拉米夫定预防和治疗肾移植受者乙型肝炎复发的临床观察

Prevention and treatment of HBV recurrence with lamivudine in HBsAg positive renal allograft recipients

目的探讨拉米夫定预防和治疗肾移植患者乙型肝炎复发的效果。方法28例肾功能衰竭患者,肾移植术前乙型肝炎表面抗原(HBsAg)阳性,其中8例乙型肝炎病毒(HBV)DNA阳性,术前患者的肝功能正常,无肝脏纤维化。供者HBsAg均为阴性。20例接受拉米夫定预防性治疗,其中14例术前HBV DNA阴性者术后即刻接受拉米夫定治疗,6例HBV DNA阳性者术前即接受拉米夫定治疗;8例于肾移植术后出现肝功能异常时开始拉米夫定治疗。拉米夫定均为口服给药,起始量为100 mg/d。结果28例患者术后随访13～54个月,平均23.6个月,2例死亡。20例预防性用药者中,仅3例术前用药者术后9.3个月出现HBV DNA滴度增高,合并轻度肝功能异常,丙氨酸转氨酶(ALT)的平均峰值为87.5 U/L,拉米夫定治疗后肝功能恢复正常,HBV DNA转阴;另外17例治疗期间HBV DNA阴性,肝功能正常。未预防用药的8例,术后4.6个月时HBV DNA转为阳性(或HBV DNA滴度明显升高),肝功能异常,ALT的平均峰值为174.5 U/L,给予拉米夫定后,肝功能恢复正常,HBV DNA转阴,但有5例在治疗期间HBV DNA反复阳性。在拉米夫定治疗期间,28例患者的血肌酐维持在正常水平,未出现严重的药物不良反应。结论HBsAg阳性的肾移植患者,在出现肝功能异常前使用拉米夫定,对于预防乙型肝炎复发是安全、有效的。

Objective To analyze the effect of prevention and treatment with lamivudine in HBsAg positive renal allograft recipients with HBV recurrence. Methods In 28 patients with chronic renal failure whose HBsAg was positive, 8 cases were positive for HBV-DNA positive, All these 28 cases had normal liver function without hepatic cirrhosis before renal transplantation. All donors were negative for HBsAg, Twenty patients received lamivudine prophylactic treatment： 14 cases positive for HBsAg but negative for HBV-DNA before transplantation received lamivudine treatment immediately after transplantation and 6 cases positive for both HBsAg and HBV-DNA received lamidudine treatment before transplantation. Eight patients were treated with lamivudine when their hepatic dysfunction with recurrent HBV antigenemia were developed after transplantation. Lamivudine was orally taken and its initial dosage was 100 mg/day. Results The follow-up period of the 28 patients were 13- 54 months with the average of 23. 6 months, and 2 died during this period. Mild hepatic dysfunction with recurrent HBV antigenemia developed in 3 of 20 hepatitis antigenemia patients received lamivudine prophylactic treatment with a mean duration of 9. 3 months after transplantation. The highest average level of serum ALT was 87. 5 U/L. The liver function returned to the normal with HBV-DNA negative after lamivudlne treatment in 3 patients. The other 17 patients maintained normal liver function with HBV-DNA negative during the follow-up period. Hepatic dysfunction with recurrent HBV antlgenemia （or HBV-DNA titer increased significantly） developed with a mean duration of 4. 6 months in all 8 patients without receiving lamivudine prophylactic treatment. The highest average level of serum ALT was 174. 5 U/L. The liver function returned to the normal with HBV-DNA negative after larnivudine treatment in the 8 cases. HBV-DNA, however, reappeared in 5 cases without any discontinuation of lamivudine. The creatinine level remained normal without any severe drug side effects in 28 patients during lamivudlne treatment. Conclusion Lamivudine treatment before hepatic dysfunction might be a safe and effective strategy for prevention of recurrence of hepatitis B viremia in HBsAgpositive renal allograft recipients.