Добавил:
Sekretar
kiopkiopkiop18@yandex.ru
t.me/Prokururor I Вовсе не секретарь, но почту проверяю
Опубликованный материал нарушает ваши авторские права? Сообщите нам.
Вуз:
Предмет:
Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_45_библиотеки_им_акад_М_И_Перельмана
.pdf
HEPATOLOGY
A clinical textbook
Mauss, Berg, Rockstroh, Sarrazin, Wedemeyer
10th Edition 2020
Mauss, Berg, Rockstroh, Sarrazin, Wedemeyer
Hepatology – A clinical textbook
Tenth Edition, 2020
HEPATOLOG Y
A clinical textbook
10th Edion 2020
Editors
Stefan Mauss
Thomas Berg
Jürgen Rockstroh
Christoph Sarrazin
Heiner Wedemeyer
Disclaimer
Hepatology is an ever-changing ield. The editors and authors of
Hepatology − A Clinical Textbook have made every efort to provide
information that is accurate and complete as of the date of publication.
However, in view of the rapid changes occurring in medical science, as
well as the possibility of human error, this book may contain technical
inaccuracies, typographical or other errors. Readers are advised to check
the product information currently provided by the manufacturer of each
drug to be administered to verify the recommended dose, the method and
duration of administration, and contraindications. It is the responsibility
of the treating physician who relies on experience and knowledge about the
patient to determine dosages and the best treatment for the patient. The
information contained herein is provided “as is” and without warranty of
any kind. The editors disclaim responsibility for any errors or omissions or
for results obtained from the use of information contained herein.
Foreword
10th Edition – 2020
Hepatology – A clinical textbook is now in its tenth edition and the editors as
the book are more mature. The current edition has again been thoroughly
updated to relect the latest medical progress. Because of this regular
revision process it remains an up-to-date reference for all aspects of clinical
hepatology. This would not have been possible without the continuous
contributions of all the authors who have dutifully revised and updated
their chapters.
Again, the book is available in print and as a free download at
www.hepatologytextbook.com
The Editors
Stefan Mauss Thomas Berg
Jürgen Rockstroh Christoph Sarrazin
Heiner Wedemeyer
© 2020 by Mauss, et al.
Design: Hanno Schaaf | Schaakopp.de
54
Preface of the first edition
Hepatology is a rapidly evolving ield that will continue to grow and
maintain excitement over the next few decades. Viral hepatitis is not unlike
HIV 10 or 15 years ago. Today, hepatitis B viral replication can be suppressed
by potent antiviral drugs, although there are risks regarding the emergence
of resistance. Strategies to enhance the eradication rates of HBV infection
still need to be developed. On the other hand, hepatitis C virus infection
can be eradicated by treatment with pegylated interferon plus ribavirin,
although the sustained virologic response rates are still suboptimal,
particularly in those infected with genotype 1. Many new antiviral drugs,
especially protease and polymerase inhibitors, are currently in clinical
development, and the data from trials reported over the last few years
provide optimism that the cure rates for patients with chronic hepatitis C
will be enhanced with these new agents, and even that all-oral regimens
are around the corner! In other areas of hepatology, e.g., hereditary and
metabolic liver diseases, our knowledge is rapidly increasing and new
therapeutic options are on the horizon.
In rapidly evolving areas such as hepatology, is the book format the right
medium to gather and summarise the current knowledge? Are these books
not likely to be outdated the very day they are published? This is indeed a
challenge that can be convincingly overcome only by rapid internet-based
publishing with regular updates. Another unmatched advantage of a webbased book is the free and unrestricted global access. Viral hepatitis and
other liver diseases are a global burden and timely information is important
for physicians, scientists, patients and health care oicials all around the
world.
The editors of this web-based book – Thomas Berg, Stefan Mauss, Jürgen
Rockstroh, Christoph Sarrazin and Heiner Wedemeyer – are young, bright,
and internationally renowned hepatologists who have created an excellent
state-of-the-art textbook on clinical hepatology. The book is well-written
and provides in-depth information without being lengthy or redundant. I
am convinced that all ive experts will remain very active in the ield and
will continue to update this book regularly as the science progresses. This
e-book should rapidly become an international standard.
