Postliver transplant allograft reinfection with a lamivudine-resistant strain of hepatitis B virus: long-term follow-up.
Postliver transplant allograft reinfection with a lamivudine-resistant strain of hepatitis B virus: long-term follow-up.
复制标题
肝移植后同种异体移植物再感染乙型肝炎病毒拉米夫定耐药株：长期随访。
DOI：
10.1155/1998/617039
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发表时间：
1998
期刊：
影响因子：
--
通讯作者：
Vincent G. Bain
中科院分区：
文献类型：
--
作者：
E. Yoshida;Mang M. Ma;Jennifer E Davis;K. Fischer;N. Kneteman;S. Erb;D. Tyrrell;Vincent G. Bain
拉米夫定是一种核苷类似物，具有抑制B型肝炎病毒（HBV）复制的功效。在先前报道的研究中，拉米夫定被用于慢性、活跃复制的HBV感染患者，这些患者随后接受了肝移植。患者在移植前接受拉米夫定治疗后血清HBV DNA呈阴性，并在移植后持续。术后即刻存活的4例患者中有2例在移植后240天和409天发生同种异体移植物再感染。分析了再感染病毒的毒株，发现病毒聚合酶的YMDD区域发生突变，从而对拉米夫定产生耐药性。报告了这两例患者的长期随访结果。第一个病人在移植物再感染后16.5个月出现腹水。拉米夫定耐药株出现后18个月进行的经颈静脉肝活检显示肝硬化和小叶性肝炎，无排斥反应。肝静脉楔压和自由压之间的梯度为13 mmHg，符合门静脉高压。第二个病人，在拉米夫定耐药株移植物再感染16个月后，没有门静脉高压的临床证据，尽管肝酶仍然升高。这两名患者都接受了泛昔洛韦的试验，该试验没有显著抑制HBV病毒血症。总之，拉米夫定耐药的HBV YMDD变异株可能具有侵袭性的临床病程，并迅速进展为肝硬化。泛昔洛韦似乎不是这两名患者的有效救援剂。
Lamivudine is a nucleoside analogue with efficacy in the suppression of hepatitis B viral (HBV) replication. In a previously reported study, lamivudine was administered to patients with chronic, actively replicating HBV infection who subsequently underwent liver transplantation. Patients became serum HBV DNA-negative in response to lamivudine before transplantation, which was continued in the post-transplant period. Two of four patients surviving the immediate postoperative period developed allograft reinfection 240 and 409 days post-transplant. The strain of the reinfecting virus was analyzed, and a mutation in the YMDD region of the viral polymerase conferring resistance to lamivudine was discovered. The long term follow-up of these two patients is reported. The first patient developed ascites 16.5 months after allograft reinfection. A transjugular liver biopsy performed 18 months after the emergence of the lamivudine-resistant strain revealed cirrhosis and lobular hepatitis without rejection. The gradient between hepatic vein wedged and free pressures was 13 mmHg, consistent with portal hypertension. The second patient, 16 months after allograft reinfection with the lamivudine-resistant strain, is without clinical evidence of portal hypertension, although liver enzymes remain elevated. Both patients were given a trial of famciclovir, which did not significantly suppress HBV viremia. In conclusion, lamivudine-resistant HBV strains with the YMDD mutation may have an aggressive clinical course with rapid progression to cirrhosis. Famciclovir did not appear to be an effective rescue agent in these two patients.