Background: In patients with chronic HCV infection, an association between IL28B genotype and insulin-resistance (IR), known predictors of sustained virological response (SVR) to pegylated interferon (PEG-IFN) and ribavirin (RBV) therapy, has been reported. The aim of this study was to investigate the association of IR and IL28B genotype in two cohorts of well-characterized HCV patients. Methods: A total of 480 non-diabetic HCV patients were analysed: 391 patients who received PEG-IFN/RBV in the MIST study and 89 previously reported patients followed at a metabolic liver diseases centre (Division of Internal Medicine, Fondazione IRCCS Ospedale Maggiore Policlinico, Milan, Italy). All were tested for IL28B rs12979860 single nucleotide polymorphism by real-time PCR and had IR measured by HOMA-IR. Staging of liver disease through liver biopsy was available for all patients. Results: Overall, 164 patients (34%) were IL28B CC. Mean HOMA-IR values (+/- sd) did not differ according to IL28B genotype, being respectively 1.14 +/- 0.79 in CC versus 1.14 +/- 0.78 in CT/TT (P=1.0) in the first, and 2.4 +/- 1.0 versus 2.5 +/- 1.0 (P=0.7) in the second cohort. HOMA-IR> 2 was not associated with IL28B genotype: 16/132 (12%) CC versus 31/259 (12%) CT/TT (P=1.0) in the first cohort and 16/32 (50%) versus 37/57 (65%; P=0.18) in the second. This held true also when using different HOMA cutoffs (> 2.5, > 3.0, > 3.5 and > 4.0). In the MIST cohort, HOMA-IR> 2 did not influence treatment outcome, SVR rates being 28/47 (60%) in HOMAIR>2 versus 214/344 (62%) in HOMA-IR=2 (P=0.8). IL28B genotype was a strong predictor of SVR: 84% (111/132) in CC versus 51% (131/259) in CT/TT patients (P<0.0001). Conclusions: In two cohorts of non-diabetic HCV patients where IL28B genotype predicted treatment outcome, we found no association between IL28B genotype and HOMA-IR.

Interleukin 28B genotype and insulin resistance in chronic hepatitis C patients / E. Degasperi, L. Valenti, A. Aghemo, R. De Francesco, M. Rumi, R. Soffredini, L. Donnici, C. Cheroni, S. Fargion, V. Zanoni, E. Orsi, M. Colombo. - In: ANTIVIRAL THERAPY. - ISSN 1359-6535. - 19:8(2014), pp. 747-753. [10.3851/IMP2743]

Interleukin 28B genotype and insulin resistance in chronic hepatitis C patients

E. Degasperi;L. Valenti;A. Aghemo;R. De Francesco;M. Rumi;R. Soffredini;L. Donnici;S. Fargion;M. Colombo
2014

Abstract

Background: In patients with chronic HCV infection, an association between IL28B genotype and insulin-resistance (IR), known predictors of sustained virological response (SVR) to pegylated interferon (PEG-IFN) and ribavirin (RBV) therapy, has been reported. The aim of this study was to investigate the association of IR and IL28B genotype in two cohorts of well-characterized HCV patients. Methods: A total of 480 non-diabetic HCV patients were analysed: 391 patients who received PEG-IFN/RBV in the MIST study and 89 previously reported patients followed at a metabolic liver diseases centre (Division of Internal Medicine, Fondazione IRCCS Ospedale Maggiore Policlinico, Milan, Italy). All were tested for IL28B rs12979860 single nucleotide polymorphism by real-time PCR and had IR measured by HOMA-IR. Staging of liver disease through liver biopsy was available for all patients. Results: Overall, 164 patients (34%) were IL28B CC. Mean HOMA-IR values (+/- sd) did not differ according to IL28B genotype, being respectively 1.14 +/- 0.79 in CC versus 1.14 +/- 0.78 in CT/TT (P=1.0) in the first, and 2.4 +/- 1.0 versus 2.5 +/- 1.0 (P=0.7) in the second cohort. HOMA-IR> 2 was not associated with IL28B genotype: 16/132 (12%) CC versus 31/259 (12%) CT/TT (P=1.0) in the first cohort and 16/32 (50%) versus 37/57 (65%; P=0.18) in the second. This held true also when using different HOMA cutoffs (> 2.5, > 3.0, > 3.5 and > 4.0). In the MIST cohort, HOMA-IR> 2 did not influence treatment outcome, SVR rates being 28/47 (60%) in HOMAIR>2 versus 214/344 (62%) in HOMA-IR=2 (P=0.8). IL28B genotype was a strong predictor of SVR: 84% (111/132) in CC versus 51% (131/259) in CT/TT patients (P<0.0001). Conclusions: In two cohorts of non-diabetic HCV patients where IL28B genotype predicted treatment outcome, we found no association between IL28B genotype and HOMA-IR.
sustained virological response; receptor substrate-1; IL28B genotype; HCV; association; infection; ribavirin; polymorphism; alpha
Settore MED/09 - Medicina Interna
2014
Centro per lo studio e la cura delle malattie metaboliche del fegato
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/260353
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