Effect of IL28B Genotype on Early Viral Kinetics during Interferon-Free Treatment of Patients with Chronic Hepatitis C

Gastroenterology. 2012 Jan 13. [Epub ahead of print]

Chu TW, Kulkarni R, Gane EJ, Roberts SK, Stedman C, Angus PW, Ritchie B, Lu XY, Ipe D, Lopatin U, Germer S, Iglesias VA, Elston R, Smith PF, Shulman NS.

Source

Roche, Nutley, NJ, USA.

Abstract

BACKGROUND & AIMS:

Although IL28B genotype affects the response of patients with chronic hepatitis C (CHC) to peginterferon and ribavirin, little is known 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 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 hrs 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 bi-phasic 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 β-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 CHC receiving interferon-free treatment.

Source