Hepatitis C: Care and Treatment: Volume 2

Contents
1: Assessment of Liver Disease Severity
1.1 Introduction
1.2 Liver Biopsy: Advantages and Inconveniences
1.3 Currently Available Non-invasive Methods
1.3.1 Biological Approach: Serum Biomarkers of Liver Fibrosis
1.3.2 Physical Approach: Measuring Liver Stiffness
1.3.2.1 Transient Elastography
1.3.2.2 Other Imaging Methods
1.4 Diagnostic Performances of Non-invasive Methods for Staging Liver Fibrosis
1.4.1 Endpoints
1.4.2 Serum Biomarkers of Fibrosis
1.4.3 Transient Elastography
1.4.4 Other Imaging Methods
1.5 Use in Clinical Practice in Patients with Chronic Hepatitis C
1.5.1 Before Starting Antiviral Treatment
1.5.2 During Antiviral Treatment
1.5.3 After Antiviral Treatment
1.6 Monitoring Disease Progression and Prognosis
1.7 Conclusions
References
2: Extrahepatic Manifestations of Hepatitis C Virus Infection
2.1 Introduction
2.2 HCV and Cryoglobulinemia Vasculitis (CryoVas)
2.2.1 Main Clinical Features
2.2.2 Biological Surrogate Markers
2.2.3 Prognosis
2.3 HCV and Kidney Disease
2.4 HCV and Diabetes
2.5 HCV and Cardiovascular Disease
2.6 HCV and Cancer
2.7 HCV, Fatigue and Depression
2.8 HCV and Other Manifestations
2.9 How to Treat HCV-CryoVas and Other Extrahepatic Manifestations
References
3: Overview of Treatment Recommendations and Pretreatment Assessment
3.1 Treatment Recommendations
3.2 Hepatic Manifestations of Chronic HCV infection
3.3 Persons at Greater Risk for Rapidly Progressive Fibrosis and Cirrhosis
3.4 Extrahepatic Manifestations of Chronic HCV Infection
3.5 Therapy to Prevent HCV Transmission
3.6 Health Care Workers
3.7 Injection Drug Users
3.8 HIV-infected Men Who Have Sex with Men
3.9 Subjects on Hemodialysis
3.10 Patients with Acute Hepatitis or Recent Exposure
3.11 Patient Evaluation
3.11.1 History and Physical Examination
3.11.2 Laboratory Testing
3.12 HCV and Other Virological Markers
3.13 Assessment of Liver Disease
3.14 Counseling Patients
3.15 Transmission Risk
3.16 Dose Adjustments of Medications
References
4: Available Agents: Contraindications and Potential Drug-Drug Interactions
4.1 Introduction
4.2 Mechanisms of Drug-Drug Interactions
4.3 Pharmacology of individual Directly Acting Antivirals
4.3.1 Sofosbuvir
4.3.2 Sofosbuvir and Ledipasvir
4.3.3 Sofosbuvir and Velpatasvir
4.3.4 Sofosbuvir, Velpatasvir and Voxilaprevir
4.3.5 Paritaprevir (+ritonavir), Ombitasvir and Dasabuvir
4.4 Grazoprevir and Elbasvir
4.5 Glecaprevir and Pibrentasvir
4.6 DDI Advice for Specific Therapeutic Areas
4.6.1 Antiretrovirals (ARVs)
4.6.2 DDIs Involving HCV NS3-4A Protease Inhibitors and HIV Drugs Which Inhibit or Induce Their Clearance
4.6.3 Interactions Involving Tenofovir Diproxil Fumarate (TDF) and Tenofovir Alafenamide (TAF)
4.6.4 Miscellaneous DDIs Involving DAAs and Antiretrovirals
4.6.5 Proton Pump Inhibitors (PPIs)
4.6.6 Anti-epileptic Drugs (AEDs)
4.6.7 Immunosuppressants
4.6.8 Antiplatelets and Anticoagulants (Table 4.5)
