Lanford R E, Michaels M G, Chavez D, Brasky K, Fung J, Starzl T E
Department of Virology and Immunology, Southwest Foundation for Biomedical Research, San Antonio, TX 78228, USA.
J Med Virol. 1995 Jul;46(3):207-12. doi: 10.1002/jmv.1890460307.
The presence of hepatitis B virus (HBV) DNA in extrahepatic tissues has been well documented. Whether HBV DNA can persist in extrahepatic tissues for long periods of time in the absence of replication in the liver has not been determined previously. Recently, two patients with end-stage liver disease secondary to chronic active HBV were treated with baboon liver xenotransplants as these animals are felt to be resistant to HBV infection. Multiple tissues from these two patients were examined for HBV DNA using polymerase chain reaction (PCR). HBV DNA was not detectable in four of five samples of the liver xenografts. A positive signal was observed in a single assay for one sample, but this sample was not positive in subsequent assays. HBV DNA was detected in peripheral blood lymphocytes, spleen, kidney, bone marrow, pancreas, lymph node, heart and small intestine. The level of HBV DNA in these tissues was too low for the detection of HBV DNA replicative intermediates by Southern hybridization; thus, it could not be determined whether the HBV DNA in these tissues represented actively replicating HBV in extrahepatic sites, integrated HBV sequences, HBV in infiltrating lymphocytes, or deposition of HBV immune complexes originating from the plasma. However, it is clear from this study that HBV DNA persisted in multiple tissues for 70 days after replication in the liver had ceased or at least was below the level of detection by PCR.
乙型肝炎病毒（HBV）DNA在肝外组织中的存在已有充分记录。在肝脏中不存在复制的情况下，HBV DNA是否能在肝外组织中长期持续存在，此前尚未确定。最近，两名继发于慢性活动性HBV的终末期肝病患者接受了狒狒肝脏异种移植治疗，因为人们认为这些动物对HBV感染具有抵抗力。使用聚合酶链反应（PCR）对这两名患者的多个组织进行了HBV DNA检测。在五个肝脏异种移植样本中的四个中未检测到HBV DNA。在一个样本的单次检测中观察到阳性信号，但该样本在随后的检测中呈阴性。在周围血淋巴细胞、脾脏、肾脏、骨髓、胰腺、淋巴结、心脏和小肠中检测到了HBV DNA。这些组织中HBV DNA的水平过低，无法通过Southern杂交检测到HBV DNA复制中间体；因此，无法确定这些组织中的HBV DNA是代表肝外部位活跃复制的HBV、整合的HBV序列、浸润淋巴细胞中的HBV，还是源自血浆的HBV免疫复合物的沉积。然而，从这项研究中可以清楚地看出，在肝脏中的复制停止或至少低于PCR检测水平后，HBV DNA在多个组织中持续存在了70天。
