PLoS ONE (Jan 2015)

Prediction of week 4 virological response in hepatitis C for making decision on triple therapy: the Optim study.

  • Manuel Romero-Gómez,
  • Juan Turnes,
  • Javier Ampuero,
  • Itziar Oyagüez,
  • Beatriz Cuenca,
  • Juan Gonzalez-Garcia,
  • Belén Muñoz-Molina,
  • Rocio Aguilar,
  • Sandra Leal,
  • Ramon Planas,
  • Javier Garcia-Samaniego,
  • Moises Diago,
  • Javier Crespo,
  • Jose Luis Calleja,
  • Miguel Angel Casado,
  • Ricard Sola

DOI
https://doi.org/10.1371/journal.pone.0122613
Journal volume & issue
Vol. 10, no. 3
p. e0122613

Abstract

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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.To develop a tool to predict first 4 weeks' viral response in patients with hepatitis C genotype 1&4 treated with P+R.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).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.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.