YMDD变异患者肝移植术后乙型肝炎病毒再感染的防治(附14例报告)

Prophylaxis of hepatitis B virus reinfection post-transplantation in patients with lamivudine-resistant YMDD mutant:14 cases report

目的探讨YMDD变异受者肝移植术后乙型肝炎病毒(HBV)再感染的防治策略及效果。方法回顾性分析14例在肝移植前伴有YMDD变异的HBV感染相关疾病受者的临床资料,14例受者在接受肝移植后,使用小剂量肌内注射乙型肝炎人免疫球蛋白(HBIG)联合阿德福韦预防术后HBV再感染。结果14例YMDD变异患者平均随访43.2个月,2例死亡,均与HBV再感染无关;移植术后血清中HBsAg和HBV-DNA平均转阴时间为12 d(3～21 d);2例患者分别于术后11个月和22个月出现HBV再感染,排除停药干扰外,实际再感染率为7%(1/14),HBV再感染后经积极治疗HBV-DNA均转阴,肝功能正常,未见阿德福韦相关肾毒性。术前HBV-DNA≥1.0×106copies/ml者术后再感染率高于术前HBV-DNA<1.0×106copies/ml者,但比较差异无统计学意义(P>0.05)。结论小剂量HBIG联合阿德福韦可安全有效地预防YMDD变异患者肝移植术后HBV再感染。

Objective To evaluate the prophylactic efficacy of adefovir （ADV） plus hepatitis B immunoglobulin （HBIG） in patients with YMDD mutant after liver transplantation. Methods From January 2004 to January 2008, fourteen patients with HBV-related end-stage liver disease had lamivudine-resistant YMDD mutants detected before liver transplantation and received treatment with ADV plus additional intramuscular HBIG after transplantation as prophylaxis against hepatitis B virus （HBV） reinfection. Tests for liver function, HBV serology （HBsAg, anti-HBs, HBeAg, anti-HBc, anti-HBe, HBV-DNA） were monitored regularly pre-or post-liver transplantation. Results The median follow-up period of these patients after liver transplantation was 43.2 months. Twelve patients survived and two patients died of hepatocellular carcinoma recurrence and severe pulmonary infection, having nothing to do with HBV reinfection. All the patients experienced a mean seroconversion period of 12 days obtaining serum negative for HBsAg and HBV-DNA. To the end of follow-up, 2 patients presented with HBV reinfection at respectively 11 and 22 month after transplantation and recovered gradually after strengthening therapy. The actual rate of HBV reinfection for patients with YMDD mutant was 7% （1/14）. No ADV-related nephrotoxicity and other side effects occurred throughout the follow-up period. Although a relative higher rate of HBV reinfection was observed in patients with HBV-DNA over 1.0 ×10^6 copies/ml compared with patients with HBV-DNA under 1.0×10^6copies/ml pre-transplantation （P 〉 0. 05 ） , no significant difference was found. Conclusion Low-dose HBIG plus ADV can effectively prevent patients with YMDD mutant pre-transplantation from HBV reinfection after liver transplantation.