The Public Health Impact of Antiviral Therapy for Chronic Hepatitis B

200 Pages·2011·3.62 MB·English

The Public Health Impact of
Antiviral Therapy for Chronic Hepatitis B
Mehlika Toy
The Public Health Impact of Antiviral Therapy for Chronic Hepatitis B
Mehlika Toy
ISBN: 978-94-91211-36-2
© Copyright 2011, Mehlika Toy
All rights reserved. No part of this thesis may be reproduced, stored in a retrieval center of any
nature, or transmitted, in any form or by any means, electronic, mechanical, photocopying,
recording or otherwise, without the permission of the author.
Cover design: Aslı Toy, www.Aslitoy.com, [email protected]
Lay out: Legtron Electronic Publishing, Rotterdam, the Netherlands
Printing: Ipskamp Drukkers, Enschede, the Netherlands
Part of the research in this thesis was financially supported by the VIRGIL EU Grant (LSHM-
CT-2004-503359), LiverDoc, and EASL Sheila Sherlock fellowship.
Financial support for the publication of this thesis was given by Erasmus University Rotterdam,
the Department of Public Health, Erasmus MC University Medical Center, and LiverDoc
The Public Health Impact of
Antiviral Therapy for Chronic Hepatitis B
Het publieke gezondheidseffect van
antivirale therapie voor chronische hepatitis B
Proefschrift
ter verkrijgen van de graad van doctor aan de
Erasmus Universiteit Rotterdam
op gezag van de
rector magnificus
Prof.dr. H.G. Schmidt
en volgens besluit van het College voor Promoties
De openbare verdediging zal plaatsvinden op
Dinsdag 7 Juni 2011 om 13:30
door
Mehlika Toy
geboren te Bursa
PROMOTIECOMISSIE
Promotor: Prof.dr. J.H. Richardus
Overige leden: Prof.dr. H.L.A. Janssen
Prof.dr. A. Hofman
Prof.dr. A.I.M. Hoepelman

CONTENTS
Chapter 1 General Introduction 9
Chapter 2 Transmission routes of hepatitis B virus infection in chronic 19
hepatitis B patients in The Netherlands
Journal of Medical Virology 2008;80:399-404
Chapter 3 Age and region specific hepatitis B prevalence in Turkey 31
estimated using generalized linear mixed models
Chapter 4 Potential impact of long-term nucleoside therapy on the 59
mortality and morbidity of active chronic hepatitis B
Hepatology 2009;50:743-751
Chapter 5 Mortality and morbidity of chronic hepatitis B and the 81
cost-effectiveness of treating eligible patients in a median
endemic country
Sumitted to Journal of Hepatology
Chapter 6 Modelling age-specific health gain and costs of antiviral 105
therapy for active chronic hepatitis B
Chapter 7 Screening and early treatment of migrants for chronic 129
hepatitis B virus infection is cost-effective
Gastroenterology 2010;138:522-530
Chapter 8 General discussion 149
Chapter 9 Summary (English) 165
Samenvatting (Dutch) 171
Özet (Turkish) 179
Abbreviations 185
Acknowledgments 187
Curriculum vitae 191
PhD Portfolio Summary 193
Chapter 1
General Introduction
10 | Chapter 1
Of the approximately 2 billion people who have been infected worldwide with the hepatitis
B virus (HBV), more than 350 million are chronic carriers.1 HBV infection accounts for
600,000-1,200,000 deaths each year.2,3 Chronic viral hepatitis B is a major global public
health problem, an important cause of morbidity and mortality from sequelae, which include
chronic hepatitis, cirrhosis, and primary liver cancer. Because the course of the disease can
go without clinical symptoms for a long time it is a ‘silent’ disease, and the contribution of
chronic hepatitis B to global morbidity and mortality is generally underestimated.
Epidemiology
On the basis of sero-epidemiological surveys, the World Health Organization (WHO) has
classified countries into three levels of endemicity according to the prevalence of chronic
HBsAg carriage: high (>8%), intermediate (2‒8%) and low (<2%).4
Man is the only reservoir of HBV. However, the extremely high ability of HBV to replicate
leads to production of high amounts of infective viral particles that are present in blood and
body fluids from infected subjects, thus making hepatitis B a highly transmissible infection.
Spread to susceptible persons may occur through several mechanisms.
Most people become chronically infected at childbirth when the mother is a hepatitis B
carrier (vertical transmission), while others become infected by close personal contact (infancy,
unprotected sex) or by injections (medical and dental instruments or intravenous drug use)
(horizontal transmission). The risk of developing chronic HBV infection after horizontal
transmission is between 30% and 50% for children infected between birth and 5 years of age,
but only 7‒10% thereafter. It has been unclear why vertical transmission is common in some
areas of the world such as Asia and horizontal transmission in children is the dominant mode
in other parts of the world such as the Mediterranean region, Eastern Europe, Alaska, and sub-
Saharan Africa. The age at which seroconversion from HBeAg to anti-HBe occurs in infected
persons appears to be a key determinant in whether HBV is transmitted at or after birth.5
Eight genotypes of HBV ranging from A to H have been identified worldwide.6
Epidemiological studies indicate that these genotypes are common in different parts of the
world: genotype A in Western Europe, North America and Africa; genotype B in North
and Southeast Asia; genotype C in Asia and the Pacific; genotype D in Southern Europe
(Mediterranean countries, Middle East); genotype E in West Africa; and genotype F in
Central and South America and Alaska, genotype G in some European countries and North
America; and genotype H has been recently reported from Central America. Most genotypes
can be further divided into subgenotypes. The most relevant distinct distribution is made
in subgenotype A. Subgenotype A1 is the dominant subgenotype in Africa and India, and