Effectiveness of telaprevir or boceprevir in treatment-experienced patients with HCV genotype 1 infection and cirrhosis.
OBJECTIVE
We investigated the effectiveness of the protease inhibitors peginterferon and ribavirin in treatment-experienced patients with hepatitis C virus (HCV) genotype 1 infection and cirrhosis.


METHODS
In the Compassionate Use of Protease Inhibitors in Viral C Cirrhosis study, 511 patients with HCV genotype 1 infection and compensated cirrhosis who did not respond to a prior course of peginterferon and ribavirin (44.3% relapsers or patients with viral breakthrough, 44.8% partial responders, and 8.0% null responders) were given either telaprevir (n = 299) or boceprevir (n = 212) for 48 weeks. We assessed percentages of patients with sustained viral responses 12 weeks after therapy and safety. This observational study did not allow for direct comparison of the 2 regimens.


RESULTS
Among patients given telaprevir, 74.2% of relapsers, 40.0% of partial responders, and 19.4% of null responders achieved SVR12. Among those given boceprevir, 53.9% of relapsers, 38.3% of partial responders, and none of the null responders achieved SVR12. In multivariate analysis, factors associated with SVR12 included prior response to treatment response, no lead-in phase, HCV subtype 1b (vs 1a), and baseline platelet count greater than 100,000/mm(3). Severe adverse events occurred in 49.9% of cases, including liver decompensation, severe infections in 10.4%, and death in 2.2%. In multivariate analysis, baseline serum albumin level less than 35 g/L and baseline platelet counts of 100,000/mm(3) or less predicted severe side effects or death.


