Journal Article

Prediction of Week 4 Virological Response in Hepatitis C for Making Decision on Triple Therapy: The Optim Study

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

2015

Overview

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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Adult / Analysis / Antiviral Agents - administration & dosage / Antiviral Agents - therapeutic use / Care and treatment / Clinical medicine / Cost analysis / Decision making / Diagnostic systems / Female / Fibrosis / Gene polymorphism / Genetic polymorphisms / Genotype & phenotype / Genotypes / Hepatitis / Hepatitis C / Hepatitis C - drug therapy / Hepatitis C - virology / Hepatitis C virus / Hepatology / HIV / Hospitals / Human immunodeficiency virus / Humans / Infections / Interferon / Interferon-alpha - administration & dosage / Interferon-alpha - chemistry / Male / Mathematical models / Middle Aged / Patients / Pharmacoeconomics / Polyethylene Glycols - chemistry / Polymorphism / Prospective Studies / Ribavirin / Ribavirin - administration & dosage / Therapy