4.6.9 Antiplatelets
4.6.10 Anticoagulants
4.6.11 Opioid Substitution Therapy (OST) and Illicit Drugs
4.6.12 Illicit/recreational Drugs
4.6.13 Opioid Substitution Therapies (OST)
4.6.14 Contraceptives
References
5: Current Management of Patients with HCV Genotype 1
5.1 Introduction
5.2 Sofosbuvir/Velpatasvir (Epclusa)
5.3 Sofosbuvir/Velpatasvir/Voxilaprevir (Vosevi)
5.4 Glecaprevir/Pibrentasvir (Maviret)
5.5 Elbasvir/Grazoprevir (Zepatier)
5.6 Conclusion
References
6: Current Management of Patients with HCV Genotype 2
6.1 Introduction
6.2 Epidemiological Data on GT2
6.3 Historical Evolution of GT2 Treatment
6.4 Genotype 2 Treatment: From Sofosbuvir and Ribavirin to Sofosbuvir and Daclatasvir
6.4.1 Sofosbuvir and Ribavirin
6.4.2 Sofosbuvir and Daclatasvir
6.4.3 GT2 Treatment Using the Pangenotypic Combination of SOF/VEL
6.4.4 Glecaprevir/Pibrentasvir
6.4.5 Sofosbuvir/Velpatasvir/Voxilaprevir
6.4.6 Drug-to-Drug Interactions (DDI)
6.4.7 GT2 Patients with Decompensated Cirrhosis
6.4.8 Re-treatment of GT2 Patients after DAA Failure
6.4.9 Treatment of Patients with Kidney Failure
6.5 Future Treatments
6.6 Conclusions/Statements
References
7: Current Management of HCV Genotype 3 Infection
7.1 Introduction
7.1.1 Epidemiology
7.1.2 Special Characteristics of HCV Genotype 3
7.2 Treatment
7.2.1 Pegylated Interferon plus Ribavirin
7.2.2 Sofosbuvir plus Ribavirin
7.2.3 Sofosbuvir plus Pegylated Interferon plus Ribavirin
7.2.4 Sofosbuvir/Ledipasvir with or Without Ribavirin
7.2.5 Sofosbuvir plus Daclatasvir with or Without Ribavirin
7.2.6 Sofosbuvir/Velpatasvir with or Without Ribavirin
7.2.7 Sofosbuvir/Velpatasvir/Voxilaprevir
7.2.8 Glecaprevir/Pibrentasvir
7.2.9 Sofosbuvir plus Grazoprevir/Elbasvir
7.2.10 Treatment of HCV-G3 in Patients with Decompensated HCV Liver Disease
7.2.11 Treatment of HIV/HCV-G3 Coinfected Patients
References
8: Current Management of Patients with HCV Genotype 4
8.1 Introduction
8.2 Direct-Acting Antivirals for HCV GT4
8.3 Sofosbuvir-Based Regimen
8.3.1 Sofosbuvir/Ledipasvir
8.3.2 Sofosbuvir/Velpatasvir
8.3.3 Sofosbuvir/Velpatasvir/Voxilaprevir
8.3.4 Glecaprevir-Pibrentasvir
8.3.5 Elbasvir/Grazoprevir
8.4 Conclusion: A Long Way to HCV Elimination
References
9: Current Management of Patients with HCV Genotype 5 or 6
9.1 Introduction
9.2 HCV Genotype 5
9.3 HCV Genotype 6
9.4 Management of Genotype 5 and 6
9.5 Treatment of Chronic Genotype 5 and 6 Infection
9.6 Direct-Acting Antivirals for HCV GT5 Infection
9.7 Sofosbuvir-Velpatasvir
9.8 Glecaprevir-Pibrentasvir
9.9 Sofosbuvir and Ledipasvir
9.10 Sofosbuvir-Velpatasvir-Voxilaprevir
9.11 Direct-Acting Antivirals for HCV-GT6 Infection
9.12 Sofosbuvir-Velpatasvir
9.13 Glecaprevir-Pibrentasvir
9.14 Sofosbuvir-Ledipasvir
9.15 Sofosbuvir-Velpatasvir-Voxilaprevir
9.16 Further Management
References
10: Management of Patients with Acute Hepatitis C
10.1 Epidemiology, Natural Course, and Diagnosis of Acute HCV Infection
10.1.1 Diagnosis of Acute HCV Infection
