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HEPATITIS B VIRUS AND LIVER DISEASE PDF

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Hepatitis B Virus and Liver Disease Jia-Horng Kao Editor Second Edition 123 Hepatitis B Virus and Liver Disease Jia-Horng Kao Editor Hepatitis B Virus and Liver Disease Second Edition Editor Jia-Horng Kao Hepatitis Research Center National Taiwan University Hospital Taipei Taiwan Graduate Institute of Clinical Medicine National Taiwan University College of Medicine Taipei Taiwan ISBN 978-981-16-3614-1 ISBN 978-981-16-3615-8 (eBook) https://doi.org/10.1007/978-981-16-3615-8 © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2021 This work is subject to copyright. All rights are solely and exclusively licensed by the Publisher, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information 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 publication 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, expressed 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 Singapore Pte Ltd. The registered company address is: 152 Beach Road, #21-01/04 Gateway East, Singapore 189721, Singapore To my mentors Professor Juei-Low Sung and Professor Ding-Shinn Chen In memory of my father Shi-Yang Kao To my mother Wen-Shu Ho Foreword Globally, hepatitis B virus (HBV) has been ubiquitous and continues to be respon- sible for significant morbidity and mortality through clinical consequences of chronic hepatitis, cirrhosis, liver failure, and hepatocellular carcinoma (HCC). Since the discovery of the virus in 1965 for which Dr. Baruch Blumberg was awarded the Nobel Prize, there have been tremendous advances in understanding the virology, the development of several serological markers in the diagnosis of the infection, and the development of effective vaccines and vaccination strategies to impact on the incidence and prevalence of HBV infection. Yet, there remains a siz- able population with chronic HBV infection. Relatively, a major challenge has been in successfully “curing” this infection while developing effective and well-tolerated HBV suppressive therapies. The second edition entitled Hepatitis B Virus and Liver Disease has compiled an outstanding group on internationally recognized “who’s who” experts in addressing complex and currently relevant topics in HBV, and it serves as good reading and a reference for practicing physicians at all levels. The list of topics is well-thought-out by the editor and placed in proper order. In an era where there is abundant online material on a given topic, there is still a need for such products put together by experts. It particularly provides the novice reader an opportunity to quickly obtain precise information presented by an expert and thus not having to surf through plen- tiful and freely available material to get their information. It begins with the fundamental and essential topic of molecular virology and life cycle of HBV and sequentially takes us through a series of topics that are essential in the day-to-day understanding of HBV infection. The book covers, extremely well, the gamut of important topics such as epidemiology, immunopathogenesis, noninvasive assessment of the degree of hepatic HBV-related fibrosis, unmet needs in basic science and clinical research, the therapeutic advances in chronic HBV infection, vaccines, and HBV reactivation. There has been a lot of interest in new and novel biomarkers that can have utility in assessing response to HBV therapy and the topic is covered well. It is up to date with little to no redundancy and ends up with a topic on the major unmet need of achieving a “cure” of this infection. This is the elusive and, at this stage, difficult to overcome barrier faced by all HBV inves- tigators. Currently, there appears to be a consensus on the definition of what consti- tutes a cure based on the serologic status of HBV, which is the right step toward achieving the goal of cure. Eradication of cccDNA, while attempting to develop vii viii Foreword serologic surrogates for this marker, appears to be the Achilles’ heel for those intensely pursuing therapies to “cure” HBV. Our struggle with efforts at curing this infection continues and one hopes that we will see advances in this direction over the next few years. As Sir Winston Churchill aptly said “Success is not final, failure is not fatal: it is the courage to continue that counts.” Indeed, I have found this second edition entitled Hepatitis B Virus and Liver Disease to be comprehensive yet precise, covering the entire spectrum of relevant topics in HBV, and very readable with good tables and figures. It certainly is a book I would like to have on my shelf as ready reference material. K. Rajender Reddy Liver Transplantation University of Pennsylvania Philadelphia PA USA Preface of the Second Edition Hepatitis B virus (HBV) was identified in the early 1960s, and it was soon found that HBV infection