肝移植术后胆道并发症的治疗

目的 探讨处理原位肝移植术后胆道并发症的有效方法.方法 叫顺性分析2001年1 1月至2012年3月南京军区福州总医院收治的316例原位肝移植（其中1例施行二次肝移植）患者的临床资料.供肝获取时采用HTK＋ UW液冷灌注,UW液保存,切取供肝后UW液灌洗胆道.尸体肝移植中采用经典原位肝移植或背驮式肝移植,活体肝移植采用左半肝移植或右半肝移植.胆道重建方式采用胆管空肠Roux-en-Y吻合或胆管胆管对端吻合.2006年前选用普通T管引流,2006年后选用6F小儿吸痰管或硬膜外导管进行T管引流,术后3～6个月予以拔除.术中常规放置经胃空肠造瘘管,术后早期开始肠内营养.术后常规采用他克莫司＋麦考酚吗乙酯＋肾上腺皮质激素3联免疫抑制治疗方案或他克莫司＋麦考酚吗乙酯＋西罗莫司＋激素4联免疫抑制治疗方案.通过移植随访中心随访2年,了解患者胆道并发症情况、预后和进行用药指导.2006年前50例患者与2006年及之后267例患者胆汁漏发生率的比较采用x2检验.结果 患者供肝热缺血时间为2 ～6 min,冷缺血时间为3～10 h.尸体肝移植患者中,经典肝移植291例次,背驮式肝移植24例次;胆管空肠Roux-en-Y吻合5例次,胆管胆管端端吻合310例次.活体肝移植患者中,左半肝移植和右半肝移植各1例,均采用胆管胆管端端吻合.术后采用3联免疫抑制治疗方案311例,4联免疫抑制治疗方案5例.316例原位肝移植患者中,38例发生胆道并发症.胆道并发症分类：胆汁漏18例,缺血性胆道损伤引起的肝内外胆管狭窄6例,单纯吻合口狭窄6例,保存性损伤所致汇管区小胆管炎症、胆汁淤积4例,胆管结石合并胆管炎2例,单纯胆道感染2例.2006年以前患者胆汁漏发生率为14.00％ （7/50）,高于2006年及以后患者的4.12％ （11/267）,两者比较,差异有统计学意义（x2=7.676,P＜0.05）.38例胆道并发症患者中,治愈及好转35例,死亡3例.18例胆汁漏患者中,15例采用保守治疗后痊愈;3例采用手术治疗（其中1例经通畅引流,加强抗感染、营养支持等处理后好转,但于术后1个月突发腹腔大出血,手术探查发现肝动脉破裂出血,最终死于失血性休克所致MODS;2例行腹腔引流术,1例治愈,1例合并腹腔感染,最终死亡）.6例缺血性胆管损伤引起的肝内外胆管狭窄患者中,1例行二次肝移植后取得良好效果,5例经保守或行ERCP或经PTCD导管球囊扩张术治疗后好转.6例单纯吻合口狭窄患者中,3例经保守或行ERCP或经内镜下柱状气囊扩张、取石、支架置入治疗后好转;1例因肝癌复发放弃治疗后死亡;1例予手术探查,行吻合口成形＋T管引流术效果良好;1例手术探查切除复发肿瘤,行胆肠吻合后痊愈.4例保存性损伤所致汇管区小胆管炎症、胆汁淤积患者采取保肝、减轻黄疸等保守治疗后痊愈.2例胆管结石合并胆管炎患者,1例行ERCP支架置入痊愈;1例经保守治疗后TBil有所下降,未予进一步处理.2例单纯胆道感染患者均经抗感染等保守治疗痊愈.结论 多数患者胆道并发症可经非手术治疗取得满意疗效;而对非手术治疗效果不佳的患者,再次行胆道探查术是较为确实可靠的治疗手段;对于部分严重缺血性胆道损伤导致移植肝失功能的患者,二次肝移植是唯一的选择.

