很多国家的移植中心对肝移植后胆道疾病的发病率都有研究，报告称10%--30%的患者在肝移植后出现了胆道并发症。在长期随访过程中发现，胆道疾病常常表现为肝酶升高，这可能会被误认为是肝炎感染复发或药物毒性。如果怀疑是胆道疾病晚期，就需要通过ERCP或PTC获得的胆管造影照片来加以证实。在这种情况下，MR胆管造影照是很有用的，可以避免进行创伤性手术。

  胆道并发症在很长一段时间内都有可能发生；但是，并发症的类型会随着时间的推移出现不同的复发特征。胆漏可能发生在手术过后的一段时期或移植后最初的3个月内；胆管狭窄在术后数月乃至数年内都有可能发生；胆道结石在移植若干年后都有可能出现。胆漏预示着正在逐步发生胆管狭窄，而胆管狭窄则表明疾病正在向胆道结石的方向发展。因此我们可以相信，胆道并发症是由围手术期事件或术后即时事件造成的。造成这种现象的原因可能是肝外胆道复杂的血管供应以及肝切除术和胆道切面对胆管供血量的影响。胆总管和肝管具有双重供血系统。胆管所需的血液大约60%是由十二指肠血管结构供应的，余下的则由肝右动脉供应。因此肝移植后的胆管完全依赖于肝动脉血流，肝动脉血栓形成就会造成缺血性胆管狭窄。此外，在肝切除术和胆道切面过程中造成的血液供应不足会导致吻合口容易出现坏死或泄露。因此我们相信患者在移植后长时期内都容易感染胆道并发症。

  胆结石：这种并发症在肝移植手术若干年后发生。胆道铸型综合征和胆汁淤积是公认的肝移植术后并发症，容易发生在肝脏缺血和胆管狭窄的情况下。生化分析显示出两种不同的胆道铸型综合征：一种的主要成分是胶原蛋白，另一种则为胆红素。ERCP可以成功治疗胆结石。

  接受无心跳供体（NHBD）脏器的患者会发生胆道疾病。这种移植用的脏器一般在心脏停止跳动后大约45分钟时取出，因此肝脏在保存过程中受到损伤，同时也会导致胆管坏死。

  肝动脉血栓形成是最可怕的一种肝移植术后并发症，会导致肝小叶广泛坏死、肝梗死和胆管狭窄。肝动脉血栓形成会引起多种肝内和肝外胆管狭窄，这些广泛而多发性的损害通常不适合放射学疗法或内窥镜干预治疗。

  对于尸体肝移植患者来说，男性、环孢素疗法、急性细胞排斥反应和肝动脉血栓形成四个因素能够预示胆道并发症的发生。环孢素能直接抑制胆汁酸生成和胆汁流动，因此证实了肝移植术后胆结石的发展与环孢素有一定的关系。急性细胞排斥是一种主要针对血管内皮细胞和胆管上皮细胞的免疫攻击行为。细胞免疫和体液免疫都与胆道损伤有联系，而胆道损伤会导致狭窄形成。因此胆道疾病与急性细胞排斥的联系，可能代表与移植术后胆道疾病病原学之间的另一种因果关系。另外还有研究发现，急性细胞排斥不是形成胆管狭窄的关键因素；但是，患者中胆管消失性狭窄和移植物ABO血型不符，二者均与胆管狭窄的形成有关。

Diliary Disease After Liver Transplantation

A number of transplant centers from different countries have studied the incidence of biliary disease after liver transplantation and reported biliary complications to occur in 10–30% of patients with liver transplantation. In the long-term follow up, biliary disease usually manifests as elevated liver enzymes and this may be mistaken for recurrence of Hepatitis infection or drug toxicity. Later biliary disease, if suspected, needs to be confirmed by obtaining a cholangiogram at ERCP or PTC. MR cholangiograms to be useful in such situations and may avoid the need for an invasive procedure.

Biliary complications occurred over a wide period of time; however, the type of complications had a pattern of occurrence over time. Bile leaks occurred in the postoperative period or in the first 3 months after transplantation. Biliary strictures presented months to years after transplantation and biliary calculi developed many years after transplantation. Bile leaks were a high predictor for the development of strictures and strictures were a high predictor for the development of calculi. This made us believe that most, if not all, biliary complications were caused by events in the perioperative or immediate postoperative period. One possible reason for this may be the complex vascular supply of the extrahepatic bile ducts and the effect of hepatectomy and transection of the bile ducts on the blood supply of the bile duct. The common bile and hepatic duct has a dual blood supply. The paraduodenal vasculature, which originates from below the duct and becomes disrupted during harvesting, supplies approximately 60% of the blood to the bile ducts and the rest is supplied by the right hepatic artery. Thus, after liver transplantation, the bile ducts are solely dependent upon the hepatic artery blood flow and hepatic artery thrombosis can cause ischemic bile duct strictures. In addition, the loss of a major source of blood supply during hepatectomy and transection of the bile ducts can leave the anastomotic site prone to necrosis and leaks. This we believe predisposes for the occurrence of biliary complications in the long term.

Biliary calculi . This complication occurred many years after the liver transplant. Biliary casts and sludge following liver transplantation are well-recognized complications and are likely to develop in the setting of hepatic ischemia and biliary strictures. Biochemical analyses have revealed two different forms of bile casts: one mainly composed of collagen and other mainly composed of bilirubin.Biliary calculi can be managed successfully at ERCP.

patients with grafts from NHBD developed biliary disease. Such grafts were harvested after a non-heart beating time period of approximately 45 min, and this may cause significant preservation injury to the liver and also lead to bile duct necrosis.

Hepatic artery thrombosis is one of the most dreaded complications of liver transplant and can cause massive hepatic necrosis, hepatic infarcts and biliary strictures. Hepatic artery thrombosis causes multiple intrahepatic and extrahepatic biliary strictures and these extensive and multiple lesions are not usually amenable to radiologic or endoscopic intervention.

There are four factors, namely male sex, cyclosporine therapy, acute cellular rejection and hepatic artery thrombosis, that significantly predicted the occurrence of biliary complications in cadaveric liver transplant patients. Cyclosporine has been implicated in the development of biliary calculi after liver transplantation by causing direct inhibition of bile acid production and bile flow as demonstrated in animals. Acute cellular rejection is an immunologic attack primarily directed at the vascular endothelium and the bile duct epithelium. Both cellular and humoral immune mechanisms have been implicated in the development of biliary injury leading to stricture formation. Thus the association of biliary disease with acute cellular rejection may represent another causative link to the etiology of biliary disease after transplantation. Others have found that acute cellular rejection is not a critical component in the formation of biliary strictures; however, patients with ductopenic rejection and ABO incompatible grafts are associated with the formation of biliary stricture.

[责任编辑:刘 聪]