title: The CUPIC algorithm: an accurate model for the prediction of sustained viral response under telaprevir or boceprevir triple therapy in cirrhotic patients.
abstract: Triple therapy using boceprevir or telaprevir remains the reference treatment for genotype 1 chronic hepatitis C in countries where new interferon-free regimens have not yet become available. Antiviral treatment is highly required in cirrhotic patients, but they represent a difficult-to-treat population. We aimed to develop a simple algorithm for the prediction of sustained viral response (SVR) in cirrhotic patients treated with triple therapy. A total of 484 cirrhotic patients from the ANRS CO20 CUPIC cohort treated with triple therapy were randomly distributed into derivation and validation sets. A total of 52.1% of patients achieved SVR. In the derivation set, a D0 score for the prediction of SVR before treatment initiation included the following independent predictors collected at day 0: prior treatment response, gamma-GT, platelets, telaprevir treatment, viral load. To refine the prediction at the early phase of the treatment, a W4 score included as additional parameter the viral load collected at week 4. The D0 and W4 scores were combined in the CUPIC algorithm defining three subgroups: 'no treatment initiation or early stop at week 4', 'undetermined' and 'SVR highly probable'. In the validation set, the rates of SVR in these three subgroups were, respectively, 11.1%, 50.0% and 82.2% (P < 0.001). By replacing the variable 'prior treatment response' with 'IL28B genotype', another algorithm was derived for treatment-naïve patients with similar results. The CUPIC algorithm is an easy-to-use tool that helps physicians weigh their decision between immediately treating cirrhotic patients using boceprevir/telaprevir triple therapy or waiting for new drugs to become available in their country.
authors.affiliation: Department of Hepatology and Gastroenterology, CHU d'Angers, Angers, France.|HIFIH, UPRES 3859, SFR 4208, Université LUNAM, Angers, France.
authors.forename: J
authors.initials: J
authors.lastname: Boursier
authors.affiliation: HIFIH, UPRES 3859, SFR 4208, Université LUNAM, Angers, France.|Virology Department, CHU d'Angers, Angers, France.
authors.forename: A
authors.initials: A
authors.lastname: Ducancelle
authors.affiliation: Department of Hepatology and Gastroenterology, Hôpital Haut-Lévêque, CHU de Bordeaux, Pessac, France.
authors.forename: J
authors.initials: J
authors.lastname: Vergniol
authors.affiliation: Department of Hepatology and Gastroenterology, CHU d'Angers, Angers, France.|HIFIH, UPRES 3859, SFR 4208, Université LUNAM, Angers, France.|Virology Department, CHU d'Angers, Angers, France.
authors.forename: P
authors.initials: P
authors.lastname: Veillon
authors.affiliation: HIFIH, UPRES 3859, SFR 4208, Université LUNAM, Angers, France.|Biochemistry Department, CHU d'Angers, Angers, France.
authors.forename: V
authors.initials: V
authors.lastname: Moal
authors.affiliation: Inserm UMR-S1136, Université Pierre-et-Marie-Curie Paris 6, Paris, France.
authors.forename: C
authors.initials: C
authors.lastname: Dufour
authors.affiliation: Department of Hepatology and Gastroenterology, CHU de Nancy, Université de Lorraine, Inserm U954, Vandoeuvre-lès-Nancy, France.
authors.forename: J-P
authors.initials: JP
authors.lastname: Bronowicki
authors.affiliation: Liver Unit-IRB-INSERM1040, Hôpital Saint Eloi, CHU de Montpellier, Montpellier, France.
authors.forename: D
authors.initials: D
authors.lastname: Larrey
authors.affiliation: Department of Hepatology and Gastroenterology, Hôpital Henri Mondor, AP-HP, Université Paris-Est, INSERM U955, Créteil, France.
authors.forename: C
authors.initials: C
authors.lastname: Hézode
authors.affiliation: Department of Hepatology, Hôpital de la Croix-Rousse, Hospices Civils de Lyon, INSERM U1052, Lyon, France.
authors.forename: F
authors.initials: F
authors.lastname: Zoulim
authors.affiliation: Department of Hepatology, Hôpital Cochin, AP-HP, Université Paris-René Descartes, Inserm U1016, Paris, France.
authors.forename: H
authors.initials: H
authors.lastname: Fontaine
authors.affiliation: Department of Hepatology and Gastroenterology, Centre Hospitalier Régional et Universitaire Claude Huriez, Lille, France.
authors.forename: V
authors.initials: V
authors.lastname: Canva
authors.affiliation: Department of Hepatology and Gastroenterology, Groupe Hospitalier Pitié-Salpétrière AP-HP, Université Pierre et Marie Curie Paris 6, INSERM UMR-S938, Paris, France.
authors.forename: T
authors.initials: T
authors.lastname: Poynard
authors.affiliation: Unit for Basic and Clinical Research on Viral Hepatitis, ANRS (France REcherche Nord & sud Sida-HIV Hépatites-FRENSH), Paris, France.
authors.forename: S
authors.initials: S
authors.lastname: Allam
authors.affiliation: Department of Hepatology and Gastroenterology, Hôpital Haut-Lévêque, CHU de Bordeaux, Pessac, France.|INSERM U1053, Université Bordeaux Segalen, Bordeaux, France.
authors.forename: V
authors.initials: V
authors.lastname: De Lédinghen
mesh_terms: D000465:Algorithms; D000998:Antiviral Agents / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D016174:Hepacivirus / Q000187:drug effects; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use; D008103:Liver Cirrhosis / Q000188:drug therapy* / Q000821:virology; D008297:Male; D008875:Middle Aged; D008962:Models, Theoretical; D009842:Oligopeptides / Q000627:therapeutic use*; D011092:Polyethylene Glycols / Q000627:therapeutic use; D011392:Proline / Q000031:analogs & derivatives* / Q000627:therapeutic use; D011897:Random Allocation; D012254:Ribavirin / Q000627:therapeutic use; D016896:Treatment Outcome; D019562:Viral Load / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D009842:Oligopeptides; 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
keywords: boceprevir; cirrhosis; hepatitis C virus; sustained viral response; telaprevir