Chronic Viral Hepatitis (Clinical Gastroenterology)

Cover Page
......Page 1
Title Page
......Page 2
PREFACE......Page 6
CONTENTS......Page 7
CONTRIBUTORS......Page 9
1 Introduction......Page 11
2 Hepatitis B Virus......Page 12
2.2 Replication Cycle......Page 13
2.3 Cellular Entry......Page 14
2.4 cccDNA......Page 15
2.5 Transcription......Page 16
2.7 Encapsidation and Reverse Transcription......Page 17
2.8 Integration......Page 18
2.9 X Protein and Hepatocarcinogenesis......Page 19
2.10 Virion Production......Page 21
2.12 Viral Mutation......Page 22
2.13 Immune-Escape Mutants......Page 23
2.14 Polymerase Mutants......Page 25
3 Hepatitis C Virus......Page 26
3.1 Replication Cycle and Experimental Systems......Page 27
3.2 Viral Entry......Page 29
3.3 Translation......Page 30
3.4 Protein Processing......Page 31
3.5 Immune System Evasion......Page 33
3.6 Inhibition of the Intracellular Antiviral Response......Page 34
3.7 HCV Proteins and Hepatocarcinogenesis......Page 35
3.8 RNA Replication......Page 36
3.9 Assembly and Secretion......Page 38
References......Page 39
Epidemiology, Risk Factors, and Natural History of ChronicHepatitis C......Page 42
1.1 Global Prevalence and Incidence......Page 43
1.2 United States Prevalence and Incidence......Page 44
1.3 Genotype......Page 46
2 Risk Factors......Page 47
2.1 Intravenous Drug Use......Page 49
2.3 High-Risk Sexual Activity......Page 50
2.4 Intrafamilial and Monogamous Sexual Transmission......Page 51
2.5 Mother to Infant Transmission......Page 53
2.7 Hemodialysis......Page 54
2.8 Intranasal Drug Use......Page 55
2.10 Health Care Setting......Page 56
3.1 Chronic Hepatitis C......Page 57
3.2 Cirrhosis, Hepatocellular Cancer, and Liver-Related Death......Page 58
3.2.1 Study Design......Page 59
3.2.2 Host-Related Factors......Page 63
3.2.3 Virus-Related Factors......Page 66
4 Conclusions......Page 68
References......Page 69
Current and Future Therapy of Chronic Hepatitis C......Page 80
References......Page 0
2 Current Standard of Care......Page 81
2.1 Current Agents......Page 82
3 Treatment of Specific Patient Groups......Page 92
4 Therapeutics Agent in Development......Page 98
Hepatitis C in Special Populations......Page 106
5 HCV and Insulin Resistance/Diabetes......Page 124
6 HCV in Chronic Kidney Diseases (CKD)......Page 127
7 Conclusions......Page 129
Extrahepatic Manifestations of Chronic Hepatitis C Infection......Page 144
1 Introduction......Page 145
2.1 Vascular......Page 147
2.2 Lymphoproliferative Disorders......Page 148
2.3 Renal......Page 149
2.4 Dermatological......Page 150
2.5 Endocrine......Page 152
2.6 Rheumatologic......Page 153
2.7 Neurological......Page 155
2.8 Pulmonary......Page 156
References......Page 157
Anti-HCV Agents in Development......Page 167
3 Current Therapy of Chronic HCV Infection......Page 171
4 Refinement of Current Therapy......Page 172
5 Specifically Targeted Antiviral Therapy (STAT-C)......Page 174
6 Drugs Targeting the Host Cell......Page 181
8 Hepatitis C Virus Vaccination......Page 182
9 Conclusion......Page 183
Epidemiology, Screening, and Natural History of Chronic Hepatitis B Infection......Page 192
2.1 Global Patterns of HBV Infection......Page 193
2.2.1 Africa......Page 194
2.2.2 United States of America......Page 196
2.2.3 Latin America......Page 198
2.2.4 Western Pacific and Southeast Asia......Page 199
2.2.5 China (Mainland)......Page 200
2.2.7 India......Page 201
2.2.9 Europe......Page 203
2.3.1 Specific Modes of Transmission......Page 204
2.4 Effect of Vaccination on the Epidemiology of Chronic Hepatitis B......Page 209
2.5.1 HBV HCV Coinfection......Page 212
2.5.3 Epidemiology of Occult HBV......Page 213
2.6 Molecular Epidemiology......Page 214
3 Screening High-Risk Populations to Identify HBV-Infected Persons......Page 217
