Reports
Clinical Pharmacology & Therapeutics (2008) doi:10.1038/clpt.2008.21
Early and Accurate Prediction of Peg-IFNs/Ribavirin Therapy Outcome in the Individual Patient With Chronic Hepatitis C by Modeling the Dynamics of the Infected Cells
P Colombatto1, P Ciccorossi1, AM Maina1,2,3, L Civitano1,2,3, F Oliveri1, B Coco1, V Romagnoli1, F Bonino2 and MR Brunetto1
- 1UO Epatologia SSN, Azienda Ospedaliero–Universitaria Pisana, Pisa, Italy
- 2Direzione Scientifica, Fondazione IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena di Milano, Milano, Italy
- 3Università di Pisa, Pisa, Italy
Correspondence: MR Brunetto, (brunetto@med-club.com)
The first two authors contributed equally to this work.
Received 25 October 2007; Accepted 21 January 2008; Published online 12 March 2008.
Abstract
A novel biomathematical model that analyzes the combined alanine transaminase (ALT) and viral-load kinetics during the first month of pegylated interferon (Peg-IFN) plus ribavirin (RBV) therapy was successfully applied in 90 of 97 (93% ) chronic hepatitis C patients in order to compute the number of infected cells at the end of therapy (Ieot). The Ieot indices were lower in sustained virological responders than in relapsers (RELs) and nonresponders (NRs) (median values: 31 vs. 2,190 vs. 1,090,000; P < 0.001), and were independently associated with treatment outcomes (P = 0.003). A threshold of 250 Ieot was shown to identify sustained virological response (SVR) with high positive predictive value (93% ) and good diagnostic accuracy (81% ). The time taken to attain 250 Ieot ranged from 3 to 11 months in patients with hepatitis C virus (HCV) genotypes 2 or 3 and from 3 to 18 months in those with HCV genotypes 1 or 4. Overall, the duration of therapy would have been 49 months less than that suggested by the most recent algorithms based on a rapid virological response (RVR) at week 4.
