Biliary Complications after Liver Transplantation: the Role of Endoscopy

• Abstract
• Introduction
• Diagnosis of Biliary Complications
• Management
• Bile Leaks
• Early Postoperative Bile Leaks
• Late Postoperative Bile Leaks
• Biloma
• Strictures
• Anastomotic Strictures
• Nonanastomotic Strictures
• Sludge, Stones, Casts, and Other Filling Defects
• Sphincter of Oddi Dysfunction and Distal Bile Duct Obstruction
• Mucocele
• Recipient and Donor Complications after Live Donor Liver Transplantation
• Recipient Complications
• Donor Complications
• Management
• Impact of Biliary Complications on Graft and Patient Survival
• Conclusion
• References

Abstract

Biliary complications are important causes of early and late postoperative morbidity and mortality after liver transplantation and are seen in 10 - 20 % of the patients. The common biliary complications include bile leaks, stones or debris, and anastomotic strictures. Less common complications are hilar strictures, intrahepatic strictures, and papillary stenosis/dysfunction. The complications are similar in living-donor and cadaveric liver transplantations, except for a higher incidence of bile leaks among living-donor transplant recipients. The clinical presentation of post-liver transplant bile duct complications is often subtle, and noninvasive imaging studies may sometimes fail to detect mild but clinically significant stenoses or small leaks. Early recognition and prompt treatment of biliary complications following liver transplantation reduces the morbidity and improves long-term graft and patient survival. In this report, we discuss the role of endoscopy in the diagnosis, treatment options, and the outcome for patients with biliary complications following liver transplantation.

Introduction

Biliary complications have been reported in up to 51 % of patients after liver transplantation, although more recent series have reported much lower rates of complications, ranging from 8 % to 20 % [1] [2] [3] [4]. The common biliary complications include bile leaks, stones or debris, and anastomotic strictures (Table [1]). In one series, 39 % of the patients had strictures, 30 % had bile leaks, 31 % had filling defects due to stones, debris, or casts, and 23 % had papillary stenoses or sphincter dysfunction. Many patients had more than one biliary complication [4]. Less common biliary complications include hilar strictures, multiple intrahepatic strictures, and papillary stenosis or sphincter of Oddi dysfunction [3] [4] [5] [6] [7] [8]. Early diagnosis of biliary complications may avoid unnecessary diagnostic procedures, reduce hospital stays and costs, and may improve outcomes. In addition, endoscopic techniques may promote improved graft function, improvement in liver enzyme values, and may make repeat surgery and percutaneous interventions unnecessary. This review discusses the incidence, diagnosis, treatment options and outcome of post-liver transplant biliary complications and analyzes the role of endoscopy in each specific situation.

There are conflicting data on the differences in the incidence of biliary complications in patients with choledochocholedochostomy and Roux-en-Y choledochojejunostomy. Whereas Stratta et al. [1] found a similar incidence of complications with both forms of biliary reconstruction, Greif et al. [2] reported a higher incidence of strictures and a similar incidence of bile leaks with Roux-en-Y choledochojejunostomy [1] [2]. We believe that access to the bile duct is an advantage after liver transplantation and that choledochocholedochal anastomosis should be considered, if it is technically feasible, even in patients undergoing live donor transplantation. Since a significant number of complications are related to T-tubes, despite comparable complication rates reported in the literature, we believe that biliary reconstruction without using a T-tube could reduce complications [9] [10] [11] [12].

Diagnosis of Biliary Complications

The first clue that a biliary complication has arisen may be an asymptomatic increase in serum transaminase or bilirubin levels. Symptoms are often nonspecific and include fever and anorexia. The right upper quadrant abdominal pain typically associated with biliary tract disorders is usually absent in liver transplant patients, because of hepatic denervation. The initial evaluation should include ultrasonography with a Doppler examination of the hepatic vessels, followed by a liver biopsy or biliary imaging, depending on the pattern of liver test abnormalities. Liver biopsy is often the most definitive test, but the interpretation of histological findings of bile flow impairment or bile duct injury can sometimes be misleading in post-transplant patients. However, noninvasive examinations often lack sufficient sensitivity and accuracy to detect small but significant sources of biliary obstruction. Since biliary stricturing is an insidious process, the absence of bile duct dilation on sonography should not preclude further evaluation in clinically suspicious cases. Moreover, bile duct dilation may not always be present in the transplanted liver, even when there is moderately severe stenosis and early obstruction.

