title: IL28B minor allele is associated with a younger age of onset of hepatocellular carcinoma in patients with chronic hepatitis C virus infection.
abstract: BACKGROUND
  IL28B polymorphisms were shown to be associated with a response to peg-interferon-based treatment in chronic hepatitis C (CHC) and spontaneous clearance. However, little is known about how this polymorphism affects the course of CHC, including the development of hepatocellular carcinoma (HCC). We evaluated the influence of IL28B polymorphisms on hepatocarcinogenesis in CHC patients.
  
  
  METHODS
  We genotyped the rs8099917 single-nucleotide polymorphism in 351 hepatitis C-associated HCC patients without history of IFN-based treatment, and correlated the age at onset of HCC in patients with each genotype.
  
  
  RESULTS
  Frequencies of TT, TG, and GG genotypes were 74.3 % (261/351), 24.8 % (87/351), and 0.9 % (3/351), respectively. The mean ages at onset of HCC for TT, TG, and GG genotypes were 69.9, 67.5 and 66.8, respectively. In multivariate analysis, IL28B minor allele (TG and GG genotypes) was an independent risk factor for younger age at onset of HCC (P = 0.02) in males (P < 0.001) with higher body mass index (BMI; P = 0.009). The IL28B minor allele was also associated with a lower probability of having aspartate aminotransferase-to-platelet ratio index (APRI) >1.5 (minor vs. major, 46.7 vs. 58.6 %; P = 0.01), lower AST (69.1 vs. 77.7 IU/L, P = 0.02), lower ALT (67.8 vs. 80.9 IU/L, P = 0.002), higher platelet count (12.8 vs. 11.2 × 10(4)/μL, P = 0.002), and higher prothrombin time (79.3 vs. 75.4 %, P = 0.002).
  
  
  CONCLUSIONS
  The IL28B minor allele was associated with lower inflammatory activity and less progressed fibrosis of the liver; however, it constituted a risk factor for younger-age onset of HCC in CHC patients.
authors.affiliation: Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Masaya
authors.initials: M
authors.lastname: Sato
authors.forename: Naoya
authors.initials: N
authors.lastname: Kato
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Tateishi
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Muroyama
authors.forename: Norie
authors.initials: N
authors.lastname: Kowatari
authors.forename: Wenwen
authors.initials: W
authors.lastname: Li
authors.forename: Kaku
authors.initials: K
authors.lastname: Goto
authors.forename: Motoyuki
authors.initials: M
authors.lastname: Otsuka
authors.forename: Shuichiro
authors.initials: S
authors.lastname: Shiina
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Yoshida
authors.forename: Masao
authors.initials: M
authors.lastname: Omata
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Koike
mesh_terms: D000367:Age Factors; D017668:Age of Onset; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D000483:Alleles; D001219:Aspartate Aminotransferases / Q000097:blood; D006528:Carcinoma, Hepatocellular / Q000453:epidemiology* / Q000235:genetics* / Q000821:virology; D005260:Female; D005838:Genotype; D019698:Hepatitis C, Chronic / Q000150:complications*; D006801:Humans; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D008113:Liver Neoplasms / Q000453:epidemiology* / Q000235:genetics* / Q000821:virology; D008297:Male; D010976:Platelet Count; D020641:Polymorphism, Single Nucleotide; D011517:Prothrombin Time; D012189:Retrospective Studies; D012307:Risk Factors; D000095022:Interferon Lambda
chemical_list: D000410:Alanine Transaminase; D001219:Aspartate Aminotransferases; D007372:Interferons; D007378:Interleukins; C000624353:interferon-lambda, human; D000095022:Interferon Lambda