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抗胸腺细胞球蛋白诱导可保护肝脏同种异体移植物免受缺血/再灌注损伤。

Thymoglobulin induction protects liver allografts from ischemia/reperfusion injury.

作者信息

Bogetti Diego, Sankary Howard N, Jarzembowski Tomasz M, Manzelli Antonio, Knight Peter S, Thielke James, Chejfec Gregorio, Cotler Scott, Oberholzer Jose, Testa Giuliano, Benedetti Enrico

机构信息

Division of Transplantation, Department of Surgery, University of Illinois Medical Center at Chicago, Chicago, IL 60612, USA.

出版信息

Clin Transplant. 2005 Aug;19(4):507-11. doi: 10.1111/j.1399-0012.2005.00375.x.

Abstract

BACKGROUND

Interventions that minimize hepatic ischemia/reperfusion injury (IRI) can expand the donor organ pool. Thymoglobulin (TG) induction therapy has been shown to ameliorate delayed graft function and possibly decrease IRI in cadaver renal transplants recipients. This controlled randomized trial was designated to assess the ability of TG to protect against IRI in liver transplant recipients.

PATIENTS AND METHODS

Twenty-two cadaveric liver transplant recipients were randomized to receive either TG (1.5 mg/kg/dose) during the anhepatic period and QOD x2 doses or no TG. No differences in recipients' demographics were present and donor characteristics were similar in terms of age, cause of death, and cold ischemia time. Maintenance immunosupression consisted of Tacrolimus (or Cyclosporine) and steroids for both groups. Donor biopsies were obtained during organ procurement, cold storage and 1 h after re-vascularization. Post-operative liver function tests were monitored. Early graft function, length of stay, patient and graft survival rates, incidence of primary non-function and rate of rejection were assessed.

RESULTS

Patient and graft survival at 3 months was 100%. There was no incidence of primary graft non-function and no need for re-transplantation. The incidence of acute rejection was similar between the two groups. Patients in the TG group had significant decreases in alanine aminotransferase test at day 1 compared to the control group (p = 0.02). There were also near significant decreases of total bilirubin at day 5 and shorter length of hospitalization. Liver biopsy (at procurement, when cold, and post-reperfusion) of TG group demonstrated a trend for increased central ballooning.

CONCLUSION

The TG allowed for more compromised liver grafts to be transplanted with less clinical evidence of IRI and improved function. Further studies on the degree of apoptosis in the liver biopsy post-reperfusion are underway.

摘要

背景

将肝缺血/再灌注损伤(IRI)降至最低的干预措施可扩大供体器官库。抗胸腺细胞球蛋白(TG)诱导疗法已被证明可改善尸体肾移植受者的移植肾功能延迟,并可能降低IRI。这项对照随机试验旨在评估TG对肝移植受者IRI的保护能力。

患者与方法

22例尸体肝移植受者被随机分为两组,一组在无肝期接受TG(1.5mg/kg/剂量),隔日给药2次,另一组不接受TG。两组受者的人口统计学特征无差异,供体特征在年龄、死亡原因和冷缺血时间方面相似。两组维持免疫抑制均采用他克莫司(或环孢素)和类固醇。在器官获取、冷保存和再灌注1小时后获取供体活检标本。监测术后肝功能检查。评估早期移植肝功能、住院时间、患者和移植物存活率、原发性无功能发生率和排斥反应率。

结果

3个月时患者和移植物存活率均为100%。无原发性移植物无功能发生,无需再次移植。两组急性排斥反应发生率相似。与对照组相比,TG组患者在术后第1天的丙氨酸转氨酶检测值显著降低(p=0.02)。术后第5天总胆红素也有近乎显著的降低,住院时间缩短。TG组肝活检(获取时、冷保存时和再灌注后)显示中央气球样变增加的趋势。

结论

TG使更多功能受损的肝移植物得以移植,且IRI的临床证据减少,功能改善。关于再灌注后肝活检中凋亡程度的进一步研究正在进行中。

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