title: Interleukin 28B genotype and insulin resistance in chronic hepatitis C patients.
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 HOMA-IR>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.
authors: Centro A.M. e A. Migliavacca, First Division of Gastroenterology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milano, Università degli Studi di Milano, Milan, Italy.
authors: Elisabetta
authors: E
authors: Degasperi
authors: Luca
authors: L
authors: Valenti
authors: Alessio
authors: A
authors: Aghemo
authors: Raffaele
authors: R
authors: De Francesco
authors: Mariagrazia
authors: M
authors: Rumi
authors: Roberta
authors: R
authors: Soffredini
authors: Lorena
authors: L
authors: Donnici
authors: Cristina
authors: C
authors: Cheroni
authors: Silvia
authors: S
authors: Fargion
authors: Valeria
authors: V
authors: Zanoni
authors: Emanuela
authors: E
authors: Orsi
authors: Massimo
authors: M
authors: Colombo
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D000998:Antiviral Agents / Q000627:therapeutic use; D015331:Cohort Studies; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism* / Q000821:virology; D006801:Humans; D007333:Insulin Resistance; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D008103:Liver Cirrhosis / Q000209:etiology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome; D055815:Young Adult; D000095022:Interferon Lambda
chemical_list: D000998:Antiviral Agents; D007372:Interferons; D007378:Interleukins; C000624353:interferon-lambda, human; D000095022:Interferon Lambda