Biliary complications after deceased-donor orthotopic liver transplantation

A wide range of potential biliary complications can occur after orthotopic liver transplantation (OLT). The most common biliary complications are bile leaks, anastomotic and intrahepatic strictures, stones, and ampullary dyfunction, which may occur in up to 20%-40% of OLT recipients. Leaks predominate in the early posttransplant period; stricture formation typically develops gradually over time. However, with the advent of new techniques, such as split-liver, reduced-size, and living-donor liver transplantation, the spectrum of biliary complications has changed. Risk factors for biliary complications comprise technical failure; T-tube or stent-related complications; hepatic artery thrombosis; bleeding; ischemia/reperfusion injury; and other immunological, nonimmunological, and infectious complications. Noninvasive diagnostic methods have been established and treatment modalities have been modified towards a primarily nonoperative, endoscopy-based strategy. Besides, the management of biliary complications after OLT requires a multidisciplinary approach, in which interventional and endoscopic treatment options have to be weighed up against surgical treatment options. The etiology and spectrum of bile duct complications, their diagnosis, and their treatment will be reviewed in this article.     

Biliary complications after liver transplantation

Abstract:  Biliary complications remain a substantial cause of morbidity following liver transplantation. They have been reported to occur in a rate of 10–15% of full-size transplantations and may be higher in living donor, split or reduced size liver transplantations. The most common biliary complications following liver transplantations are leaks and strictures. In both, the incidence varies with respect to type of graft and donor as well as the type of biliary anastomosis. The management of the biliary complications requires a multidisciplinary approach and has changed over the past decade, favoring endoscopic and radiological techniques. Surgical revision including retransplantation is reserved for patients in whom endoscopic and interventional modalities are unsuccessful.     

肝移植术后胆道并发症病因分析

目的探讨原位肝移植术后胆道并发症的病因.方法回顾性分析235例尸体供肝和36例活体供肝原位肝移植的临床资料,总结术后胆道并发症的病因.结果36例活体肝移植受体术后胆道并发症的发生率为5.6%,235例尸体供肝肝移植受体术后胆道并发症的发生率为19.1%;肝内胆道狭窄和胆道铸型结石形成等严重胆道并发症在活体肝移植中未发生.讨论缺血时间尤其热缺血时间是导致严重胆道并发症的最主要的原因,所留取的受体胆道长度也是影响胆道并发症的一个主要因素.     

Predisposing factors for biliary complications following liver transplantation

INTRODUCTION: Biliary complications remain a major cause of morbidity and mortality in patients following liver transplantation. We sought to identify possible risk factors predisposing to biliary complications after OLT using duct-to-duct biliary reconstruction. MATERIALS AND METHODS: We retrospectively reviewed 5 years of prospectively collected donor and recipient data between April 1999 and April 2004. We evaluated the presence of biliary complications, donor and recipient age, cold ischemia time, hepatic artery thrombosis, non-heart-beating donor (NHBD), and graft steatosis (>30%). The results were compared with a control group of OLT patients without biliary complications. RESULTS: Among 173 OLT recipients, biliary complications occurred in 28 patients (16.2%), of whom 12 were leaks, 15 strictures, and 1 a nonanastomotic intrahepatic stricture. The mortality following biliary complications was 11%, compared to 6% in the control group. CONCLUSION: Biliary complications remain a persistent problem in OLT. Analysis of risk factors identified hepatic artery thrombosis and steatosis as predisposing factors. With greater experience, NHBD livers may also prove to be at greater risk of biliary complications.     

