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Mauss − Berg − Rockstroh − Sarrazin − Wedemeyer
Short Guide to Hepatitis C
2012 Edition
The PDF of the
2012 Flying Publisher Short Guide to Hepatitis C
is freely available from www.FlyingPublisher.com
thanks to an educational grant provided by
Stefan Mauss
Thomas Berg
Jürgen Rockstroh
Christoph Sarrazin
Heiner Wedemeyer
The Flying Publisher
Short Guide to
Hepatitis C
2012 Edition
Flying Publisher
4 |
Copy Editor:
Rob Camp
[email protected]
Disclaimer
Hepatitis C management is an ever-changing field. The publishers and
author of The Flying Publisher Short Guide to Hepatitis C have made every
effort to provide information that is accurate and complete as of the
date of publication. However, in view of the rapid changes occurring in
hepatitis C management, as well as the possibility of human error, this
site may contain technical inaccuracies, typographical or other errors.
It is the responsibility of the physician to rely on experience and
knowledge about the patient to determine the most adequate
treatment. The information contained herein is provided “as is” and
without warranty of any kind. The contributors to this book, including
Flying Publisher & Kamps, can not be held responsible for any errors or
omissions or for results obtained from the use of information contained
herein.
This work is protected by copyright both as a whole and in part.
© 2012 by Flying Publisher & Kamps
Design: Attilio Baghino, www.baghino.com
ISBN: 978-3-942687-11-9
Printed in Germany by Druckhaus Süd, www.druckhaus-sued.de
| 5
Preface
Hepatitis C is a rapidly developing area of medicine – diagnostic
tools are ever more refined, and entirely new treatments and
treatment strategies are arriving, with more on the horizon. And
because the virus affects such a large and varying population –
up to 170 million at last count – we think it is important to have
a pocket reference especially devoted to hepatitis C. We look
forward to your comments on the usefulness of our 2012 Short
Guide to Hepatitis C, which is an expansion and update of the
HCV chapters in Hepatology – A Clinical Textbook (2012), also
published by Flying Publisher. As always, we invite qualified
people everywhere to translate this book into other languages,
and make them available widely. This web-based free-of-charge
concept is made possible by unrestricted educational grants
from the pharmaceutical industry and has allowed the material
to reach countries usually not covered by print media. We are
convinced that this new pocket guide concept, focusing here on
hepatitis C, will become a valuable source of information for our
readers.
Stefan Mauss
Thomas Berg
Jürgen Rockstroh
Christoph Sarrazin
Heiner Wedemeyer
The Editors
March 2012
6 | The 2012 Short Guide to Hepatitis C
Contributing Authors
Thomas Berg Svenja Hardtke
Sektion Hepatologie Dept. of Gastroenterology,
Klinik und Poliklinik für Hepatology and Endocrinology
Gastroenterologie & Medical School of Hannover
Rheumatologie Carl-Neuberg-Str. 1
Universitätsklinikum Leipzig 30625 Hannover, Germany
Liebigstr. 20
04103 Leipzig, Germany Bernd Kupfer
Bonn University Hospital
Leber- und Studienzentrum am Department of Medicine I
Checkpoint
Sigmund-Freud-Strasse 25
Charlottenstrasse 81
53015 Bonn, Germany
10969 Berlin
Christian Lange
Christoph Boesecke
J. W. Goethe University
Department of Medicine I
Hospital
University Hospital Bonn
Sigmund-Freud-Strasse 25 Medical Department I
53105 Bonn, Germany Theodor-Stern-Kai 7
60590 Frankfurt/Main,
Albrecht Böhlig Germany
Sektion Hepatologie
Klinik und Poliklinik für Michael P. Manns
Gastroenterologie & Dept. of Gastroenterology,
Rheumatologie Hepatology
Universitätsklinikum Leipzig and Endocrinology
Liebigstr. 20 Medical School of Hannover
04103 Leipzig, Germany Carl-Neuberg-Str. 1
30625 Hannover, Germany
Markus Cornberg
Dept. of Gastroenterology, Stefan Mauss
Hepatology Center for HIV and
and Endocrinology Hepatogastroenterology
Medical School of Hannover Grafenberger Allee 128a
Carl-Neuberg-Str. 1 40237 Duesseldorf, Germany
30625 Hannover, Germany
| 7
Kerstin Port Martin Schäfer
Dept. of Gastroenterology, Department of Psychiatry
Hepatology and Endocrinology and Psychotherapy
Medical School of Hannover Kliniken Essen-Mitte
Carl-Neuberg-Str. 1 Ev. Huyssenstift
30625 Hannover, Germany Henricistraße 92
45136 Essen, Germany
Karl-Philipp Puchner
Charité, Campus Virchow- Carolynne Schwarze-Zander
Klinikum, Department of Medicine I
Universitätsmedizin University Hospital Bonn
Medizinische Klinik m. S. Sigmund-Freud-Strasse 25
Hepatologie und 53105 Bonn, Germany
Gastroenterologie
Augustenburger Platz 1 Jan-Christian Wasmuth
13353 Berlin, Germany Department of Medicine I
University Hospital Bonn
J. K. Rockstroh Sigmund-Freud-Strasse 25
Department of Medicine I 53105 Bonn, Germany
University Hospital Bonn
Sigmund-Freud-Strasse 25 Heiner Wedemeyer
53105 Bonn, Germany Dept. of Gastroenterology,
Hepatology
Christoph Sarrazin and Endocrinology
J. W. Goethe University Medical School of Hannover
Hospital Carl-Neuberg-Str. 1
Medical Department I 30625 Hannover, Germany
Theodor-Stern-Kai 7
60590 Frankfurt/Main,
Germany
8 | The 2012 Short Guide to Hepatitis C
Abbreviations
ADV: adefovir dipivoxil IPF: idiopathic pulmonary
AHA: autoimmune haemolytic fibrosis
anaemia ITP: immune
ALT: alanine aminotransferase thrombocytopenic purpura
AST: aspartate LDL: low density lipoproteins
aminotransferase MELD: Model for End-Stage
BID: twice a day Liver Disease
BOC: bocepravir NHL: non-Hodgkin lymphoma
cccDNA: covalently closed NPV: negative predictive value
circular DNA NTR: non-translated regions
CP: Child-Pugh PCR: polymerase chain
EHM: extrahepatic reaction
