FULTEXT
Editors
Stefan Mauss
Thomas Berg
Juergen Rockstroh
Christoph Sarrazin
Heiner Wedemeyer

Content
Part 1
Basics
Chapter 1: Hepatitis A – Epidemiology, transmission and natural history ….21
Genomic Organisation…………………………………………………………………………..21
Epidemiology ………………………………………………………………………………………21
Transmission………………………………………………………………………………………..21
Clinical course ……………………………………………………………………………………..21
Clinical Presentation……………………………………………………………………………..22
Extrahepatic manifestations …………………………………………………………………..22
Laboratory findings ………………………………………………………………………………23
Diagnosis …………………………………………………………………………………………….23
Treatment…………………………………………………………………………………………….23
References …………………………………………………………………………………………..24
Chapter 2: Hepatitis B – Epidemiology, transmission and natural history ….25
Introduction …………………………………………………………………………………………25
Transmission………………………………………………………………………………………..26
Natural history and clinical manifestations………………………………………………29
References …………………………………………………………………………………………..34
Chapter 3: Hepatitis C – Epidemiology, transmission and natural history ….37
Epidemiology ………………………………………………………………………………………37
Transmission………………………………………………………………………………………..37
Clinical manifestations and natural history of HCV infection…………………….40
Acute hepatitis ……………………………………………………………………………………..40
Chronic hepatitis C……………………………………………………………………………….41
Natural history ……………………………………………………………………………………..42
Cirrhosis and hepatic decompensation…………………………………………………….42
References …………………………………………………………………………………………..46
Chapter 4: Hepatitis E – Epidemiology, transmission and natural history….49
Introduction …………………………………………………………………………………………49
Epidemiology and Transmission …………………………………………………………….49
Clinical features……………………………………………………………………………………50
Diagnosis …………………………………………………………………………………………….51
Pregnancy ……………………………………………………………………………………………51
Treatment…………………………………………………………………………………………….51
12 Content
Chapter 5: HBV – Virology……………………………………………………………………….55
Introduction …………………………………………………………………………………………55
Taxonomic classification of the Hepadnaviridae ……………………………………..55
Structure of virus particles and organization of the viral genome ……………….57
The HBV replication cycle…………………………………………………………………….59
Pathogenesis of hepadnavirus infections………………………………………………….61
Animal models for HBV infections ………………………………………………………..62
Cell culture models for in vitro phenotyping ……………………………………………64
References …………………………………………………………………………………………..65
Chapter 6: HCV – Virology ………………………………………………………………………75
History ………………………………………………………………………………………………..75
Taxonomy and genotypes………………………………………………………………………75
Viral structure………………………………………………………………………………………76
Genome organization ……………………………………………………………………………77
Genes and proteins ……………………………………………………………………………….79
Viral lifecycle ………………………………………………………………………………………83
Model systems for HCV research …………………………………………………………..87
References …………………………………………………………………………………………..88
Chapter 7: Prophylaxis and vaccination of viral hepatitis………………………….99
Introduction …………………………………………………………………………………………99
Prophylaxis of hepatitis viruses………………………………………………………………99
Vaccination against hepatitis A…………………………………………………………….101
Vaccination against hepatitis B …………………………………………………………….102
Safety of HBV vaccines ………………………………………………………………………104
Vaccination against hepatitis C …………………………………………………………….105
Vaccination against hepatitis E …………………………………………………………….106
References …………………………………………………………………………………………106
Part 2
Hepatitis B and D
Chapter 8: Acute and chronic hepatitis B – Diagnostic tests……………………..113
Introduction ……………………………………………………………………………………….113
Aims of diagnostic tests in the management of HBV infection…………………113
Molecular assays in the diagnosis and management of HBV ……………………114
Conclusion and future aspects………………………………………………………………116
References …………………………………………………………………………………………116
Content 13
Chapter 9: HBV Treatment – Standard of care ……………………………………….119
Introduction ……………………………………………………………………………………….119
Goals of antiviral therapy …………………………………………………………………….121
Indication for antiviral therapy……………………………………………………………..123
Treatment indication: Summary of the German guidelines recommendations
…………………………………………………………………………………………………………125
References …………………………………………………………………………………………138
Chapter 10: HBV – Resistance and implications for therapeutic strategies
143
Introduction ……………………………………………………………………………………….143
Principles of antiviral HBV therapy – how to avoid resistance …………………144
Treatment endpoints ……………………………………………………………………………144
Resistance patterns of HBV polymerase inhibitors………………………………….145
Combination therapy of chronic hepatitis B to enhance antiviral efficacy and
delay development of resistance……………………………………………………………148
Management of drug resistance…………………………………………………………….149
Special considerations in HIV/HBV-coinfected patients………………………….149