Role of choledochojejunostomy in liver transplantation

AIM: This study analyzes the efficacy and rate of complications related to Roux-en-Y choledochojejunostomy need either as the primary biliary reconstruction during orthotopic liver transplantation (OLT) or to treat biliary complications. METHODS: One hundred seventy-seven transplantation procedures were performed from September 1991 to December 2003 in recipients of mean age 51.9 years. Patients were reviewed for the type of biliary reconstruction, the prevalence of biliary complications, and the choice of treatment for these complications. Duct-to-duct anastomosis (group CDC) was performed in 153 patients (85.6%), and choledochojejunostomy (group CDJ) in 24 patients (14.4%). Biliary complications, including stenosis, bile leakage, calculosis, and extensive biliary necrosis, required hospitalization, surgical interventions or endoscopic approaches. Biliary complications in the CDC group first were addressed by endoscopic treatments. When endoscopic therapy failed, they were approached by surgical reintervention. All biliary complications in group CDJ were surgically treated, namely, revision of the Roux-en-Y choledochojejunostomy. The chi square test was used to compare frequencies, with Yates correction when necessary; P values were considered significant at <.05. The Mann-Whitney U test was used to evaluate survival. RESULTS: Fifty-eight (32.8%) biliary complications in 47 patients required endoscopic or surgical approaches. In group CDJ, 1 patient had bile leakage requiring surgical treatment. The prevalence of biliary complications was lower in the CDJ group than the CDC group (P < .05). Endoscopic treatment applied in 23 patients, failed in 11. Surgical approaches were performed in 11 patients after endoscopic failure, and in 13 patients as the first option to treat biliary complications. No failure was observed with surgical treatment. Cholangitis occurred in 3 patients who received surgical treatment and 4 patients who received endoscopic treatment. There was no statistically significant difference when comparing the mortality rates of the 3 types of treatment for biliary complications: endoscopy, surgery, and endoscopy followed by surgery. Survival rates were similar for the 3 types of treatment of biliary complications. CONCLUSION: Roux-en-Y choledochojejunostomy is a useful tool to treat biliary complications after OLT, especially when endoscopic treatment fails. In our experience, the rate of complications directly related to this technique is significantly lower than common duct anestomosis, whether used for biliary reconstruction during OLT or for posttransplantation biliary complications.     

活体肝移植的胆道重建与胆道并发症

To systematically summarize the current status of surgical techniques in biliary reconstruction and biliary complications following living donor liver transplantation and analyze the biliary reconstruction techniques and difficulties in the prevention of biliary complications.The refinements of surgical techniques and successful prevention and therapeutic strategies for reducing biliary complications after living donor liver transplantation are discussed.     

Management of biliary anastomotic strictures after liver transplantation

Biliary strictures constitute 40% to 60% of the biliary complications after liver transplantation. They are more common after living donor related liver transplantation (LDLT) than orthotopic liver transplantation (OLT). Balloon dilation followed by multiple plastic stent insertion leads to a mean resolution rate of 84% in the treatment of ASs after OLT. Endoscopic treatment of ASs after LDLT is more difficult because of the small size of the ASs, their multiple number and peripheral location. Balloon dilation followed by multiple plastic stent insertion had a mean resolution rate of 53%. Percutaneous transhepatic biliary drainage was required in 16% to 44% of the patients. Refractory cases with complete biliary obstruction and severe stenosis, in whom the stricture could not be traversed with a guidewire, can be treated by magnetic compression anastomosis as a rescue therapy, if the anatomy of the bile ducts is suitable.In this review, we will focus on the endoscopic treatment of ASs, with special emphasis to refractory cases.     

肝移植供肝修整的经验

目的：探讨肝移植供肝修整的方法与技巧。方法：回顾性分析64例原位肝移植供肝修整以及血管变异时处理的方法和技巧。结果：修整的64例供肝全部用于肝移植。发现13例存在肝动脉解剖变异，其中5例行变异肝动脉重建，动脉重建方法包括将变异动脉与脾动脉(3/5)、胃十二指肠动脉(2/5)吻合。无因供肝修整而出现的手术并发症。结论：供肝血管及胆道的正确修整可减少肝移植后并发症，是供肝修整成败的关键。     

Biliary tract complications after orthotopic liver transplantation: still the "Achilles heel"?

