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

被引：82

作者：

Chu, Tom W.

Kulkarni, Rohit ^{[2
]}

Gane, Edward J. ^{[3
]}

Roberts, Stuart K. ^{[4
]}

Stedman, Catherine ^{[5
]}

Angus, Peter W. ^{[6
]}

Ritchie, Brett ^{[7
]}

Lu, Xiao-Yu ^{[2
]}

Ipe, David ^{[2
]}

Lopatin, Uri

Germer, Soren ^{[1
]}

Iglesias, Victor A. ^{[8
]}

Elston, Robert ^{[9
]}

Smith, Patrick F.

Shulman, Nancy S.

机构：

[1] Roche, TRS, Nutley, NJ USA

[2] Genentech Inc, San Francisco, CA 94080 USA

[3] Auckland Clin Studies, Auckland, New Zealand

[4] Alfred Hosp, Melbourne, Vic, Australia

[5] Christchurch Clin Studies, Christchurch, New Zealand

[6] Austin Hosp, Heidelberg, Vic 3084, Australia

[7] Royal Adelaide, Adelaide, SA, Australia

[8] Roche, Basel, Switzerland

[9] Roche, Welwyn Garden City, England

来源：

GASTROENTEROLOGY | 2012年 / 142卷 / 04期

关键词：

INFORM-1; Genetics; Direct-Acting Antiviral Agents; DAA; GENETIC-VARIATION; TELAPREVIR; PEGINTERFERON; THERAPY; RIBAVIRIN; DYNAMICS;

D O I：

10.1053/j.gastro.2011.12.057

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

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 beta-phase of viral decay. A mixed effect on the beta-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.

引用

页码：790 / 795

页数：6

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