Immune escape and polymerase inhibitor resistance ……………………………….150
Conclusion…………………………………………………………………………………………150
References …………………………………………………………………………………………151
Chapter 11: Hepatitis D – Diagnostic procedures and therapy ……………….155
Introduction ……………………………………………………………………………………….155
Virology of Delta hepatitis …………………………………………………………………..156
Epidemiology of delta hepatitis…………………………………………………………….157
Pathogenesis of HDV infection…………………………………………………………….159
Clinical course of delta hepatitis …………………………………………………………..160
Diagnosis of delta hepatitis ………………………………………………………………….160
Treatment of Delta Hepatitis ………………………………………………………………..161
References …………………………………………………………………………………………164
14 Content
Part 3
Hepatitis C
Chapter 12: Acute and chronic hepatitis C – Diagnostic tests ………………..171
Introduction ……………………………………………………………………………………….171
Serologic assays …………………………………………………………………………………172
Nucleic acid testing for HCV ……………………………………………………………….173
Quantitative HCV RNA detection…………………………………………………………174
HCV genotyping…………………………………………………………………………………177
Implications for diagnosing and managing acute and chronic hepatitis C…..179
References …………………………………………………………………………………………180
Chapter 13: Standard of care ……………………………………………………………….183
Management of acute hepatitis C ………………………………………………………….183
Standard therapy of chronic hepatitis C …………………………………………………184
Individualisation and optimisation strategies………………………………………….188
Side effects and complications ……………………………………………………………..193
Treatment of hepatitis C in special populations ………………………………………196
Treatment in the future and the drug pipeline …………………………………………197
Treatment of patients with previous antiviral treatment failure…………………198
Chapter 14: New agents for treatment…………………………………………………..211
Introduction ……………………………………………………………………………………….211
HCV life cycle and targets for STAT-C…………………………………………………213
Viral attachment and entry …………………………………………………………………..214
HCV RNA translation and post-translational protein processing ………………214
HCV replication …………………………………………………………………………………224
Resistance to specific antivirals ……………………………………………………………231
Nucleoside inhibitors…………………………………………………………………………..232
Host proteins as targets in treating hepatitis C………………………………………..233
Novel interferons………………………………………………………………………………..235
Albinterferon ……………………………………………………………………………………..235
IFN &豩-2bXL ………………………………………………………………………………………236
Novel ribavirin derivates ……………………………………………………………………..237
Outlook ……………………………………………………………………………………………..237
References …………………………………………………………………………………………238
Content 15
Chapter 15: Management of adverse drug reactions ……………………………..245
Introduction ……………………………………………………………………………………….245
Flu-like symptoms, fever, arthralgia and myalgia……………………………………245
Gastrointestinal disorders …………………………………………………………………….246
Weight loss ………………………………………………………………………………………..246
Asthenia and fatigue……………………………………………………………………………246
Cough and dyspnoea …………………………………………………………………………..247
Disorders of the thyroid gland………………………………………………………………247
Psychiatric adverse events……………………………………………………………………247
Chapter 16: Extrahepatic manifestations of chronic HCV……………………..255
Introduction ……………………………………………………………………………………….255
Mixed cryoglobulinaemia…………………………………………………………………….257
Lymphoproliferative disorders ……………………………………………………………..262
HCV-related thrombocytopaenia ………………………………………………………….263
HCV-related autoimmune haemolytic anaemia ………………………………………264
Endocrine manifestations …………………………………………………………………….264
Dermatological and miscellaneous manifestations ………………………………….265
References …………………………………………………………………………………………267
Part 4
Coinfections
Chapter 17: Management of HBV/HIV coinfection ……………………………….275
Introduction ……………………………………………………………………………………….275
HBV therapy in HBV/HIV-coinfected patients without antiretroviral therapy
…………………………………………………………………………………………………………276
ARV treatment of chronic hepatitis B in HBV/HIV coinfection……………….279
Management of resistance to HBV polymerase inhibitors ……………………….281
Conclusion…………………………………………………………………………………………281
Chapter 18: Management of HCV/HIV coinfection……………………………….285
Epidemiology of HIV/HCV coinfection ………………………………………………..285
Specific aspects concerning the diagnosis of HCV in HIV coinfection ……..286
Natural course of hepatitis C in HIV-positive patients …………………………….287
Effect of hepatitis C on HIV infection …………………………………………………..287
Effect of HAART on hepatitis C…………………………………………………………..287
Therapy……………………………………………………………………………………………..288
Conclusion…………………………………………………………………………………………294
16 Content
Chapter 19: Management of HBV/HCV coinfection………………………………297
Epidemiology of HBV/HCV coinfection……………………………………………….297
Screening for HBV/HCV coinfection ……………………………………………………297
Viral interactions between HBV and HCV …………………………………………….297
Clinical scenarios of HBV and HCV infection ……………………………………….298