is among the most frequent and important in humans. HBV causes a wide spectrum of liver diseases, spanning from acute/fulminant hepatitis to chronic hepatitis/cirrhosis and hepatocellular carcinoma. It is also related to certain extrahepatic manifestations. Over the past few decades, the understanding of HBV infection, especially the virology, immunopathogenesis, and management, has evolved dramatically. The pathogenesis of HBV infection is getting clearer after vigorous basic, clinical, and epidemiological studies. More constructively, acute HBV infection can now be prevented by effective vaccines, and chronic infection can be suppressed efficiently by antiviral agents, shedding light at the end of the tunnel toward HBV cure and even elimination of HBV infection. The rapid progress prompted late Professor Ding-Shinn Chen and myself to edit the first edition of the monograph Hepatitis B Virus and Liver Disease, which was published by Springer Singapore Pte Ltd in 2018. We aimed to provide a compre- hensive, state-of-the-art review of HBV infection and liver disease. Owing to the quick advance of HBV-related studies in these years, a new up-to-date book is thus urgently required. The new book updated the results of basic and translational medi- cine including hepatitis B viral life cycle, unmet needs of basic research, immuno- pathogenesis of HBV-induced chronic liver disease, pathology, molecular carcinogenesis, and viral and host genetic factors affecting disease progression. The clinical aspects of chronic HBV infection were elucidated by experts in epidemiol- ogy, natural history, hepatitis B vaccination, new biomarkers, noninvasive assess- ment of fibrosis, current treatment options, coinfection with hepatitis C or D viruses and human immunodeficiency virus, and management of special populations like children, pregnant women, and those under immunosuppressive therapy. The impli- cations of occult HBV infection were also discussed. Finally, the advances and per- spectives in the development of novel treatments for the cure of HBV infection and the possibility of HBV cure were included. In June 2020, Professor Ding-Shinn Chen, the main driver and great helmsman of the nationwide hepatitis B vaccination program in Taiwan, passed away. Professor Chen’s lifetime research has disclosed the causal relationship of HBV and HCV with chronic hepatitis, cirrhosis, and hepatocellular carcinoma. His important dis- covery and insightful perspective starting from Taiwan have successfully led to a global campaign of universal hepatitis B vaccination, which has saved millions of ix x Preface of the Second Edition lives across the world. Professor Chen is a role model for physician scientists. His research career originated from the curiosity for knowledge, persisted in pursuit of academic excellence, translated into clinical practices, and eventually extended to patient-centered care. His legacy will continue and guide us to eliminate HBV infection in the foreseeable future, not only in Taiwan but also in other parts of the world. I hope this new edition of book covering all relevant aspects of HBV infection can serve as a useful resource for every reader who has interest in the management and study of patients with hepatitis B. Taipei, Taiwan Jia-Horng Kao Contents 1 Molecular Virology and Life Cycle of Hepatitis B Virus . . . . . . . . . . . . 1 Fleur Chapus, Maria Guadalupe Martinez, Barbara Testoni, and Fabien Zoulim 2 Unmet Needs in Basic Research of Hepatitis B Virus Infection: In Vitro and In Vivo Models . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29 C. Nelson Hayes and Kazuaki Chayama 3 Unmet Needs in Clinical Research Hepatitis B . . . . . . . . . . . . . . . . . . . 51 Geoffrey Dusheiko 4 Immunopathogenesis of Hepatitis B Virus Infection . . . . . . . . . . . . . . . 73 Conan Chua, Loghman Salimzadeh, and Adam J. Gehring 5 Pathology of Hepatitis B Virus (HBV) Infection and HBV-Related Hepatocellular Carcinoma . . . . . . . . . . . . . . . . . . . . . . . . 99 Bicong Wu and Matthew M. Yeh 6 Molecular Carcinogenesis of Hepatitis B Virus-Related Hepatocellular Carcinoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 123 Amanda Jean Craig and Xin Wei Wang 7 Epidemiology and Natural History of Hepatitis B Virus Infection: Time- Dependent Driving Factors of Chronic Hepatitis B Progression . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 143 Hwai-I Yang and Chien-Jen Chen 8 Hepatitis B Vaccines . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 169 John W. Ward 9 Viral and Host Factors Affecting Disease Progression of Hepatitis B Virus Infection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 205 Hung-Chih Yang and Tung-Hung Su 10 Novel Biomarkers for the Management of Chronic Hepatitis B Virus Infection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 231 Chih-Lin Lin and Jia-Horng Kao xi

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