Postoperative biliary tract complications after liver transplantation (LT) still lead to early and late morbidity and mortality. Modern interventional endoscopic techniques can replace surgical repair as the first line of treatment. Nevertheless surgical intervention plays an important role in specific situations. We performed a retrospective analysis of patients with biliary complications after LT over a 12-year period. We compared treatment programs based on duration and success rate. The rate of biliary complications was 24.5% (60/245). The side-to-side choledocholedochostomy (CDC) technique showed the significantly lowest rate. The rate of complications after hepaticojejunostomy (HJS) was considerably lower, albeit not significantly. Eighty-one percent of complications after CDC were treated with interventional endoscopy. The duration of treatment of strictures, was 10 times greater than that of leakages. Surgical repair was necessary for 19% of complications occurring after CDC. The treatment options after HJS largely comprised surgical repairs. From a surgical standpoint, choosing the correct method for biliary reconstruction and ensuring normal arterial flow are the best preventive techniques to avoid biliary complications. Over the past 10 years, the primary treatment regimen has moved from surgical repair to interventional endoscopy. Only when endoscopy fails, should one consider surgical repair. The treatment after HJS is still primarily surgical. Percutaneous transhepatic approaches should be avoided. Creation of an inspection stoma to allow endoscopic access is an option.     

原位肝移植70例报告

目的　探讨肝移植治疗终末期肝病的临床效果。方法　在过去2年内,70例终末期肝病患者接受了72例次原位肝移植手术,其中包括1例小儿减体肝移植。结果　手术近期死亡18例（25.7%）,随访期间死亡14例(26.9%),术后胆道并发症发生率23%,肝动脉并发症20%。术后生存时间超过6个月者30例,超过1年者17例,其中肝癌组（31例）,有9例术后生存已超过6个月,3例超过1年。结论　减少外科手术并发症是提高肝移植手术成功率以及长期存活的关键。对于肝硬化合并原发性肝癌的患者,肝移植应作为首选的治疗方法。     

The bile duct anastomosis in liver transplantation

In spite of the dramatic improvement of survival after orthotopic liver transplantation over the last decades, biliary tract complications are still the 'achilles heal' of liver transplantation with a potential risk of significant morbidity and mortality. Biliary leaks or strictures, the major types of biliary complications, may occur after direct choledocho-choledochostomy (CC) or Roux-Y choledocho-jejunostomy (CRY). The majority of these biliary complications, however, are often a consequence of surgical technique and therefore potentially amenable to improved surgical technique.     

肝移植术后胆管非吻合口狭窄的病因分析

目的探讨肝移植术后胆管非吻合口狭窄的成因及分类,寻找胆管非吻合口狭窄的防治方法。方法回顾性分析2000年5月至2005年12月5年间381例次(373例)肝移植患者的临床资料,其中20例患者术后发生胆管非吻合口狭窄,随访时间5～71个月。结果20例胆管非吻合口狭窄患者中,肝内外弥漫型狭窄6例,肝外局限型狭窄者14例,胆管非吻合口狭窄发生率5.25% (20/381),所有患者均经T管造影、ERCP或MRCP确诊。6例患者弥漫型狭窄的原因为:肝动脉血栓形成1例,供肝未进行有效胆道冲洗3例,腔静脉吻合口出血行再次吻合(致使胆道二次热缺血时间超过3 h)1例,不明原因1例。14例局限型狭窄的原因为:变异血管损伤2例,其他原因可能为冷热缺血时间过长、肝门解剖过度及供肝获取方法不当等。结论肝移植术后胆管非吻合口狭窄原因复杂,最主要的原因包括胆管的血供损伤、胆管的二次热缺血时间延长、供肝胆管是否及时有效的冲洗以及合理的取肝方法。     

Liver transplantation in adults: postoperative management and development during the first months

