Advanced Therapy for Hepatitis C

Professor Geoff McCaughan is Director of the AW Morrow Liver Centre and Physician in Charge at the Australian National Liver Transplant Unit. John McHutchison is a professor of medicine at Duke University Medical Center, and since 2002, Director of the DCRI’s Gastroenterology and Hepatology Research division.

Contributors vii

Preface xi

Section I Foundations for Understanding Antiviral Therapies in HCV

1 HCV Replication 3
Michael R. Beard

2 Hepatitis C Virus Genotypes 12
Scott A. Read and Mark W. Douglas

3 Immune Responses to HCV: Implications for Therapy 17
David G. Bowen

4 Mechanisms of Action of Antiviral Drugs: The Interferons 25
Edmund Tse and Michael R. Beard

5 Pharmacology and Mechanisms of Action of Antiviral Drugs: Ribavirin Analogs 36
Fred Poordad and Grace M. Chee

6 Pharmacology and Mechanisms of Action of Antiviral Drugs: Polymerase Inhibitors 43
Lotte Coelmont Leen Delang Mathy Froeyen Piet Herdewijn and Johan Neyts

7 Pharmacology and Mechanisms of Action of Antiviral Drugs: Protease Inhibitors 53
Laurent Chatel-Chaix Martin Baril and Daniel Lamarre

8 Measuring Antiviral Responses 60
Jean-Michel Pawlotsky and Stephane Chevaliez

Section II Efficacy and Clinical Use of Antiviral Therapies

9 Genotype 1: Standard Treatment 67
Rebekah G. Gross and Ira M. Jacobson

10 Individually Tailored Treatment Strategies in Treatment-na¨ive Chronic Hepatitis C Genotype 1 Patients 74
Johannes Wiegand and Thomas Berg

11 Genotype 1 Relapsers and Non-responders 84
Salvatore Petta and Antonio Craxì

12 Standard Therapy for Genotypes 2/3 90
Kenneth Yan and Amany Zekry

13 Altered Dosage or Durations of Current Antiviral Therapy for HCV Genotypes 2 and 3 97
Alessandra Mangia Leonardo Mottola and Angelo Andriulli

14 Genotypes 2 and 3 Relapse and Non-response 104
Stella Martinez Jose Maria Sanchez-Tapias and Xavier Forns

15 Hepatitis C Genotype 4 Therapy: Progress and Challenges 113
Sanaa M. Kamal

16 Antivirals in Acute Hepatitis C 127
Heiner Wedemeyer

17 Antivirals in Cirrhosis and Portal Hypertension 132
Diarmuid S. Manning and Nezam H. Afdhal

18 Treatment of Recurrent Hepatitis C Following Liver Transplantation 140
Ed Gane

19 Antiviral Treatment in Chronic Hepatitis C Virus Infection with Extrahepatic Manifestations 150
Benjamin Terrier and Patrice Cacoub

20 Cytopenias: How they Limit Therapy and Potential Correction 160
Mitchell L. Shiffman

21 The Problem of Insulin Resistance and its Effect on Therapy 169
Venessa Pattullo and Jacob George

22 HIV and Hepatitis C Co-infection 177
Gail V. Matthews and Gregory J. Dore

23 HCV and Racial Differences 185
Andrew J. Muir

24 HCV and the Pediatric Population 190
Kathleen B. Schwarz

25 New Horizons: IL28 Direct-acting Antiviral Therapy for HCV 196
Alexander J. Thompson John G. McHutchison and Geoffrey W. McCaughan

Index 215