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Current Management of Hepatitis C Virus, An Issue of Clinics in Liver Disease, E-Book

Current Management of Hepatitis C Virus, An Issue of Clinics in Liver Disease, E-Book

Fred Poordad

(2016)

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Book Details

Abstract

Clinical information about Hepatitis C is quickly outdated, so Dr. Poordad has assembled expert authors to provide state-of-the-art clinjcal reviews for hepatologists. This issue is uniquely organized to present articles based on therapeutic regimens for certain types of patients:
 Regimens for the Treatment-Naïve Patient; Regimens for Treatment of the Interferon-Failure Patient; Regimens for DAA Failure Patients; Regimens for the Cirrhotic Patient; Regimens for the Peri-Transplant Patient; Regimens for the HIV-Co-Infected Patient; and Next-generation Regimens: The Future of HCV Therapy. This presentation will be very clinically relevant for the practicing hepatologist.

Table of Contents

Section Title Page Action Price
Front Cover Cover
Current Management of\rHepatitis C Virus i
Copyright ii
Contributors iii
CONSULTING EDITOR iii
EDITOR iii
AUTHORS iii
Contents v
Preface: Hepatitis C Therapy: Simple for the Patient, not so Simple for the Clinician v
Evaluation of Hepatitis C Patients in the Direct-Acting Antiviral Era v
Meet the Classes of Directly Acting Antiviral Agents: Strengths and Weaknesses v
Regimens for the Hepatitis C Treatment-Naive Patient v
Direct-Acting Antiviral Agents: Regimens for the Interferon Failure Patient v
Mechanisms of Virologic Failure with Direct-Acting Antivirals in Hepatitis C and Strategies for Retreatment vi
Regimens for Cirrhotic Patients vi
Current Management of Hepatitis C Virus: Regimens for Peri-Liver Transplant Patients vi
Regimens for Patients Coinfected with Human Immunodeficiency Virus vi
Next-Generation Regimens: The Future of Hepatitis C Virus Therapy vii
CLINICS IN LIVER DISEASE viii
FORTHCOMING ISSUES viii
February 2016 viii
May 2016 viii
August 2016 viii
RECENT ISSUES viii
August 2015 viii
May 2015 viii
February 2015 viii
Preface: Hepatitis C Therapy: Simple for the Patient, not so Simple for the Clinician ix
Evaluation of Hepatitis C Patients in the Direct-Acting Antiviral Era 591
Key points 591
INTRODUCTION 591
SCREENING 592
CLINICAL EVALUATION 593
Pretreatment Investigations 594
Hepatitis C Virus Investigations 594
Other Investigations 596
Fibrosis Staging 597
DRUG-DRUG INTERACTIONS 599
COUNSELING 599
WHEN TO TREAT 599
SUMMARY 601
REFERENCES 601
Meet the Classes of Directly Acting Antiviral Agents 605
Key points 605
INTRODUCTION 605
THE HEPATITIS C VIRUS LIFE CYCLE 606
VIRAL ENTRY 606
VIRAL REPLICATION 606
THE ISSUE OF POLYMORPHISMS AND DRUG RESISTANCE 608
NS3/4A PROTEASE INHIBITORS 610
NS5A INHIBITORS 610
NS5B POLYMERASE INHIBITORS 611
Nucleoside/Nucleotide Analogue Inhibitors of Hepatitis C Virus NS5B Polymerase 611
NON-NUCLEOSIDE INHIBITORS OF HEPATITIS C VIRUS NS5B POLYMERASE 612
THE RATIONALE BEHIND COMBINATION THERAPY 614
SUMMARY 614
REFERENCES 615
Regimens for the Hepatitis C Treatment-Naive Patient 619
Key points 619
INTRODUCTION 619
TREATMENT IN NAIVE PATIENTS WITHOUT CIRRHOSIS 620
Hepatitis C Virus Genotype 1 620
Hepatitis C Virus Genotype 2 622
Hepatitis C Virus Genotype 3 622
TREATMENT IN NAIVE PATIENTS WITH CIRRHOSIS 623
Hepatitis C Virus Genotype 1 623
Hepatitis C Virus Genotype 2 623
Hepatitis C Virus Genotype 3 624
TREATMENT OF HEPATITIS C VIRUS GENOTYPE 4 INFECTION 624
TREATMENT OF HEPATITIS C VIRUS GENOTYPE 5 AND 6 INFECTION 625
FUTURE THERAPY 625
SUMMARY 626
REFERENCES 626
Direct-Acting Antiviral Agents 629
Key points 629
INTRODUCTION 629
HISTORY OF INTERFERON-CONTAINING REGIMENS 629
