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Hepatitis C Virus: The Next Epidemic, An issue of Gastroenterology Clinics of North America, E-Book

Hepatitis C Virus: The Next Epidemic, An issue of Gastroenterology Clinics of North America, E-Book

K. Rajender Reddy

(2016)

Additional Information

Abstract

There are over 180 million people with chronic HCV infection worldwide with between 2.7 and 3.9 million in the United States. Hepatitis C most significantly affects Asia and Africa, with rates up to 15% in countries such as Egypt and up to 30% in certain regions such as Punjab, Pakistan. Hepatitis C places a significant burden on the public health infrastructure, as it remains the leading cause of chronic liver disease, accounting for 50-75% of primary liver cancers and is responsible for 30% of all liver transplantations. It is estimated to have cost the United States $5.5 billion in 1997, comparable to the national cost of asthma, $5.8 billion in 1994.This number is only expected to grow as the current HCV population ages, increasing overall rates of compensated cirrhosis/end-stage liver disease. The evolution of directly acting anti-virals has ushered in a new era for chronic hepatitis C. Ongoing drug development strategy has involved targeting several replication steps of the virus and the hope is to see all oral therapies by late 2014 or early 2015. Thus we are at an exciting cross roads with regard to new information and challenges with HCV: rising disease burden with associated high costs, the challenges globally and in multiple patient populations, and the impending availability of effective and well tolerated treatments. Therefore there is a need to commission an exclusive issue of GCNA for HCV.