Stefan Zeuzem – Frankfurt, Germany, January 2009
Therapeutic options and diagnostic procedures in hepatology have
quickly advanced during the last decade. In particular, the management
of viral hepatitis has completely changed since the early nineties. Before
nucleoside and nucleotide analogues were licensed to treat hepatitis B and
before interferon α + ribavirin combination therapy were approved for the
treatment of chronic hepatitis C, very few patients infected with HBV or
HCV were treated successfully. The only option for most patients with endstage liver disease or hepatocellular carcinoma was liver transplantation.
And even if the patients were lucky enough to be successfully transplanted,
reinfection of the transplanted organs remained major challenges. In
the late eighties and early nineties discussions were held about rejecting
patients with chronic hepatitis from the waiting list as posttransplant
outcome was poor. Today, just 15 years later, hepatitis B represents one of
the best indications for liver transplantations, as basically all reinfection
can be prevented. In addition, the proportion of patients who need to be
transplanted is declining − almost all HBV-infected patients can nowadays
be treated successfully with complete suppression of HBV replication and
some well-selected patients may even be able to clear HBsAg, the ultimate
endpoint of any hepatitis B treatment.
Hepatitis C has also become a curable disease with a sustained response
of 50–80% using pegylated interferons in combination with ribavirin. HCV
treatment using direct HCV enzyme inhibitors has started to bear fruit (we
draw your attention to the HCV chapters).
Major achievements for the patients do sometimes lead to signiicant
challenges for the treating physician. Is the diagnostic work-up complete?
Did I any recent development to evaluate the stage and grade of liver
disease? What sensitivity is really necessary for assays to detect hepatitis
viruses? When do I need to determine HBV polymerase variants, before and
during treatment of hepatitis B? When can I safely stop treatment without
risking a relapse? How to treat acute hepatitis B and C? When does a health
care worker need a booster vaccination for hepatitis A and B? These are
just some of many questions we have to ask ourselves frequently during
our daily routine practice. With the increasing number of publications,
guidelines and expert opinions it is getting more and more diicult to
stay up-to-date and to make the best choices for the patients. That is why
Hepatology – A Clinical Textbook is a very useful new tool that gives a
state-of-the art update on many aspects of HAV, HBV, HCV, HDV and HEV
infections. The editors are internationally-known experts in the ield of
viral hepatitis; all have made signiicant contributions to understanding
the pathogenesis of virus-induced liver disease, diagnosis and treatment of
hepatitis virus infections.
Hepatology – A Clinical Textbook gives a comprehensive overview on
the epidemiology, virology, and natural history of all hepatitis viruses
6 7
including hepatitis A, D and E. Subsequent chapters cover all major aspects
https://t.me/medicina_free
of the management of hepatitis B and C including coinfections with HIV and
liver transplantation. Importantly, complications of chronic liver disease
such as hepatocellular carcinoma and recent developments in assessing
the stage of liver disease are also covered. Finally, interesting chapters on
autoimmune and metabolic non-viral liver diseases complete the book.
We are convinced that this new up-to-date book covering all clinically
relevant aspects of viral hepatitis will be of use for every reader. The editors
and authors must be congratulated for their eforts.
