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目的研究恩替卡韦对乙型肝炎相关性终末期肝病患者肝移植术后血清及外周血单个核细胞(PBMC)内HBV DNA的抑制作用。方法选取从2007年8~12月的20例HBsAg阳性肝移植受者作为研究对象(围手术期组),给予口服恩替卡韦每天0.5 mg联合肌注乙肝免疫球蛋白作为HBV再感染的预防方案,分别于术前1 d和术后1、4、12周采用实时荧光定量PCR法检测血清及PBMC内HBV DNA定量。同时回顾性分析2006年8月至2007年8月共34例行同种异体原位肝移植,术后长期使用恩替卡韦联合肌注乙肝免疫球蛋白的患者(随访组),随访时间4.0~22.5个月,同样的方法检测血清及PBMC内HBV DNA定量。结果20例受者血清HBV DNA在恩替卡韦治疗12周时全部转阴。术前1 d和术后1、4、12周PBMC内HBV DNA阳性率分别为85.0%(17/20)和45.0%(9/20)、45.0%(9/20)、40.0%(8/20),术后1周与术前比较差异有统计学意义(P=0.004),但1周以后阳性率无显著变化;围手术期PBMC内HBV DNA定量均值分别为104.07±2.07和101.69±1.96、101.51±1.72、101.30±1.63拷贝/106细胞,同样术后1周与术前比较差异有统计学意义(P=0.01),但随术后时间的延长,下降趋缓,术后4周后定量值的下降差异无统计学意义(P>0.05)。随访组平均随访13.6个月,均未发现HBV再感染(血清HBV DNA均阴性),PBMC内HBVDNA阳性率为32.4%(11/34),定量均值101.03±0.26拷贝/106细胞。结论恩替卡韦对肝移植术后血清及PBMC内HBVDNA均具有较好的抑制效果,但PBMC内HBVDNA下降趋势在术后4周后即维持在相对稳定状态,不能完全被清除。
Objective To investigate the inhibitory effect of entecavir on HBV DNA in serum and peripheral blood mononuclear cells (PBMC) after liver transplantation in patients with hepatitis B-related end-stage liver disease. Methods Twenty HBsAg-positive liver transplant recipients from August 2007 to December 2007 were enrolled in this study. Perioperative patients were enrolled in this study. 0.5 mg of entecavir combined with intramuscular injection of hepatitis B immunoglobulin was given as a prophylactic regimen of HBV reinfection. HBV DNA levels in serum and PBMCs were detected by real-time fluorescence quantitative PCR at 1 day before operation and 1, 4, 12 weeks after operation. At the same time, a retrospective analysis of 34 patients with allograft orthotopic liver transplantation from August 2006 to August 2007 after long-term use of entecavir in combination with intramuscular injection of hepatitis B immunoglobulin (follow-up group) was performed. The follow-up time ranged from 4.0 to 22.5 Month, the same method to detect HBV DNA in serum and PBMC quantitative. Results Serum HBV DNA of 20 patients were all negative after 12 weeks of entecavir treatment. The positive rates of HBV DNA in peripheral blood mononuclear cells were 85.0% (17/20) and 45.0% (9/20), 45.0% (9/20) and 40.0% (8 / 20). There was significant difference between preoperative and postoperative one week (P = 0.004), but there was no significant difference in the positive rate after one week. The quantitative average of HBV DNA in perioperative PBMC was 104.07 ± 2.07 and 101.69 ± 1.96 , 101.51 ± 1.72 and 101.30 ± 1.63 copies / 106 cells, respectively. There was also a statistically significant difference between preoperative 1 week and preoperative one (P = 0.01), but with the extension of postoperative time, the decline slowed down. After 4 weeks There was no significant difference in the decrease of the quantitative value (P> 0.05). Follow-up group was followed up for an average of 13.6 months. No HBV re-infection was found (serum HBV DNA was negative). The positive rate of HBVDNA in PBMC was 32.4% (11/34) and the average value was 101.03 ± 0.26 copies / 106 cells. Conclusion Entecavir has a good inhibitory effect on HBVDNA in serum and PBMC after liver transplantation. However, the trend of decrease of HBVDNA in PBMC is relatively stable after 4 weeks and can not be completely eliminated.