title: Viability of pegIFNα-RBV for CHC in the direct acting antiviral era: a practical algorithm between efficacy and cost containment.
abstract: The classical pegylated interferon α (peg-IFNα) and ribavirin (RBV) treatment of chronic hepatitis C (CHC) is progressively being replaced by new direct acting antivirals, whose costs remain a major barrier to widespread use. Using baseline data and viral kinetics, we developed a predictive algorithm to allocate to DAA patients who are not going to respond to peg-IFNα/RBV. This prospective study evaluated 205 CHC patients treated with peg-IFNα/RBV. HCVRNA kinetics during the initial 3 days of therapy and baseline variables including age, genotype, fibrosis and ALTs were used to construct a prediction rule in terms of sustained virological response (SVR). One hundred and twenty-one patients achieved an SVR (59%). Variables independently associated with SVR were HCVRNA, ALT, glycaemia, viral genotype, and fibrosis. The decline of viremia from baseline to 48/72 h was significantly different in SVR compared to non-SVR patients (2.2 vs. 0.65 log10 IU/mL; p < 0.001), and was influenced by viral genotype, levels of ALT, stage of fibrosis and IL28B polymorphism. In genotype 1, HCVRNA decline <0.8 logs had a negative predictive value of 90%, and in genotype 2, HCVRNA decline >1.2 logs had a positive predictive value of 92%. A combination of HCVRNA kinetics and a score based on pre-treatment parameters was highly accurate in predicting SVR in most patients. Outcome of peg-IFNα/RBV treatment may be predicted combining evaluation of baseline variables and HCVRNA kinetics. This allows to individualize treatment, reserving newer and more expensive DAAs to CHC patients who are in most need of them.
authors.affiliation: a Internal Medicine , Second University of Naples, AORN dei Colli Ospedale Monaldi , Napoli , Italy.
authors.forename: Pia Clara
authors.initials: PC
authors.lastname: Pafundi
authors.affiliation: a Internal Medicine , Second University of Naples, AORN dei Colli Ospedale Monaldi , Napoli , Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Parrella
authors.affiliation: a Internal Medicine , Second University of Naples, AORN dei Colli Ospedale Monaldi , Napoli , Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Iossa
authors.affiliation: a Internal Medicine , Second University of Naples, AORN dei Colli Ospedale Monaldi , Napoli , Italy.
authors.forename: Rosa
authors.initials: R
authors.lastname: Molaro
authors.affiliation: a Internal Medicine , Second University of Naples, AORN dei Colli Ospedale Monaldi , Napoli , Italy.
authors.forename: Carminia
authors.initials: C
authors.lastname: Battimelli
authors.affiliation: b Microbiology and Virology , AORN dei Colli Monaldi-Cotugno-CTO , Napoli , Italy.
authors.forename: Erasmo
authors.initials: E
authors.lastname: Falco
authors.affiliation: b Microbiology and Virology , AORN dei Colli Monaldi-Cotugno-CTO , Napoli , Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Sodano
authors.affiliation: a Internal Medicine , Second University of Naples, AORN dei Colli Ospedale Monaldi , Napoli , Italy.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Utili
authors.affiliation: a Internal Medicine , Second University of Naples, AORN dei Colli Ospedale Monaldi , Napoli , Italy.
authors.forename: Emanuele
authors.initials: E
authors.lastname: Durante-Mangoni
mesh_terms: D000465:Algorithms; D000998:Antiviral Agents / Q000494:pharmacology*; D003363:Cost Control; D004359:Drug Therapy, Combination; D005260:Female; D016174:Hepacivirus / Q000187:drug effects*; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000191:economics* / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000494:pharmacology*; D011446:Prospective Studies; D012367:RNA, Viral / Q000235:genetics; D011994:Recombinant Proteins / Q000494:pharmacology; D012254:Ribavirin / Q000494:pharmacology*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C100416:peginterferon alfa-2a
keywords: Chronic Hepatitis C; Pharmacokinetics; Predictive value of tests; Ribavirin; Sofosbuvir; Viremia