Michael P. Manns – Hannover, January 2009
Contributing Authors
Fernando Agüero
Infectious Diseases Service
Hospital Clinic – IDIBAPS
University of Barcelona
Villarroel, 170
08036 Barcelona, Spain
Hikmet Akkiz
Department of Gastroenterology and
Hepatology
Çukurova University
School of Medicine
Adana, Turkey
Akif Altinbas
Diskapi Yildirim Beyazit Education
and Research Hospital
Gastroenterology Clinic
Ankara, Tu rke y
Matthias J. Bahr
Dept. of Medicine I
Sana Kliniken Lübeck
Kronsforder Allee 71-73
23560 Lübeck, Germany
Lars P. Bechmann
Department of Gastroenterology and
Hepatology,
University Hospital Essen
Hufelandstr. 55
45122 Essen, Germany
Susanne Beckebaum
Department of Internal Medicine,
Gastroenterology and Hepatology
St. Josef Krankenhaus
Heidbergweg 22-24
45257 Essen, Germany
Thomas Berg
Sektion Hepatologie
Klinik und Poliklinik ür
Gastroenterologie & Rheumatologie
Universitätsklinikum Leipzig
Liebigstr. 20
04103 Leipzig, Germany
thomas.berg@medizin.uni-leipzig.de
Albrecht Böhlig
Sektion Hepatologie
Klinik und Poliklinik ür
Gastroenterologie & Rheumatologie
Universitätsklinikum Leipzig
Liebigstr. 20
04103 Leipzig, Germany
Florian van Bömmel
Sektion Hepatologie
Klinik und Poliklinik ür
Gastroenterologie & Rheumatologie
Universitätsklinikum Leipzig
Liebigstr. 20
04103 Leipzig, Germany
Christoph Boesecke
Department of Medicine I
University Hospital Bonn
Sigmund-Freud-Strasse 25
53105 Bonn, Germany
Kathrin van Bremen
Department of Medicine I
University Hospital Bonn
Sigmund-Freud-Strasse 25
53105 Bonn, Germany
8 9
Ali Canbay
https://t.me/medicina_free
Universitätsklinik ür
Gastroenterologie, Hepatologie und
Infektiologie
Otto-von-Guericke-Universität
Universitätsklinikum Magdeburg A.ö.R.
Leipziger Str. 44
39120 Magdeburg, Germany
Carlos Cervera
Infectious Diseases Service
Hospital Clínic − IDIBAPS
University of Barcelona
Villarroel, 170
08036 Barcelona, Spain
Vito R. Cicinnati
Department of Internal Medicine,
Gastroenterology and Hepatology
St. Josef Krankenhaus
Heidbergweg 22-24
45257 Essen, Germany
Markus Cornberg
Dept. of Gastroenterology, Hepatology
and Endocrinology
Medical School of Hannover
Carl-Neuberg-Str. 1
30625 Hannover, Germany
Maura Dandri
Center for Internal Medicine
I. Department of Internal Medicine
and
German Center for Infection Research
(DZIF)
Hamburg - Lübeck - Borstel - Riems
University Medical Center
Hamburg-Eppendorf
Martinistr. 52
20246 Hamburg, Germany
Alejandro Forner
Barcelona Clinic Liver Cancer Group
Liver Unit
Hospital Clínic − IDIBAPS
University of Barcelona
Villarroel, 170
08036 Barcelona, Spain
Juan-Carlos García-Valdecasas
Liver Transplant Unit, Department of
Surgery
Hospital Clínic − IDIBAPS
University of Barcelona
Villarroel, 170
08036 Barcelona, Spain
Guido Gerken
Department of Gastroenterology,
University Hospital Essen
Hufelandstr. 55
45122 Essen, Germany
PD Dr. Frank Grünhage
Chefarzt Klinik ür Gastroenterologie
und Onkologie
Von Werth-Straße 5
41515 Grevenbroich, Germany
Christoph Höner zu Siederdissen
Dept. of Gastroenterology, Hepatology
and Endocrinology
Medical School of Hannover
Carl-Neuberg-Str. 1
30625 Hannover, Germany
Anna Hüsing
Department of Transplant Medicine
University Hospital Münster
Albert-Schweitzer-Campus 1
48149 Münster, Germany
Iyad Kabar
Department of Transplant Medicine
University Hospital Münster
Albert-Schweitzer-Campus 1
48149 Münster Germany
Bernd Kupfer
Endenicher Strasse 266
53121 Bonn, Germany
Montserrat Laguno