If there is a clinical suspicion of bile duct obstruction or bile leakage, an early cholangiogram should be obtained. Hepatobiliary scintigraphy with hepato-iminodiacetic acid (HIDA) may be used when bile leakage is suspected, but in our experience its usefulness is limited. The role of magnetic resonance cholangiopancreatography (MRCP) has not been clearly elucidated in transplant recipients, but increasing numbers of transplant centers are using MRCP as a diagnostic modality. Hepatic angiography may be indicated if Doppler ultrasonography suggests hepatic vascular obstruction. When the threshold for detecting an abnormality is low, it is reasonable to use MRCP before doing invasive procedures. One study prospectively evaluated 113 post-liver transplant patients with suspected biliary complications using MRCP, and compared the results with the gold standard of cholangiography and clinical history [13]. The overall accuracy of MRCP in the study was 93 %, with sensitivity and specificity rates over 90 % each, and a positive predictive value of 86 %. MRCP is the diagnostic modality of choice when there is a low suspicion of biliary tract disease, when there is a low probability of endoscopic therapy being performed, or when endoscopic retrograde cholangiopancreatography (ERCP) and/or percutaneous transhepatic cholangiography (PTC) are not successful. While a T-tube cholangiogram can easily be obtained in patients with an indwelling T-tube, the best invasive approach in those without a percutaneous catheter depends on the type of biliary reconstruction, the likelihood of therapeutic intervention, and the availability of local expertise. We believe that direct cholangiography via endoscopic retrograde cholangiography (ERC) is the definitive diagnostic test in individuals with a duct-to-duct anastomosis, and via PTC in patients with a Roux-en-Y choledochojejunostomy to visualize the biliary tree.

Management

In a large series in Pittsburgh, approximately one-third of the biliary complications were diagnosed within 1 month of surgery and 80 % were diagnosed within 6 months [2]. The most common biliary complications were leaks and strictures. Leaks tend to occur in the early postoperative period (within 1 month of surgery or immediately after T-tube removal), and stricture formation develops gradually over several months to years, depending on the degree of the insult. After the first postoperative year, the annual incidence of biliary complications is less than 4 %. When there is biliary obstruction, patients should be treated with broad-spectrum antibiotics, followed by drainage of the bile duct and any associated abscesses. Based on the nature of the biliary reconstruction and complication, this can be accomplished either percutaneously or via ERCP [1] [2] [3] [4] [14] [15] [16] [17] [18] [19] [20]. Surgical revision is rarely required, except in some cases of live-donor liver transplantation or failure of endoscopic therapy [14] [15]. When surgery is necessary, a Roux-en-Y choledochojejunostomy is an excellent rescue technique in cases of biliary obstruction, with a 5-year patient survival rate of around 70 % [21].

Bile Leaks

Bile may leak from a variety of sites, including the anastomotic site, the cystic duct, damaged accessory bile ducts, the T-tube tract, and rarely from an incidental intrahepatic injury. In addition, in live-donor liver transplantation, bile may leak from the cut surface of the liver. Nonanastomotic leaks often result from vascular insufficiency, and therefore the possibility of hepatic artery thrombosis (HAT) or compromise must be excluded [22] [23]. In our experience, bile leakage is the second most common biliary complication requiring endoscopic intervention [4]. Our anecdotal experience suggests that early intervention may minimize morbidity and the hospitalization period. Bile leaks can be divided into early (within 4 weeks of the transplant) and late postoperative periods.

Early Postoperative Bile Leaks

Early leaks, usually occurring at the anastomotic site, are often caused by technical problems. The incidence of early postoperative bile leaks is not related to the type of biliary reconstruction used. Technical factors that predispose grafts to early bile leaks include the following:

• Insufficient blood flow from the hepatic artery anastomosis

• Active bleeding from the cut ends of the bile duct or ducts before anastomosis

• Excessive dissection of periductal tissue during organ procurement

• Excessive tension on the ductal anastomosis

• Use of electrocautery to control biliary duct bleeding

If a T-tube is present, duct-to-duct anastomotic leaks are easily diagnosed with a T-tube cholangiogram and can be managed conservatively by leaving the T-tube open to divert bile flow. In the absence of a T-tube, HIDA scanning or MRCP may be effective in diagnosing bile leaks. However, if there is strong clinical suspicion, ERC with stenting of the bile duct (using a plastic internal stent) is preferable, since ERC is both diagnostic and therapeutic. In our experience, ERC identifies the site of leaks in over 90 % of patients [3] [4]. When the clinical diagnosis is not in doubt, there is no advantage in demonstrating the leak, since more than 95 % of leaks can be managed successfully by stent placement. When leakage is suspected with a T-tube in situ, a 10-Fr biliary stent is placed parallel to the T-tube and the T-tube is removed immediately after ERC, or a day or two later. Both approaches are safe. In general - in contrast to postcholecystectomy leaks - the stent is usually left in place for approximately 2 - 3 months. Although some studies have had success in sealing leaks with 6 weeks of stenting, we believe it is preferable to leave the stent for about 2 - 3 months, since healing is delayed probably due to immunosuppressive drug treatment in these patients [3]. The occurrence of bile leaks through the T-tube exit site despite 3 - 4 months of T-tube placement provides circumstantial support for this approach.

Large bilomas, if present, should be drained percutaneously, and antibiotics are administered as necessary. Surgical intervention is required when conservative management fails, when there is evidence of HAT, or if the duct-to-duct anastomotic defect is too large. Traditionally, the duct-to-duct anastomosis is converted to a Roux-en-Y choledochojejunostomy, which allows wide debridement of necrotic and infected tissue. Regional sepsis and poor postoperative infection control can result in recurrent biliary leaks. Primary repair of duct-to-duct anastomotic leaks has been reported in technically ideal situations.

