Basal core promoter mutations of hepatitis B virus increase the risk of hepatocellular carcinoma in hepatitis B carriers
Basal core promoter mutations of hepatitis B virus increase the risk of hepatocellular carcinoma in hepatitis B carriers
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DOI：
10.1053/gast.2003.50053
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发表时间：
2003-02-01
期刊：
影响因子：
29.4
通讯作者：
Chen, DS
中科院分区：
文献类型：
--
作者：
Kao, JH;Chen, PJ;Chen, DS
背景和目标：与基因型B相比，B型肝炎病毒（HBV）C基因型与肝细胞癌（HCC）的发生相关;然而，导致致病差异的病毒学因素仍不清楚。我们调查了T1762/A1764基础核心启动子突变体在250例基因型B或C感染的HBV携带者中的患病率，以阐明该突变体在肝癌发生中的可能作用。研究方法：对60例非活动性HBV携带者和190例经病理证实的慢性肝病和肝癌患者进行HBV基因组基本核心启动子序列测定。结果如下：基因型C的T1762/A1764突变发生率高于基因型B（比值比，5.18; 95%可信区间[CI]，2.59-10.37; P < 0.001）。T1762/A1764突变的可能性与肝脏疾病的进展平行，从非活动性携带者的3%到HCC患者的64%（比值比，20.04; 95%CI，7.25-55.41; P < 0.001）。多因素Logistic回归分析显示，T1762/A1764突变与HCC的发生显著相关（OR为10.60; 95% CI为4.92-22.86; P < 0.001），基因型B和C均为HCC的危险因素。此外，T1762/A1764突变在年轻HCC患者中的患病率与老年HCC患者相当，但显著高于年龄匹配的非活动携带者，无论基因型如何。结论.我们的数据表明，HBV携带者与T1762/A1764基础核心启动子突变的HCC的风险增加，这种突变可能有助于HBV感染的发病机制。
Background & Aims: Hepatitis B viral (HBV) genotype C is associated with the development of hepatocellular carcinoma (HCC) compared with genotype B; however, the virologic factors contributing to the pathogenic differences remain unknown. We investigated the prevalence of T1762/A1764 basal core promoter mutant in a cohort of 250 genotype B- or C-infected HBV carriers with different stages of liver disease to clarify a possible role for this mutant in hepatocarcinogenesis. Methods: The sequences of basal core promoter of HBV genome were determined in 60 inactive HBV carriers and 190 patients with histologically verified chronic liver disease and HCC. Results: Genotype C has a higher prevalence of T1762/A1764 mutation than genotype B (odds ratio, 5.18; 95% confidence interval [CI], 2.59-10.37; P < 0.001). The likelihood of T1762/A1764 mutation parallels the progression of liver disease, from 3% in inactive carriers to 64% in HCC patients (odds ratio, 20.04; 95% Cl, 7.25-55.41; P < 0.001). By multiple logistic regression analysis, patients with T1762/A1764 mutation were significantly associated with the development of HCC than those without (odds ratio, 10.60; 95% Cl, 4.92-22.86; P < 0.001), and the risk was observed for both genotypes B and C. In addition, the prevalence of T1762/A1764 mutation in younger HCC patients was comparable with older HCC patients but was significantly higher than that in age-matched inactive carriers, irrespective of genotypes. Conclusions. Our data suggest that HBV carriers with T1762/A1764 basal core promoter mutant are at increased risk for HCC and that this mutant may contribute to the pathogenesis of HBV infection.