肝移植后乙型病毒性肝炎复发的临床病理研究

Clinicopathological analysis of HBV recurrence in post-liver transplantation patients

目的探讨肝移植后乙型病毒性肝炎（简称“乙肝”）复发的临床特点及常见的组织病理学特征。方法回顾分析17例肝移植后乙肝复发患者的临床和组织病理学检查资料。结果乙肝复发时间为肝移植后（21．2±13．2）个月（4-48个月）。12例因乙型肝炎病毒（HBV）DNA出现酪氨酸-蛋氨酸-门冬氨酸-门冬氨酸（YMDD）变异，3例因原发性肝癌（HCC）复发后的化疗，2例因自行停用拉米夫定。12例存在YMDD变异者将拉米夫定替换为恩替卡韦或加用阿德福韦治疗，2例停用拉米夫定者继续应用拉米夫定治疗，3例HCC复发者将拉米夫定替换为恩替卡韦治疗。经抗病毒治疗后，3例分别因纤维淤胆型肝炎所致肝功能衰竭和肿瘤复发而死亡，其余14例肝功能逐渐恢复正常，HBVDNA拷贝均〈10^2IU／ml。乙肝复发后移植肝组织病理特点以肝细胞变性、坏死，以及汇管区炎症和纤维化为主。乙肝复发后随着时间的延长，HBV在肝细胞内的复制增多，急性排斥反应发生次数增加，肝组织纤维化增生，纤维间隔形成，甚至出现假小叶。结论肝移植后乙肝复发时出现纤维化的时间早、进展快，HBV复制水平与肝组织坏死和炎症反应密切相关。尽早发现乙肝复发和有效的抗病毒治疗能显著改善患者预后。

Objective To investigate the clinicopathological characteristics of HBV recurrence after liver transplantation. Methods The retrospective analysis of the clinicopathological changes was performed on 17 patients who had HBV recurrence after liver transplantation in our medical department. Results HBV recurrence happened from 4 to 48 months. Twelve of them which were identified to be YMDD mutation switched to entecavir or added adefovir. Three of them receiving chemotherapy when liver cancer recurred switched to entecavir. Two of them with withdrawal of lamivudine were given lamivudine continuously. Liver function returned to the normal level and HBVDNA was 〈 10^2 U/ml after anti-hepatitis B virus. The histological changes in the transplanted livers included hepatocellular degeneration, necrosis and apoptosis, portal infiltrations and fibrosis. With time after recurrence, it was easier to see hepatitis B virus replication in liver cells, incidence of acute rejection, increases of liver fibrosis and the formation of fibrous septa, even pseudolobule. Conclusion In native HBV infection livers, fibrosis occurs more early and develops rapidly. The number of virus is closely related to liver necrosis and inflammation. Early discovery and change to quick and effective treatment of anti-hepatitis B virus in time can improve greatly the prognosis of the patients.