IL28B polymorphisms, IP-10 and viral load predict virological response to therapy in chronic hepatitis C

被引:82
作者
Fattovich, G. [1 ,2 ]
Covolo, L. [3 ]
Bibert, S. [4 ,5 ]
Askarieh, G. [6 ]
Lagging, M. [6 ]
Clement, S. [2 ]
Malerba, G. [7 ]
Pasino, M. [1 ]
Guido, M. [8 ]
Puoti, M. [9 ]
Gaeta, G. B. [10 ]
Santantonio, T. [11 ]
Raimondo, G. [12 ]
Bruno, R. [13 ]
Bochud, P. -Y. [4 ,5 ]
Donato, F. [3 ]
Negro, F. [2 ,14 ,15 ]
机构
[1] Univ Verona, Gastroenterol Clin, Dept Med, I-37134 Verona, Italy
[2] Univ Hosp Geneva, Div Clin Pathol, Geneva, Switzerland
[3] Univ Brescia, Inst Hyg Epidemiol & Publ Hlth, Brescia, Italy
[4] Univ Lausanne Hosp, Dept Internal Med, Infect Dis Serv, Lausanne, Switzerland
[5] Univ Lausanne, Lausanne, Switzerland
[6] Univ Goteborg, Dept Infect Dis, Gothenburg, Sweden
[7] Univ Verona, Sect Biol & Genet, Dept Life & Reprod Sci, I-37134 Verona, Italy
[8] Univ Padua, Dept Diagnost Sci & Special Therapies, Padua, Italy
[9] AO Osped Niguarda Ca Grande, Dept Infect Dis, Milan, Italy
[10] Univ Naples 2, Viral Hepatitis Unit, Naples, Italy
[11] Univ Foggia, Clin Infect Dis, Foggia, Italy
[12] Univ Messina, Dept Internal Med, Messina, Italy
[13] Univ Pavia, Inst Infect & Trop Dis, I-27100 Pavia, Italy
[14] Univ Hosp Geneva, Div Gastroenterol, Geneva, Switzerland
[15] Univ Hosp Geneva, Div Hepatol, Geneva, Switzerland
基金
瑞士国家科学基金会;
关键词
INTERFERON PLUS RIBAVIRIN; VIRUS-COINFECTED PATIENTS; INSULIN-RESISTANCE; COMBINATION THERAPY; GENETIC-VARIATION; TREATMENT DURATION; PEG-INTERFERON; PEGINTERFERON; ASSOCIATION; EXPRESSION;
D O I
10.1111/j.1365-2036.2011.04635.x
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
P>Background Hepatitis C virus (HCV) is a major cause of chronic liver disease, cirrhosis and hepatocellular carcinoma and the identification of the predictors of response to antiviral therapy is an important clinical issue. Aim To determine the independent contribution of factors including IL28B polymorphisms, IFN-gamma inducible protein-10 (IP-10) levels and the homeostasis model assessment of insulin resistance (HOMA-IR) score in predicting response to therapy in chronic hepatitis C (CHC). Methods Multivariate analysis of factors predicting rapid (RVR) and sustained (SVR) virological response in 280 consecutive, treatment-naive CHC patients treated with peginterferon alpha and ribavirin in a prospective multicentre study. Results Independent predictors of RVR were HCV RNA < 400 000 IU/mL (OR 11.37; 95% CI 3.03-42.6), rs12980275 AA (OR 7.09; 1.97-25.56) and IP-10 (OR 0.04; 0.003-0.56) in HCV genotype 1 patients and lower baseline gamma-glutamyl-transferase levels (OR = 0.02; 0.0009-0.31) in HCV genotype 3 patients. Independent predictors of SVR were rs12980275 AA (OR 9.68; 3.44-27.18), age < 40 years (OR = 4.79; 1.50-15.34) and HCV RNA < 400 000 IU/mL (OR 2.74; 1.03-7.27) in HCV genotype 1 patients and rs12980275 AA (OR = 6.26; 1.98-19.74) and age < 40 years (OR 5.37; 1.54-18.75) in the 88 HCV genotype 1 patients without a RVR. RVR was by itself predictive of SVR in HCV genotype 1 patients (OR 33.0; 4.06-268.32) and the only independent predictor of SVR in HCV genotype 2 (OR 9.0, 1.72-46.99) or genotype 3 patients (OR 7.8, 1.43-42.67). Conclusions In HCV genotype 1 patients, IL28B polymorphisms, HCV RNA load and IP-10 independently predict RVR. The combination of IL28B polymorphisms, HCV RNA level and age may yield more accurate pre-treatment prediction of SVR. HOMA-IR score is not associated with viral response.
引用
收藏
页码:1162 / 1172
页数:11
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