Fowler M J, Greenfield C, Chu C M, Karayiannis P, Dunk A, Lok A S, Lai C L, Yeoh E K, Monjardino J P, Wankya B M
J Hepatol. 1986;2(2):218-29. doi: 10.1016/s0168-8278(86)80080-0.
Hundred and ten liver biopsy specimens from various parts of the world were examined for episomal and integrated HBV-DNA sequences. In 54 patients with HBsAg chronic liver disease episomal HBV-DNA was found in 83% of HBeAg-positive patients, compared to only 22% of patients with anti-HBe. Furthermore episomal HBV-DNA in the latter predominated among the Asians. Integrated HBV-DNA was found only in 5.5% of HBeAg-positive patients but in 16.5% of patients with anti-HBe. In 28 HBsAg-positive patients with hepatoma, episomal HBV-DNA was found in 50% of HBeAg-positive patients but in only 11% of anti-HBe patients. Conversely integrated sequences were less common (25%) in HBe-Ag-positive patients than in anti-HBe patients (50%), giving an overall incidence of integration in this group of 45%. No episomal, and only one case of integrated sequences of HBV-DNA, could be detected among 10 patients with HBsAg-negative hepatoma. In addition neither episomal nor integrated HBV-DNA could be detected in 18 patients with non-HBV-related liver disease. Our data suggests that stable integration of HBV-DNA into the host's genome is not necessarily a prerequisite for the maintenance of the state of malignant transformation but may be necessary for its initiation. Alternatively, the detection of integrated HBV-DNA may represent a 'snap shot' of a random integration event amplified by clonal expansion promoted by other factors.
对来自世界各地的110份肝活检标本进行了游离型和整合型乙肝病毒DNA序列检测。在54例乙肝表面抗原（HBsAg）慢性肝病患者中，83%的HBeAg阳性患者检测到游离型乙肝病毒DNA，而抗-HBe患者中这一比例仅为22%。此外，后者中的游离型乙肝病毒DNA在亚洲人中占主导。仅5.5%的HBeAg阳性患者检测到整合型乙肝病毒DNA，而抗-HBe患者中的这一比例为16.5%。在28例HBsAg阳性肝癌患者中，50%的HBeAg阳性患者检测到游离型乙肝病毒DNA，而抗-HBe患者中这一比例仅为11%。相反，HBeAg阳性患者中整合序列（25%）比抗-HBe患者（50%）少见，该组的总体整合发生率为45%。在10例HBsAg阴性肝癌患者中未检测到游离型乙肝病毒DNA，仅1例检测到整合型序列。此外，在18例非乙肝病毒相关肝病患者中未检测到游离型和整合型乙肝病毒DNA。我们的数据表明，乙肝病毒DNA稳定整合到宿主基因组中不一定是维持恶性转化状态的先决条件，但可能是启动恶性转化所必需的。或者，整合型乙肝病毒DNA的检测可能代表了由其他因素促进的克隆扩增所放大的随机整合事件的“快照”。
