title: Prediction of week 4 virological response in hepatitis C for making decision on triple therapy: the Optim study.
abstract: BACKGROUND
  Virological response to peginterferon + ribavirin (P+R) at week 4 can predict sustained virological response (SVR). While patients with rapid virological response (RVR) do not require triple therapy, patients with a decline <1 log10 IU/ml HCVRNA (D1L) should have treatment discontinued due to low SVR rate.
  
  
  OBJECTIVE
  To develop a tool to predict first 4 weeks' viral response in patients with hepatitis C genotype 1&4 treated with P+R.
  
  
  METHODS
  In this prospective and multicenter study, HCV mono-infected (n=538) and HCV/HIV co-infected (n=186) patients were included. To develop and validate a prognostic tool to detect RVR and D1L, we segregated the patients as an estimation cohort (to construct the model) and a validation cohort (to validate the model).
  
  
  RESULTS
  D1L was reached in 509 (80.2%) and RVR in 148 (22.5%) patients. Multivariate analyses demonstrated that HIV co-infection, Forns' index, LVL, IL28B-CC and Genotype-1 were independently related to RVR as well as D1L. Diagnostic accuracy (AUROC) for D1L was: 0.81 (95%CI: 0.76 ̶ 0.86) in the estimation cohort and 0.71 (95%CI: 0.62 ̶ 0.79) in the validation cohort; RVR prediction: AUROC 0.83 (95%CI: 0.78 ̶ 0.88) in the estimation cohort and 0.82 (95%CI: 0.76 ̶ 0.88) in the validation cohort. Cost-analysis of standard 48-week treatment indicated a saving of 30.3% if the prognostic tool is implemented.
  
  
  CONCLUSIONS
  The combination of genetic (IL28B polymorphism) and viral genotype together with viral load, HIV co-infection and fibrosis stage defined a tool able to predict RVR and D1L at week 4. Using this tool would be a cost-saving strategy compared to universal triple therapy for hepatitis C.
authors.affiliation: UCM Digestive Diseases & ciberehd, Valme University Hospital, Sevilla, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Romero-Gómez
authors.affiliation: Complejo Hospitalario de Pontevedra, Pontevedra, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Turnes
authors.affiliation: UCM Digestive Diseases & ciberehd, Valme University Hospital, Sevilla, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Ampuero
authors.affiliation: Pharmacoeconomics & Outcomes Research Iberia, Madrid, Spain.
authors.forename: Itziar
authors.initials: I
authors.lastname: Oyagüez
authors.affiliation: Hospital Infanta Cristina, Parla, Madrid, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Cuenca
authors.affiliation: Hospital Universitario La Paz, Madrid, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Gonzalez-Garcia
authors.affiliation: Unidad de Hepatología, Roche Farma, Spain.
authors.forename: Belén
authors.initials: B
authors.lastname: Muñoz-Molina
authors.affiliation: FISEVI, Sevilla, Spain.
authors.forename: Rocio
authors.initials: R
authors.lastname: Aguilar
authors.affiliation: FISEVI, Sevilla, Spain.
authors.forename: Sandra
authors.initials: S
authors.lastname: Leal
authors.affiliation: Hospital Germans Trias i Pujol & ciberehd, Badalona, Barcelona, Spain.
authors.forename: Ramon
authors.initials: R
authors.lastname: Planas
authors.affiliation: Hospital Carlos III & ciberehd, Madrid, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Garcia-Samaniego
authors.affiliation: Hospital General de Valencia, Valencia, Spain.
authors.forename: Moises
authors.initials: M
authors.lastname: Diago
authors.affiliation: Hospital Marqués de Valdecilla, Santander, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Crespo
authors.affiliation: Hospital Puerta de Hierro, Madrid, Spain.
authors.forename: Jose Luis
authors.initials: JL
authors.lastname: Calleja
authors.affiliation: Pharmacoeconomics & Outcomes Research Iberia, Madrid, Spain.
authors.forename: Miguel Angel
authors.initials: MA
authors.lastname: Casado
authors.affiliation: Hospital del Mar, IMIM, Barcelona, Spain.
authors.forename: Ricard
authors.initials: R
authors.lastname: Sola
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D006526:Hepatitis C / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage / Q000737:chemistry; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000737:chemistry; D011446:Prospective Studies; D012254:Ribavirin / Q000008:administration & dosage
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D011092:Polyethylene Glycols; D012254:Ribavirin
references.citation: Hepatology. 2002 Oct;36(4 Pt 1):986-92
references.pmid: 12297848
references.citation: Hepatology. 2003 Aug;38(2):518-26
references.pmid: 12883497
references.citation: J Hepatol. 1991 Nov;13(3):372-4
references.pmid: 1808228
references.citation: Hepatology. 2006 Jan;43(1):72-80
references.pmid: 16374857
references.citation: Hepatology. 2007 Jul;46(1):32-6
references.pmid: 17567829
references.citation: Hepatology. 2008 Dec;48(6):1753-60
references.pmid: 18925643
references.citation: Hepatology. 2009 Apr;49(4):1335-74
references.pmid: 19330875
references.citation: N Engl J Med. 2009 Aug 6;361(6):580-93
references.pmid: 19625712
references.citation: Nature. 2009 Sep 17;461(7262):399-401
references.pmid: 19684573
references.citation: J Gastroenterol Hepatol. 2010 Apr;25(4):758-65
references.pmid: 20492331
references.citation: Gastroenterology. 2010 Jul;139(1):120-9.e18
references.pmid: 20399780
references.citation: Lancet. 2010 Aug 28;376(9742):705-16
references.pmid: 20692693
references.citation: J Viral Hepat. 2011 Apr;18(4):e52-60
references.pmid: 20738775
references.citation: Clin Gastroenterol Hepatol. 2011 Apr;9(4):344-350.e2
references.pmid: 20728570
references.citation: N Engl J Med. 2011 Mar 31;364(13):1195-206
references.pmid: 21449783
references.citation: PLoS One. 2011;6(3):e18322
references.pmid: 21479134
references.citation: J Viral Hepat. 2011 Jun;18(6):400-7
references.pmid: 20500548
references.citation: N Engl J Med. 2011 Jun 23;364(25):2405-16
references.pmid: 21696307
references.citation: Aliment Pharmacol Ther. 2011 Aug;34(3):297-305
references.pmid: 21623851
references.citation: N Engl J Med. 2011 Sep 15;365(11):1014-24
references.pmid: 21916639
references.citation: J Hepatol. 2012 Jun;56(6):1276-82
references.pmid: 22314423
references.citation: AIDS. 2013 Jan 14;27(2):163-73
references.pmid: 23135173
references.citation: J Hepatol. 2013 Mar;58(3):479-87
references.pmid: 23183529
references.citation: PLoS One. 2014;9(8):e103370
references.pmid: 25084272