Science+Business Media, LLC 2010 All rights reserved. This work may not be translated or copied in whole or in part without the written permission of the publisher (Humana Press, c/o Springer Science+Business Media, LLC, 233 Spring Street, New York, NY 10013, USA), except for brief excerpts in connection with reviews or scholarly analysis. Use in connection with any form of information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed is forbidden. The use in this publication of trade names, trademarks, service marks, and similar terms, even if they are not identified as such, is not to be taken as an expression of opinion as to whether or not they are subject to proprietary rights. While the advice and information in this book are believed to be true and accurate at the date of going to press, neither the authors nor the editors nor the publisher can accept any legal responsibility for any errors or omissions that may be made. The publisher makes no warranty, express or implied, with respect to the material contained herein. Printed on acid-free paper Humana Press is part of Springer Science+Business Media (www.springer.com)
Preface
Acute and chronic viral hepatitis infections are serious public health threats around the world. The different infections have different epidemiology and natural histories, and children play important roles in each of these. For example, children are important reservoirs for acute hepatitis A, childhood infections are responsible for most of the global morbidity associated with chronic hepatitis B, and perinatal transmission of hepatitis C continues to occur, even as the overall incidence of new infections wanes. Some non-A through E viral hepatitis infections are seen predominantly in infants and young children, while others have specific implications for this population. Therapeutic options for children with chronic viral hepatitis are limited when compared to those available for adults, especially for hepatitis B, and considerations given to long-term therapy have dramatic implications when dealing with the long life expectancy of these young patients. With these issues in mind, this unique volume has been created to address the special considerations regarding viral hepatitis in children. It includes the latest information and recommendations specifically directed at the pediatric population, and highlights the knowledge gaps which will need to be filled to improve our understanding of these infections and treatment of this special group. Experienced practitioners from around the world have contributed these reviews, incorporating the latest studies, the current recommendations, and the distinctive pediatric issues that shape clinical care, and will determine the research agenda for this field going forward. There is a chapter dedicated only to immunoprophylaxis, emphasizing the critical nature of this aspect of care in the important goals of control and eventual eradication of some of these infections. Another chapter is aimed specifically at the primary care issues that arise during evaluation and management of infants and children who are at risk for or affected by viral hepatitis. It is hoped that this work will be a valuable resource for pediatricians, pediatric gastroenterologists, and hepatologists and infectious disease specialists who may care for children with viral hepatitis. Boston, MA
Maureen M. Jonas
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Contents
1 Hepatitis A in Children............................................................................. Michelle Rook and Philip Rosenthal
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2 Epidemiology and Natural History of Hepatitis B in Children............. Szu-Ta Chen and Mei-Hwei Chang
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3 Treatment of Chronic Hepatitis B in Children........................................ Annemarie Broderick
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4 Epidemiology and Natural History of Hepatitis C in Children............. Nanda Kerkar
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5 Treatment of Chronic Hepatitis C in Children....................................... Karen F. Murray
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6 Hepatitis D and Hepatitis E in Children.................................................. Rima Fawaz
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7 Hepatitis in Children due to Non-A–E Viruses....................................... 111 Karan Emerick 8 Immunoprophylaxis of Hepatitis A and Hepatitis B in Children.......... 129 Scott A. Elisofon 9 Primary Care of Children with Viral Hepatitis: Diagnosis, Monitoring, and General Management................................................... 151 Jessi Erlichman, Will Mellman, and Barbara A. Haber Index.................................................................................................................. 169
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Contributors
Annemarie Broderick, MB, MMedSc, DCH, MRCPI (Paeds) Consultant Paediatric Gastroenterologist, Our Lady’s Children’s Hospital, Crumlin, Dublin12, Ireland & UCD Senior Clinical Lecturer, School of Medicine and Medical Science, University College Dublin, Dublin 4, Ireland Mei-Hwei Chang, MD Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan Szu-Ta Chen, MD Yun-Lin Branch, National Taiwan University Hospital, Taipei, Taiwan Scott A. Elisofon, MD Instructor in Pediatrics, Division of Gastroenterology and Nutrition, Children’s Hospital Boston, Harvard Medical School, Boston MA, USA Karan Emerick, MD Division of Gastroenterology, Connecticut Children’s Medical Center, Hartford CT, USA Jessi Erlichman, MPH Division of Gastroenterology, Hepatology, and Nutrition, The Children’s Hospital of Philadelphia, Philadelphia PA, USA Rima Fawaz, MD Instructor in Pediatrics, Children’s Hospital Boston, Boston MA, USA Barbara A. Haber, MD Associate Professor of Pediatrics, Division of Gastroenterology, Hepatology, and Nutrition, The Children’s Hospital of Philadelphia, School of Medicine, University of Pennsylvania, Philadelphia PA, USA
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Contributors
Nanda Kerkar, MD Associate Professor of Pediatrics and Surgery, Medical Director, Pediatric Liver and Liver Transplant Program, Mount Sinai School of Medicine, New York NY, USA Will Mellman, MSW Division of Gastroenterology, Hepatology, and Nutrition, The Children’s Hospital of Philadelphia, Philadelphia PA, USA Karen F. Murray, MD Director, Hepatobiliary Program Division of Gastroenterology and Hepatology, Seattle Children’s Hospital, Seattle WA, USA Michelle Rook, MD Fellow, Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, University of California, San Francisco CA, USA Philip Rosenthal, MD Professor of Pediatrics and Surgery, Medical Director, Pediatric Liver Transplantation Center, Director, Pediatric Hepatology, University of California, San Francisco CA, USA
Hepatitis A in Children Michelle Rook and Philip Rosenthal
Key Concepts • Hepatitis A virus is the most common viral hepatitis globally. • Hepatitis A virus is a serious public health concern, and causes significant morbidity and mortality. • The changing epidemiological features of hepatitis A are associated with the inception of vaccine programs. • Hepatitis A infection has numerous clinical presentations. Keywords Hepatitis A • Epidemiology • Clinical manifestations • Prevention • Public health
Introduction Hepatitis A virus (HAV), a non-enveloped ribonucleic acid (RNA) virus of the Picornaviridae family, was first detected by immune electron microscopy by Purcell in 1973. Globally, it is the most common form of viral hepatitis. It is transmitted via the fecal–oral route, spreading primarily through close individual contact, and has been the most common cause of acute hepatitis in the United States, and throughout the world. Due to advances in detection, prevention, and prophylaxis, infection with HAV has been on the decline. The development of accurate serologic tests has allowed for investigations into the epidemiology, clinical features, natural history, and rapid diagnosis of this disease.
