title: Genetic variation near interleukin 28B and the risk of hepatocellular carcinoma in patients with chronic hepatitis C.
abstract: BACKGROUND
  We aimed to clarify the association between single nucleotide polymorphism (SNP) located near interleukin 28B and hepatocellular carcinoma (HCC).
  
  
  METHODS
  A cohort comprising 792 patients treated with interferon for chronic hepatitis C was investigated. SNPs at rs8099917 and rs12979860 were determined. Cumulative incidence and HCC risk were analyzed by Kaplan-Meier and Cox proportional hazard analyses for a mean follow-up period of 4.9 years. Fibrosis progression rate (FPR) was determined in these patients with a known time of infection (n = 294).
  
  
  RESULTS
  Cumulative HCC incidence was significantly higher in rs8099917 nonTT (minor homozygote or heterozygote) patients than in rs8099917 TT (major homozygote) patients (20.8 vs. 10.5% over 10 years, logrank test, p = 0.002). This difference was notable in patients infected with genotype 1 and those treated with pegylated interferon and ribavirin. Among nonSVRs, interferon had a limited effect in suppressing alanine aminotransferase (ALT) and/or α-fetoprotein (AFP) levels in nonTT patients. The suppression of these values after interferon therapy was associated with a lower incidence of HCC. FPR were similar in TT and nonTT patients.
  
  
  CONCLUSIONS
  rs8099917 nonTT is related to higher HCC development in patients with HCV genotype 1 and those treated with pegylated interferon and ribavirin. Higher HCC incidence observed in nonTT patients partly results from the limited suppression of ALT and/or AFP by interferon in these patients.
authors.affiliation: Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, 1-26-1 Kyonan-cho, Musashino-shi, Tokyo, 180-8610, Japan, asahina.gast@tmd.ac.jp.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Asahina
authors.forename: Kaoru
authors.initials: K
authors.lastname: Tsuchiya
authors.forename: Takashi
authors.initials: T
authors.lastname: Nishimura
authors.forename: Masaru
authors.initials: M
authors.lastname: Muraoka
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Nobuharu
authors.initials: N
authors.lastname: Tamaki
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Yasui
authors.forename: Takanori
authors.initials: T
authors.lastname: Hosokawa
authors.forename: Ken
authors.initials: K
authors.lastname: Ueda
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nakanishi
authors.forename: Jun
authors.initials: J
authors.lastname: Itakura
authors.forename: Yuka
authors.initials: Y
authors.lastname: Takahashi
authors.forename: Masayuki
authors.initials: M
authors.lastname: Kurosaki
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Enomoto
authors.forename: Mina
authors.initials: M
authors.lastname: Nakagawa
authors.forename: Sei
authors.initials: S
authors.lastname: Kakinuma
authors.forename: Mamoru
authors.initials: M
authors.lastname: Watanabe
authors.forename: Namiki
authors.initials: N
authors.lastname: Izumi
mesh_terms: D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000378:metabolism; D000998:Antiviral Agents / Q000627:therapeutic use; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000821:virology; D015331:Cohort Studies; D018450:Disease Progression; D004359:Drug Therapy, Combination; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000188:drug therapy; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use; D016899:Interferon-beta / Q000627:therapeutic use; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D008113:Liver Neoplasms / Q000235:genetics* / Q000821:virology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012254:Ribavirin / Q000627:therapeutic use; D000509:alpha-Fetoproteins / Q000378:metabolism; D000095022:Interferon Lambda
chemical_list: D000410:Alanine Transaminase; D000998:Antiviral Agents; D016898:Interferon-alpha; D016899:Interferon-beta; D007372:Interferons; D007378:Interleukins; D012254:Ribavirin; D000509:alpha-Fetoproteins; C097353:AFP protein, human; C000624353:interferon-lambda, human; D000095022:Interferon Lambda