title: T1653 mutation in the box alpha increases the risk of hepatocellular carcinoma in patients with chronic hepatitis B virus genotype C infection.
abstract: BACKGROUND
  Most patients with chronic hepatitis B virus infection become carriers of inactive virus after hepatitis B e antigen seroconversion; however, a subgroup of patients have persistent abnormal transaminase levels and develop hepatocellular carcinoma after seroconversion.
  
  
  METHODS
  In an age-matched case-control study, 40 carriers of inactive virus (mean age+/-standard deviation [SD], 50.9 +/- 11.1 years), 40 patients with chronic hepatitis (mean age+/-SD, 50.2 +/- 8.9 years), and 40 patients with hepatocellular carcinoma (mean age+/-SD, 50.7 +/- 9.4 years) who were infected with hepatitis B virus genotype C and had test results positive for antibody to hepatitis B e antigen were analyzed.
  
  
  RESULTS
  The prevalence of T1653 in the box alpha was significantly higher among patients with hepatocellular carcinoma than among carriers of inactive virus who did not have hepatocellular carcinoma (70% vs. 25%; P < .0001) or chronic hepatitis (70% vs. 35%; P = .003). Mutations in the basic core promoter region (T1762/A1764) were frequently found in all groups, regardless of clinical status (in 77.5% of carriers of inactive virus, 77.5% of patients with chronic hepatitis, and 90% of patients with hepatocellular carcinoma). In the multivariate analysis, the presence of T1653, an alanine aminotransferase level of > or = 37 U/L, and a platelet count of < 18 x 10(4) platelets/mm3 were independent predictive values for hepatocellular carcinoma (odds ratio [95% confidence interval], 5.05 [1.56-16.35], 12.56 [3.05-51.77], and 11.5 [3.47-38.21], respectively). High alpha -fetoprotein level was the only independent predictive value for T1653 in patients with hepatocellular carcinoma (odds ratio, 12.67; 95% confidence interval, 1.19-134.17]). Among patients with test results positive for antibody to hepatitis B e antigen who had hepatocellular carcinoma and were infected with different genotypes of hepatitis B virus, the prevalence of T1653 was 40%, 15%, 25%, 25%, 67%, and 23% in patients infected with hepatitis B virus genotypes Aa, Ae, Ba, Bj, C, and D, respectively (P<.05 for genotype C vs. genotypes Ae, Ba, Bj, or D).
  
  
  CONCLUSIONS
  Our data indicate that the addition of T1653 mutation in the box alpha to the basic core promoter mutation increases the risk of hepatocellular carcinoma in patients with hepatitis B virus genotype C.
authors.affiliation: Department of Clinical Molecular Informative Medicine, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Kiyoaki
authors.initials: K
authors.lastname: Ito
authors.forename: Yasuhito
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Etsuro
authors.initials: E
authors.lastname: Orito
authors.forename: Masaya
authors.initials: M
authors.lastname: Sugiyama
authors.forename: Kei
authors.initials: K
authors.lastname: Fujiwara
authors.forename: Fuminaka
authors.initials: F
authors.lastname: Sugauchi
authors.forename: Takanobu
authors.initials: T
authors.lastname: Kato
authors.forename: Hajime
authors.initials: H
authors.lastname: Tokita
authors.forename: Namiki
authors.initials: N
authors.lastname: Izumi
authors.forename: Michio
authors.initials: M
authors.lastname: Kato
authors.forename: Man-Fung
authors.initials: MF
authors.lastname: Yuen
authors.forename: Ching-Lung
authors.initials: CL
authors.lastname: Lai
authors.forename: Robert G
authors.initials: RG
authors.lastname: Gish
authors.forename: Ryuzo
authors.initials: R
authors.lastname: Ueda
authors.forename: Masashi
authors.initials: M
authors.lastname: Mizokami
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000209:etiology* / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D005838:Genotype; D006515:Hepatitis B virus / Q000145:classification / Q000235:genetics*; D019694:Hepatitis B, Chronic / Q000150:complications*; D006801:Humans; D008113:Liver Neoplasms / Q000209:etiology* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D012307:Risk Factors