YMDD变异受体肝移植术后乙型肝炎病毒再感染的预防

Post-transplant prophylaxis of the recurrence of lamivudine-resistant YMDD mutant hepatitis B virus in liver recipients

目的探讨YMDD变异受体肝移植术后乙型肝炎病毒(HBV)再感染的预防方法。方法2004年3月～2006年5月本中心20例术前合并YMDD变异的肝移植受体给予口服阿德福韦酯(ADV)联合肌肉注射乙肝免疫球蛋白(HBIG)作为预防方案,持续监测术前及术后的移植肝功能、血清HBV标志物、HBV-DNA定量、血肌酐等。结果患者术后平均随访33.5个月,除1例死于肝癌复发外,其余患者均存活。术前HBV-DNA≥106copies/ml患者YMDD变异率为12.4%,HBV-DNA<106 copies/ml患者为2.5%,两组间差异有统计学意义(P<0.05)。95.0%(19/20)的患者于肝移植术后4周内HBV-DNA转阴性,5.0%(1/20)于术后6个月转阴性。此后长期复查HBsAg、HBeAg、HBV-DNA均阴性,所有患者均未出现HBV再感染。1例患者在服用ADV1年后出现血肌酐水平持续增高。结论应用ADV可有效预防YMDD变异受体肝移植术后HBV再感染。ADV有较低的肾毒性,用药期间仍需定期监测肾功能。

Objective To evaluate the prophylactic efficacy of adefovir dipivoxil （ADV） for post-transplant recurrence of hepatitis B virus （HBV） with lamivudine-resistant YMDD mutation in liver recipients. Methods From March 2004 to May 2006, 20 patients with chronic hepatitis B associated with YMDD mutant HBV prior to liver transplantation received treatment with ADV and additional intramuscular hepatitis B immunoglobulin （HBIG） for prevention of post-transplant graft reinfection. The liver function, serum HBsAg, anti-HBs （HBIG）, HBeAg, anti-HBc, anti-HBe, HBV DNA and creatinine were examined in all the patients before and after the transplantation. Results The median follow-up duration of these patients after the transplantation was 33.5 months. Nineteen patients survived and one patient died of recurrent hepatocellular carcinoma. There was significant difference in YMDD mutation rate between the patients with HBV-DNA over 106 copies/ml and those with HBV-DNA less than 106 copies/ml （12.4% vs 2.5%, P〈0.05）. HBV-DNA was undetectable at 4 weeks after the transplantation in 95.0% of the patients （19/20） and at 6 months in one case. No recurrence of hepatitis B was detected by long-term regular testing of HBsAg, HBeAg and HBV-DNA. Serum creatinine increased in 1 case 1 year after the use of ADV. Conclusion ADV offers protection against recurrence of HBV with YMDD mutation after liver transplantation with only mild nephrotoxicity, but renal function monitoring during the use of ADV is still necessary.