Shafritz D A
J Cell Biochem. 1982;20(3):303-16. doi: 10.1002/jcb.240200310.
The hepatitis B virus carrier state (persistent HBV infection) is characterized by the presence of viral surface antigen (HBsAg) and virion particles (Dane particles) in the blood. From 1% to 10% of carriers develop chronic liver disease and/or hepatocellular carcinoma. Recent studies have demonstrated integrated HBV-DNA in hepatocellular carcinomas and in several human hepatoma cell lines. In hepatoma patients, integrated HBV-DNA has been found in all HBsAg carriers. Nontumorous liver also revealed integrated HBV-DNA with the same or a different hybridization pattern from that observed in the tumor. To explore when integration occurs, carriers of short-term (less than 2 years) or long-term (greater than 8-10 years) were evaluated. DNA extracts from percutaneous (needle) liver biopsies showed free viral DNA with no specific integration bands in short-term carriers. In long-term carriers, HBV-DNA was integrated into the host genome with either a diffuse or a unique hybridization pattern. HBV-DNA integration correlated with the duration of the carrier state and absence of virions in the serum but did not correlate with histologic evidence of chronic hepatitis. These studies suggest that integration of HBV-DNA occurs during persistent HBV infection irrespective of liver disease and precedes development of hepatocellular carcinoma.
乙肝病毒携带状态（持续性乙肝病毒感染）的特征是血液中存在病毒表面抗原（HBsAg）和病毒颗粒（Dane颗粒）。1%至10%的携带者会发展为慢性肝病和/或肝细胞癌。最近的研究已证实在肝细胞癌和几种人类肝癌细胞系中存在整合的乙肝病毒DNA。在肝癌患者中，已在所有HBsAg携带者中发现整合的乙肝病毒DNA。非肿瘤性肝脏也显示出整合的乙肝病毒DNA，其杂交模式与肿瘤中观察到的相同或不同。为了探究整合何时发生，对短期（少于2年）或长期（多于8至10年）携带者进行了评估。经皮（穿刺）肝活检的DNA提取物显示，短期携带者中有游离病毒DNA，无特异性整合条带。在长期携带者中，乙肝病毒DNA以弥漫或独特的杂交模式整合到宿主基因组中。乙肝病毒DNA整合与携带状态的持续时间以及血清中病毒颗粒的缺失相关，但与慢性肝炎的组织学证据无关。这些研究表明，乙肝病毒DNA的整合发生在持续性乙肝病毒感染期间，与肝脏疾病无关，且在肝细胞癌发生之前。