Infectious Diseases Service
Hospital Clínic − IDIBAPS
University of Barcelona
Villarroel, 170
08036 Barcelona, Spain
Frank Lammert
Medical Department II
Saarland University Hospital
Kirrbergerstr. 1
66421 Homburg, Germany
Christian Lange
J. W. Goethe-University Hospital
Medizinische Klinik 1
Theodor-Stern-Kai 7
60590 Frankfurt am Main, Germany
Anna Lligoña
Psychiatry Department
Hospital Clínic − IDIBAPS
University of Barcelona
Villarroel, 170
08036 Barcelona, Spain
Benjamin Maasoumy
Dept. of Gastroenterology,
Hepatology and Endocrinology
Medical School of Hannover
Carl-Neuberg-Str. 1
30625 Hannover, Germany
Michael P. Manns
Dept. of Gastroenterology, Hepatology
and Endocrinology
Medical School of Hannover
Carl-Neuberg-Str. 1
30625 Hannover, Germany
Christian Manzardo
Infectious Diseases Service
Hospital Clínic − IDIBAPS
University of Barcelona
Villarroel, 170
08036 Barcelona, Spain
Stefan Mauss
Center for HIV and
Hepatogastroenterology
Humboldtstraße 18
40237 Duesseldorf, Germany
stefan.mauss@center-duesseldorf.de
José M. Miró
Infectious Diseases Service
Hospital Clínic − IDIBAPS
University of Barcelona
Villarroel, 170
08036 Barcelona, Spain
Raphael Mohr
Department of Medicine I
University Hospital Bonn
Sigmund-Freud-Strasse 25
53105 Bonn, Germany
Asuncion Moreno
Infectious Diseases Service
Hospital Clínic − IDIBAPS
University of Barcelona
Villarroel, 170
08036 Barcelona, Spain
10 11
Claus Niederau
https://t.me/medicina_free
Katholische Kliniken Oberhausen
gGmbH, St. Josef Hospital
Department of Internal Medicine
Academic Teaching Hospital of the
University
Duisburg-Essen
Mülheimer Str. 83
46045 Oberhausen, Germany
Jörg Petersen
Liver Unit IFI Institute for
Interdisciplinary Medicine
Asklepios Klinik St George Hamburg
Lohmühlenstr. 5
20099 Hamburg, Germany
Sven Pischke
Department of Medicine I
University Medical Centre Hamburg-
Eppendorf (UKE)
Martinistrasse 52
20246 Hamburg, Germany
Kerstin Port
Dept. of Gastroenterology, Hepatology
and Endocrinology
Medical School of Hannover
Carl-Neuberg-Str. 1
30625 Hannover, Germany
Karl-Philipp Puchner
Charité, Campus Virchow-Klinikum,
Universitätsmedizin
Medizinische Klinik m. S. Hepatologie
und Gastroenterologie
Augustenburger Platz 1
13353 Berlin, Germany
Antonio Rimola
Liver Transplant Unit – CIBEREHD
Hospital Clínic − IDIBAPS
University of Barcelona
Villarroel, 170
08036 Barcelona, Spain
J. K. Rockstroh
Department of Medicine I
University Hospital Bonn
Sigmund-Freud-Strasse 25
53105 Bonn, Germany
rockstroh@uni-bonn.de
Christoph Sarrazin
Medizinische Klinik II
St. Josefs-Hospital Wiesbaden GmbH
Beethovenstr. 20
65189 Wiesbaden, Germany
CSarrazin@joho.de
Martin Schäfer
Department of Psychiatry
and Psychotherapy
Kliniken Essen-Mitte
Ev. Huyssenstit
Henricistraße 92
45136 Essen, Germany
Carolynne Schwarze-Zander
Department of Medicine I
University Hospital Bonn
Sigmund-Freud-Strasse 25
53105 Bonn, Germany
Philipp Solbach
Dept. of Gastroenterology, Hepatology
and Endocrinology
Medical School of Hannover
Carl-Neuberg-Str. 1
30625 Hannover, Germany
Ulrich Spengler
Department of Internal Medicine 1
University Hospitals of Bonn
University
Sigmund-Freud-Strasse 25
53105 Bonn, Germany
Christian P. Strassburg
Department of Medicine I
University Hospital Bonn
Sigmund-Freud-Strasse 25
53105 Bonn, Germany
Montserrat Tuset
Pharmacy Department
Hospital Clínic − IDIBAPS
University of Barcelona
Villarroel, 170
08036 Barcelona, Spain
Jan-Christian Wasmuth
Department of Medicine I
