Lu Shi-Chun, Yan Lu-Nan, Li Bo, Wen Tian-Fu, Zhao Ji-Chun, Cheng Nan-Sheng, Liu Chong, Liu Jun, Wang Xiao-Bo, Li Xiao-Dong, Qin Shan, Zhao Lian-Shan, Lei Bin-Jun, Zhang Xiu-Hui
Department of General Surgery, West China Hospital, Sichuan University, Chengdu 610041, China.
Hepatobiliary Pancreat Dis Int. 2004 Feb;3(1):26-32.
Liver allograft hepatitis B virus (HBV) reinfection and hepatitis B (HB) recurrence jeopardize the long-term survival of recipient and liver allograft. Lamivudine has been referred as a novel antiviral agent against HBV in HBV cirrhotic patients even in liver transplantation setting. We assessed the prophylatic effect of lamivudine on liver allograft HBV reinfection and clarified the dynamic changes of HBV markers in HBV related decompensated liver cirrhosis after liver transplantation.
Twenty-five recipients were divided into three groups: HBV active replication group (15 recipients), HBV inactive replication group (7), and control group (3). 100 mg/d lamivudine was administered preoperatively except in the control group. The HBV markers of serial sera and liver biopsy samples of the 25 recipients were evaluated regularly with enzyme-linked radioimmunoassay, HBV DNA fluorescent quantitative assay, immunohistochemical staining, labelled streptavidin biotin (LSAB) and digoxin labelled HBV DNA hybridization in situ. The dynamic alternation of HBV markers under lamivudine prophylaxis was observed.
In the HBV active replication group who had received lamivudine 2 weeks before liver transplantation, serum HBV DNA positive converted to negative by 80%. HBsAg of all recipients disappeared after liver transplantation, but corresponding antibodies of HBV appeared within one week after the operation. HBsAb 9/15, HBcAb 13/15 and HBeAb 11/15 appeared and subsided gradually within 24 weeks. HBV DNA in sera was kept negative; HBsAg, HBcAg and HBV DNA hybridization in situ of liver biopsy samples remained negative after use of lamivudine. Ten of the 15 recipients showed clearance of HBV, and per se HBV markers were undetectable both in serum and liver biopsy samples between 12 to 44 weeks (24 weeks on average). The 1-, 2-year survival rates were 83% in this group. Two of the 15 recipients developed HBV allograft reinfection or recurrence of hepatitis 2 years after lamivudine monoprophylaxis (2/15, 13.3%). In the HBV inactive replication group, the outcome was similar to that of the HBV active group. The HBV antibody frequency was HBsAb 4/7, HBcAb 6/7, and HBeAb 2/7. Three of 7 recipients showed HBV clearance both in sera and liver biopsy samples, whereas in the control group all 3 recipients developed HBV allograft reinfection and recurrent hepatitis 8, 10, 12 months postoperatively; one of them died of fibrosing cholestatic hepatitis, and the remaining 2 recovered after additional lamivudine therapy. The overall allograft reinfection rate was 9.1% (2/22) and the overall 1-, 2-year survival rates were 87% in the lamivudine prophylaxis group.
Lamivudine prophylaxis can prevent effectively liver allograft from HBV reinfection in patients with HBV-related decompensated liver cirrhosis even in HBV active replication recipient after liver transplantation. Its long-term outcome remains to be studied.
肝移植受者的乙肝病毒（HBV）再感染和乙肝（HB）复发会危及受者及移植肝的长期存活。拉米夫定在HBV肝硬化患者甚至肝移植患者中被视为一种新型抗HBV病毒药物。我们评估了拉米夫定对移植肝HBV再感染的预防作用，并阐明了肝移植术后HBV相关失代偿性肝硬化患者HBV标志物的动态变化。
25例受者分为三组：HBV活跃复制组（15例受者）、HBV非活跃复制组（7例）和对照组（3例）。除对照组外，术前给予100mg/d拉米夫定。采用酶联放射免疫法、HBV DNA荧光定量检测、免疫组织化学染色、链霉亲和素生物素标记法（LSAB）及地高辛标记HBV DNA原位杂交技术，定期检测25例受者系列血清及肝活检组织样本中的HBV标志物，观察拉米夫定预防下HBV标志物的动态变化。
在肝移植前2周接受拉米夫定治疗的HBV活跃复制组中，80%的患者血清HBV DNA由阳性转为阴性。所有受者的HBsAg在肝移植后消失，但术后1周内出现相应的HBV抗体。9/15出现HBsAb、13/15出现HBcAb、11/15出现HBeAb，并在24周内逐渐消退。血清HBV DNA持续阴性；肝活检组织样本经拉米夫定治疗后，HBsAg、HBcAg及HBV DNA原位杂交均为阴性。15例受者中有10例HBV清除，血清及肝活检组织样本在12至44周（平均24周）内均未检测到HBV自身标志物。该组1年、2年生存率为83%。15例受者中有2例在拉米夫定单药预防2年后发生移植肝HBV再感染或肝炎复发（2/15，13.3%）。HBV非活跃复制组的结果与HBV活跃组相似。HBV抗体出现频率为：HBsAb 4/7、HBcAb 6/7、HBeAb 2/7。7例受者中有3例血清及肝活检组织样本HBV清除，而对照组3例受者均在术后8、10、12个月发生移植肝HBV再感染及肝炎复发；其中1例死于纤维淤胆型肝炎，另外2例在加用拉米夫定治疗后康复。拉米夫定预防组移植肝总体再感染率为9.1%（2/22），1年、2年总体生存率为87%。
拉米夫定预防可有效防止HBV相关失代偿性肝硬化患者移植肝发生HBV再感染，即使是肝移植后HBV活跃复制的受者。其长期疗效仍有待研究。
