Book on hepatitis from page 18 to 29
18 Hepatology 2012
14. Hepatitis C: New Drugs 239
Christian Lange, Christoph Sarrazin 239
Introduction 239
HCV life cycle and treatment targets 240
NS3-4A protease inhibitors 241
Molecular biology 241
Ciluprevir (BILN 2061) 243
Telaprevir (Incivek/Incivo
®
) and boceprevir (Victrelis
®
) 244
Other NS3 protease inhibitors 245
Resistance to NS3-4A inhibitors 246
NS5B polymerase inhibitors 248
Molecular biology 248
Nucleoside analogs 249
Non-nucleoside analogs 250
NS5A inhibitors 251
Compounds targeting viral attachment and entry 252
Host factors as targets for treatment 252
Cyclophilin B inhibitors 252
Nitazoxanide 253
Silibinin 253
Miravirsen 253
Newer combination therapies 253
Quadruple therapy 254
All-oral therapy without ribavirin 255
All-oral therapy with ribavirin 255
Novel interferons 256
Conclusions 257
References 257
15. Management of Adverse Drug Reactions 262
Martin Schaefer and Stefan Mauss 262
Introduction 262
Flu-like symptoms, fever, arthralgia and myalgia 262
Gastrointestinal disorders 263
Weight loss 263
Asthenia and fatigue 263
Cough and dyspnea 264
Disorders of the thyroid gland 264
Psychiatric adverse events 264
Incidence and profile of psychiatric adverse events 264
Preemptive therapy with antidepressants 266
Sleep disturbances 266
Hematological and immunologic effects 267
Skin disorders and hair loss 267
Adverse events with telaprevir and boceprevir 268
Adherence 269
Conclusion 269
References 269
19
16. Extrahepatic Manifestations of Chronic HCV 272
Karl-Philipp Puchner, Albrecht Böhlig and Thomas Berg 272
Introduction 272
Mixed cryoglobulinemia 272
Diagnosis 274
Clinical presentation 275
Malignant lymphoproliferative disorders/NHL 276
Etiology and pathogenesis of LPDs in patients with HCV infection 276
Treatment of lymphoproliferative disorders 277
Mixed cryoglobulinemia 277
Systemic vasculitis 278
Peripheral neuropathy 278
Further hematological manifestations 281
HCV-associated thrombocytopenia 281
HCV-related autoimmune hemolytic anemia 281
HCV-related glomerulonephritis 282
Endocrine manifestations 283
Dermatologic and miscellaneous manifestations 284
References 285
17. Management of HBV/HIV coinfection 291
Stefan Mauss and Jürgen Kurt Rockstroh 291
Introduction 291
HBV therapy in HBV/HIV-coinfected patients without HIV therapy 293
Treatment of chronic hepatitis B in HBV/HIV-coinfected patients 296
Management of resistance to HBV polymerase inhibitors 298
Conclusion 298
References 298
18. Management of HCV/HIV Coinfection 302
Christoph Boesecke, Stefan Mauss, Jürgen Kurt Rockstroh 302
Epidemiology of HIV and HCV coinfection 302
Diagnosis of HCV in HIV coinfection 303
Natural course of hepatitis C in HIV coinfection 304
Effect of hepatitis C on HIV infection 305
Effect of HAART on hepatitis C 305
Treatment of hepatitis C in HIV coinfection 306
The choice of antiretrovirals while on HCV therapy 310
Treatment of HCV for relapsers or non-responders 310
Treatment of acute HCV in HIV 311
Liver transplantation in HIV/HCV-coinfected patients 312
Conclusion 313
References 313
19. HBV/HCV Coinfection 318
Carolynne Schwarze-Zander and Jürgen Kurt Rockstroh 318
Epidemiology of HBV/HCV coinfection 318
Screening for HBV/HCV coinfection 318
Viral interactions between HBV and HCV 319
20 Hepatology 2012
Clinical scenarios of HBV and HCV infection 319
Acute hepatitis by simultaneous infection of HBV and HCV 319
HCV superinfection 319
HBV superinfection 320