University Hospital Bonn
Sigmund-Freud-Strasse 25
53105 Bonn, Germany
Heiner Wedemeyer
Direktor der Klinik ür
Gastroenterologie, Hepatologie und
Endokrinologie
Zentrum Innere Medizin
Medizinische Hochschule Hannover
OE6810
Carl-Neuberg-Str. 1
30625 Hannover, Germany
gastroenterologie@mh-hannover.de
Johannes Wiegand
Sektion Hepatologie
Klinik und Poliklinik ür
Gastroenterologie & Rheumatologie
Universitätsklinikum Leipzig
Liebigstr. 20
04103 Leipzig, Germany
Stefan Zeuzem
J. W. Goethe-University Hospital
Medizinische Klinik 1
Theodor-Stern-Kai 7
60590 Frankfurt am Main, Germany
12 13
Table of Contents
https://t.me/medicina_free
1. Hepatitis A 29
Sven Pischke and Heiner Wedemeyer
The virus 29
Epidemiology 29
Transmission 30
Clinical course 31
Extrahepatic manifestations 33
Diagnosis 33
Treatment and prognosis 34
References 35
2. Hepatitis B 37
Kathrin van Bremen, Christoph Boesecke and Jan-Christian Wasmuth
Introduction 37
Transmission 38
Sexual transmission 39
Percutaneous inoculation 39
Perinatal transmission 39
Horizontal transmission 41
Blood transfusion 41
Nosocomial infection 42
Organ transplantation 43
Postexposure prophylaxis 43
Natural history and clinical manifestations 44
Acute hepatitis 44
Chronic hepatitis 45
Prognosis and survival 47
Extrahepatic manifestations 49
References 50
14 15
3. Hepatitis C 53
Jenny Bischof, Christoph Boesecke and Jan-Christian Wasmuth
Epidemiology 53
Transmission 54
Injection drug use 54
Nosocomial/Unsafe medical procedures and injections 55
Blood transfusion 55
Organ transplantation 56
People in prison 56
Men who have sex with men 56
https://t.me/medicina_free
Heterosexual or household contact
Perinatal transmission
Other rare transmission routes
58
57
58
Clinical manifestations 58
Acute HCV 58
Chronic HCV
Extrahepatic manifestations
59
61
Natural history 61
Cirrhosis and hepatic decompensation 62
Disease progression 62
References 65
4. Hepatitis E: a relevant disease with many aspects 69
Sven Pischke and Heiner Wedemeyer
Introduction 69
Genetic characteristics of HEV 70
Hepatitis E diagnosis 71
Worldwide distribution of HEV infections 72
Transmission of HEV 74
Acute hepatitis E in immunocompetent individuals 76
Acute and chronic HEV infections in organ transplant recipients 76
Hepatitis E in patients with HIV infection
or other immunological deiciencies 78
Extrahepatic manifestations of hepatitis E 79
Treatment of chronic hepatitis E 79
Vaccination 81
Conclusions and recommendations 81
References 82
Taxonomy and genotypes 110
Viral structure 110
Genome organisation 112
Genes and proteins 114
Viral life cycle 119
Adsorption and viral entry 119
Translation and post-translational processes
HCV RNA replication
Assembly and release
123
124
122
Model systems for HCV research 125
References 128
7. Prophylaxis and vaccination 135
Heiner Wedemeyer
Introduction 135
Prophylaxis of hepatitis viruses 135
Hepatitis A and E 135
Hepatitis B and D 136
Hepatitis C 137
Vaccination against HAV 139
Vaccination against HBV 140
Eicacy of vaccination against HBV 142
Post-exposure prophylaxis 142
Safety of HBV vaccines 142
Long-term immunogenicity of HBV vaccination 143
Prevention of vertical HBV transmission 143
Vaccination against HCV 144
Vaccination against HEV 146
References 147
5. HBV virology 87
Maura Dandri, Jörg Petersen
Introduction 87
Taxonomic classiication and genotypes 88
HBV structure and genomic organisation 88
HBV structural and non-structural proteins 91
