Effect of IL28B genotype on early viral kinetics during interferon-free treatment of patients with chronic hepatitis C.
Gastroenterology
; 142(4): 790-5, 2012 Apr.
Article
en En
| MEDLINE
| ID: mdl-22248659
ABSTRACT
BACKGROUND & AIMS:
Although interleukin 28B (interferon, lambda 3) (IL28B) genotype affects the response of patients with chronic hepatitis C to peginterferon and ribavirin, little is known regarding its effect on response to direct-acting antivirals in interferon-free combinations. We analyzed the effects of IL28B genotype on the viral kinetic (VK) response to an interferon-free combination of the nucleoside polymerase inhibitor mericitabine (RG7128) and the hepatitis C virus (HCV) protease inhibitor danoprevir.METHODS:
We performed a double-blind, dose-escalation study of patients with chronic HCV genotype 1 infection who were interferon treatment naive or had not responded to previous therapy with peginterferon and ribavirin. Patients were sequentially assigned to 1 of 7 cohorts then randomly assigned to groups that received up to 13 days of treatment with mericitabine (500 or 1000 mg, twice daily) plus danoprevir (100 or 200 mg, every 8 hours, or 600 or 900 mg, twice daily) or placebo. Eighty-three of 87 patients were genotyped for the IL28B single-nucleotide polymorphism rs12979860. VKs were analyzed only in patients who received 13 days of treatment, at optimal doses, using a biphasic model to describe first- and second-phase slopes of viral decay during therapy.RESULTS:
At day 14 (the end of interferon-free treatment), the mean reduction in the serum level of HCV RNA was slightly greater in patients with the CC polymorphism (5.01 log(10) IU/mL) than those without (4.59 log(10) IU/mL). Modeling revealed that patients with the CC polymorphism had slightly better early VKs, most apparent in the ß-phase of viral decay. A mixed effect on the α-phase was observed, which was reduced in magnitude but prolonged in patients with CC, who also had better on-treatment response to peginterferon and ribavirin during follow up.CONCLUSIONS:
IL28B genotype appears to affect early VKs in patients with chronic hepatitis C receiving interferon-free treatment.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Antivirales
/
Sulfonamidas
/
Interleucinas
/
Hepacivirus
/
Hepatitis C Crónica
/
Polimorfismo de Nucleótido Simple
/
Desoxicitidina
/
Lactamas
Tipo de estudio:
Clinical_trials
/
Diagnostic_studies
/
Prognostic_studies
/
Risk_factors_studies
Límite:
Humans
País/Región como asunto:
Oceania
Idioma:
En
Revista:
Gastroenterology
Año:
2012
Tipo del documento:
Article
País de afiliación:
Estados Unidos