Advanced Therapy for Hepatitis C

Hepatologists, both researchers and front-line clinicians, now have a comprehensive guide to the treatment of patients with the HCV virus. This book focuses mainly on the efficacy and clinical use of antiviral therapies, including the use of antivirals post liver transplantation and in the presence of the HIV virus. It also explores the foundations for understanding antiviral therapies in HCV, such as the complex pharmacology and mechanisms of antiviral drugs. A 'late-breaking information' chapter contains the most recent trial results on the latest antiviral drugs.

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

"I think it is an invaluable respository of knowledge for anyone embarking on a career caring for patients with viral hepatitis. This book summarises the hard won clinical knowledge of the past 20 years." (The Irish Medical Journal, 1 January 2013)

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.

According to the WHO, 170 million people, or 3% of the world's population, are infected with Hepatitis C and at risk of developing liver cirrhosis and/or liver cancer. 3-4 million people each year are newly diagnosed carriers of the virus.

Advanced Therapy for Hepatitis C Infection provides you with expert guidance from the world's leading hepatologists on the very latest treatment options for patients with the HCV virus. Focusing mainly on the efficacy and clinical use of antiviral therapies, key topics include:

• Treatment of recurrent hepatitis C following liver transplantation
• Antivirals in Cirrhosis and Portal Hypertension
• HIV and Hepatitis C co-infection
• Cytopenias: how they limit therapy and potential correction
• The problem of insulin resistance and its effect on therapy
• Antivirals in Acute Hepatitis C

In addition, it fully covers the foundations for understanding antiviral therapies in HCV, such as the complex pharmacology and mechanisms of antiviral drugs. Finally, a chapter on New Horizons: Interleukin 28 and direct-acting antiviral therapy for HCV, offers you a glimpse into the future possibilities for HCV therapy.

Edited by a team of outstanding international reputation, Advanced Therapy for Hepatitis C Infection is an essential tool for all hepatologists and gastroenterologists involved in the management of patients with Hepatitis C.