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Quantitation of Pretreatment Serum Interferon-γ-Inducible Protein-10 Improves the Predictive Value of an IL28B Gene Polymorphism for Hepatitis C Treatment Response
被引:93
作者:
Darling, Jama M.
[1
]
Aerssens, Jeroen
[2
]
Fanning, Gregory
[2
]
McHutchison, John G.
[3
]
Goldstein, David B.
[3
]
Thompson, Alexander J.
[3
]
Shianna, Kevin V.
[3
]
Afdhal, Nezam H.
[4
]
Hudson, Michael L.
[1
]
Howell, Charles D.
[5
]
Talloen, Willem
[6
]
Bollekens, Jacques
[2
]
De Wit, Mieke
[2
]
Scholliers, Annick
[2
]
Fried, Michael W.
[1
]
机构:
[1] Univ N Carolina, Chapel Hill, NC 27599 USA
[2] Tibotec BVBA, Mechelen, Belgium
[3] Duke Univ, Durham, NC USA
[4] Harvard Univ, Sch Med, Boston, MA 02115 USA
[5] Univ Maryland, College Pk, MD 20742 USA
[6] Janssen Pharmaceut NV, Johnson & Johnson Pharmaceut R&D, Beerse, Belgium
来源:
基金:
美国国家卫生研究院;
关键词:
ALPHA-2B PLUS RIBAVIRIN;
PEGINTERFERON ALPHA-2B;
ANTIVIRAL THERAPY;
PEGYLATED INTERFERON;
VIROLOGICAL RESPONSE;
AMERICAN PATIENTS;
VIRUS-INFECTION;
VIRAL RESPONSE;
EXPRESSION;
ASSOCIATION;
D O I:
10.1002/hep.24056
中图分类号:
R57 [消化系及腹部疾病];
学科分类号:
摘要:
Polymorphisms of the IL28B gene are highly associated with sustained virological response (SVR) in patients with chronic hepatitis C treated with peginterferon and ribavirin. Quantitation of interferon-gamma-inducible protein-10 (IP-10) may also differentiate antiviral response. We evaluated IP-10 levels in pretreatment serum from 115 nonresponders and 157 sustained responders in the Study of Viral Resistance to Antiviral Therapy of Chronic Hepatitis C cohort, including African American (AA) and Caucasian American (CA) patients. Mean IP-10 was lower in sustained responders compared with nonresponders (437 +/- 31 vs 704 +/- 44 pg/mL, P < 0.001), both in AA and CA patients. The positive predictive value of low IP-10 levels (<600 pg/mL) for SVR was 69%, whereas the negative predictive value of high IP-10 levels (>600 pg/mL) was 67%. We assessed the combination of pretreatment IP-10 levels with IL28B genotype as predictors of treatment response. The IL28B polymorphism rs12979860 was tested in 210 participants. The CC, CT, and TT genotypes were found in 30%, 49%, and 21% of patients, respectively, with corresponding SVR rates of 87%, 50%, and 39% (P < 0.0001). Serum IP-10 levels within the IL28B genotype groups provided additional information regarding the likelihood of SVR (P < 0.0001). CT carriers with low IP-10 had 64% SVR versus 24% with high IP-10. Similarly, a higher SVR rate was identified for TT and CC carriers with low versus high IP-10 (TT, 48% versus 20%; CC, 89% versus 79%). IL28B genotype and baseline IP-10 levels were additive but independent when predicting SVR in both AA and CA patients. Conclusion: When IL28B genotype is combined with pretreatment serum IP-10 measurement, the predictive value for discrimination between SVR and nonresponse is significantly improved, especially in non-CC genotypes. This relationship warrants further investigation to elucidate the mechanisms of antiviral response and prospective validation. (HEPATOLOGY 2011;53:14-22)
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页码:14 / 22
页数:9
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