Occult HBV infection in patients with HCV infection 320
Chronic hepatitis in HBV/HCV coinfection 320
Cirrhosis 322
Hepatocellular carcinoma 322
Treatment of HBV and HCV coinfection 322
Conclusion 323
References 323
20. Assessment of Hepatic Fibrosis in Chronic Viral Hepatitis 326
Frank Grünhage and Frank Lammert 326
Introduction 326
Mechanisms of liver fibrosis in chronic viral hepatitis 327
Liver biopsy – the gold standard for staging of liver fibrosis 327
Surrogate markers of liver fibrosis in chronic viral hepatitis 329
Transient elastography 330
Other imaging techniques for the 333
assessment of liver fibrosis 333
Clinical decision algorithms 333
Summary 334
References 334
21. Diagnosis, Prognosis & Therapy of Hepatocellular Carcinoma 338
Ulrich Spengler 338
Classification of HCC 338
Epidemiology 339
Surveillance of patients at high risk and early HCC diagnosis 339
Diagnosis 340
Stage-adapted therapy for liver cancer 341
Potentially curative therapy in BCLC stages 0-A 341
Palliative therapy in BCLC stages B and C 343
Prophylaxis of liver cancer 345
References 346
22. Update in Transplant Hepatology 349
S. Beckebaum, G. Gerken, V. R. Cicinnati 349
Introduction 349
Timing and indications for liver transplantation 349
Patient evaluation 351
Pretransplant management issues 351
Waiting list monitoring of hepatitis B liver transplant candidates 352
Waiting list monitoring and treatment of hepatitis C liver transplant candidates
353
Adjunctive treatment and staging of HCC transplant candidates 353
Living donor liver transplantation: indications, donor evaluation,
and outcome 354
Perioperative complications 355
21
Long-term complications after liver transplantation 356
Opportunistic infections 356
Chronic ductopenic rejection 357
CNI-induced nephrotoxicity and alternative immunosuppressive
protocols 358
Other side effects of CNI 359
Corticosteroid minimization/avoidance protocols 359
De novo malignancies 360
Biliary complications 361
Metabolic bone disease 362
Recurrent diseases after liver transplantation 363
Recurrence of hepatitis B in the allograft 363
Recurrence of hepatitis C in the allograft 365
Recurrence of cholestatic liver diseases and autoimmune hepatitis 368
Outcome in patients transplanted for hepatic malignancies 370
Recurrent alcohol abuse after liver transplantation for
alcoholic liver disease 371
Experiences with liver transplantation in inherited
metabolic liver diseases in adult patients 372
Outcome after liver transplantation for acute hepatic failure 373
Conclusion 373
References 375
23. End-stage Liver Disease, HIV Infection and Liver Transplantation 386
José M. Miró, Fernando Agüero, Montserrat Laguno,
Christian Manzardo, Montserrat Tuset, Carlos Cervera,
Neus Freixa, Asuncion Moreno, Juan-Carlos García-Valdecasas,
Antonio Rimola, and the Hospital Clinic OLT in HIV Working Group 386
Introduction 386
Epidemiology 386
Clinical features of coinfected patients with ESLD 387
Prognosis after decompensation 388
Management of cirrhosis complications 389
Substance abuse 390
HCV/HBV management 390
Combination antiretroviral therapy (HAART) 391
Orthotopic liver transplant (OLT) 392
Liver disease criteria 392
HIV infection criteria 392
Clinical criteria 392
Immunological criteria 393
Virologic criteria 393
Other criteria 394
22 Hepatology 2012
Outcome of OLT in HIV-positive patients 394
HIV/HCV coinfection 395
HIV/HVB coinfection 397
Hepatocellular carcinoma 398
Liver retransplantation 398
