Gruessner R W, Nakhleh R E, Benedetti E, Pirenne J, Belani K G, Beebe D, Carr R, Troppmann C, Gruessner A C
Department of Surgery, University of Minnesota, Minneapolis, USA.
Arch Surg. 1997 Oct;132(10):1077-85. doi: 10.1001/archsurg.1997.01430340031004.
Rejection remains a major obstacle to successful bowel transplantation in humans. It has been suggested that a simultaneous liver transplant would shield the bowel graft from immunologic attack, but the liver shortage would be aggravated. In a preclinical model, we studied the influence of simultaneous liver grafting by comparing the incidence of early bowel rejection after combined liver-total (small- and large-) bowel transplants vs total bowel transplants alone.
We assessed the incidence of early post-transplant rejection, graft-vs-host disease, and infection after combined liver-total bowel transplants (group 1, n = 10) and total bowel transplants alone (group 2, n = 9) in outbred Yorkshire Landrace pigs. Liver and bowel grafts were transplanted orthotopically with portal vein drainage after recipient hepatectomy (group 1) and total enterectomy (groups 1 and 2). Posttransplant immunosuppression was performed with intravenous tacrolimus (whole blood levels, 15 to 30 ng/mL) and prednisolone. In groups 1 and 2, bowel biopsy specimens from the ileostomy were obtained daily. In group 1, liver biopsy specimens were obtained weekly. Rejection was graded according to a 4-point scoring system (none, mild, moderate, and severe).
Overall graft survival at days 7, 14, and 21 was 89%, 44%, and 11%, respectively, in group 1 vs 100%, 100%, and 86%, respectively, in group 2 (P < .001). Death rates owing to (irreversible) rejection at days 7, 14, and 21 were 0% in groups 1 and 2 (P = .48). Grading of bowel rejection episodes, based on the results of daily biopsy specimens, was not significantly different between the groups whether on individual days or overall. In group 1, the incidence of liver rejection episodes was as high as 66% (day 14 and at autopsy). At autopsy, generalized graft-vs-host disease (skin, native intestine, and native liver) was noted in 55% of group 1 and 43% of group 2 pigs (P = .55). Graft-vs-host disease was noted concurrently with rejection episodes of the liver or bowel grafts.
Simultaneous liver grafting did not further reduce the incidence of early bowel rejection or graft-vs-host disease when compared with total bowel transplants alone. Based on the results of this preclinical study, simultaneous liver grafting is not indicated for patients with short-bowel syndrome and normal liver function.
排斥反应仍然是人类肠道移植成功的主要障碍。有人提出同时进行肝脏移植可以保护肠道移植物免受免疫攻击，但肝脏短缺问题会加剧。在一个临床前模型中，我们通过比较肝-全（小肠和大肠）肠联合移植与单纯全肠移植后早期肠道排斥反应的发生率，研究了同时进行肝脏移植的影响。
我们评估了杂种约克郡大白猪在接受肝-全肠联合移植（第1组，n = 10）和单纯全肠移植（第2组，n = 9）后移植后早期排斥反应、移植物抗宿主病和感染的发生率。在受体肝切除术后（第1组）和全肠切除术后（第1组和第2组），将肝脏和肠道移植物原位移植并采用门静脉引流。移植后采用静脉注射他克莫司（全血水平为15至30 ng/mL）和泼尼松龙进行免疫抑制。在第1组和第2组中，每天从回肠造口处获取肠道活检标本。在第1组中，每周获取肝脏活检标本。根据4分评分系统（无、轻度、中度和重度）对排斥反应进行分级。
第1组在第7、14和21天的总体移植物存活率分别为89%、44%和11%，而第2组分别为100%、100%和86%（P <.001）。第1组和第2组在第7、14和21天因（不可逆）排斥反应导致的死亡率均为0%（P =.48）。根据每日活检标本结果对肠道排斥反应发作进行分级，无论是在个别天数还是总体上，两组之间均无显著差异。在第1组中，肝脏排斥反应发作的发生率高达66%（第14天和尸检时）。尸检时，第1组55%的猪和第2组43%的猪出现全身性移植物抗宿主病（皮肤、自体肠道和自体肝脏）（P =.55）。移植物抗宿主病与肝脏或肠道移植物的排斥反应发作同时出现。
与单纯全肠移植相比，同时进行肝脏移植并没有进一步降低早期肠道排斥反应或移植物抗宿主病的发生率。基于这项临床前研究的结果，对于短肠综合征且肝功能正常的患者，不建议同时进行肝脏移植。
