Book on hepatitis from page 13 to 17
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Table of Contents
1. Hepatitis A 27
Sven Pischke and Heiner Wedemeyer 27
The virus 27
Epidemiology 27
Transmission 27
Clinical course 28
Extrahepatic manifestations 29
Diagnosis 29
Treatment and prognosis 30
References 30
2. Hepatitis B 32
Christoph Boesecke and Jan-Christian Wasmuth 32
Introduction 32
Transmission 33
Sexual transmission 33
Percutaneous inoculation 33
Perinatal transmission 34
Horizontal transmission 34
Blood transfusion 34
Nosocomial infection 35
Organ transplantation 36
Postexposure prophylaxis 36
Natural history and clinical manifestations 36
Acute hepatitis 36
Chronic hepatitis 37
Prognosis and survival 39
Extrahepatic manifestations 41
References 41
3. Hepatitis C 44
Christoph Boesecke and Jan-Christian Wasmuth 44
Epidemiology 44
Transmission 45
Injection drug use 45
Blood transfusion 45
Organ transplantation 46
Sexual or household contact 46
Perinatal transmission 46
Hemodialysis 47
Other rare transmission routes 47
Needlestick injury 47
Clinical manifestations 47
Acute hepatitis 47
Chronic hepatitis C 48
Extrahepatic manifestations 49
Natural history 49
14 Hepatology 2012
Cirrhosis and hepatic decompensation 49
Disease progression 50
References 52
4. Hepatitis E: an underestimated problem? 55
Sven Pischke and Heiner Wedemeyer 55
Introduction 55
HEV: genetic characteristics of the virus 55
Diagnosis of hepatitis E 56
Worldwide distribution of HEV infections 57
Transmission of HEV 58
Acute hepatitis E in immunocompetent individuals 59
Acute and chronic HEV infections in organ 60
transplant recipients 60
Hepatitis E in patients with HIV infection 60
Extrahepatic manifestations of hepatitis E 61
Treatment of chronic hepatitis E 61
Vaccination 61
Conclusions/Recommendations 62
References 62
5. HBV Virology 65
Maura Dandri, Jörg Petersen 65
Introduction 65
Taxonomic classification and genotypes 66
HBV structure and genomic organization 66
HBV structural and non-structural proteins 68
The HBV replication cycle 71
Animal models of HBV infection 75
References 78
6. HCV Virology 85
Bernd Kupfer 85
History 85
Taxonomy and genotypes 86
Viral structure 86
Genome organization 87
Genes and proteins 89
Viral lifecycle 93
Adsorption and viral entry 93
Translation and posttranslational processes 95
HCV RNA replication 96
Assembly and release 96
Model systems for HCV research 97
References 99
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7. Prophylaxis and Vaccination 108
Heiner Wedemeyer 108
Introduction 108
Prophylaxis of hepatitis viruses 108
Hepatitis A and E 108
Hepatitis B and D 109
Hepatitis C 109
Vaccination against hepatitis A 110
Vaccination against hepatitis B 111
Efficacy of vaccination against hepatitis B 112
Post-exposure prophylaxis 113
Safety of HBV vaccines 113
Long-term immunogenicity of hepatitis B vaccination 113
Prevention of vertical HBV transmission 114
Vaccination against hepatitis C 114
Vaccination against hepatitis E 115
References 115
8. Hepatitis B: Diagnostic Tests 119
Jörg Petersen 119
Introduction 119
Serological tests for HBV 119
Collection and transport 119
Hepatitis B surface antigen and antibody 120
Hepatitis B core antigen and antibody 120
Hepatitis B e antigen and antibody 121
Serum HBV DNA assays 121
HBV genotypes 122
Antiviral resistance testing 122
Assessment of liver disease 123
Acute HBV infection 123
Past HBV infection 123
Chronic HBV infection 124
Serum transaminases 124
Occult HBV infection 125
Assessment of HBV immunity 125
Liver biopsy and noninvasive liver transient elastography 125
References 126
9. Hepatitis B Treatment 128
Florian van Bömmel, Johannes Wiegand, Thomas Berg 128
Introduction 128
Indication for antiviral therapy 128