manifestation PCT: porphyria cutanea tarda
ER: endoplasmic reticulum PEG-IFN: pegylated interferon
EVR: early virologic response PT: prothrombin time
GH: growth hormone QD: once a day
GM-CSF: granulocyte QW: once a week
macrophage RF: rheumatoid factor
colony-stimulating factor RVR: rapid virologic response
GN: glomerulonephritis SSRI: selective serotonin
HBsAg: hepatitis B surface reuptake inhibitor
antigen SVR: sustained virologic
HBV: hepatitis B virus response
HCV: hepatitis C virus TGF: transforming growth
HCV RNA: riboneucleic acid factor
of hepatitis C virus RBV: ribavirin
HCC: hepatocellular carcinoma TID: three times a day
IFN alfa: interferon alfa TLP: telapravir
IGF-1: insulin growth factor-1 TSH: thyroid stimulating
INR: international normalised hormone
ratio
| 9
Table of Contents
1. Epidemiology, Transmission and Natural History .................. 15
Christoph Boesecke and Jan-Christian Wasmuth .................. 15
Epidemiology ........................................................................... 15
Transmission............................................................................ 16
Acute Hepatitis ........................................................................ 17
Chronic Hepatitis .................................................................... 17
Natural History ................................................................... 18
Cirrhosis and Hepatic Decompensation........................... 18
Disease progression ............................................................ 18
2. HCV Structure and Viral Replication ....................................... 21
Bernd Kupfer ............................................................................ 21
Taxonomy and Genotypes ...................................................... 21
Viral Structure ......................................................................... 21
Genome Organization ........................................................ 22
HCV Proteins ....................................................................... 23
Viral Lifecycle .......................................................................... 24
Adsorption and viral entry ................................................ 24
Translation and posttranslational processes .................. 25
HCV RNA replication .......................................................... 26
Assembly and release ......................................................... 26
Model systems for research .............................................. 26
3. Diagnostic Tests in Acute and Chronic Hepatitis C ................ 28
Christian Lange and Christoph Sarrazin ............................... 28
Serologic Assays ...................................................................... 28
Nucleic Acid Testing for HCV................................................. 29
HCV Genotyping ...................................................................... 31
Implications for Diagnosis and Management ...................... 32
Diagnosing acute hepatitis C ............................................. 32
Diagnosing chronic hepatitis C ......................................... 32
Diagnostics in the management of therapy .................... 33
10 | The 2012 Short Guide to Hepatitis C
4. Hepatitis C Standard of Care ..................................................... 34
Markus Cornberg, Svenja Hardtke, Kerstin Port,
Michael P. Manns, Heiner Wedemeyer .................................. 34
Basic therapeutic concepts and medication ........................ 34
Predictors of treatment response ......................................... 35
Antiviral resistance ................................................................. 38
Treatment of HCV genotype 1 ............................................... 39
Treatment of naïve patients .............................................. 39
Treatment of patients with prior antiviral treatment
failure ................................................................................... 45
Treatment of HCV genotypes 2 and 3 ................................... 48
Naïve patients ..................................................................... 48
Treatment of HCV G2/3 patients with prior antiviral
treatment failure ................................................................ 49
Treatment of HCV genotypes 4, 5, and 6 .............................. 50
Optimisation of HCV treatment ............................................ 51
Adherence to therapy ........................................................ 51
Management of side effects and complications.............. 52
Drug interactions................................................................ 53
Treatment of hepatitis C in special populations ................. 54
Patients with acute hepatitis C ......................................... 54
Patients with compensated liver cirrhosis ...................... 55
Patients after liver transplantation ................................. 57
Outlook ..................................................................................... 57
5. New Drugs .................................................................................... 58
Christian Lange and Christoph Sarrazin ............................... 58
NS3-4A protease inhibitors .................................................... 61
Molecular biology ............................................................... 61
Telaprevir (Incivek/Incivo®) and
boceprevir (Victrelis®) ........................................................ 62
Other NS3 protease inhibitors .......................................... 63
Resistance to NS3-4A inhibitors ....................................... 64
