Wu Chih-Feng, Yu Ming-Whei, Lin Chih-Lin, Liu Chun-Jen, Shih Wei-Liang, Tsai Keh-Sung, Chen Chien-Jen
Research Center for Genes, Environment and Human Health and Graduate Institute of Epidemiology, College of Public Health, National Taiwan University, Xuzhou Road Zhongzheng District, Taipei 10055, Taiwan.
Carcinogenesis. 2008 Jan;29(1):106-12. doi: 10.1093/carcin/bgm252. Epub 2007 Nov 13.
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.
关于乙肝病毒（HBV）载量的纵向变化过程及其与肝细胞癌（HCC）发生发展的关系，目前所知甚少。我们在一个由2874名30岁及以上的台湾男性政府雇员组成的队列中开展了一项病例队列研究，这些雇员均为乙肝表面抗原阳性。我们使用基于聚合酶链反应的检测方法，对112例病例和1031名非病例的血浆样本进行了HBV基因型和DNA水平（即病毒载量）检测。在诊断前，从每位男性身上采集了多个样本（共7706个样本），检测其HBV DNA的血浆水平，采集时间跨度长达诊断前16年。基线病毒载量影响HBV基因型特异性HCC风险，并可预测导致HCC的高病毒载量（≥4.39 log拷贝/毫升）的持续存在情况。在9年内观察到病毒载量有中度到高度的追踪性。乙肝e抗原（P<0.0001）、C基因型HBV感染（P = 0.0369）以及纵向丙氨酸氨基转移酶（ALT）升高（定义为在≥50%的就诊中ALT异常）（P = 0.0005）与高病毒载量持续时间较长呈正相关。经过多变量调整后，C基因型HBV（比值比[OR]=5.97，95%置信区间[CI]=3.44 - 10.34）、在≥50%的就诊中检测到高病毒载量（与持续低病毒载量相比：OR = 5.04，95% CI = 2.31 - 11.00）以及纵向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病例的43.5%、57.2%和24.9%。结果表明，将病毒载量维持在<4.39 log拷贝/毫升与ALT水平持续正常化以及HCC风险降低相关。