Conclusions 399
References 399
24. Metabolic Liver Diseases: Hemochromatosis 405
Claus Niederau 405
Definition and classification of iron overload diseases 405
Type 1 HFE hemochromatosis 406
History 406
Epidemiology 407
Etiology and pathogenesis 407
Diagnosis 409
Early diagnosis and screening 411
Complications of iron overload 415
Therapy 418
Prognosis 418
Juvenile hereditary hemochromatosis 419
Transferrin receptor 2 (TFR2)-related type 3 hemochromatosis 419
Type 4 hemochromatosis – Ferroportin Disease 420
Secondary hemochromatosis 421
Pathophysiology 421
References 422
25. NAFLD and NASH 427
Claus Niederau 427
Introduction 427
Prevalence 427
Demographics and risk factors 428
Pathogenesis 428
Natural history 429
Diagnosis 430
Diet and lifestyle recommendations 431
Pharmacological treatment 432
Surgery for obesity 432
Liver transplantation (LTX) for NASH 433
References 433
26. Wilson’s Disease 437
Claus Niederau 437
Introduction 437
Clinical presentation 437
23
Diagnosis 440
Serum ceruloplasmin 440
Serum copper 441
Urinary copper excretion 442
Hepatic copper concentration 442
Radiolabelled copper 442
Liver biopsy findings 442
Neurology and MRI of the CNS 443
Genetic Studies 443
Treatment 443
Monitoring of treatment 447
References 449
27. Autoimmune Liver Diseases: AIH, PBC and PSC 453
Christian P. Strassburg 453
Autoimmune hepatitis (AIH) 453
Definition and diagnosis of autoimmune hepatitis 453
Epidemiology and clinical presentation 455
Natural history and prognosis 457
Who requires treatment? 457
Who does not require treatment? 458
Standard treatment strategy 458
Treatment of elderly patients 461
Alternative Treatments 462
Budesonide 463
Deflazacort 463
Cyclosporine A 464
Tacrolimus 464
Mycophenolic acid 464
Cyclophosphamide 464
Anti-TNF α antibodies 465
Ursodeoxycholic acid 465
Liver transplantation 466
Recurrence and de novo AIH after liver transplantation 466
Primary biliary cirrhosis 467
Introduction 467
Definition and prevalence of PBC 468
Diagnostic principles of PBC 469
Therapeutic principles in PBC 470
Primary sclerosing cholangitis 473
Diagnosis of primary sclerosing cholangitis (PSC) 473
Differential diagnosis: sclerosing cholangitis 473
Association of PSC with inflammatory bowel disease 475
PSC as a risk factor for cancer 476
Medical therapy of PSC 477
Therapy of IBD in PSC 478
References 479
24 Hepatology 2012
28. Alcoholic Hepatitis 488
Claus Niederau 488
Health and social problems due to alcohol 488
overconsumption 488
Classification and natural history of alcoholic liver disease 488
Clinical features and diagnosis of alcoholic 490
hepatitis 490
Course and severity 491
Mechanisms of alcohol-related liver injury 492
Treatment 495
Abstinence from alcohol 495
Supportive therapy 495
Corticosteroids 495
Pentoxifylline 496
N-acetyl cysteine 497
Anti-TNF-α therapy 497
Nutritional support 497
Other pharmacologic treatments 498
Liver transplantation 498
Summary 498
References 499
29. Vascular Liver Disease 509
Matthias J. Bahr 509
Disorders of the hepatic sinusoid 509
Sinusoidal obstruction syndrome 509
Peliosis hepatis 513
Disorders of the hepatic artery 514
Hereditary hemorrhagic teleangiectasia (Osler-Weber-Rendu syndrome) 516
Disorders of the portal vein 518
Portal vein thrombosis 518
Nodular regenerative hyperplasia 521
Hepatoportal sclerosis 521
Disorders of the hepatic veins 522
Budd-Chiari syndrome 522
References 524
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