Hepatitis C: Epidemiology, Prevention and Elimination Volume 1

Contents
1: HCV Virology
	1.1 Experimental Systems to Study HCV Life Cycle
	1.2 Structural Organization of Viral Particles
		1.2.1 Nonenveloped Nucleocapsids
		1.2.2 Canonical Particle Structure
		1.2.3 LVP Structure
	1.3 The Viral Proteins
		1.3.1 Core
		1.3.2 E1 and E2
		1.3.3 P7
		1.3.4 NS2
		1.3.5 NS3/4A
		1.3.6 NS4B
		1.3.7 NS5A
		1.3.8 NS5B
	1.4 Life Cycle
		1.4.1 Entry
		1.4.2 Replication
		1.4.3 Assembly
		1.4.4 Maturation/Release
	1.5 Direct-Acting Antivirals (DAA) and Their Mode of Action
	1.6 Host-Targeting Agents and Their Mechanisms of Action
	1.7 Conclusion
	References
2: Hepatitis C Virus Origin
	2.1 The Peculiar Virology of HCV
	2.2 Nonhuman Hosts of HCV-Like Viruses
	2.3 The Paradox of the Global HCV
	References
3: Classification, Genetic Diversity and Global Distribution of Hepatitis C Virus (HCV) Genotypes and Subtypes
	3.1 HCV Classification
		3.1.1 Recombinants
		3.1.2 Additional Hierarchy Within HCV Genotypes
	3.2 The Global Distribution of HCV Clades
		3.2.1 Introduction
		3.2.2 Global Prevalence of HCV Clades
		3.2.3 Global Distribution of HCV Clades
		3.2.4 Genotype 1
		3.2.5 Genotype 2
		3.2.6 Genotype 3
		3.2.7 Genotype 4
		3.2.8 Genotype 5
		3.2.9 Genotype 6
		3.2.10 Genotype 7
	3.3 Conclusions
	References
4: Laboratory Diagnosis
	4.1 Historical Perspective
	4.2 Markers of HCV Infection
	4.3 Diagnostic Algorithm
		4.3.1 Temporal Evolution of Diagnostic Markers
		4.3.2 Testing for HCV Antibodies
			4.3.2.1 Confirmation of HCV Serostatus
			4.3.2.2 HCV Antibody Testing in Sub-Saharan Africa
		4.3.3 Testing in Recent Infection
		4.3.4 Diagnosing Reinfection
		4.3.5 Testing for HCV RNA
		4.3.6 Testing for HCV Core Antigen
		4.3.7 Evolving Screening Strategies
			4.3.7.1 Alternative Sampling and Testing Methods
			4.3.7.2 Point-of-Care Testing
	4.4 Guiding and Monitoring Treatment
		4.4.1 Viral Load
		4.4.2 Simplified Approaches
		4.4.3 HCV Genotype
			4.4.3.1 Viral Genetic Diversity
			4.4.3.2 The Need for Genotyping
			4.4.3.3 Genotyping Methods
		4.4.4 HCV Drug Resistance
			4.4.4.1 Mechanisms and Principles of Drug Resistance
			4.4.4.2 Which Test to Use
			4.4.4.3 When to Perform Resistance Testing
			4.4.4.4 Interpretation of Resistance Test Results
	4.5 Conclusions
	References
5: Global HCV Burden
	5.1 Introduction
	5.2 Global Burden of HCV Infection
	5.3 Global HCV Incidence Estimates
	5.4 Global HCV Burden in Specific Populations
		5.4.1 Global Burden of HCV Infection Among People Who Inject Drugs (PWIDs)
		5.4.2 Global Burden of Infection in People Coinfected with HIV and HCV (HIV/HCV Coinfected)
		5.4.3 Global Burden of Infection in Prisoners and Detainees
	5.5 Global Burden of HCV Disease
	5.6 Monitoring Burden of HCV Infection and Disease
	5.7 Summary
	References
6: Epidemiology of Hepatitis C Virus: People Who Inject Drugs and Other Key Populations
	6.1 Introduction
	6.2 People Who Inject Drugs
		6.2.1 Prevalence and Trends
		6.2.2 Incidence
		6.2.3 Genotypes
		6.2.4 HIV Co-infection
		6.2.5 Risk Factors
		6.2.6 Disease Progression, Cirrhosis, Hepatocellular Carcinoma, Burden of Disease and Mortality
		6.2.7 Prevalence and Incidence of Injecting/Number of People Who Inject Drugs
		6.2.8 Prevention and Harm Reduction for People Who Inject Drugs
		6.2.9 HCV Treatment of People Who Inject Drugs
	6.3 Men Who Have Sex with Men
	6.4 Patients at Risk of Nosocomial Infection
	6.5 Migrants
	6.6 Reinfection
	6.7 Discussion
	References
7: Natural History of Hepatitis C Infection
	7.1 Introduction
	7.2 Acute HCV Infection
	7.3 Chronic HCV Infection
		7.3.1 Fibrosis Progression in Chronic HCV Infection
		7.3.2 Co-factors Affecting Fibrosis Progression
			7.3.2.1 Age
			7.3.2.2 Gender
			7.3.2.3 Ethnicity
			7.3.2.4 Genetic Background
			7.3.2.5 Viral Genotype
			7.3.2.6 ALT Values
			7.3.2.7 HIV and HBV Coinfection
			7.3.2.8 Alcohol Intake
			7.3.2.9 Steatosis, Obesity, and Insulin Resistance
	7.4 HCV-Related Cirrhosis and Complications
	7.5 HCV Extrahepatic Manifestations
	7.6 Natural History of Cirrhosis Following HCV Eradication
	7.7 Conclusions
	References
8: Epidemiology: Modeling of Natural History
	8.1 Introduction
	8.2 Approaches to Model the Natural History of Chronic Hepatitis C
	8.3 CHC-Based Models
	8.4 Fibrosis-Based Models
		8.4.1 Estimating Constant FPR (Indirect Method)
		8.4.2 Estimating Stage-Specific FPR
			8.4.2.1 Estimating Stage-Specific FPR from Serial Biopsy Data
			8.4.2.2 Estimating Stage-Specific FPR from Single Biopsy Data (MML Method)
	8.5 Using Models of Natural History of Chronic Hepatitis C to Estimate Progression to Cirrhosis and to Project the Burden of D...