INTERFERON INTOLERABILITY 630
INTERFERON FAILURE 631
Currently Recommended Treatment Regimens for Interferon Failure Patients: A Review of the Evidence and Current Guidelines 631
GENOTYPES 1A AND 1B TREATMENT RECOMMENDATIONS 634
GENOTYPES 2 AND 3 TREATMENT RECOMMENDATIONS 637
GENOTYPES 4, 5, AND 6 TREATMENT RECOMMENDATIONS 637
SUMMARY 638
REFERENCES 638
Mechanisms of Virologic Failure with Direct-Acting Antivirals in Hepatitis C and Strategies for Retreatment 641
Key points 641
INTRODUCTION 641
MECHANISMS OF DIRECT-ACTING ANTIVIRAL DRUGS 643
Protease Inhibitors 643
NS5A Inhibitors 644
NS5B Non-nucleoside Polymerase Inhibitors 644
NS5B Nucleoside Polymerase Inhibitors 644
POTENTIAL FAILURE POPULATIONS 644
Mono–Direct-Acting Antiviral Therapy with Protease Inhibitor 644
Mono-Sofosbuvir Failures 645
All Oral Treatment Failures 645
MECHANISM OF NONRESPONSE TO ANTIVIRAL 646
Viral Factors 646
Host Factors 648
Altered Pharmacokinetics 650
Portosystemic Shunting and Cirrhosis 650
THERAPEUTIC OPTIONS FOR RETREATMENT OF DIRECT-ACTING ANTIVIRAL FAILURES 651
Clinical Trials Inclusive of Sofosbuvir Failures in Genotype 1 651
Retreatment of Sofosbuvir Failures with Genotype 2 or 3 652
Approach to Patients Requiring Retreatment 653
Cocktail Mixology for Hepatitis C Virus 653
SUMMARY 653
REFERENCES 654
Regimens for Cirrhotic Patients 657
Key points 657
TREATMENT OPTIONS: GENOTYPE 1 658
Treatment Options for Genotype 1 Individuals Who Have Failed Previous Therapy 659
GENOTYPE 2 661
GENOTYPE 3 661
GENOTYPE 4 663
GENOTYPES 5 AND 6 664
REFERENCES 665
Current Management of Hepatitis C Virus 669
Key points 669
INTRODUCTION 669
HEPATITIS C VIRUS TREATMENT BEFORE LIVER TRANSPLANT TO ACHIEVE CURE 671
HEPATITIS C VIRUS TREATMENT BEFORE LIVER TRANSPLANT TO PREVENT HEPATITIS C VIRUS RECURRENCE 677
PREEMPTIVE HEPATITIS C VIRUS TREATMENT AFTER LIVER TRANSPLANT TO ACHIEVE CURE 678
HEPATITIS C VIRUS TREATMENT AFTER LIVER TRANSPLANT TO ACHIEVE CURE 679
Significant Fibrosis/Compensated Cirrhosis 679
Decompensated Cirrhosis 681
PRETRANSPLANT VERSUS POSTTRANSPLANT THERAPY: WHICH IS BETTER? 682
Wait-Listed Patients 682
Post–Liver Transplant Recipients 682
SUMMARY 684
REFERENCES 684
Regimens for Patients Coinfected with Human Immunodeficiency Virus 689
Key points 689
INTRODUCTION 689
Epidemiology and Natural History of Hepatitis C Virus in Patients with Human Immunodeficiency Virus 1 690
Special Consideration in Evaluation of Patients Coinfected with Human Immunodeficiency Virus 690
Treatment of Hepatitis C Virus in Patients with Human Immunodeficiency Virus Using Interferon-containing Regimens 691
Antiretroviral Therapy Considerations and Drug-Drug Interactions 692
Current Regimens for Hepatitis C Virus Genotype 1 Treatment in Patients with Human Immunodeficiency Virus 1 693
Nucleotide-based Hepatitis C Virus Treatment Regimens 693
Sofosbuvir plus interferon 693
Sofosbuvir plus RBV 695
Sofosbuvir-antiretroviral drug interactions 696
Sofosbuvir plus an NS5A inhibitor 696
NS5A inhibitor drug interactions and implications for sofosbuvir/NS5A regimens 698
Sofosbuvir plus an NS3 protease inhibitor 699
NS3 protease inhibitor–based regimens 699
Human Immunodeficiency Virus Control During Direct-acting Antiviral Therapy 701
SUMMARY 701
REFERENCES 702
Next-Generation Regimens 707
Key points 707
INTRODUCTION 707
LIMITATIONS OF PAST REGIMENS 707
PHASE III TRIALS 708
Daclatasvir/Asunaprevir/Beclabuvir 708
Daclatasvir/Sofosbuvir 708
PHASE II TRIALS 709
Grazoprevir (MK-5172)/Elbasvir (MK-8742) 709
GS-5816/Sofosbuvir 710
ACH-3102 710
PHASE I 710
ABT-493/ABT-530 710
MK-3682 (Formally IDX21437) 710
PRECLINICAL AGENTS 713
MK-8408 713
HOST TARGETED AGENTS 713
MIRAVIRSEN 713
RG-101 713
FUTURE FRONTIERS 714
REFERENCES 714