4.1.1 Immune-Tolerant Phase......Page 219
4.1.2 Immune-Reactive Phase......Page 220
4.1.3 Low-Replicative Phase......Page 221
4.1.4 Reactivation Phase......Page 222
4.3.1 Chronic HBV Infection and Cirrhosis......Page 223
4.3.2 Chronic HBV Infection and HCC......Page 224
4.3.3 HBV DNA Levels and Disease Progression......Page 225
4.3.4 ALT Levels and Disease Progression......Page 226
4.3.6 Histology in Patients with Normal ALT......Page 227
4.4 Natural History of HBV- and HCV-Coinfected Patients......Page 229
4.5 Natural History of Chronic Hepatitis B in HIV-Coinfected Patients......Page 231
4.6 Natural History of Occult HBV Infection......Page 233
References......Page 235
Current Treatment of Chronic Hepatitis B......Page 249
3 Indications for Treatment......Page 253
4 Approved Drugs for Treatment of Chronic Hepatitis B......Page 254
4.1 Peginterferon Alfa-2a......Page 255
4.3 Adefovir Dipivoxil......Page 256
4.5 Telbivudine......Page 257
6.1 Combination Therapy......Page 258
7 Roadmap Concept for on-Treatment Management......Page 259
8 Conclusion......Page 260
Management of Patients Co-Infected with ChronicHepatitis B (CHB) and the Human Immunodeficiency Virus (HIV)......Page 264
2 Epidemiology......Page 265
3.2 Influence of HIV on Outcome of HBV Disease......Page 266
3.3 Elevated Serum ALT Levels During HAART Therapy in HBV/HIV Co-infection......Page 267
4.2.2 Who and When to Treat HBV......Page 268
4.3 Interferon......Page 269
4.6 Entecavir......Page 270
4.8 Which Regimen to Use?......Page 271
4.9 Patients Who Do Not Require Treatment for HIV......Page 272
4.12 When to Stop Therapy?......Page 273
References......Page 274
Management of Antiviral Resistance in Chronic Hepatitis B......Page 278
2 Why Does Antiviral Resistance Develop?......Page 279
3.1 Primary Antiviral Treatment Failure (or Primary Non-Response)......Page 280
3.6 Recognition of Antiviral Resistance......Page 281
4.1 l -Nucleosides......Page 282
4.2 Acyclic Phosphonates......Page 283
5 Clinical Consequences of Antiviral Resistance......Page 284
6 Management of Antiviral Resistance......Page 285
6.1 Options for Management of Antiviral Resistance......Page 286
7 Prevention of Antiviral Resistance......Page 288
References......Page 289
Herbal and Non-Traditional Therapies for Viral Hepatitis......Page 293
1 Economics of Complimentary Alternative Medicine......Page 294
2 Burden of Viral Hepatitis......Page 295
3.1 Silymarin......Page 296
3.1.2 Silymarin Use in Hepatitis B......Page 297
3.3 Phyllanthus amarus......Page 298
3.4 TJ-9 (Xiao-Chai-Hutang/Sho-Saiko-To)......Page 299
3.7 Herbal Medicine 861......Page 300
4 Antioxidants and Dietary Supplements......Page 301
5 Discussion......Page 302
References......Page 305
Hepatitis B Reactivation in the Setting of Chemotherapy and Immunosuppression......Page 310
1 Introduction......Page 311
2 History of Hepatitis B Reactivation......Page 312
3 Incidence/Prevalence of Hepatitis B Reactivation......Page 313
4 Risk Factors for Reactivation......Page 314
4.1 A. Host Risk Factors for HBV Reactivation......Page 315
4.2 Role of Chemotherapeutic Agents/Steroids/Immunosuppressants......Page 317
5 Pathophysiology of Reactivation......Page 318
6 Clinical Manifestations of Hepatitis B Reactivation......Page 319
7 Screening of Patients Prior to Chemotherapy or Immunosuppression......Page 321
9 Management of Established HBV Reactivation......Page 322
10 Preemptive Antiviral Therapy Against HBV Reactivation......Page 324
11 Cost-Effectiveness of Preemptive Therapy......Page 327
13 Addendum......Page 328
References......Page 329
Support of Patients During Antiviral Therapyfor Hepatitis B and C......Page 340
2 Chronic Hepatitis C......Page 341
2.1.1 Anemia......Page 342
2.1.2 Thrombocytopenia......Page 343
2.1.3 Neutropenia......Page 344
