核苷类似物联合HBIG干预下肝移植后HBV再感染的危险因素及预后分析
The risk factors and prognosis of hepatitis B virus re-infection after liver transplantation with prophylaxis of combined low-dose hepatitis B immunoglobulin and nucleoside analogues
目的 探讨肝移植术后在核苷类似物联合低剂量乙肝免疫球蛋白(HBIG)的干预下乙型肝炎病毒(HBV)再感染的危险因素及其预后.方法 回顾性分析340例因HBV相关性终末期肝病行肝移植患者的临床资料.所有患者术前即开始给予核苷类似物控制病情,术中和术后均给予核苷类似物联合低剂量HBIG的预防方案.术后对患者进行定期随访,监测患者的HBV再感染发生率、存活率及预后.记录患者性别、年龄、原发病、术前2周HBV DNA水平、HbeAg水平、YMDD变异以及术后免疫抑制剂和核苷类似物使用情况等指标进行单因素分析,将P<0.1的变量纳入COX多因素回归分析,筛选出影响术后HBV再感染的危险因素.结果 340例患者术后发生HBV再感染33例,再感染率为9.7%,再感染时间为术后(8.4±13.2)个月(2~49个月),术后1、3、5年再感染率分别为7.0%、10%、13%.33例患者HBV再感染后均停用HBIG,并调整核苷类似物的用量,除3例HBV DNA定量为3 log10~5 log10拷贝/ml外,其余均控制在3 log10拷贝/ml以下.340例患者术后1、3、5年存活率分别为89%、83%和82%,其中HBV再感染者分别为94%,87%,81%,未再感染者分别为89%,82%,82%,Log-rank检验显示HBV再感染对患者长期存活率无明显影响(P=0.828).经COX多因素回归分析表明,原发病为原发性肝癌(P=0.035)、HBVDNA定量>5 log10拷贝/ml(P<0.001)是发生HBV再感染的危险因素.进一步分层分析显示,原发性肝癌复发后HBV再感染发生率显著高于未复发者,分别为27.9%和8.7%(P=0.001).结论 原发病为原发性肝癌及术前HBV DNA>5 log10拷贝/ml是影响HBV再感染的高危因素.在核苷类似物联合HBIG预防方案的干预下,HBV再感染对预后影响不大.
更多Objective To investigate the risk factors and prognosis of hepatitis B virus (HBV) re-infection after liver transplantation with prophylaxis of combined low-dose hepatitis B immunoglobulin (HBIG) and nucleoside analogues. Methods The clinical data of 340 patients who have underwent liver transplantation for HBV related end-stage liver disease and have received long-term follow-up were retrospectively analyzed. All patients received nucleoside analogues therapy formally before entering into the waiting list And nucleoside analogues combined with low-dose HBIG therapy was prescribed during and after transplantation. Patients were regularly followed up at the outpatient clinic by monitoring the HBV re-infection, survival and prognosis. Univariable analysis was performed to determine whether gender, age, concomitance with HCC, serum positive HBeAg, HBV DNA >5 log10 copies/ml, YMDD mutants or type of nucleoside analogues predicted HBV recurrence. Parameters with P<0. 1 in the univariable analysis were entered into multivariate Cox regression analysis. Results Thirty-three patients suffered from HBV re-infection post transplantation, with the overall re-infection rate being 9. 7 % (33/340). The mean HBV recurrence time was 8. 4 ± 13. 2 months (2~49 months). 1-, 3-, 5-year recurrence rate was 7. 0 %, 10 %, 13 % respectively. HBIG was terminated and the dose of nucleoside analogues was modulated in 33 patients who developed HBV re-infection. Except 3 patients whose HBV DNA was between 3 log10-5 log10 copies/ml, the other patients' HBV DNA was controlled less than 3 log10 copies/ml. The 1 -, 3-, 5- year survival rate of 340 patients was 94 %,87 %,and 81 % respectively. There was no significant difference in the survival rate between re-infection group and control group (94 %,87 %,81 % vs 89 %,82 %,82 %). COX regression analysis revealed that risk factors for HBV re-infection were hepatocellula carcinoma (P = 0.035) and HBV-DNA load over 5 log10 copies/ml (P<0.001). Further stratified analysis showed that patients who suffered from carcinoma recurrence had a higher incidence of HBV recurrence than those who did not, which was 27. 9 % and 8. 7 % respectively (P = 0. 001). Conclusion The risk factors for HBV recurrence are HCC and HBV-DNA load with this combined therapy. HBV recurrence is not the main cause of graft loss and death under the prophylaxis of nucleoside analogues and low-dose HBIG.
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