Treatment of biliary complications after liver transplantation

Objective To investigate the effective strategies to prevent and treat biliary complications after orthotopic liver transplantation. Methods The clinical data of 316 patients who received orthotopie liver transplantation at the Fuzhou General Hospital of Nanjing Military Command from November 2001 to March 2012 were retrospectively analyzed. Cold perfusion with HTK ＋ UW solution was applied when obtaining the liver graft, and then the liver graft was preserved in the UW solution. The bile duct was perfused with UW solution thereafter.Orthotopic liver transplantation or piggyback liver transplantation were adopted in the cadaver liver transplantation. Left liver transplantation and right liver transplantation were adopted in the living donor liver transplantation. Choledochojejunal Roux-en-Y anastomosis or duct-to-duct choledochostomy were used for biliary reconstruction. Ordinary T tubes were used for drainage before 2006, and then 6 F pediatric suction catheter or epidural catheter were applied for drainage thereafter. The Ttube was pulled out 3-6 months after the operation. Enteral nutrition was applied to patients at the early phase after operation. The immunosuppressive agents used including tacrolimus ＋ mycophenolatemofetil ＋ adrenal cortical hormone, and for some patients, tacrolimus ＋ mycophenolatemofetil ＋ sirolimus ＋ hormone were used. Patients were followed up for 2 years to learn the incidence of biliary complications and guide the medication. The difference in the incidence of bile leakage between patients who were admitted before 2006 and those admitted after 2006 were compared using the chi-square test. Results The warm ischemia time was 2-6 minutes, and the cold ischemia time was 3-10 hours. For patients who received cadaver liver transplantation, orthotopic liver transplantation was carried out for 291 times and piggyback liver transplantation for 24 times; biliojejunal Roux-en-Y anastomosis was carried out for 5 times and bile duct end-to-end anastomosis for 310 tittles. For patients who received living donor liver transplantation, 1 received left liver transplantation and 1 received right liver transplantation, and they received bile duct end-to-end anastomosis. A total of 311 patients received immunosuppressive treatment with tacrolimus ＋ mycophenolatemofetil ＋ adrenal cortical hormone, and 5 patients reveived tacrolimus ＋ mycophenolatemofetil ＋ sirolimus ＋ hormone. Of the 316 patients who received orthotopic liver transplantation, 38 had biliary complications after the operation, including bile leakage in 18 patients, intra- and extra-hepatic bile duct stricture in 6 patients, anastomotic stricture in 6 patients, biliary complications included cholangitis in the portal area and cholestasis in 4 patients, choledocholithiasis and cholangitis in 2 patients and biliary infection in 2 patients. The incidence of bile leakage before 2006 was 14.00% （7/50）, which was significantly higher than 4. 12% （11/267） of bile leakage after 2006 （X2 = 7. 676, P 〈 0. 05）. Of the 38 patients with biliary complications, the condition of 35 patients was improved, and 3 patients died. Of the 18 patients with bile leakage, 15 was cured by conservative treatment, 3 received surgical treatment （the condition of 1 patient was improved by drainage, anti-infection treatment and nutritional support, but died of peritoneal hemorrhage at postoperative 1 month; 2 patients received peritoneal drainage, 1 was cured and 1 died of peritoneal infection）. For the 6 patients with intra- and extra-hepatic bile duct stricture, 1 was cured by liver retransplantation and 5 were cured by conservative treatment, endoscopic retrograde cholangio-pancreatography （ERCP） or balloon dilation. For the 6 patients with anastomotic stricture, the condition of 3 patients was improved by conservative treatment, balloon dilation or stent implantation, 1 gave up treatment due to hepatic cancer recurrence and died thereafter, 1 received anastomosis ＋ T tube drainage, 1 was cured by recurrent tumor resection and choledochojejunostomy. Four patients with cholangitis in the portal area and cholestasis were cured by conservative treatment. For the 2 patients with choledocholithiasis and cholangitis, 1 was cured by stent implantation with ERCP, and 1 received conservative treatment, and the level of total bilirubin was decreased. Two patients with biliary infection were cured by anti-infection treatment. Conclusions Most of the biliary complications could be treated by non-surgical treatments. For patients with severe biliary complications or those could not be treated by non-surgical treatment, re-exploration of the bile duct is effective. Liver re-transplantation is the only choice for patients with dysfunction of liver graft caused by severe ischemic biliary injury.