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T1653 Mutation in the Box a Increases the Riskof Hepatocellular Carcinoma in Patients with Chronic Hepatitis B Virus Genotype C Infection

肝细胞癌 医学 基因型 病毒学 突变 乙型肝炎病毒 丙型肝炎病毒 病毒 慢性肝炎 内科学 基因 遗传学 生物
作者
Kiyoaki Ito,Yasuhito Tanaka,Etsuro Orito,Masaya Sugiyama,Kei Fujiwara,Fuminaka Sugauchi,Takanobu Kato,Hajime Tokita,Namiki Izumi,Michio Kato,Man‐Fung Yuen,Ching‐Lung Lai,Robert G. Gish,Ryuzo Ueda,Masashi Mizokami
出处
期刊:Clinical Infectious Diseases [Oxford University Press]
卷期号:42 (1): 1-7 被引量:60
标识
DOI:10.1086/498522
摘要

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. 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. The prevalence of T1653 in the box α 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 ⩾ 37 U/L, and a platelet count of <18 × 104 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 α -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). Our data indicate that the addition of T1653 mutation in the box α to the basic core promoter mutation increases the risk of hepatocellular carcinoma in patients with hepatitis B virus genotype C.
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