Table of Contents

Section Title Page Action Price
Front Cover Cover
Hepatitis C Virus:The Next \rEpidemic i
Copyright\r ii
Contributors iii
CONSULTING EDITOR iii
EDITOR iii
AUTHORS iii
Contents vii
Foreword: Hepatitis C Virus\r vii
Preface: Hepatitis C: Unfolding the Challenges\r vii
Epidemiology of Hepatitis C Virus: A Battle on New Frontiers\r vii
Natural History of Hepatitis\r vii
Immunopathogenesis of Hepatitis C Virus Infection\r vii
Impact of Hepatitis C Virus Infection on Hepatocellular Carcinoma\r viii
Extrahepatic Manifestations of Hepatitis C Virus\r viii
Hepatitis C: An Eastern Perspective\r viii
Hepatitis C Virus: A European Perspective\r viii
Current and Evolving Treatments of Genotype 1 Hepatitis C Virus\r ix
Hepatitis C Virus: Current and Evolving Treatments for Genotypes 2 and 6\t\r ix
Hepatitis C Virus: Current and Evolving Treatments for Genotype 4 \r ix
Current Treatment Options in Patients with Hepatitis C Virus Genotype 6\r ix
Treatment of Chronic Hepatitis C in Special Populations\r x
Hepatitis C: Issues in Children\r x
GASTROENTEROLOGY\rCLINICS OF NORTH AMERICA\x0B xi
FORTHCOMING ISSUES xi
March 2016 xi
June 2016 xi
September 2016 xi
RECENT ISSUES xi
September 2015 xi
June 2015 xi
March 2015 xi
Foreword: Hepatitis C Virus \r xiii
Preface: Hepatitis C: Unfolding the Challenges \r xv
Epidemiology of Hepatitis C Virus 699
Key points 699
INTRODUCTION 699
HEPATITIS C VIRUS EPIDEMIOLOGY: THE FIRST 20 YEARS (1975–1995) 700
Hepatitis C Virus Unmasked 700
Hepatitis C Virus Epidemic: the Early Days 700
HEPATITIS C VIRUS EPIDEMIOLOGY: 1995 TO 2015 701
Current Hepatitis C Virus Epidemiology in Developed Nations 701
Current Hepatitis C Virus Epidemiology in Developing Nations 706
ACUTE HEPATITIS C VIRUS: AN EMERGING THREAT 708
SUMMARY 710
REFERENCES 710
Natural History of Hepatitis C 717
Key points 717
INTRODUCTION 717
ACUTE HEPATITIS C 718
NATURAL HISTORY OF CHRONIC HEPATITIS C 718
NATURAL HISTORY OF CIRRHOSIS 720
FACTORS THAT INFLUENCE THE OUTCOME OF CHRONIC HEPATITIS C 720
Host Factors 720
Age at infection 720
Gender 721
Race 721
Obesity 721
Steatosis 722
Insulin resistance/diabetes 722
Genetics 722
Alanine aminotransferase levels 723
Exercise 723
VIRAL FACTORS 723
Hepatitis C Virus RNA Level 723
Hepatitis C Virus Quasispecies/Genotype 724
Coinfection with Hepatitis B Virus 724
Coinfection with Human Immunodeficiency Virus 724
ENVIRONMENTAL FACTORS 725
Alcohol 725
Smoking 725
Cannabis 726
Caffeine 726
Herbals 726
SUMMARY 727
REFERENCES 727
Immunopathogenesis of Hepatitis C Virus Infection 735
Key points 735
INTRODUCTION 735
INTRAHEPATOCYTIC SENSING AND SIGNALING 736
INDUCTION OF CELLULAR AND ADAPTIVE IMMUNE RESPONSES 738
Dendritic Cell Dysfunction 738
Antiviral Effect of Nonparenchymal Liver Cells 739
Innate Cellular Responses to Hepatitis C Virus Infection 739
Adaptive Cellular Response to Hepatitis C Virus Infection 741
SUMMARY 743
REFERENCES 744
Impact of Hepatitis C Virus Infection on Hepatocellular Carcinoma 761
Key points 761
INTRODUCTION 761
EPIDEMIOLOGY 762
RISK FACTORS FOR HEPATOCELLULAR CARCINOMA 762
Concurrent Liver Disease 763
Lifestyle Factors 763
Inherent Viral Factors 764
VIROLOGY AND PATHOGENESIS 764
IMPACT OF ANTIVIRAL THERAPY ON HEPATOCELLULAR CARCINOMA 766
Impact of Interferon Therapy 766
Impact of Direct-acting Antivirals 766
Predictors of Hepatocellular Carcinoma After Sustained Virologic Response 766
SURVEILLANCE 767
PROGNOSIS/OUTCOMES 768
Trends in Mortality 768