M. Rook (*) Department of Pediatrics, University of California San Francisco, 500 Parnassus Avenue MU4E, San Francisco, CA 94108, USA e-mail:
[email protected] M.M. Jonas (ed.), Viral Hepatitis in Children: Unique Features and Opportunities, Clinical Gastroenterology, DOI 10.1007/978-1-60761-373-2_1, © Springer Science + Business Media, LLC 2010
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M. Rook and P. Rosenthal
Epidemiology United States Hepatitis A has been one of the most frequently reported infectious diseases, with an average of 28,000 cases per year reported between 1987 and 1997 [1]. The incidence of HAV in the United States reported by the CDC has declined 92% from 12 cases per 100,000 population in 1995 to 1.0 case per 100,000 in 2007, with the decline being the greatest in children [1]. There has been a drastic decrease in the reported cases of HAV (Table 1). The most recent data from 2007 suggest that acute symptomatic disease occurred in 2,979 individuals, with an estimation of 25,000 cases of asymptomatic disease and/or underreporting compared with 22,000–36,000 HAV cases reported annually from 1980 to 1995 [1, 2]. The lower incidence of HAV infections in the United States can most likely be attributed to the introduction of the hepatitis A vaccine in 1995 [1, 2]. Incidence of HAV infections in the United States varies based on geographic location, age, sex, race, and ethnicity [1]. The highest rates of HAV in the United States prior to 2002 were observed in western regions [1]. Prior to vaccination programs, the highest incidence of HAV occurred in children and young adults, and the lowest incidence in adults older than 40 years of age [1–3]. Current data demonstrate the reversal of these trends. During 2001–2007, the lowest incidence was found in children 8%), intermediate (2–8%), and low (8% HBsAg positivity) in the world, such as China, South Korea, Taiwan, Thailand and Vietnam [23]. Some countries in this area, such as Japan, Australia, and New Zealand, have low HBsAg prevalence rates. In the high endemic areas, perinatal infection and household contact with chronically infected patients during early childhood are the predominant modes of transmission [23]. For example, in Taiwan, before the implementation of a universal HBV immunization program, the HBsAg seropositivity rate of children in highly endemic areas was 5% in infants
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and increased to 10% at 2 years of age, remaining at the same rate thereafter. However, the anti-HBc antibody seropositivity rate reached 50% by the age of 15 years. This suggests that most HBsAg carriers in this population were infected before 2 years of age due to perinatal or early childhood transmission [5, 24]. In low prevalence areas, HBV infection is acquired mainly in adolescents and adults. Childhood HBV infection in this population is concentrated in immigrants from hyperendemic areas and in high-risk groups, such as children of intravenous drug users.
Africa After Asia, Africa has the second largest number of individuals with chronic HBV infection, approaching 58 million [25]. Although overall Africa is considered a high endemic area with 7–26% prevalence of HBsAg, Tunisia, Morocco, and Zambia have intermediate endemicity [26]. In some countries in western Africa, e.g., Senegal and Gambia, over 90% of the population are exposed to and become infected with HBV during their lives [27]. Because of high HBV endemicity, Gambia was the first country in Africa to implement a mass infant immunization program in 1990, and demonstrated a reduced HBV burden in children, with HBsAg prevalence decreasing from 10.0 to 0.6% [6, 7]. In contrast to Asia, where mother-to-infant transmission is an important route, horizontal transmission in early life is considered to be the predominant mode of transmission in most of subSaharan Africa [28]. In rural areas of west Africa, HBV infection rates increase rapidly from the age of 6 months, and by the age of 2 years, 40% of children are infected and 15% develop chronic infection. By the age of 10 years, 90% of children become infected and 20% are chronic carriers [29].
HBV Transmission in Children Major routes of HBV transmission include perinatal infection, horizontal infection, sexual behaviors, and intravenous drugs use. The transmission patterns differ in countries according to HBV endemicity. In hyperendemic areas, perinatal and horizontal infections in childhood are responsible for most transmission of infection; in intermediate endemic areas, a mix of various routes of transmission are observed; and in low endemic countries, most new infections occur in young adults through sexual intercourse or injecting drugs. Perinatal transmission from HBsAg-positive mothers to their infants is an important route of transmission in children (Table 1), and accounts for 40–50% before and 90% after the HBV vaccination era of HBsAg carriers in endemic areas in Asia such as Taiwan [5]. The young age of HBV infection and maternal hepatitis B e antigen (HBeAg) seropositivity are important factors in determining chronicity in children [30–33]. Chronic HBV infection develops in 90% of infected neonates or infants but only in 1–5% of
Epidemiology and Natural History of Hepatitis B in Children
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Table 1 Outcome of HBV infection in infants with different immunoprophylaxis strategies and maternal HBeAg status Infant HBsAg (+) mother No vaccination Vaccination HBIG + vaccination HBeAg (+) >90% chronic 20–25% chronic 10–15% chronic infection infection [30] infection HBeAg (−)
