Quantitation of pretreatment serum interferon-γ–inducible protein-10 improves the predictive value of an IL28B gene polymorphism for hepatitis C treatment response
✍ Scribed by Jama M. Darling; Jeroen Aerssens; Gregory Fanning; John G. McHutchison; David B. Goldstein; Alexander J. Thompson; Kevin V. Shianna; Nezam H. Afdhal; Michael L. Hudson; Charles D. Howell; Willem Talloen; Jacques Bollekens; Mieke De Wit; Annick Scholliers; Michael W. Fried
- Publisher
- John Wiley and Sons
- Year
- 2011
- Tongue
- English
- Weight
- 579 KB
- Volume
- 53
- Category
- Article
- ISSN
- 0270-9139
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✦ Synopsis
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-c-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 6 31 vs 704 6 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.