	References
9: Prevention: Secondary Prevention and Screening
	9.1 Introduction
	9.2 Rationale for Performing Screening for Hepatitis C
	9.3 Key Drivers of Cost-Effectiveness of HCV Screening
	9.4 Screening Approaches
	9.5 How to Implement Screening: Integrated vs. Non-integrated Programs
	9.6 How to Test for HCV in Screening Programs
	9.7 Ethical Issues in HCV Screening Programs
	References
10: Hepatitis C Elimination and Advocacy Groups
	References
11: HCV Elimination in Australia
	11.1 Introduction
	11.2 History of Response to Hepatitis C in Australia: Paving the Path Towards HCV Elimination
	11.3 Initial DAA Uptake
	11.4 Diversity of Models of Care and Ease of DAA Access
		11.4.1 Case Study 1: Kirketon Road Centre
		11.4.2 Case Study 2: Nurse-Led Model of Care in the Prison Setting
		11.4.3 Case Study 3: ETHOS
		11.4.4 Case Study 4: Kombi Clinic
	11.5 Insights from Mathematical Modelling Studies
	11.6 Empirical Evidence for HCV Treatment as Prevention
	11.7 Monitoring and Evaluation of HCV Elimination
	11.8 Moving Forward
	References
12: Egypt: Towards Successful Elimination of HCV in Low-Income Countries
	12.1 Strategic and Action Plan Evolution During Egyptian Journey Towards HCV Elimination
		12.1.1 Addressing HCV Problem and Raising the Awareness Against HCV Transmission
		12.1.2 Implementing Universal Screening
		12.1.3 Treating HCV Patients and Ending Hepatitis C Transmission with Antiviral Medication
	12.2 Revulsions of Patients´ Assessments in NCCVH Affiliated Centers
	12.3 Addressing DAA Availability
	12.4 It Could Be Very Soon
	References
13: National Hepatitis C Elimination Program of Georgia
	13.1 HCV Epidemiology in Georgia
	13.2 National Elimination Program
	13.3 HCV Cascade and Treatment Outcomes
	13.4 Beyond Cascade
	13.5 Achieving the Goal of Elimination
	References
14: Micro-elimination: A Key Component of Global Hepatitis C Elimination
	14.1 Introduction
		14.1.1 General Framework of the WHO Viral Hepatitis Strategy
			Box 14.1 Pillars of the WHO Global Health Sector Strategy on Viral Hepatitis 2016-2021 [1]
			Box 14.2 12 Target Population Candidates for an HCV Micro-elimination Approach
		14.1.2 Hepatitis C Treatment Delivery and Efficacy and Policies
		14.1.3 What Do We Mean by HCV Micro-elimination?
			Box 14.3 Potential Advantages of a Micro-elimination Approach
		14.1.4 Historical Background of Micro-elimination
	14.2 The Footprints of HCV Micro-elimination in Research and Policy
		14.2.1 The HCV Micro-elimination Evidence Base
		14.2.2 Official Documents That Include Aspects of Micro-elimination
			Box 14.4 Mention of Elimination Targets Among Key Populations in Relevant International Strategic Documents, Guidelines, and N...
	14.3 General Principles of Micro-elimination Strategies: Achieving HCV Micro-elimination Requires Ensuring Equity and Human Ri...
	14.4 Basic Requirements to Embark on the Path of HCV Micro-elimination
	14.5 Tools and Resources to Implement Micro-elimination Approaches
	14.6 Known and Potential Barriers to HCV Micro-elimination
	14.7 Recommendations and Conclusions
	References