Treatment of HBV and HCV coinfection ………………………………………………301
Conclusion…………………………………………………………………………………………301
References …………………………………………………………………………………………302
Part 5
Liver Fibrosis
Chapter 20: Assessment of hepatic fibrosis in chronic viral hepatitis……..307
Introduction ……………………………………………………………………………………….307
Mechanisms of liver fibrosis in chronic viral hepatitis…………………………….307
Liver biopsy – the gold standard for staging of liver fibrosis ……………………308
Surrogate markers of liver fibrosis in chronic viral hepatitis…………………….310
Transient elastography ………………………………………………………………………..311
Other imaging techniques for the assessment of liver fibrosis ………………….312
Clinical decision algorithms…………………………………………………………………312
Summary……………………………………………………………………………………………314
References …………………………………………………………………………………………314
Part 6
Hepatocellular Carcinoma
Chapter 21: Diagnosis, Prognosis & Therapy of Hepatocellular Carcinoma
321
Classification of HCC …………………………………………………………………………321
Epidemiology …………………………………………………………………………………….322
Surveillance of patients at high risk and early HCC diagnosis………………….322
Diagnosis …………………………………………………………………………………………..323
Stage-adapted therapy for liver cancer…………………………………………………..324
Prophylaxis of liver cancer…………………………………………………………………..328
References …………………………………………………………………………………………329
Content 17
Part 7
Transplantation
Chapter 22: Management of patients before and after liver transplantation
335
Introduction ……………………………………………………………………………………….335
Timing and indications for liver transplantation ……………………………………..335
Patient evaluation ……………………………………………………………………………….337
Pretransplant management issues………………………………………………………….338
Living donor liver transplantation:………………………………………………………..341
Indications, donor evaluation, and outcome……………………………………………341
Long-term complications after liver transplantation………………………………..342
Recurrent diseases after liver transplantation………………………………………….349
Outcome after liver transplantation for acute hepatic failure…………………….359
Conclusion…………………………………………………………………………………………359
References …………………………………………………………………………………………361
Chapter 23: Liver transplantation in hepatitis B and C and HIV coinfection
375
Introduction ……………………………………………………………………………………….375
Epidemiology …………………………………………………………………………………….375
Clinical features of coinfected patients with ESLD …………………………………376
Prognosis after decompensation……………………………………………………………376
Management of cirrhosis complications ………………………………………………..378
Substance abuse………………………………………………………………………………….378
HCV/HBV management………………………………………………………………………378
ART………………………………………………………………………………………………….379
OLT (Orthotopic liver transplantation) ………………………………………………….380
Liver disease criteria …………………………………………………………………………..380
HIV infection criteria ………………………………………………………………………….380
Clinical criteria …………………………………………………………………………………..381
Immunological criteria ………………………………………………………………………..381
Virologic criteria ………………………………………………………………………………..382
Other criteria………………………………………………………………………………………382
Outcome of OLT in HIV-infected patients …………………………………………….382
Conclusions ……………………………………………………………………………………….386
References …………………………………………………………………………………………386
18 Content
Part 8
Autoimmune and Metabolic Liver Disease
Chapter 24: Metabolic Liver Diseases: Haemochromatosis ……………………395
Definition and classification of iron overload diseases…………………………….395
Type 1 HFE haemochromatosis ……………………………………………………………397
Secondary haemochromatosis ………………………………………………………………412
References …………………………………………………………………………………………413
Chapter 25: NAFLD and NASH……………………………………………………………419
Introduction ……………………………………………………………………………………….419
Prevalence………………………………………………………………………………………….419
Demographics and risk factors ……………………………………………………………..419
Pathogenesis ………………………………………………………………………………………420
Natural history ……………………………………………………………………………………421
Diagnosis …………………………………………………………………………………………..422
Diet and lifestyle recommendations………………………………………………………424
Pharmacological treatment …………………………………………………………………..424
Surgery for obesity ……………………………………………………………………………..425
Liver transplantation (LTX) for NASH………………………………………………….425
References …………………………………………………………………………………………425
Chapter 26: Wilson’s Disease………………………………………………………………..429
Introduction ……………………………………………………………………………………….429
Clinical Presentation……………………………………………………………………………429
Diagnosis …………………………………………………………………………………………..433
Treatment…………………………………………………………………………………………..436
Monitoring of Treatment ……………………………………………………………………..440
References …………………………………………………………………………………………442
Chapter 27: Autoimmune liver diseases: AIH, PBC and PSC………………..447
Autoimmune hepatitis (AIH)………………………………………………………………..447
Primary biliary cirrhosis………………………………………………………………………470
Primary sclerosing cholangitis ……………………………………………………………..481
References …………………………………………………………………………………………486