The 2012 Flying Short Publisher Guide to Hepatitis C PDF
Preview The 2012 Flying Short Publisher Guide to Hepatitis C
More books at www.FlyingPublisher.com 1 1 # goo.gl/1slAf goo.gl/1slAf the Flying Publisher al. t Short Guide to e the Flying Publisher s s Short Guide to Hepatitis C / 2012 u a M Hepatitis C edited by 2012 Mauss, Berg, Rockstroh, Sarrazin, Wedemeyer edited by Mauss, Berg, Rockstroh, Sarrazin, Wedemeyer #11 Exciting new treatment approaches make the management of hepatitic C C one of the most rapidly developing areas s ti of medicine. ti a p The 2012 Flying Publisher Short Guide He to Hepatitis C is an up-to-date source of o t information for physicians, residents and de i advanced medical students. u G www.flyingpublisher.com rt o h S 2 1 0 2 R 11 e h s li 11 b u P ISBN 978-3-942687-11-9 g ## n i y l F Flying PublisheR 9 783942 687119 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
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