499. Clinical Hepatology

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499. Clinical Hepatology

 

 

CATEGORY: Medical & Medicine – 500 Courses

COURSE NUMBER: 499

FEES: 555/- INR only

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Syllabus

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
Jorg 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® Amplicor HCV 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
RealTime HCV 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 (RealTimeTM 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

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

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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

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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

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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
30. Acute Liver Failure 526
Akif Altinbas, Lars P. Bechmann, Hikmet Akkiz, Guido Gerken, Ali Canbay 526
Introduction and definition 526
Epidemiology and etiologies 526
Intoxication 527
Amanita intoxication 528
Viral hepatitis 529
Immunologic etiologies 529
Wilson’s Disease 529
Vascular disorders 529
Pregnancy-induced liver injury 530
Undetermined 530

Molecular mechanisms and clinical presentation 530
Prognosis 532
Treatment 533
General management 533
Hepatic encephalopathy 533
Coagulopathy 534
Liver Transplantation 534
Extracorporal liver support systems 534
Specific treatment options 535
References 536

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