Recent improvements in the results of orthotopic liver transplantation (OLT) have made this a well-accepted treatment for patients with severe hepatic failure. Current problems encountered following OLT are discussed. Immediate complications comprise surgical bleeding, primary graft non-function, and graft failure due to hepatic artery occlusion. Secondary complications are frequent. Surgical ones include biliary and vascular (hepatic artery thrombosis most often) problems, as well as intra-abdominal abscesses associated with gastrointestinal perforation, biliary leak, graft ischaemia or an infected haematoma. 40% of patients having undergone OLT will be reoperated on, 2/3 of them within 3 months. Non-surgical complications are mostly pulmonary. The risk of pneumonitis is increased by prolonged mechanical ventilation; it is always potentially disastrous in the immunosuppressed, transplanted patient. Hypertension is also often seen in the early postoperative period; it requires prompt treatment. Early renal impairment after OLT is common, and of better prognosis than late onset renal failure, which is generally associated with shock, graft failure, sepsis or use of nephrotoxic agents. Seizures, usually only one, occur in about 10% of patients; recovery is complete. Encephalopathy with intracranial oedema related to fulminant hepatitis has a worse prognosis, but survival figures are quite encouraging. Three type of rejection are described after OLT: 1) severe accelerated rejection (very rare), 2) acute rejection encountered in about 70% of patients over the first 3 months, and 3) late rejection, which can lead to the vanishing bile duct syndrome (VBDS). Diagnosis of rejection is made by liver biopsy. Prophylactic immunosuppression includes cyclosporin, methylprednisolone and azathioprine. Cyclosporin toxicity and drug interactions are reviewed. Treatment of acute rejection episodes comprises an initial bolus of high doses of corticoid drugs; if there is no response, antilymphocyte globulin or monoclonal antibodies may have to be used. Infection is the main cause of death following OLT. Early infections, mostly intra-abdominal and pulmonary, are bacterial or fungal. Vital (especially CMV) and other opportunistic infections occur generally after the second week. Retransplantation, carried out in 10 to 25% of patients, may be urgent in case of primary graft failure, or hepatic artery thrombosis associated with graft failure, or hepatic artery thrombosis associated with graft failure. Other indications are early graft rejection with severe hepatic dysfunction, chronic rejection with severe VBDS, and recurrence of the initial disease.     

Transhepatic biliary catheterization before graft implant in living donor liver transplantation

AIM: Despite the evolution in surgical technique, the biliary anastomosis remains the technical Achilles' heel of liver transplantation, especially in living donor liver transplantation. Interventional radiology or endoscopic procedures constitute the most common options to treat complications from the biliary anastomosis. We report a novel technique to prevent biliary complications following the transplant. METHODS: During the donor procedure a wire guide was introduced in the severed duct, left or right, in retrograde fashion. The liver surface was then perforated and the wire guide exposed. A 4F catheter was then attached to the wire guide and pulled into the bile duct passing through the end-to-end duct-to-duct anastomosis or hepaticojejunostomy. RESULTS: This technique was performed in six living donor grafts: one right lobe, two left lobes, and three left lateral segments. All patients had no complications from the stent placement, biliary strictures, or leaks. One developed a hepatic artery thrombosis on the posttransplant day 14 with no major biliary complications.     

24例不置T管胆总管对端吻合式肝移植术后胆道并发症的病因分析

目的通过观察不置T管胆总管对端吻合式（choledocholedochostomy without a T tube,CC）肝移植术的临床疗效,探讨新的胆管对端吻合法及胆道并发症的病因。方法回顾分析我院24例CC的肝移植患者临床资料,并对其中4例胆道并发症的病因进行探讨。结果经手术或磁共振胆胰管成像（magnetic resonance cholangiopancreatography,MRCP）等检查确诊胆道并发症4例（占16．7％）,其中术后早期肝内外胆管坏死伴胆瘘2例,均死亡;术后早期一过性胆瘘2例,其中1例又出现晚期肝门部胆管狭窄,均治愈。结论CC在肝移植的应用是安全可靠的。供体术前肝素化不充分导致胆管小分支微血栓形成,供肝胆道冲洗不彻底、冷热缺血时间过长、胆管保留过长及胆道供血系统破坏等均可引起胆管损伤,增加胆道并发症的发生率。     

