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

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 (I(eot)). The I(eot) 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 I(eot) 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 I(eot) 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.

Positive and negative prediction of sustained virologic response at weeks 2 and 4 of treatment with albinterferon alfa-2b or peginterferon alfa-2a in treatment-naïve patients with genotype 1, chronic hepatitis C

“…The exhaustive search strategy in the present analysis allowed selection of the best negative and positive predictive algorithm, but the robustness of the algorithm needs validation in prospective studies. This prediction algorithm was based on a cohort of 368 patients and, although sizeable in comparison with other studies of viral kinetics-based prediction [7,[14][15][16], the results need to be validated in the framework of larger, imminent datasets.…”

Improvement of ALT decay kinetics by all-oral HCV treatment: Role of NS5A inhibitors and differences with IFN-based regimens

“…In the context of IFN-based therapy, modeling papers tend to support a correlation between HCV-RNA and ALT kinetics [4], though with large inter-patients variability according to liver status [12]. This correlation was explained by IFN use, that acts by establish a non-virus-specific antiviral state[15], ultimately leading to a progressive clearance of serum HCV-RNA mediated by both clearance of circulating virions (first-phase) and, afterwards, by the death or clearance of productively-infected hepatocytes (second-phase)[1], eventually leading to serum ALT increase.…”

Modelling hepatitis C therapy—predicting effects of treatment

“…51,67–69 For example, the viral kinetics observed in patients treated for 4 weeks with various doses of alisporivir (a cyclophilin inhibitor) or alisporivir/PEG-IFN have been modelled. 23,69 The investigators used what has been called a PK-VK model, i.e.…”