Long-term tracking of hepatitis B viral load and the relationship with risk for hepatocellular carcinoma in men
Long-term tracking of hepatitis B viral load and the relationship with risk for hepatocellular carcinoma in men
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DOI：
10.1093/carcin/bgm252
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发表时间：
2008-01-01
期刊：
影响因子：
4.7
通讯作者：
Chen, Chien-Jen
中科院分区：
文献类型：
--
作者：
Wu, Chih-Feng;Yu, Ming-Whei;Chen, Chien-Jen
关于乙型肝炎病毒（HBV）载量的纵向病程及其与肝细胞癌（HCC）发展的关系知之甚少。我们对2874名30岁或以上的台湾男性政府雇员进行了一项病例队列研究。采用基于聚合酶链反应的检测方法对112例病例和1031例非病例的血浆样本进行HBV基因型和DNA水平（即病毒载量）检测。在诊断前长达16年的时间里，从每位男性收集的多个样本（总共7706个样本）中测量了诊断前血浆HBV DNA水平。基线病毒载量影响HBV基因型特异性HCC风险，并预测持续高病毒载量（>= 4.39 log拷贝/ml）可导致HCC。在9年内观察到中度到高度的病毒载量追踪。乙型肝炎e抗原（P < 0.0001）、基因型C型HBV感染（P = 0.0369）和纵向丙氨酸转氨酶（ALT）升高（定义为>= 50%就诊时ALT异常）（P = 0.0005）与高病毒载量持续时间延长呈正相关。多因素调整后，HBV基因型C[优势比(OR) = 5.97, 95%可信区间(CI) = 3.44-10.34]、>时检测到高病毒载量= 50%（与持续低病毒载量相比：OR = 5.04, 95% CI = 2.31-11.00）和纵向ALT升高（与持续正常ALT水平相比：OR = 2.84, 95% CI = 1.46-5.51）分别占hcc的43.5%、57.2和24.9%。结果表明，维持病毒载量< 4.39 log copies/ml与ALT水平持续正常化和HCC风险降低相关。
Little is known about the longitudinal course of hepatitis B virus (HBV) load and its relationship with the development of hepatocellular carcinoma (HCC). We conducted a case-cohort study nested within a cohort of 2874 HBV surface antigen-positive male Taiwanese government employees aged 30 years or older. HBV genotype and DNA levels (i.e. viral load) were tested using polymerase chain reaction-based assays on plasma samples from 112 cases and 1031 non-cases. Prediagnostic plasma levels of HBV DNA were measured in multiple samples collected from each man (total 7706 samples), taken over periods of up to 16 years before diagnosis. Baseline viral load influenced HBV genotype-specific HCC risks and predicted the persistence of high viral load (>= 4.39 log copies/ml) that can cause HCC. Moderate to high tracking of viral load was observed within 9 years. Hepatitis B e antigen (P < 0.0001), genotype C HBV infection (P = 0.0369) and longitudinal alanine aminotransferase (ALT) elevation (defined as ALT abnormality in >= 50% of the visits) (P = 0.0005) were positively related to longer duration of persistence for high viral load. After multivariate adjustment, HBV genotype C [odds ratio (OR) = 5.97, 95% confidence interval (CI) = 3.44-10.34], high viral load detected at >= 50% of the visits (compared with sustained low viral load: OR = 5.04, 95% CI = 2.31-11.00) and longitudinal ALT elevation (compared with sustained normal ALT levels: OR = 2.84, 95% CI = 1.46-5.51) accounted for 43.5, 57.2 and 24.9% of HCCs, respectively. The results suggest that maintenance of viral load < 4.39 log copies/ml was associated with sustained normalization of ALT levels and decreased risk of HCC.