Chirurgie und Organtransplantation

Liver and kidney transplantations have been performed for almost 50 years and is nowadays a routine procedure for the treatment of terminal liver failure and terminal-stage renal failure. Under given optimal conditions and increasing experience good results can be achieved. Improvements in surgical techniques have led to a decrease in the incidence of surgical complications after transplantation. Nevertheless after liver and kidney transplantation complications can occur and increase the morbidity and mortality. There are a number of possible complications which range from harmless wound healing disorders to severe vascular, biliary or urinary complications that can be associated with graft dysfunction and lead to graft loss. In order to identify risk factors preoperatively and achieve good outcome after transplantation a good preparation of the recipients is necessary. Furthermore, a good interdisciplinary cooperation is necessary both to recognize complications early and to treat these adequately.     

Biliary Complications After Liver Transplantation Using Side-to-Side Choledochocholedochostomy Reconstruction With or Without T-Tube

Background

Biliary complications are a frequent cause of morbidity, graft loss, and death after orthotopic liver transplantation (OLT). The choledochocholedochostomy anastomosis without a T-tube is controversial, as it has been related to more biliary complications.

Aims

The aims of this study were to determine the incidence and to identify the risk factors of post-OLT biliary complications after reconstruction with or without a T-tube.

Materials and Methods

Ninety-five consecutive adult patients with deceased donor liver transplantations (overall survival rate, 86.3%; mean follow-up, 22.2 months) were analyzed to determine the incidence and type of biliary complications in 2 groups: choledochocholedochostomy with (45 patients, Group I) or without a T-tube (50 patients, Group II). The incidence of biliary complications in Groups I and II was 40% (18/45) and 30% (15/50), respectively (P > .05). In Group I, 49% of the complications were directly related to the T-tube. Biliary anastomosis stricture was more frequent in Group II (28% vs 8.9% in Group I; P = .018). Endoscopic retrograde cholangiopancreatography (ERCP) was the most common therapeutic procedure for the resolution of biliary complications in both groups (Group I, 66.5%; Group II, 58.2%). Arterial thrombosis, high pretransplantation Model for End-Stage Liver Disease (MELD) score, and donor obesity were identified as risk factors for biliary complications after OLT.

Conclusion

OLT biliary reconstruction without a T-tube is not related to an increased risk of biliary complications, although stricutre of the anastomosis is more frequent in this group of patients. Donor obesity, arterial thrombosis, and high pretransplantation MELD score are associated with a higher incidence of biliary complications after OLT.     

Endoscopic stenting of the gallbladder for symptomatic gallbladder disease in patients with end-stage liver disease awaiting orthotopic liver transplantation.

Cholecystectomy in patients with advanced cirrhosis is associated with excessive morbidity and mortality. Because open cholecystectomy in patients with Child's class C cirrhosis has a reported mortality rate as high as 83%, symptomatic gallbladder disease in patients awaiting orthotopic liver transplantation (OLT) poses a unique clinical problem. The goal of this study is to determine whether the treatment of symptomatic gallbladder disease with endoscopic stenting of the gallbladder effectively reduces biliary symptoms and complications or the need for cholecystectomy. Thirteen patients with symptomatic gallbladder disease with and without cholelithiasis and advanced cirrhosis who were candidates for OLT underwent placement of a biliary stent from the gallbladder to the duodenum at endoscopic retrograde cholangiography. In each patient, biliary symptoms and complications ceased after stent placement. Seven patients underwent successful OLT 1 to 24 months after the procedure. One patient subsequently became a noncandidate for OLT and died of diabetes complications 3 years after the procedure. Five others are awaiting OLT (6 to 28 months postprocedure). One patient had recurrent pericholecystic fluid collection requiring percutaneous drainage and antibiotic therapy 8 months after the procedure. No patient has had recurrent symptoms, and currently all patients are free of complications. None required surgical intervention of the gallbladder or biliary tree. We conclude that endoscopic stenting of the gallbladder is the preferred treatment for symptomatic gallbladder disease in patients with end-stage liver disease awaiting OLT. This approach is noninvasive, safe, and effective in preventing potential morbidity and mortality.     

