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

Autor: Jessica Cusato, Chiara Simona Cardellino, Antonio D'Avolio, Amedeo De Nicolò, Lucio Boglione, Giuseppe Cariti, Giovanni Di Perri
Rok vydání: 2016
Předmět:
0301 basic medicine
Liver Cirrhosis
Male
IL28B
Gene Expression
Hepacivirus
Gastroenterology
Polyethylene Glycols
chemistry.chemical_compound
0302 clinical medicine
Interferon
Genotype
Prospective Studies
Prospective cohort study
Genotype 4
Middle Aged
Viral Load
Genotype 1
Recombinant Proteins
Infectious Diseases
Treatment Outcome
HCV
030211 gastroenterology & hepatology
Drug Therapy
Combination
Female
medicine.drug
Microbiology (medical)
Adult
medicine.medical_specialty
Biology
PEG-IFN
Microbiology
Antiviral Agents
03 medical and health sciences
Internal medicine
PEG ratio
Ribavirin
Genetics
medicine
Humans
Molecular Biology
Contraindication
Ecology
Evolution
Behavior and Systematics
Fibrosis
Interleukins
Interferon-alpha
Hepatitis C
Chronic
030104 developmental biology
chemistry
Immunology
Interferons
Hepatic fibrosis
Pharmacogenetics
Zdroj: Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases. 51
ISSN: 1567-7257
Popis: 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. Naive 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: naive 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 2 weeks of 1800 ng/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 < 1800 ng/mL at 2 weeks (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.
Databáze: OpenAIRE
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