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

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

doi:http://dx.doi.org/10.1371/journal.pone.0122613

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

Citation

Romero-Gómez M, Turnes J, Ampuero J, Oyagüez I, Cuenca B, Gonzalez-Garcia J. et. al. Prediction of Week 4 Virological Response in Hepatitis C for Making Decision on Triple Therapy: The Optim Study. /n PLoS One. 2015 Mar 31;10(3):e0122613. doi: 10.1371/journal.pone.0122613. eCollection 2015.

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. AIM: 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:/nThe 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.