T1653 mutation in the box alpha increases the risk of hepatocellular carcinoma in patients with chronic hepatitis B virus genotype C infection.
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.
Ito
Kiyoaki
K
Department of Clinical Molecular Informative Medicine, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
Tanaka
Yasuhito
Y
Orito
Etsuro
E
Sugiyama
Masaya
M
Fujiwara
Kei
K
Sugauchi
Fuminaka
F
Kato
Takanobu
T
Tokita
Hajime
H
Izumi
Namiki
N
Kato
Michio
M
Yuen
Man-Fung
MF
Lai
Ching-Lung
CL
Gish
Robert G
RG
Ueda
Ryuzo
R
Mizokami
Masashi
M
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