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

Giovanna Fattovich (1, 2) , Loredana Covolo (3) , Stéphanie Bibert (4) , Galia Askarieh (5) , Martin Lagging (5) , Sophie Clément (2) , Giovanni Malerba (6) , Michela Pasino (1) , Maria Guido (7) , Massimo Puoti (8) , Giovanni B. Gaeta (9) , Teresa Santantonio (10) , Giovanni Raimondo (11) , Raffaele Bruno (12) , Pierre-Yves Bochud (1) , Francesco Donato (1) , Francesco Negro (2)

1 Clinic of Gastroenterology, Department of Medicine
2 Division of Clinical Pathology
3 Institute of Hygiene, Epidemiology and Public Health
4 Infectious Disease Service, Department of Internal Medicine
5 Department of Infectious Diseases
6 Section of Biology & Genetics
7 Department of Diagnostic Sciences & Special Therapies
8 Department of infectious Diseases
9 Infectious Diseases
10 Clinic of Infectious Diseases
11 Department of Internal Medicine
12 Institute of Infectious and Tropical Diseases

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 multicenter study. Results Independent predictors of RVR were HCV RNA < 400,000 IU/ml (OR11.37; 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 g-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 yrs (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 yrs (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 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.

Mots clés: Medicine

Giovanna Fattovich, Loredana Covolo, Stéphanie Bibert, Galia Askarieh, Martin Lagging, et al.. IL28B polymorphisms, IP-10 and viral load predict virological response to therapy in chronic hepatitis C. Alimentary Pharmacology and Therapeutics, 2011, 33 (10), pp.1162. ⟨10.1111/j.1365-2036.2011.04635.x⟩. ⟨hal-00627150⟩