Effect of Hepatocellular Carcinoma on Posttransplant Survival 768
SUMMARY 769
REFERENCES 770
Extrahepatic Manifestations of Hepatitis C Virus 775
Key points 775
INTRODUCTION 775
MIXED CRYOGLOBULINEMIA 777
TREATMENT OF MIXED CRYOGLOBULINEMIA SYNDROME 778
LYMPHOPROLIFERATIVE DISORDERS 781
TREATMENT OF LYMPHOPROLIFERATIVE DISORDERS 782
PORPHYRIA CUTANEA TARDA 783
LICHEN PLANUS 783
THYROID DISORDERS 783
ARTHRALGIAS AND ARTHRITIS 783
SICCA SYNDROME AND SJÖGREN SYNDROME 783
DIABETES MELLITUS AND VASCULAR DISORDERS 784
NEUROCOGNITIVE IMPAIRMENT 784
SUMMARY 784
REFERENCES 785
Hepatitis C: An Eastern Perspective 793
Key points 793
INTRODUCTION 793
THE EAST AS CLUSTERS OF SIMILAR COUNTRIES 794
VARIED EPIDEMIOLOGY 795
COMPLEX GENOTYPE DISTRIBUTION 795
DIFFERING HEPATITIS C VIRUS TREATMENTS 796
IMPLICATIONS OF FAVORABLE INTERFERON-RESPONSIVE GENES 798
DIVERSE BARRIERS IN ACCESS TO CARE 798
Registration Trials Are Needed in Some Asian Countries 798
Registration Time Lines 799
Health Care Systems in the East 799
Public Health Policies 800
Cost-Effectiveness Analysis in the East 801
Cost-Effectiveness Versus Affordability: Competition for the Health Dollar 801
Access and Other Programs 801
MANAGEMENT OF HEPATITIS C VIRUS INFECTION IN THE EAST 802
LOOKING AHEAD TO THE FUTURE 803
SUMMARY 803
REFERENCES 803
Hepatitis C Virus 807
Key points 807
INTRODUCTION 807
THE EPIDEMIOLOGY OF HEPATITIS C VIRUS INFECTION IN EUROPE 808
Hepatitis C Virus Prevalence, Diagnosis Rate, and Screening Strategies 808
Routes of Hepatitis C Virus Transmission 810
Iatrogenic transmission 810
Injective drug use 810
Hepatitis C virus in the migrant population 811
Genotype Distribution 811
Hepatitis C Virus–Related Mortality, Transplant, and Future Perspectives 811
Hepatitis C virus and mortality 811
Hepatitis C virus and transplant 812
Future perspectives of hepatitis C virus disease burden in Europe 813
APPROVED HEPATITIS C VIRUS TREATMENT OPTIONS IN THE EUROPEAN UNION 814
Genotypes 1 and 4 814
Sofosbuvir + ribavirin 814
Sofosbuvir + simeprevir ± ribavirin 814
Sofosbuvir + daclatasvir ± ribavirin 816
Paritaprevir/ritonavir + ombitasvir + dasabuvir ± ribavirin 817
Sofosbuvir + ledipasvir ± ribavirin 818
Genotype 2 818
Sofosbuvir + ribavirin 818
Current and Evolving Treatments of Genotype 1 Hepatitis C Virus 825
Key points 825
INTRODUCTION 825
GOAL OF THERAPY 826
PATIENT EVALUATION OVERVIEW 827
TREATMENT OPTIONS 827
Treatment-Naive Patients 828
Ledipasvir plus sofosbuvir 828
Paritaprevir/ritonavir/ombitasvir and dasabuvir 831
Sofosbuvir plus simeprevir 831
Treatment-Experienced Patients 832
Ledipasvir plus sofosbuvir 832
Paritaprevir/ritonavir/ombitasvir and dasabuvir 832
Sofosbuvir plus simeprevir 833
Patients with Established Cirrhosis 833
Patients Who Failed Previous Therapy Including a Direct-Acting Antiviral 835
DRUG INTERACTIONS 836
Sofosbuvir 836
Ledipasvir/Sofosbuvir 836
Simeprevir 837
Ombitasvir/Paritaprevir/Ritonavir plus Dasabuvir 838
MONITORING DURING THERAPY 838
SAFETY OF DIRECT-ACTING ANTIVIRALS 838
FUTURE THERAPY 838
SUMMARY 839
REFERENCES 840
Dedication 844
Hepatitis C Virus 845
Key points 845
INTRODUCTION 845
HEPATITIS C VIRUS GENOTYPE 2 846
Treatment Options for Hepatitis C Virus Genotype 2 847
Treatment-naive patients: direct-acting antivirals in combination with peginterferon/ribavirin 847
Treatment-naive patients: interferon-free regimen with direct-acting antivirals 847
Treatment-experienced patients: direct-acting antivirals in combination with peginterferon/ribavirin 848