10.1.2 Definition of Acute HCV Infection
10.1.2.1 Prediction of Spontaneous Clearance
10.1.2.2 Prevention of HCV Infection
10.2 Management of Acute HCV Infection
10.2.1 Treatment of Acute HCV Infection with Interferon Alfa
10.2.2 Treatment of Acute HCV Infection with IFN-Free Regimens
10.3 Reinfection after Treatment of Acute HCV Infection
10.4 Prevention of HCV Infection by Preemptive DAA Therapy
References
11: Management of Transplant Patients Infected with HCV
11.1 Introduction
11.1.1 Natural History of HCV Recurrence
11.1.2 Management of HCV Recurrence
11.1.2.1 New Direct-Acting Antiviral Agents
11.1.2.2 Monitoring and Timing of the Initiation of Antiviral Therapy (Fig. 11.1)
11.1.2.3 Pretransplant Antiviral Therapy
11.1.2.4 Posttransplant Antiviral Treatment
Preemptive Treatment
Treatment of Established Infection on the Graft
11.1.2.5 Unmet Medical Needs Regarding DAA in Transplant Recipients
Treatment Duration and the Use of Ribavirin
Drug-Drug Interactions
Virologic Failure
11.1.3 Management of Human Immunodeficiency Virus/HCV Coinfected Liver Transplant Recipients
11.1.4 HCV Antibody-Positive Donors
11.2 Conclusion
References
12: Management of Patients with Renal Impairment: Direct-Acting Antivirals and Renal Function
12.1 Impact of DAAs on Renal Function
12.1.1 Non-Transplant Setting
12.1.2 Transplant Setting
12.2 Interferon-Free Regimens in Patients with CHC and CKD (Table 12.2)
12.2.1 Interferon-Free Regimens Approved for CHC and CKD
12.2.1.1 Ombitasvir/Paritaprevir/Dasabuvir-Based Regimens
12.2.1.2 Elbasvir/Grazoprevir
12.2.1.3 Glecaprevir/Pibrentasvir
12.2.2 Interferon-Free Antiviral Regimens Not Approved for CHC and CKD
12.3 Interferon-Free Regimens in Kidney Transplant Recipients with CHC (Table 12.3)
12.4 Cryoglobulinemia-Related Kidney Disease
12.5 Conclusions
References
13: Management of Hepatitis C Viral Infection in People Who Inject Drugs
13.1 Prevalence of HCV Infection in People Who Inject Drugs
13.2 Natural History of HCV Infection in People Who Inject Drugs
13.3 Prevention of HCV Infection in People Who Inject Drugs
13.4 Screening for HCV Infection in People Who Inject Drugs
13.5 HCV Infection Treatment in People Who Inject Drugs
13.6 Barriers to Treatment for HCV Infection in People Who Inject Drugs
13.7 Addressing Barriers to Care of HCV Infection in People Who Inject Drugs
13.7.1 Models of HCV Treatment Delivery to People Who Inject Drugs
13.7.1.1 Referral for HCV Care
13.7.1.2 Integrated Care
13.7.1.3 Virtual Integration
13.7.2 Support Services to Promote the Engagement of People Who Inject Drugs for Hepatitis C Care
13.7.2.1 Educational Support
13.7.2.2 Case Management
13.7.2.3 Patient and Peer Navigation
13.8 Follow-Up of PWID Following HCV Cure
References
14: Patient-Reported Outcomes in Hepatitis C Infection
14.1 Health-Related Quality of Life (HRQL)
14.2 HRQL Measurement Tools
14.3 Impact of Treatment on HCV PROs
14.4 Importance of PROS in C-HC
References