Analysis of long-term outcomes of 3200 liver transplantations over two decades: a single-center experience

OBJECTIVE: Few studies have evaluated long-term outcomes after orthotopic liver transplantation (OLT). This work analyzes the experience of nearly 2 decades by the same team in a single center. Outcomes of OLT and factors affecting survival were analyzed. METHODS: Retrospective analysis of 3200 consecutive OLTs that were performed at our institution, between February 1984 and December 31, 2001. RESULTS: Of 2662 recipients, 578 (21.7%) and 659 (24.7%) were pediatric and urgent patients, respectively. Overall 1-, 5-, 10-, and 15-year patient and graft survival estimates were 81%, 72%, 68%, 64% and 73%, 64%, 59%, 55%, respectively. Patient survival significantly improved in the second (1992-2001) versus the era I (1984-1991) of transplantation (P < 0.001). Similarly, graft survival was better in the era II of transplantation (P < 0.02). However, biliary and infectious complications increased in era II. When OLT indications were considered, best recipient survival was obtained in children with biliary atresia (82%, 79%, and 78% at 1, 5, and 10 years, respectively), while malignant disease in adult patients resulted in the worst outcomes of 68% and 43% at 1 and 5 years, post-OLT. Further, patients <18 years and nonurgent recipients exhibited superior survival when compared with recipients >18 years (P < 0.001) or urgent patients (P < 0.001). Of 13 donor and recipient variables, era of OLT, recipient age, urgent status, donor age, donor length of hospital stay, etiology of liver disease, retransplantation, warm and cold ischemia, but not graft type (whole, split, living-donor), significantly impacted patient survival. CONCLUSIONS: Long-term benefits of OLT are greatest in pediatric and nonurgent patients. Multiple factors involving the recipient, etiology of liver disease, donor characteristics, operative variables, and surgical experience influence long-term survival outcomes. By balancing and matching these factors with a given recipient, optimum results can be achieved.     

Primary sclerosing cholangitis: surgical options, prognostic variables and outcome

The natural history of primary sclerosing cholangitis (PSC) is poorly defined and its management remains controversial. Forty-eight symptomatic patients (median age 39 years, range 8-67 years; 30 male) with PSC were reviewed retrospectively. Thirty patients had inflammatory bowel disease. Four patients (8 per cent) developed or had an associated malignancy. Twenty-one (44 per cent) died; overall 5 year actuarial survival was 30 per cent. Twenty-three patients had 27 non-transplant related biliary operations (16 patients specifically for PSC) of whom 12 died. Serum bilirubin was the only parameter to improve after biliary surgery. Seventeen patients (35 per cent) underwent orthotopic liver transplantation (OLT) of whom nine are currently alive (1 year projected survival of 55 per cent). Previous biliary surgery correlated with a poor outcome (P less than 0.0001) after OLT. Being male, presence of cirrhosis, duration of symptomatic disease (greater than 3 years) and a serum bilirubin level greater than 100 mumol/l at presentation, were independently associated with a poor outcome (P less than 0.05). These data provide evidence that PSC is a progressive disease and conventional surgical options have little influence on the outcome. Previous biliary surgery adversely affects outcome following OLT. For progressive liver disease, liver transplantation should be considered the treatment of choice.