Treatment-experienced patients: interferon-free regimen with direct-acting antivirals 848
HEPATITIS C VIRUS GENOTYPE 3 848
Treatment Options for Hepatitis C Virus Genotype 3 849
Treatment-naive patients: direct-acting antivirals in combination with peginterferon/ribavirin 849
Treatment-naive patients: interferon-free regimen with direct-acting antivirals 849
Treatment-experienced patients: direct-acting antivirals in combination with peginterferon/ribavirin 851
Treatment-experienced patients: interferon-free regimen with direct-acting antivirals 852
COST-EFFECTIVENESS OF NOVEL REGIMENS 852
NEW CHALLENGES TO OPTIMIZE THERAPY FOR HEPATITIS C VIRUS 2 AND 3 853
SUMMARY 855
REFERENCES 855
Hepatitis C Virus 859
Key points 859
HEPATITIS C VIRUS GENOTYPE 4 EPIDEMIOLOGY AND VIRUS DIVERSITY 860
PEGYLATED INTERFERON PLUS RIBAVIRIN: HISTORICAL PERSPECTIVES 860
NEW HOPE WITH DATA AVAILABLE WITH DIRECT-ACTING ANTIVIRALS FOR HEPATITIS C VIRUS GENOTYPE 4 860
DIRECT-ACTING ANTIVIRALS PLUS PEGYLATED INTERFERON PLUS RIBAVIRIN 861
SOFOSBUVIR PLUS PEGYLATED INTERFERON PLUS RIBAVIRIN (NEUTRINO STUDY) 861
SIMEPREVIR PLUS PEGYLATED INTERFERON PLUS RIBAVIRIN (RESTORE STUDY) 863
DACLATASVIR PLUS PEGYLATED INTERFERON PLUS RIBAVIRIN (COMMAND STUDY) 864
INTERFERON-FREE REGIMEN 864
Sofosbuvir Plus Ribavirin 864
SOFOSBUVIR PLUS LEDIPASVIR (SYNERGY STUDY AND TRIAL GS 1119) 865
SOFOSBUVIR AND SIMEPREVIR 865
SOFOSBUVIR AND DACLATASVIR 866
OMBITASVIR/PARITAPREVIR/RITONAVIR (PEARL STUDY) 867
DACLATASVIR, ASUNAPREVIR, AND BECLABUVIR 867
SUMMARY 868
REFERENCES 868
Current Treatment Options in Patients with Hepatitis C Virus Genotype 6 871
Key points 871
INTRODUCTION 871
PHARMACOLOGIC TREATMENT OPTIONS 872
Pegylated Interferon and Ribavirin 872
Telaprevir-based or Boceprevir-based Regimens 874
Sofosbuvir 874
Simeprevir 875
Daclatasvir 875
Ledipasvir 875
Grazoprevir-Elbasvir (Merck, Kenilworth, NJ) 876
Ritonavir-boosted Paritaprevir, Ombitasvir, and Dasabuvir (Viekira Pak, AbbVie Inc, North Chicago, IL) 876
TREATMENT RESISTANCE/COMPLICATIONS 877
EVALUATION OF OUTCOMES AND LONG-TERM RECOMMENDATIONS 878
SUMMARY/DISCUSSION 878
REFERENCES 878
Treatment of Chronic Hepatitis C in Special Populations 883
Key points 883
INTRODUCTION 883
TREATMENT OF HEPATITIS C VIRUS IN PATIENTS WITH END-STAGE RENAL DISEASE 884
Overview 884
Epidemiology 884
Natural history 884
Management 885
Interferon-based therapy 885
All-oral direct-acting antiviral therapy 885
TREATMENT OF HEPATITIS C VIRUS IN PATIENTS WITH DECOMPENSATED CIRRHOSIS 888
Overview 888
Management 888
Interferon-based therapy 888
All-oral direct-acting antiviral therapy 889
TREATMENT OF HEPATITIS C VIRUS IN LIVER TRANSPLANT RECIPIENTS 890
Overview 890
Epidemiology 890
Natural history 890
Management 891
Interferon-based therapy 891
All-oral direct-acting antiviral therapy 892
TREATMENT OF HEPATITIS C VIRUS IN HUMAN IMMUNODEFICIENCY VIRUS–INFECTED PERSONS 893
Overview 893
Epidemiology 893
Natural history 894
Management 894
Interferon-based therapy 894
All-oral direct-acting antiviral therapy 894
ACKNOWLEDGMENTS 896
REFERENCES 896
Hepatitis C 901
Key points 901
INTRODUCTION 901
ACUTE INFECTION 901
NATURAL HISTORY 902
CASE IDENTIFICATION 902
DIAGNOSIS 902
MALIGNANCY 903
TREATMENT 903
CURRENTLY APPROVED TREATMENTS FOR CHILDREN 904
Pegylated Interferon and Ribavirin 904
Genotype 1 904
Genotypes 2 and 3 905
Dosing 905
Adverse Effects 905
Prevention of Transmission 907
SUMMARY 907
REFERENCES 907
Index 911