title: Influence of hepatitis C virus and IL28B genotypes on liver stiffness.
abstract: Liver fibrosis has been associated with hepatitis C virus (HCV) genotype and genetic variation near the interleukin 28B (IL28B) gene, but the relative contribution is unknown. We aimed to investigate the relation between HCV genotypes, IL28B and development of liver stiffness.
  
  
  
  This cross-sectional study consists of 369 patients with chronic hepatitis C (CHC). Liver stiffness was evaluated using transient elastograhy (TE). Factors associated with development of liver fibrosis were identified by logistic regression analysis.
  
  
  
  We identified 369 patients with CHC. 235 were male, 297 Caucasians, and 223 had been exposed to HCV through intravenous drug use. The overall median TE value was 7.4 kPa (interquartile range (IQR) 5.7-12.1). HCV replication was enhanced in patients carrying the IL28B CC genotype compared to TT and TC (5.8 vs. 5.4 log10 IU/mL, p = 0.03). Patients infected with HCV genotype 3 had significantly higher TE values (8.2 kPa; IQR, 5.9-14.5) compared to genotype 1 (6.9 kPa; IQR, 5.4-10.9) and 2 (6.7 kPa; IQR, 4.9-8.8) (p = 0.02). Within patients with genotype 3, IL28B CC genotype had the highest TE values (p = 0.04). However, in multivariate logistic regression, using various cut-off values for fibrosis and cirrhosis, only increasing age (odds ratio (OR) 1.09 (95% confidence interval (CI), 1.05-1.14 per year increment)), ALT (OR 1.01 (95% CI, 1.002-1.011), per unit increment) and HCV genotype 3 compared to genotype 1 (OR 2.40 (95% CI, 1.19-4.81), were consistently associated with cirrhosis (TE>17.1 kPa).
  
  
  
  Age, ALT and infection with HCV genotype 3 were associated with cirrhosis assessed by TE. However, IL28B genotype was not an independent predictor of fibrosis in our study.
authors.affiliation: Department of Infectious Diseases, Hvidovre Hospital, University of Copenhagen, Copenhagen, Denmark; Clinical Research Centre, Hvidovre Hospital, University of Copenhagen, Copenhagen, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Lene Fogt
authors.initials: LF
authors.lastname: Lundbo
authors.affiliation: Department of Infectious Diseases, Hvidovre Hospital, University of Copenhagen, Copenhagen, Denmark; Clinical Research Centre, Hvidovre Hospital, University of Copenhagen, Copenhagen, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Louise Nygaard
authors.initials: LN
authors.lastname: Clausen
authors.affiliation: Department of Infectious Diseases, Hvidovre Hospital, University of Copenhagen, Copenhagen, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Nina
authors.initials: N
authors.lastname: Weis
authors.affiliation: Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Department of Clinical Microbiology, Hvidovre Hospital, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Kristian
authors.initials: K
authors.lastname: Schønning
authors.affiliation: Department of Infectious Diseases, Hvidovre Hospital, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Lene
authors.initials: L
authors.lastname: Rosenørn
authors.affiliation: Department of Infectious Diseases, Hvidovre Hospital, University of Copenhagen, Copenhagen, Denmark; Clinical Research Centre, Hvidovre Hospital, University of Copenhagen, Copenhagen, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Thomas
authors.initials: T
authors.lastname: Benfield
authors.affiliation: Department of Infectious Diseases, Odense University Hospital, Odense, Denmark.
authors.forename: Peer Brehm
authors.initials: PB
authors.lastname: Christensen
mesh_terms: D000328:Adult; D054459:Elasticity Imaging Techniques; D005260:Female; D020022:Genetic Predisposition to Disease; D016174:Hepacivirus / Q000502:physiology*; D019698:Hepatitis C, Chronic / Q000235:genetics / Q000821:virology; D006801:Humans; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D008099:Liver / Q000473:pathology / Q000821:virology; D008103:Liver Cirrhosis / Q000235:genetics* / Q000821:virology*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012307:Risk Factors; D019562:Viral Load; D000095022:Interferon Lambda
chemical_list: D007372:Interferons; D007378:Interleukins; C000624353:interferon-lambda, human; D000095022:Interferon Lambda