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.

"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)

• Contributors viiPreface xiSection I Foundations for Understanding Antiviral Therapies in HCV1 HCV Replication 3Michael R. Beard2 Hepatitis C Virus Genotypes 12Scott A. Read and Mark W. Douglas3 Immune Responses to HCV: Implications for Therapy 17David G. Bowen4 Mechanisms of Action of Antiviral Drugs: The Interferons 25Edmund Tse and Michael R. Beard5 Pharmacology and Mechanisms of Action of Antiviral Drugs: Ribavirin Analogs 36Fred Poordad and Grace M. Chee6 Pharmacology and Mechanisms of Action of Antiviral Drugs: Polymerase Inhibitors 43Lotte Coelmont Leen Delang Mathy Froeyen Piet Herdewijn and Johan Neyts7 Pharmacology and Mechanisms of Action of Antiviral Drugs: Protease Inhibitors 53Laurent Chatel-Chaix Martin Baril and Daniel Lamarre8 Measuring Antiviral Responses 60Jean-Michel Pawlotsky and Stephane ChevaliezSection II Efficacy and Clinical Use of Antiviral Therapies9 Genotype 1: Standard Treatment 67Rebekah G. Gross and Ira M. Jacobson10 Individually Tailored Treatment Strategies in Treatment-na¨ive Chronic Hepatitis C Genotype 1 Patients 74Johannes Wiegand and Thomas Berg11 Genotype 1 Relapsers and Non-responders 84Salvatore Petta and Antonio Craxì12 Standard Therapy for Genotypes 2/3 90Kenneth Yan and Amany Zekry13 Altered Dosage or Durations of Current Antiviral Therapy for HCV Genotypes 2 and 3 97Alessandra Mangia Leonardo Mottola and Angelo Andriulli14 Genotypes 2 and 3 Relapse and Non-response 104Stella Martinez Jose Maria Sanchez-Tapias and Xavier Forns15 Hepatitis C Genotype 4 Therapy: Progress and Challenges 113Sanaa M. Kamal16 Antivirals in Acute Hepatitis C 127Heiner Wedemeyer17 Antivirals in Cirrhosis and Portal Hypertension 132Diarmuid S. Manning and Nezam H. Afdhal18 Treatment of Recurrent Hepatitis C Following Liver Transplantation 140Ed Gane19 Antiviral Treatment in Chronic Hepatitis C Virus Infection with Extrahepatic Manifestations 150Benjamin Terrier and Patrice Cacoub20 Cytopenias: How they Limit Therapy and Potential Correction 160Mitchell L. Shiffman21 The Problem of Insulin Resistance and its Effect on Therapy 169Venessa Pattullo and Jacob George22 HIV and Hepatitis C Co-infection 177Gail V. Matthews and Gregory J. Dore23 HCV and Racial Differences 185Andrew J. Muir24 HCV and the Pediatric Population 190Kathleen B. Schwarz25 New Horizons: IL28 Direct-acting Antiviral Therapy for HCV 196Alexander J. Thompson John G. McHutchison and Geoffrey W. McCaughanIndex 215

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.

"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)

