Viral Hepatitis: Acute Hepatitis Resat Ozaras Joop E. Arends Editors 123 Viral Hepatitis: Acute Hepatitis Resat Ozaras • Joop E. Arends Editors Viral Hepatitis: Acute Hepatitis Editors Resat Ozaras Joop E. Arends Cerrahasa Medical School University Medical Center Utrecht Istanbul University Cerrahasa Medical GA Utrecht, Utrecht School The Netherlands Istanbul Turkey ISBN 978-3-030-03534-1 ISBN 978-3-030-03535-8 (eBook) https://doi.org/10.1007/978-3-030-03535-8 Library of Congress Control Number: 2018965731 © Springer Nature Switzerland AG 2019 This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recita- tion, broadcasting, reproduction on microfilms or in any other physical way, and transmission or infor- mation storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publica- tion does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. The publisher, the authors, and the editors are safe to assume that the advice and information in this book are believed to be true and accurate at the date of publication. Neither the publisher nor the authors or the editors give a warranty, express or implied, with respect to the material contained herein or for any errors or omissions that may have been made. The publisher remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. This Springer imprint is published by the registered company Springer Nature Switzerland AG The registered company address is: Gewerbestrasse 11, 6330 Cham, Switzerland Dr. Resat Ozaras dedicates this book to his deceased mother and father and Dr. Joop E. Arends dedicates this book to his loving family. Foreword Viral hepatitis is a major public health problem in need of an urgent response. It is estimated that the yearly mortality rate deriving from acute and chronic viral hepa- titis exceeds 1.3 million, approaching that of tuberculosis, and increasing. This is in contrast to TB, HIV and malaria, all of which show a steady decrease in mortality. Although two-thirds of deaths are attributable to hepatitis B, 30% are caused by complications of chronic hepatitis C, 3% to hepatitis E, which can be responsible for fulminant hepatitis in pregnant women, and only 0.8% to hepatitis A. The afore- mentioned scenario has induced WHO to develop a strategical set of recommenda- tions in an effort to achieve elimination in most countries by 2030. These include (1) achieving 90% coverage of three-dose HBV vaccination preventing 90% of mother to child transmission; (2) 100% screened blood donations and 90% implementation of reuse-prevention devices; (3) harm reduction interventions in at-risk populations such as PWID; and (4) high frequency of diagnosis and linkage to care for hepatitis C, to insure a 90% reduction of incidence and 65% drop in mortality rate. These targets are rather ambitious and probably achievable in a minority of virtuous coun- tries that have implemented universal HBV vaccination and access to the highly efficacious direct-acting antivirals for HCV cure, as well as “one health” approaches to limit the risk of HAV and HEV infections. However, HAV has re-emerged as a sexually transmitted pathogen in MSM over the past 3 years, calling for the imple- mentation of capillary vaccination programmes in at-risk communities. Moreover, HDV is also a re-emerging pathogen, having re-appeared together with the dramatic new wave of infections in PWID. In this setting, the five major hepatitis viruses play different roles, both in terms of potentially severe acute onset and ability to persist in the host for an indefinite period of time. This last property has for long been considered restricted to HBV, HDV and HCV, while it is now clear that certain HEV genotypes can cause chronic liver dis- ease and cirrhosis in immune suppressed patients. Acute presentation of viral hepati- tis is slowly decreasing globally and this is further compounded by an underestimation of cases due to the large number of asymptomatic, anicteric forms, particularly for hepatitis C. Nonetheless, the focus of this excellent collection of review articles, contributed by outstanding investigators in the field and edited by Drs. Ozaras and Arends, is both timely and appropriate. The chapters are unique in that they provide updated information for all hepatitis viruses in terms of global epidemiology, patho- genesis, molecular virology and clinical presentation. They will be extremely useful vii viii Foreword not only to hepatologists who will enjoy the feature of finding practical reference information on acute hepatitis caused by all major viruses, but also to non-specialists who, I am sure, will appreciate the essentially clear style of the e-book, capable of conveying a flawless message both to sophisticated and basic readers. The editors and authors should be unconditionally praised for their effort. Division of Infectious Diseases and Immunology, Mario U. Mondelli Fondazione IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy Preface Although a jaundice-like clinical disease patron was known already for centuries after its early descriptions by Hippocrates (Trepo et al. Liver Int. 2014 Feb;34 Suppl 1:29–37), its causative agents remained quite a mystery. The infectious origin was recognized through its epidemic form as opposed to the more recent serum origin, which was described by Lührman in 1885 who reported patients developing hepati- tis after smallpox vaccination. It was not until the last 50 years that true remarkable discoveries have unraveled most of the mysteries regarding viral hepatitis. It started with the discovery of the Australia antigen in 1963 by Blumberg (Blumberg BS, Alter HJ, Visnich A. A ‘new’ antigen in leukemia sera. JAMA 1965; 191: 541–6). We now live in an era in which many viral causes for hepatitis have been identi- fied, visualized, extensively studied, and curative or suppressive through antiviral therapy. Although hepatitis A is known to cause outbreaks, especially in poor hygienic circumstances, vaccines are available and societies know how to react with isolation and hygiene measures once an outbreak has been confirmed. Successful worldwide vaccination campaign after childbirth has resulted in a sharp decline in prevalence among children in many countries. In addition, the antiviral and immu- nomodulatory drugs are capable of suppressing the virus with subsequent slowing down of fibrosis progression and lowering the chances of developing hepatocellular carcinoma. In conjunction with this, the prevalence and comorbidity of hepatitis D has gone down worldwide as well. For hepatitis C it is a true success story following the development of direct-acting antiviral agents (DAAs) in the past years. Viral clearances rates over 95% after short courses of therapy resulted in numerous coun- tries speculating about hepatitis C elimination. Also, the World Health Organization (WHO) has set ambitious goals to reduce the burden of viral hepatitis worldwide. Finally, for hepatitis E, it remains to be seen what the future holds. On the one hand, the epidemic genotypes 1 and 2 should be regarded as hepatitis A. However, geno- type 3 in Western countries is probably highly spread within the food chain and thus putting numerous people at risk of acquiring the disease. This is mostly problematic for immunocompromised patients, due to the extensive growth in immune modula- tory agents, in a growing population. With only ribavirin at hand, treatment pros- pects for these patients are not so good in the near future. In addition, new types of hepatitis E, like the recently described rat-type hepatitis E, have been described to cause disease in humans. ix x Preface Given all these developments in the world of viral hepatitis, it is important to bundle this knowledge and transfer knowledge for educational purposes. That is precisely the aim of this book on acute viral hepatitis. We have asked experts with an outstanding reputation in the field to write chapters on different aspects of acute hepatitis A through E. We hope you enjoy this book and that it gives you new insights that will help you in giving the best care to patients with an acute viral hepatitis. Istanbul, Turkey Resat Ozaras Utrecht, The Netherlands Joop E. Arends Contents 1 Global Epidemiology of Acute Viral Hepatitis A–E . . . . . . . . . . . . . . . . . 1 Hubert E. Blum 2 Acute Hepatitis A . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17 Erica Patricia Turse, Brett Rossow, and Veysel Tahan 3 Acute Hepatitis B . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25 Aliye Bastug and Hurrem Bodur 4 Acute Hepatitis C . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45 Joop E. Arends, Maria Cristina Leoni, and Dominique Salmon 5 Acute HBV/HDV Infection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 67 Cihan Yurdaydin 6 A Review of Acute Viral Hepatitides Including Hepatitis E . . . . . . . . . . 77 Mohammad Sultan Khuroo xi