Acute hepatitis B 128
Chronic hepatitis B 129
Summary of treatment indications in the German Guidelines of 2011 132
Endpoints of antiviral treatment 132
How to treat 136
16 Hepatology 2012
Treatment options 136
Interferons 139
Nucleoside and nucleotide analogs 141
Choosing the right treatment option 146
Prognostic factors for treatment response 147
Monitoring before and during antiviral therapy 151
Treatment duration and stopping rules 152
References 154
10. Management of Resistance in HBV Therapy 160
Stefan Mauss and Heiner Wedemeyer 160
Introduction 160
Antiviral HBV therapy – how to avoid resistance 161
Treatment endpoints 162
Resistance patterns of HBV polymerase inhibitors 163
Combination therapy of chronic hepatitis B to delay
development of resistance 166
Management of drug resistance 166
Special considerations in HIV/HBV coinfection 168
Immune escape and polymerase inhibitor 168
resistance 168
Conclusion 169
References 169
11. Hepatitis D – Diagnosis and Treatment 174
Heiner Wedemeyer 174
Introduction 174
Virology of hepatitis delta 175
Epidemiology of hepatitis delta 176
Pathogenesis of HDV infection 178
Clinical course of delta hepatitis 179
Acute HBV/HDV coinfection 179
Chronic delta hepatitis 179
Diagnosis of delta hepatitis 180
Treatment of delta hepatitis 181
Nucleoside and nucleotide analogs 181
Recombinant interferon α 182
Pegylated interferon α 182
Liver transplantation for hepatitis delta 183
References 184
12. Hepatitis C: Diagnostic Tests 189
Christian Lange and Christoph Sarrazin 189
Serologic assays 190
HCV core antigen assays 191
Nucleic acid testing for HCV 191
Qualitative assays for HCV RNA detection 192
Qualitative RT-PCR 192
Transcription-mediated amplification (TMA) of HCV RNA 192
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Quantitative HCV RNA detection 193
Competitive PCR: Cobas
®
AmplicorHCV 2.0 monitor 193
Branched DNA hybridisation assay (Versant
®
HCV RNA 3.0
quantitative assay) 194
Real-time PCR-based HCV RNA detection assays 194
Cobas
®
TaqMan
®
HCV test 195
RealTimeHCV test 196
HCV genotyping 196
Reverse hybridising assay (Versant®HCV Genotype 2.0 System (LiPA)) 197
Direct sequence analysis (Trugene
®
HCV 5’NC genotyping kit) 197
Real-time PCR technology (RealTime™ HCV Genotype II assay) 197
Implications for diagnosing and managing acute and chronic hepatitis C 197
Diagnosing acute hepatitis C 197
Diagnosing chronic hepatitis C 198
Diagnostic tests in the management of hepatitis C therapy 198
References 199
13. Standard Therapy of Chronic Hepatitis C Virus Infection 202
Markus Cornberg, Svenja Hardtke, Kerstin Port,
Michael P. Manns, Heiner Wedemeyer 202
Goal of antiviral therapy 202
Basic therapeutic concepts and medication 202
Predictors of treatment response 206
Antiviral resistance 206
Treatment of HCV genotype 1 207
Treatment of naïve patients 207
Treatment of patients with prior antiviral treatment failure 212
PEG-IFN maintenance therapy 215
Treatment of HCV genotypes 2 and 3 215
Naïve patients 215
Treatment of HCV G2/3 patients with prior antiviral treatment failure 218
Treatment of HCV genotypes 4, 5, and 6 218
Optimisation of HCV treatment 220
Adherence to therapy 220
Management of side effects and complications 221
Drug interactions 225
Treatment of hepatitis C in special populations 226
Patients with acute hepatitis C 226
Patients with normal aminotransferase levels 227
Patients with compensated liver cirrhosis 228
Patients after liver transplantation 229
Hemodialysis patients 230
Drug abuse and patients on stable maintenance substitution 230
Patients with coinfections 230
Patients with hemophilia 230
Patients with extrahepatic manifestations 230
References 231
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