Yoshida E M, Ma M M, Davis J E, Fischer K P, Kneteman N M, Erb S R, Tyrrell D L, Bain V G
Department of Medicine, University of British Columbia.
Can J Gastroenterol. 1998 Mar;12(2):125-9. doi: 10.1155/1998/617039.
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.
拉米夫定是一种核苷类似物，对抑制乙型肝炎病毒（HBV）复制有效。在先前报道的一项研究中，对慢性、HBV活跃复制感染且随后接受肝移植的患者给予拉米夫定治疗。患者在移植前因拉米夫定治疗而血清HBV DNA转阴，并在移植后继续使用该药物。术后即刻存活的4例患者中有2例在移植后240天和409天发生了移植肝再感染。对再感染病毒的毒株进行了分析，发现病毒聚合酶的YMDD区域发生了突变，导致对拉米夫定耐药。本文报道了这2例患者的长期随访情况。首例患者在移植肝再感染16.5个月后出现腹水。在拉米夫定耐药毒株出现18个月后进行的经颈静脉肝活检显示为肝硬化和小叶性肝炎，无排斥反应。肝静脉楔压与自由压之间的梯度为13 mmHg，符合门静脉高压。第二例患者在移植肝被拉米夫定耐药毒株再感染16个月后，虽肝酶仍升高，但无门静脉高压的临床证据。对这2例患者均试用了泛昔洛韦，但未显著抑制HBV病毒血症。总之，具有YMDD突变的拉米夫定耐药HBV毒株可能具有侵袭性临床病程，可迅速进展为肝硬化。泛昔洛韦在这2例患者中似乎不是一种有效的补救药物。
