Thomas H C, Lok A S
Semin Liver Dis. 1984 Feb;4(1):36-46. doi: 10.1055/s-2008-1040644.
In patients with autoimmune chronic liver disease, a defect in the regulatory system of the immune response allows proliferation of clones of cells reacting with hepatocyte antigens. Identification of these target antigens, their isolation, and purification will allow further study of the nature of the immune diathesis and permit development of specific therapy designed to eliminate the malregulated clones of immunocytes. The mechanisms resulting in hepatocyte damage during chronic HBV infection are more complex. Both lobular focal and periportal piecemeal necrosis of hepatocytes is seen. Current evidence is consistent with the view that focal necrosis represents T-cell lysis of hepatocytes containing replicating virus, whereas piecemeal necrosis is a reflection of an autoimmune response to native liver membrane antigens, initiated by viral replication. The latter response would be expected to be greatest during viral replication, but because of the increase in suppressor T-cell concentrations that occurs at this time, the liver membrane antibody response is largely suppressed. When viral replication ceases, in patients with normal suppressor cells, the liver membrane antibody response is suppressed. In some patients, suppressor cells are relatively reduced and the liver membrane antibody response continues after cessation of viral replication. At this stage, the composition of the inflammatory infiltrate in the liver is similar to that seen in autoimmune (lupoid) chronic active hepatitis. The destruction of hepatocytes containing integrated HBV-DNA is probably dependent on an immune response to HBs antigen. Failure of this elimination process, for immunogenetic or environmental reasons, results in persistence of clones of cells from which malignantly derived cells may ultimately arise. Adequate therapy of this condition must not only stop the replication of the virus, thereby reducing hepatic inflammatory activity, but eliminate clones of cells containing integrated HBV-DNA so that the danger of malignant transformation of hepatocytes is removed.
在自身免疫性慢性肝病患者中，免疫反应调节系统的缺陷使得与肝细胞抗原发生反应的细胞克隆得以增殖。鉴定这些靶抗原、将其分离和纯化，将有助于进一步研究免疫素质的本质，并开发旨在消除免疫细胞失调克隆的特异性疗法。慢性乙型肝炎病毒感染期间导致肝细胞损伤的机制更为复杂。可见肝细胞的小叶局灶性坏死和汇管区碎屑样坏死。目前的证据与以下观点一致，即局灶性坏死代表含有复制病毒的肝细胞的T细胞溶解，而碎屑样坏死反映了由病毒复制引发的对天然肝细胞膜抗原的自身免疫反应。预计后一种反应在病毒复制期间最为强烈，但由于此时抑制性T细胞浓度增加，肝细胞膜抗体反应在很大程度上受到抑制。当病毒复制停止时，在抑制性细胞正常的患者中，肝细胞膜抗体反应受到抑制。在一些患者中，抑制性细胞相对减少，并且在病毒复制停止后肝细胞膜抗体反应仍持续。在这个阶段，肝脏中炎性浸润的组成与自身免疫性（类狼疮样）慢性活动性肝炎中所见的相似。含有整合型乙肝病毒DNA的肝细胞的破坏可能依赖于对乙肝表面抗原的免疫反应。由于免疫遗传或环境原因，这种清除过程失败会导致细胞克隆持续存在，恶性衍生细胞可能最终从中产生。对这种情况的充分治疗不仅必须阻止病毒复制，从而降低肝脏炎症活动，而且要消除含有整合型乙肝病毒DNA的细胞克隆，以便消除肝细胞恶性转化的危险。