The HBV replication cycle 94
Animal models of HBV infection 100
References 104
6. HCV virology 109
Bernd Kupfer
History 109
16 17
8. Hepatitis B: diagnostic tests 151
Jörg Petersen
Introduction 151
Serological tests for HBV 151
Collection and transport 151
Hepatitis B surface antigen and antibody 152
Hepatitis B core antibody 153
Hepatitis B e antigen and antibody 154
Serum HBV DNA assays 155
HBV genotypes 155
Antiviral resistance testing 156
Future markers that are not yet in clinical practice 156
Assessment of liver disease 158
Acute HBV infection 159
https://t.me/medicina_free
Past HBV infection
Chronic HBV infection
Serum transaminases
Occult HBV infection
Assessment of HBV immunity
Liver biopsy and noninvasive liver transient elastography
159
160
161
161
162
162
References 163
9. Treatment of hepatitis B infections 165
Florian van Bömmel, Johannes Wiegand, Thomas Berg
Introduction 165
Goals of treatment 166
Endpoints of treatment 167
Indication for antiviral therapy 173
Treatment of acute hepatitis B 173
Treatment of chronic hepatitis B 175
How to treat 178
Treatment options 178
Interferons 181
Nucleoside and nucleotide analogues 184
Choosing the right treatment option 191
Prognostic factors for treatment response 192
Monitoring before and during antiviral therapy 197
Treatment duration and stopping rules 198
Management of HBV resistance 201
Treatment of HBV infections in special populations 204
Novel treatments for HBV infections 207
References 209
10. Hepatitis D – diagnosis and treatment 215
Heiner Wedemeyer
Introduction 215
Virology of HDV 216
Epidemiology of HDV 218
Pathogenesis of HDV 220
Clinical course of HDV 223
Acute HBV/HDV coinfection 223
Chronic HDV 223
Diagnosis of HDV 224
Treatment of HDV 227
Nucleoside and nucleotide analogues 227
Recombinant interferon α 229
Pegylated interferon α
New drugs against HDV in clinical development
Liver transplantation for HDV
229
233
234
References 235
11. Hepatitis C: diagnostic tests 241
Christian Lange and Christoph Sarrazin
Serologic assays 242
HCV core antigen assays 243
Nucleic acid testing for HCV 244
Qualitative assays for HCV RNA detection 246
Qualitative T-PC 246
Transcription-mediated ampliication (TMA) of HCV RNA 246
Quantitative HCV RNA detection 247
Competitive PCR: Cobas® Amplicor™ HCV 2.0 monitor 248
Branched DNA hybridisation assay
(Versant™ HCV RNA 1.0 quantitative assay) 248
Real-time PC-based HCV RNA detection assays 248
®
TaqMan® HCV test 250
Cobas
RealTime HCV test 251
Artus hepatitis C virus QS-GQ assay 251
Versant HCV 1.0 kPC assay 251
Cepheid Xpert HCV Viral Load Assay and
Beckman Coulter DxN Veris HCV Assay 252
HCV genotyping 252
Reverse hybridising assay (Versant® HCV Genotype 2.0 System (LiPA)) 253
®
Direct sequence analysis (Trugene
Real-time PC technology (RealTime™ HCV Genotype II assay) 254
®
HCV genotyping test 254
Cobas
HCV 5’NC genotyping kit) 253
Implications for diagnosing and managing
acute and chronic hepatitis C 254
Diagnosing acute hepatitis C 254
Diagnosing chronic hepatitis C 255
Diagnostic tests in the management of hepatitis C therapy 255
References 261
12. Standard therapy of chronic hepatitis C virus infection 265
Markus Cornberg, Christoph Höner zu Siederdissen, Christoph Beier,
Benjamin Maasoumy, Michael P. Manns
Preface 265
Goal of antiviral therapy 265
Therapeutic concepts and medication 266
Development of antiviral treatment 266
18 19
Соседние файлы в папке Библиотека им академика М.И. Перельмана