title: Effects of IL28B rs12979860 CC genotype on metabolic profile and sustained virologic response in patients with genotype 1 chronic hepatitis C.
abstract: OBJECTIVE
  Patients with genotype 1 chronic hepatitis C (G1 CHC) frequently develop steatosis and insulin resistance (IR), caused by metabolic and viral factors. These accelerate the progression of liver disease and reduce the response to therapy. A sustained virologic response (SVR) to therapy in patients with G1 CHC is associated strongly with polymorphisms near the interleukin-28B (IL28B) gene, but the interaction between IL28B genotype and IR, and their combined effects on SVR, have not been defined. We tested the association between the IL28B rs12979860 single-nucleotide polymorphism and metabolic features, including IR, and evaluated their effects on SVR.
  
  
  METHODS
  We performed genotype analysis of IL28B rs12979860 for 434 white G1 CHC patients who underwent consecutive biopsy analysis at 3 tertiary centers. Metabolic profile analyses included assessments of lipid levels and IR by the homeostasis model assessment.
  
  
  RESULTS
  Patients with the CC polymorphism in IL28B had higher levels of total and low-density lipoprotein cholesterol, lower levels of triglycerides, and a lower prevalence of IR and moderate-severe steatosis (P < .05) than patients without this genotype. By multiple logistic regression analysis, body mass index (odds ratio [OR], 1.223; P < .001), level of triglycerides (OR, 1.007; P = .006), the CC polymorphism in IL28B (OR, 0.378; P = .001), and levels of HCV RNA greater than 850,000 IU/mL (OR, 1.803; P = .01) were associated with IR. The CC polymorphism in IL28B (OR, 8.350; P < .001) and IR (OR, 0.432; P = .005), but not steatosis (OR, 0.582; P = 0.25), was associated with an SVR.
  
  
  CONCLUSIONS
  In white patients with G1 CHC, the IL28B rs12979860 CC genotype is associated with reduced IR. IL28B rs12979860 genotype and IR by the homeostasis model assessment strongly affect the outcome of antiviral therapy.
authors.affiliation: Division of Gastroenterology, Dipartimento Biomedico di Medicina Interna e Specialistica, University of Palermo, Palermo, Italy. petsa@inwind.it
authors.forename: Salvatore
authors.initials: S
authors.lastname: Petta
authors.forename: Chiara
authors.initials: C
authors.lastname: Rosso
authors.forename: Reynold
authors.initials: R
authors.lastname: Leung
authors.forename: Maria Lorena
authors.initials: ML
authors.lastname: Abate
authors.forename: David
authors.initials: D
authors.lastname: Booth
authors.forename: Federico
authors.initials: F
authors.lastname: Salomone
authors.forename: Roberto
authors.initials: R
authors.lastname: Gambino
authors.forename: Mario
authors.initials: M
authors.lastname: Rizzetto
authors.forename: Paolo
authors.initials: P
authors.lastname: Caviglia
authors.forename: Antonina
authors.initials: A
authors.lastname: Smedile
authors.forename: Stefania
authors.initials: S
authors.lastname: Grimaudo
authors.forename: Calogero
authors.initials: C
authors.lastname: Cammà
authors.forename: Antonio
authors.initials: A
authors.lastname: Craxì
authors.forename: Jacob
authors.initials: J
authors.lastname: George
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Bugianesi
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D015331:Cohort Studies; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000145:classification* / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000150:complications / Q000188:drug therapy / Q000235:genetics* / Q000821:virology; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics*; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D008297:Male; D055442:Metabolome; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012367:RNA, Viral / Q000097:blood; D016896:Treatment Outcome; D019562:Viral Load; D000095022:Interferon Lambda
chemical_list: D000998:Antiviral Agents; D007372:Interferons; D007378:Interleukins; D012367:RNA, Viral; C000624353:interferon-lambda, human; D000095022:Interferon Lambda