CONCLUSIONS
Relatively high percentages of real-life, treatment-experienced patients with HCV genotype 1 infection and cirrhosis respond to the combination of peginterferon and ribavirin with telaprevir or boceprevir. However, side effects are frequent and often severe. Baseline levels of albumin and platelet counts can be used to guide treatment decisions. ClinicalTrials.gov number: NCT01514890.
Department of Hepatology and Gastroenterology, Hôpital Henri Mondor, AP-HP, Université Paris-Est, INSERM U955, Créteil, France.
Christophe
C
Hézode
Department of Hepatology, Hôpital Cochin, AP-HP, Université Paris-René Descartes, INSERM U1016, Paris, France.
Helene
H
Fontaine
INSERM UMR-S 1136, Université Pierre et Marie Curie Paris 6, Paris, France.
Celine
C
Dorival
Department of Hepatology, Hospices Civils de Lyon, INSERM U1052, Université de Lyon, Lyon, France.
Fabien
F
Zoulim
Liver Unit-IRB-INSERM1040, Hôpital Saint Eloi, Montpellier, France.
Dominique
D
Larrey
Department of Hepatology and Gastroenterology, Centre Hospitalier Régional et Universitaire Claude Huriez, Lille, France.
Valerie
V
Canva
Department of Hepatology and Gastroenterology, Hôpital Haut-Lévêque, Pessac, INSERM U1053, Université Bordeaux Segalen, Bordeaux, France.
Victor
V
De Ledinghen
Department of Hepatology and Gastroenterology, Groupe Hospitalier Pitié-Salpétrière, AP-HP, Université Pierre et Marie Curie Paris 6, INSERM UMR-S938, Paris, France.
Thierry
T
Poynard
Centre Hépato-Biliaire, Hôpital Paul Brousse, AP-HP, UMR-S785, Université Paris-Sud, INSERM U785, Villejuif, France.
Didier
D
Samuel
Department of Hepatology and Gastroenterology, Hôpital Saint Joseph, Marseille, France.
Marc
M
Bourliere
Department of Internal Medicine and Digestive Diseases, UMR-152, Toulouse III University, Toulouse, France.
Laurent
L
Alric
Department of Hepatology and Gastroenterology, Centre Hospitalier Régional, Metz, France.
Jean-Jacques
JJ
Raabe
Department of Hepatology and Gastroenterology, Centre Hospitalo-Universitaire, INSERM U823, Grenoble, France.
Jean-Pierre
JP
Zarski
Department of Hepatology, Hôpital Beaujon, AP-HP, Université Paris-Diderot, INSERM CRB3, Clichy, France.
Patrick
P
Marcellin
Department of Hepatology and Gastroenterology, CHU Charles Nicolle, Rouen, France.
Ghassan
G
Riachi
Service d'Hépatologie et Gastroentérologie, Hôpital Saint-André, Bordeaux, INSERM U1053, Université Bordeaux Segalen, Bordeaux, France.
Pierre-Henri
PH
Bernard
Department of Hepatology and Gastroenterology, CHU Dupuytren, Université de Limoges, UMR INSERM U1092, Limoges, France.
Veronique
V
Loustaud-Ratti
Department of Hepatology, Hôpital Saint-Antoine, AP-HP, Paris, France.
Olivier
O
Chazouilleres
Department of Hepatology and Gastroenterology, CHU Estaing, Université d'Auvergne, UMR 6284, Clermont-Ferrand, France.
Armand
A
Abergel
Service des Maladies du Foie, CHU Rennes, Université de Rennes 1, INSERM U991, Rennes, France.
Dominique
D
Guyader
Department of Hepatology and Gastroenterology, CHU Purpan, Toulouse, France.
Sophie
S
Metivier
Digestive Center, Centre Hospitalier Universitaire de Nice, INSERM U1065-8, Nice, France.
Albert
A
Tran
Service d'Hépatologie, CHU Jean Minjoz, Université de Franche Comté, Besançon, France.
Vincent
V
Di Martino
Department of Hepatology and Gastroenterology and Digestive Oncology, CHR La Source, Orléans, France.
Xavier
X
Causse
Department of Hepatology and Gastroenterology, CHU, INSERM U1075, Caen, France.
Thong
T
Dao
Department of Hepatology and Gastroenterology, Groupe Hospitalier de l'Institut Catholique Lillois, Faculté Libre de Médecine, Lille, France.
Damien
D
Lucidarme
Department of Hepatology and Gastroenterology, Hôpital de la Conception, Marseille, France.
Isabelle
I
Portal
Department of Internal Medicine, Groupe Hospitalier Pitié-Salpêtrière, AP-HP, Université Pierre et Marie Curie Paris 6, INSERM, UMR-S959, CNRS, UMR 7211, Paris, France.
Patrice
P
Cacoub
Department of Hepatology and Gastroenterology, Hôpital Hôtel-Dieu, Nantes, France.
Jerome
J
Gournay
Department of Hepatology and Gastroenterology, Hôpital Jean Verdier, AP-HP, Université Paris 13, Bondy, France.
Veronique
V
Grando-Lemaire
Department of Hepatology and Gastroenterology, CHU de Dijon, Université de Bourgogne, Dijon, France.
Patrick
P
Hillon
Department of Hepatology and Gastroenterology, Hôpital de Bicêtre, AP-HP, Le Kremlin-Bicêtre, France.
Pierre
P
Attali
Department of Hepatology and Gastroenterology, Hôpital P Oudot, Bourgoin-Jallieu, France.
Thierry
T
Fontanges
Department of Hepatology and Gastroenterology, Centre Hospitalier Intercommunal, Créteil, France.
Isabelle
I
Rosa
Unit for Basic and Clinical Research on Viral Hepatitis, French National Agency for Research on AIDS and Viral Hepatitis, Paris, France.
Ventzislava
V
Petrov-Sanchez
INSERM UMR-S 1136, Université Pierre et Marie Curie Paris 6, Paris, France.
Yoann
Y
Barthe
National Reference Center for Viral Hepatitis B, C and Delta, Department of Virology, Hôpital Henri Mondor, AP-HP, Université Paris-Est, INSERM U955, Créteil, France.
Jean-Michel
JM
Pawlotsky
Department of Hepatology, Hôpital Cochin, AP-HP, Université Paris-René Descartes, INSERM U1016, Paris, France.
Stanislas
S
Pol
INSERM UMR-S 1136, Université Pierre et Marie Curie Paris 6, Paris, France; Department of Public Health, Hôpital Saint-Antoine, AP-HP, Paris, France.
Fabrice
F
Carrat
Department of Hepatology and Gastroenterology, Centre Hospitalier Universitaire de Nancy, Université de Lorraine, INSERM U954, Vandoeuvre-les-Nancy, France. Electronic address: jp.bronowicki@chu-nancy.fr.
Jean-Pierre
JP
Bronowicki
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D015331:Cohort Studies; D015897:Comorbidity; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000453:epidemiology / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use; D008103:Liver Cirrhosis / Q000188:drug therapy* / Q000453:epidemiology / Q000821:virology; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009842:Oligopeptides / Q000009:adverse effects / Q000627:therapeutic use*; D011092:Polyethylene Glycols / Q000627:therapeutic use; D011392:Proline / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D011446:Prospective Studies; D011994:Recombinant Proteins / Q000627:therapeutic use; D012254:Ribavirin / Q000627:therapeutic use; D017211:Treatment Failure; D016896:Treatment Outcome
D000998:Antiviral Agents; D016898:Interferon-alpha; D009842:Oligopeptides; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C486464:telaprevir; C512204:N-(3-amino-1-(cyclobutylmethyl)-2,3-dioxopropyl)-3-(2-((((1,1-dimethylethyl)amino)carbonyl)amino)-3,3-dimethyl-1-oxobutyl)-6,6-dimethyl-3-azabicyclo(3.1.0)hexan-2-carboxamide; D011392:Proline; C100416:peginterferon alfa-2a
CUPIC; Chronic Hepatitis C; DAA; Triple Therapy