Hepatology 2009



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

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