Interleukin-28B Polymorphism Improves Viral Kinetics and Is the Strongest Pretreatment Predictor of Sustained Virologic Response in Genotype 1 Hepatitis C Virus

被引：587

作者：

Thompson, Alexander J.

Muir, Andrew J. ^{[1
]}

Sulkowski, Mark S. ^{[2
]}

Ge, Dongliang

Fellay, Jacques

Shianna, Kevin V.

Urban, Thomas

Afdhal, Nezam H. ^{[3
]}

Jacobson, Ira M. ^{[4
]}

Esteban, Rafael ^{[5
]}

Poordad, Fred ^{[6
]}

Lawitz, Eric J. ^{[7
]}

McCone, Jonathan ^{[8
]}

Shiffman, Mitchell L. ^{[9
]}

Galler, Greg W. ^{[10
]}

Lee, William M. ^{[11
]}

Reindollar, Robert ^{[12
]}

King, John W. ^{[13
]}

Kwo, Paul Y. ^{[14
]}

Ghalib, Reem H. ^{[15
]}

Freilich, Bradley ^{[16
]}

Nyberg, Lisa M. ^{[17
]}

Zeuzem, Stefan ^{[18
]}

Poynard, Thierry ^{[19
]}

Vock, David M.

Pieper, Karen S.

Patel, Keyur

Tillmann, Hans L.

Noviello, Stephanie ^{[21
]}

Koury, Kenneth ^{[21
]}

Pedicone, Lisa D. ^{[21
]}

Brass, Clifford A. ^{[21
]}

Albrecht, Janice K. ^{[21
]}

Goldstein, David B. ^{[20
]}

McHutchison, John G. ^{[1
]}

机构：

[1] Duke Univ, Med Ctr, Duke Clin Res Inst, POB 17969, Durham, NC 27715 USA

[2] Johns Hopkins Univ, Sch Med, Baltimore, MD USA

[3] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA

[4] Weill Cornell Med Coll, New York, NY USA

[5] Hosp Gen Univ Valle Hebron, Barcelona, Spain

[6] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA

[7] Alamo Med Res, San Antonio, TX USA

[8] Mt Vernon Endoscopy Ctr, Alexandria, VA USA

[9] Liver Inst Virginia, Newport News, VA USA

[10] Kelsey Res Fdn, Houston, TX USA

[11] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA

[12] Piedmont Healthcare, Statesville, NC USA

[13] Louisiana State Univ Hlth Sci Ctr, Shreveport, LA 71105 USA

[14] Indiana Univ, Sch Med, Indianapolis, IN USA

[15] Methodist Dallas Med Ctr, Liver Inst, Dallas, TX USA

[16] Kansas City Gastroenterol & Hepatol, Kansas City, MO USA

[17] Kaiser Permanente, San Diego, CA USA

[18] Goethe Univ Frankfurt, Frankfurt, Germany

[19] Grp Hosp Pitie Salpetriere, F-75634 Paris, France

[20] Duke Univ, Ctr Human Genome Variat, Durham, NC USA

[21] Schering Plough Corp, Res Inst, Kenilworth, NJ 07033 USA

来源：

GASTROENTEROLOGY | 2010年 / 139卷 / 01期

基金：

英国医学研究理事会;

关键词：

Genetics; IL-28B; Interferon-Lambda; Peg-Interferon-Alfa; PEGINTERFERON ALPHA-2B; COMBINATION THERAPY; PLUS RIBAVIRIN;

D O I：

10.1053/j.gastro.2010.04.013

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

BACKGROUND & AIMS: We recently identified a polymorphism upstream of interleukin (IL)-28B to be associated with a 2-fold difference in sustained virologic response (SVR) rates to pegylated interferon-alfa and ribavirin therapy in a large cohort of treatment-naive, adherent patients with chronic hepatitis C virus genotype 1 (HCV-1) infection. We sought to confirm the polymorphism's clinical relevance by intention-to-treat analysis evaluating on-treatment virologic response and SVR. METHODS: HCV-1 patients were genotyped as CC, CT, or TT at the polymorphic site, rs12979860. Viral kinetics and rates of rapid virologic response (RVR, week 4), complete early virologic response (week 12), and SVR were compared by IL-28B type in 3 self-reported ethnic groups: Caucasians (n = 1171), African Americans (n = 300), and Hispanics (n = 116). RESULTS: In Caucasians, the CC IL-28B type was associated with improved early viral kinetics and greater likelihood of RVR (28% vs 5% and 5%; P < .0001), complete early virologic response (87% vs 38% and 28%; P < .0001), and SVR (69% vs 33% and 27%; P < .0001) compared with CT and TT. A similar association occurred within African Americans and Hispanics. In a multivariable regression model, CC IL-28B type was the strongest pretreatment predictor of SVR (odds ratio, 5.2; 95% confidence interval, 4.1-6.7). RVR was a strong predictor of SVR regardless of IL-28B type. In non-RVR patients, the CC IL-28B type was associated with a higher rate of SVR (Caucasians, 66% vs 31% and 24%; P < .0001). CONCLUSIONS: In treatment-naive HCV-1 patients treated with pegylated interferon and ribavirin, a polymorphism upstream of IL-28B is associated with increased on-treatment and sustained virologic response and effectively predicts treatment outcome.

引用

页码：120 / +

页数：28

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