乙型肝炎患者肝移植后抗病毒治疗的远期效果分析

An analysis of long term prophylaxis of virus recurrence with antiviral treatment in HBV infected liver transplant recipient patients

目的通过观察乙型肝炎相关肝移植受体在拉米夫定或（和）乙型肝炎免疫球蛋白预防性用药时,体内HBV标志物的变化,探讨预防复发及个体优化治疗措施。方法ELISA法、HBV DNA荧光定量PCR、免疫组织化学法定期检测术前及术后各时期血清及肝穿刺组织中的HBV标志物,回顾性观察96例受体术后HBV标志物在随访中的动态变化。结果术后最长7年随访时间内共有17例（17.71%）乙型肝炎复发患者。2年乙型肝炎实际总体复发率为22.0%,术前病毒复制状态对术后乙型肝炎复发有影响（P〈0.05）;82.4%（14/17）乙型肝炎复发者发生在术后3年内,是3年后复发人数的4.7倍（P〈0.01）;3年内复发者中,术前为HBV活跃复制者占78.6%（11/14）。抗-HBc和抗-HBe检出率随时间下降,但仍长期存在。结论术后乙型肝炎复发依然存在。对于术前非HBV活跃复制受体,在术后严格联合预防用药且有补救方案前提下,以术后3年作为时间尺度来尝试停用或降低乙型肝炎免疫球蛋白用量,从而建立一套不同病毒及免疫状态下的个体用药方案值得进一步研究。

Objectives No optimal prophylactic protocol of hepatitis B immunoglobulin （HBIG） combined with nucleos（t）ide analogue for HBV recurrence has been established yet. By investigating the alterations of HBV markers in HBV related liver disease patients, recipients of a liver transplant, under lamivudine or/and HBIG prophylaxis, we aim to explore the possible HBV recurrence mechanism involved and to find a new option in the prophylaxis of HBV recurrence and to tailor individualized therapy. Methods Serial liver biopsy specimens and sera were obtained intraoperationally and at definite time points during follow-up. ELISA and chemiluminescent microparticle immunoassay, HBV DNA fluorescent quantification, immunohistochemistry staining and HBV DNA in situ hybridization were performed. Alterations of HBV markers in specimens of 96 liver transplant recipients were investigated retrospectively. Results All 17 cases had HBV recurrence （median 37 months） which occurred in the follow-up period after liver transplantation. The overall actual HBV recurrence rate at 2 years was 22% with a significant difference between that of the active and inactive groups （P 〈 0.05）; 82.4% HBV recurrence took place within the first 3 years after the operation, and the recurrence ratio of first 3 years to 3 years later after transplantation was 4.7 （P 〈 0.01）. The HBV DNA positive patients accounted for 78.6% of the total number of recurrences within the first 3 years.HBcAb and HBeAb positive rates went down with time, but their positivity remained. Conclusion HBV recurrence happens after liver transplantation. In inactive HBV replicative patients with strictly combined prophylaxis and availability of other medications and using 3 years after liver transplantation as a point of time, we think that tapering down the dosage of HBIG and tailoring individualized treatment methods based on virological and immunological situations of each recipient are worth trying.