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
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)
引用
收藏
页码:14 / 22
页数:9
相关论文
共 34 条
[1]   Systemic and Intrahepatic Interferon-Gamma-Inducible Protein 10 kDa Predicts the First-Phase Decline in Hepatitis C Virus RNA and Overall Viral Response to Therapy in Chronic Hepatitis C [J].
Askarieh, Galia ;
Alsio, Asa ;
Pugnale, Paolo ;
Negro, Francesco ;
Ferrari, Carlo ;
Neumann, Avidan U. ;
Pawlotsky, Jean-Michel ;
Schalm, Solko W. ;
Zeuzem, Stefan ;
Norkrans, Gunnar ;
Westin, Johan ;
Soderholm, Jonas ;
Hellstrand, Kristoffer ;
Lagging, Martin .
HEPATOLOGY, 2010, 51 (05) :1523-1530
[2]   Plasma chemokine levels correlate with the outcome of antiviral therapy in patients with hepatitis C [J].
Butera, D ;
Marukian, S ;
Iwamaye, AE ;
Hembrador, E ;
Chambers, TJ ;
Di Bisceglie, AM ;
Charles, ED ;
Talal, AH ;
Jacobson, IM ;
Rice, CM ;
Dustin, LB .
BLOOD, 2005, 106 (04) :1175-1182
[3]   Race, insulin resistance and hepatic steatosis in chronic hepatitis C [J].
Conjeevaram, Hari S. ;
Kleiner, David E. ;
Everhart, Jay E. ;
Hoofnagle, Jay H. ;
Zacks, Steven ;
Afdhal, Nezam H. ;
Wahed, Abdus S. .
HEPATOLOGY, 2007, 45 (01) :80-87
[4]   Peginterferon and ribavirin treatment in African American and Caucasian American patients with hepatitis C genotype 1 [J].
Conjeevaram, Hari S. ;
Fried, Michael W. ;
Jeffers, Lennox J. ;
Terrault, Norah A. ;
Wiley-Lucas, Thelma E. ;
Afdhal, Nezam ;
Brown, Robert S. ;
Belle, Steven H. ;
Hoofnagle, Jay H. ;
Kleiner, David E. ;
Howell, Charles D. .
GASTROENTEROLOGY, 2006, 131 (02) :470-477
[5]   Early virologic response to treatment with peginterferon alfa-2b plus ribavirin in patients with chronic hepatitis C [J].
Davis, GL ;
Wong, JB ;
McHutchison, JG ;
Manns, MP ;
Harvey, J ;
Albrecht, J .
HEPATOLOGY, 2003, 38 (03) :645-652
[6]   Association of pretreatment serum interferon γ inducible protein 10 levels with sustained virological response to peginterferon plus ribavirin therapy in genotype 1 infected patients with chronic hepatitis C [J].
Diago, M ;
Castellano, G ;
García-Samaniego, J ;
Pérez, C ;
Fernández, I ;
Romero, M ;
Iacono, OL ;
García-Monzón, C .
GUT, 2006, 55 (03) :374-379
[7]   Hepatic gene expression during treatment with peginterferon and ribavirin: Identifying molecular pathways for treatment response [J].
Feld, Jordan J. ;
Nanda, Santosh ;
Huang, Ying ;
Chen, Weiping ;
Cam, Maggie ;
Pusek, Susan N. ;
Schweigler, Lisa M. ;
Theodore, Dickens ;
Zacks, Steven L. ;
Liang, T. Jake ;
Fried, Michael W. .
HEPATOLOGY, 2007, 46 (05) :1548-1563
[8]   Predicting sustained virological responses in chronic hepatitis C patients treated with peginterferon alfa-2a (40 KD)/ribavirin [J].
Ferenci, P ;
Fried, MW ;
Shiffman, ML ;
Smith, CI ;
Marinos, G ;
Gonçales, FL ;
Häussinger, D ;
Diago, M ;
Carosi, G ;
Dhumeaux, D ;
Craxì, A ;
Chaneac, M ;
Reddy, KR .
JOURNAL OF HEPATOLOGY, 2005, 43 (03) :425-433
[9]   Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. [J].
Fried, MW ;
Shiffman, ML ;
Reddy, KR ;
Smith, C ;
Marinos, G ;
Goncales, FL ;
Haussinger, D ;
Diago, M ;
Carosi, G ;
Dhumeaux, D ;
Craxi, A ;
Lin, A ;
Hoffman, J ;
Yu, J .
NEW ENGLAND JOURNAL OF MEDICINE, 2002, 347 (13) :975-982
[10]   Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance [J].
Ge, Dongliang ;
Fellay, Jacques ;
Thompson, Alexander J. ;
Simon, Jason S. ;
Shianna, Kevin V. ;
Urban, Thomas J. ;
Heinzen, Erin L. ;
Qiu, Ping ;
Bertelsen, Arthur H. ;
Muir, Andrew J. ;
Sulkowski, Mark ;
McHutchison, John G. ;
Goldstein, David B. .
NATURE, 2009, 461 (7262) :399-401