2.2 Psychiatric Side Effects......Page 345
2.4 Pulmonary Side Effects......Page 346
2.5 Endocrine Side Effects......Page 347
2.7 General Side Effects......Page 348
3.1 Standard Interferon Alfa-2b or Pegylated Interferon Alfa-2a......Page 349
3.3 Adefovir Dipivoxil......Page 350
3.6 Tenofovir......Page 351
References......Page 352
Viral Hepatitis, A Through E, In Pregnancy......Page 355
1 Introduction......Page 356
3 Viral Hepatitis in Pregnancy......Page 357
3.1 Hepatitis A......Page 358
3.2 Hepatitis E......Page 360
3.3.2 Prophylaxis to Prevent Perinatal Transmission......Page 362
3.3.4 Postexposure Prophylaxis During Pregnancy......Page 363
3.3.6 Treatment of HBV in Pregnancy......Page 364
3.4 Hepatitis D (Delta)......Page 366
3.5.2 Vertical Transmission of HCV......Page 367
4 Conclusions......Page 369
References......Page 370
Chronic Viral Hepatitis and Liver Transplantation......Page 376
1 Introduction......Page 377
3.1 Mechanisms of Recurrent Hepatitis B......Page 378
3.3 Factors Affecting HBV Recurrence......Page 379
4.1 Treatment Prior to LT......Page 380
4.2.1 Prevention of Hepatitis B Following Liver Transplantation......Page 383
5 Liver Transplantation for Viral Hepatitis C......Page 387
6.3 Patterns of Recurrent hepatitis C......Page 388
6.4 Factors Affecting HCV Recurrence......Page 389
7.1 Prior to LT (Pre-Transplant Antiviral Therapy)......Page 391
7.2 Treatment of LT Recipients......Page 392
7.3 IFN and the Risk of Rejection in Liver Transplant Recipients......Page 394
8.2 Use of Anti-Hepatitis B Core (Anti-HBc-Positive) Grafts......Page 395
10 Conclusions......Page 396
References......Page 397
Treatment of Viral Hepatitis in Children 2008......Page 405
1 Hepatitis B: Introduction......Page 406
2 Natural History......Page 407
3 Screening and Prevention......Page 408
4 Treatment......Page 409
5.1 Interferons......Page 410
5.4 Lamivudine......Page 413
5.5 Combination Therapy......Page 414
5.7 Adefovir......Page 415
7 Hepatitis C: Introduction......Page 416
8 Natural History......Page 417
9 Screening and Prevention......Page 418
10 Treatment......Page 419
10.1 Interferon Alpha......Page 420
10.2 Interferon-Alpha and Ribavirin......Page 421
10.3 Pegylated Interferon (PEG-IFN) Monotherapy......Page 422
10.4 Peginterferon and Ribavirin Combination Therapy......Page 423
10.6 Considerations and Recommendations......Page 424
References......Page 425
Viral Hepatitis and Hepatocellular Carcinoma......Page 430
2.2 Viral Factors......Page 431
3 Diagnostic Evaluation......Page 434
4 Treatment......Page 437
4.2.1 Very Early Stage......Page 438
4.2.2 Early Stage HCC......Page 439
4.4 Advanced Stage......Page 440
5.1 Hepatitis B......Page 441
Hepatitis B Vaccines......Page 447
7 Hepatitis B Virus Mutants Following Immunization Against HBV......Page 454
8 Mode of Administration......Page 455
10 Strategies of Immunization andWorldwide Impact......Page 456
12 Rationale for Immunization of Special Populations at Risk......Page 458
13 Non-Responders to Conventional Vaccination......Page 459
T-Cell-Mediated Immunity and Immunotherapy of Chronic Hepatitis C......Page 469
1 Introduction......Page 470
2 T-Cell-Mediated Immune Responses To HCV Infection......Page 471
3 General Overview of T-Cell-Mediated Immunity......Page 472
3.1 Cells of the Immune System......Page 473
3.3 Cellular Immunity in Response to Endogenous (Intracellular) Antigens......Page 476
3.4 Th1 vs. Th2 Cells: Cell-Mediated vs. Antibody-Mediated Immunity......Page 477
3.5 Regulatory T Cells......Page 478
4.1 Conventional Vaccine Approaches......Page 479
4.3 Vaccine Approaches that Target Pattern Recognition Receptors......Page 481
5 Goals and Evaluation of Immunotherapy in Chronic HCV Infection......Page 483
6 Summary......Page 484
References......Page 485
Index
......Page 489