Treatment with PEG-IFN and ribavirin in patients with chronic hepatitis C, low grade of hepatic fibrosis, genotype 1 and 4 and favorable IFNL3 genotype: A pharmacogenetic prospective study.
The new direct-acting antivirals agents (DAAs) rapidly changed the treatment approach in chronic hepatitis C (CHC); however, the interferon (IFN)-free therapies availability is currently different in some countries, due to higher costs of these drugs. Naïve treated patients, who are not eligible for IFN-free therapies, could be selected for standard dual treatment with pegylated (PEG)-IFN and ribavirin (RBV), through IFN lambda 3 gene polymorphisms and fibrosis stage evaluation. Inclusion criteria were: naïve treated CHC patients with GT1 or GT4, without major contraindication to PEG-IFN or RBV, with fibrosis stage F0-F2 and IFNL3 rs8099917/rs12979860 TT/CC genotypes. 65 patients were included in the study. Overall SVR was observed in 50 patients (76.9%); SVR rates among different genotypes were as follows: 15 with GT1a (71.4%), 27 with GT1b (79.4%) and 8 for GT4 (80%). The RBV cutoff at 2weeks of 1800ng/mL, predictor of RVR, was determined (p=0.003; sensibility=60.4%, specificity=88.2%, positive predictive value=88.9%, negative predictive value=100%). In multivariate analysis, factors significantly associated with treatment failure were living alone condition (OR=4.302; 95%IC=1.254-16.257; p=0.034) and RBV plasma level <1800ng/mL at 2weeks (OR=4.970; 95%IC=1.405-17.565; p=0.009). Considering a pharmacogenetic-guided approach, dual therapy with PEG-IFN and RBV can be considered a reliable option for patients ineligible for IFN-free treatments, who are motivated and well informed about all the aspects related to PEG-IFN administration.
Unit of Infectious Diseases, University of Turin, Department of Medical Sciences, Amedeo di Savoia Hospital, Turin, Italy. Electronic address: lucio.boglione@unito.it.com.
Lucio
L
Boglione
Unit of Infectious Diseases, University of Turin, Department of Medical Sciences, Amedeo di Savoia Hospital, Turin, Italy.
Chiara Simona
CS
Cardellino
Unit of Infectious Diseases, University of Turin, Department of Medical Sciences, Amedeo di Savoia Hospital, Turin, Italy.
Jessica
J
Cusato
Unit of Infectious Diseases, University of Turin, Department of Medical Sciences, Amedeo di Savoia Hospital, Turin, Italy.
Amedeo
A
De Nicolò
Unit of Infectious Diseases, University of Turin, Department of Medical Sciences, Amedeo di Savoia Hospital, Turin, Italy.
Giuseppe
G
Cariti
Unit of Infectious Diseases, University of Turin, Department of Medical Sciences, Amedeo di Savoia Hospital, Turin, Italy.
Giovanni
G
Di Perri
Unit of Infectious Diseases, University of Turin, Department of Medical Sciences, Amedeo di Savoia Hospital, Turin, Italy.
Antonio
A
D'Avolio
D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D015870:Gene Expression; D005838:Genotype; D016174:Hepacivirus / Q000145:classification / Q000187:drug effects* / Q000235:genetics / Q000276:immunology; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D007372:Interferons; D007378:Interleukins / Q000235:genetics* / Q000276:immunology; D008103:Liver Cirrhosis / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology / Q000821:virology; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011446:Prospective Studies; D011994:Recombinant Proteins / Q000627:therapeutic use; D012254:Ribavirin / Q000627:therapeutic use*; D016896:Treatment Outcome; D019562:Viral Load / Q000187:drug effects; D000095022:Interferon Lambda
D000998:Antiviral Agents; D016898:Interferon-alpha; D007372:Interferons; D007378:Interleukins; D011092:Polyethylene Glycols; D011994:Recombinant Proteins; D012254:Ribavirin; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C100416:peginterferon alfa-2a
Fibrosis; Genotype 1; Genotype 4; HCV; IL28B; PEG-IFN