• Contributors viiPreface xiSection I Foundations for Understanding Antiviral Therapies in HCV1 HCV Replication 3Michael R. Beard2 Hepatitis C Virus Genotypes 12Scott A. Read and Mark W. Douglas3 Immune Responses to HCV: Implications for Therapy 17David G. Bowen4 Mechanisms of Action of Antiviral Drugs: The Interferons 25Edmund Tse and Michael R. Beard5 Pharmacology and Mechanisms of Action of Antiviral Drugs: Ribavirin Analogs 36Fred Poordad and Grace M. Chee6 Pharmacology and Mechanisms of Action of Antiviral Drugs: Polymerase Inhibitors 43Lotte Coelmont Leen Delang Mathy Froeyen Piet Herdewijn and Johan Neyts7 Pharmacology and Mechanisms of Action of Antiviral Drugs: Protease Inhibitors 53Laurent Chatel-Chaix Martin Baril and Daniel Lamarre8 Measuring Antiviral Responses 60Jean-Michel Pawlotsky and Stephane ChevaliezSection II Efficacy and Clinical Use of Antiviral Therapies9 Genotype 1: Standard Treatment 67Rebekah G. Gross and Ira M. Jacobson10 Individually Tailored Treatment Strategies in Treatment-na¨ive Chronic Hepatitis C Genotype 1 Patients 74Johannes Wiegand and Thomas Berg11 Genotype 1 Relapsers and Non-responders 84Salvatore Petta and Antonio Craxì12 Standard Therapy for Genotypes 2/3 90Kenneth Yan and Amany Zekry13 Altered Dosage or Durations of Current Antiviral Therapy for HCV Genotypes 2 and 3 97Alessandra Mangia Leonardo Mottola and Angelo Andriulli14 Genotypes 2 and 3 Relapse and Non-response 104Stella Martinez Jose Maria Sanchez-Tapias and Xavier Forns15 Hepatitis C Genotype 4 Therapy: Progress and Challenges 113Sanaa M. Kamal16 Antivirals in Acute Hepatitis C 127Heiner Wedemeyer17 Antivirals in Cirrhosis and Portal Hypertension 132Diarmuid S. Manning and Nezam H. Afdhal18 Treatment of Recurrent Hepatitis C Following Liver Transplantation 140Ed Gane19 Antiviral Treatment in Chronic Hepatitis C Virus Infection with Extrahepatic Manifestations 150Benjamin Terrier and Patrice Cacoub20 Cytopenias: How they Limit Therapy and Potential Correction 160Mitchell L. Shiffman21 The Problem of Insulin Resistance and its Effect on Therapy 169Venessa Pattullo and Jacob George22 HIV and Hepatitis C Co-infection 177Gail V. Matthews and Gregory J. Dore23 HCV and Racial Differences 185Andrew J. Muir24 HCV and the Pediatric Population 190Kathleen B. Schwarz25 New Horizons: IL28 Direct-acting Antiviral Therapy for HCV 196Alexander J. Thompson John G. McHutchison and Geoffrey W. McCaughanIndex 215

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.

"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)

• Contributors viiPreface xiSection I Foundations for Understanding Antiviral Therapies in HCV1 HCV Replication 3Michael R. Beard2 Hepatitis C Virus Genotypes 12Scott A. Read and Mark W. Douglas3 Immune Responses to HCV: Implications for Therapy 17David G. Bowen4 Mechanisms of Action of Antiviral Drugs: The Interferons 25Edmund Tse and Michael R. Beard5 Pharmacology and Mechanisms of Action of Antiviral Drugs: Ribavirin Analogs 36Fred Poordad and Grace M. Chee6 Pharmacology and Mechanisms of Action of Antiviral Drugs: Polymerase Inhibitors 43Lotte Coelmont Leen Delang Mathy Froeyen Piet Herdewijn and Johan Neyts7 Pharmacology and Mechanisms of Action of Antiviral Drugs: Protease Inhibitors 53Laurent Chatel-Chaix Martin Baril and Daniel Lamarre8 Measuring Antiviral Responses 60Jean-Michel Pawlotsky and Stephane ChevaliezSection II Efficacy and Clinical Use of Antiviral Therapies9 Genotype 1: Standard Treatment 67Rebekah G. Gross and Ira M. Jacobson10 Individually Tailored Treatment Strategies in Treatment-na¨ive Chronic Hepatitis C Genotype 1 Patients 74Johannes Wiegand and Thomas Berg11 Genotype 1 Relapsers and Non-responders 84Salvatore Petta and Antonio Craxì12 Standard Therapy for Genotypes 2/3 90Kenneth Yan and Amany Zekry13 Altered Dosage or Durations of Current Antiviral Therapy for HCV Genotypes 2 and 3 97Alessandra Mangia Leonardo Mottola and Angelo Andriulli14 Genotypes 2 and 3 Relapse and Non-response 104Stella Martinez Jose Maria Sanchez-Tapias and Xavier Forns15 Hepatitis C Genotype 4 Therapy: Progress and Challenges 113Sanaa M. Kamal16 Antivirals in Acute Hepatitis C 127Heiner Wedemeyer17 Antivirals in Cirrhosis and Portal Hypertension 132Diarmuid S. Manning and Nezam H. Afdhal18 Treatment of Recurrent Hepatitis C Following Liver Transplantation 140Ed Gane19 Antiviral Treatment in Chronic Hepatitis C Virus Infection with Extrahepatic Manifestations 150Benjamin Terrier and Patrice Cacoub20 Cytopenias: How they Limit Therapy and Potential Correction 160Mitchell L. Shiffman21 The Problem of Insulin Resistance and its Effect on Therapy 169Venessa Pattullo and Jacob George22 HIV and Hepatitis C Co-infection 177Gail V. Matthews and Gregory J. Dore23 HCV and Racial Differences 185Andrew J. Muir24 HCV and the Pediatric Population 190Kathleen B. Schwarz25 New Horizons: IL28 Direct-acting Antiviral Therapy for HCV 196Alexander J. Thompson John G. McHutchison and Geoffrey W. McCaughanIndex 215