Roux-en-Y choledochojejunostomy anastomotic leaks are less frequent, but the intestinal loop of the anastomosis may contribute to an increased chance of intra-abdominal abscess formation, bacteremia, and sepsis. In the clinical scenario of a Roux-en-Y choledochojejunostomy without a transanastomotic catheter in place, a bile leak can be diagnosed with hepatobiliary scintigraphy and in selected cases with PTC. A therapeutic endoscopic approach is often not feasible because of the Roux-en-Y construction. Initial management is to resolve the infection with percutaneous transhepatic biliary drainage and/or percutaneous transabdominal abscess drainage. The infection must be fully resolved before surgical reconstruction or repair of the anastomosis. Nonsurgical conservative treatment involves carrying out a PTC with placement of an internal-external drain that can be sequentially up-sized for a total period of 3 - 6 months of stenting. Prophylactic antibiotics should be administered before percutaneous intervention to reduce the risk of infectious complications, especially in patients with a Roux-en-Y choledochojejunostomy. In a significant number of cases, surgical management with primary repair or refashioning of the anastomosis is required.

Late Postoperative Bile Leaks

Late postoperative bile duct leaks are nearly always related to elective or inadvertent removal of the T-tube. Up to 31 % of patients with a T-tube in place may experience a leak, and the incidence of late bile duct leakage is 7 %, with a mean time to presentation of 118 days after transplantation, despite prolonged T-tube placement. This has prompted many transplant centers to abandon the routine use of T-tubes. The delay in T-tube tract maturation is believed to occur because of the use of immunosuppressive agents, resulting in a decreased inflammatory reaction to the T-tube.

A leak at the T-tube site is suspected when the patient complains of abdominal discomfort or pain when the T-tube is removed. Usually, the symptoms resolve spontaneously or with mild analgesics, but further intervention is required if symptoms persist. T-tube leaks are managed nonsurgically by endoscopic identification and placement of internal transanastomotic stents. T-tube leaks have been found to have a near 100 % resolution rate with endoscopic stenting and are significantly easier to heal than other leaks after liver transplantation [3]. Bile leaks are often self-limiting and can be managed by short-term stenting [24]. Some centers have used nasobiliary catheters to treat bile leaks. The advantage of a nasobiliary tube is that it allows for frequent cholangiographic follow-up (every 3 - 5 days) and is easily removed without the need for another endoscopic intervention. In one study, patients obtained symptomatic relief within 12 h of nasobiliary stenting, and the fistula closed at a mean of 6.3 days (range 3 - 13 days) [25]. However, the disadvantages of this approach are that patients will have to tolerate the inconvenience of a tube exiting from their nose, their hospital stay may become prolonged, and the diversion of bile from the intestine may affect the bioavailability of immunosuppressants such as cyclosporine. In our experience, the majority of patients can be discharged within 48 h after ERC and internal stenting. Biliary tract stenting, with or without endoscopic sphincterotomy, can successfully treat over 90 % of biliary tract leaks [3] [4] [24] [25] [26].

Some reports have recommended surgery as the initial treatment of bile leaks after T-tube removal [14]. Our own experience and that of others suggests that the endoscopic approach is the treatment of choice for these patients and that excellent results can be achieved, with minimal morbidity [2] [3] [4] [20] [22] [23] [24] [25] [26]. Surgery or the percutaneous transhepatic approach should be reserved for patients in whom the endoscopic approach fails.

Biloma

Severe bile duct necrosis can lead to bile duct rupture and extravasation of bile into the intrahepatic parenchyma or free abdominal cavity, resulting in a biloma. Most bilomas encountered after liver transplantation are outside the liver, usually in the perihepatic spaces. Intrahepatic bile lakes that communicate with the biliary tree may resolve spontaneously, may require percutaneous catheter drainage, or may benefit from endoscopic sphincterotomy with or without stent placement. However, it is important to note that the role of ERC in this clinical scenario is primarily diagnostic. Large or infected bilomas are drained percutaneously by placing an indwelling catheter, and intravenous antibiotics are administered. Surgery is necessary only when the bile leak cannot be controlled by conservative approaches, as discussed earlier.

Strictures

Bile duct strictures are the most common biliary complications after liver transplantation. In one series, 39 % of bile duct complications were due to strictures, and 75 % of these patients had strictures at the anastomotic site or just proximal to the anastomosis [4]. Stricture formation is insidious and is often first detected when biliary obstruction results in abnormalities in liver enzymes and/or infection. Strictures may occur with either type of biliary reconstruction, with an overall incidence of 3 - 6 %, but in two large series, strictures were more common with Roux-en-Y choledochojejunostomy reconstruction [1]. Strictures can occur anywhere in the biliary tract, but can be classified as anastomotic or nonanastomotic, depending on the stricture site. In addition, depending on the time of presentation, strictures can be classified as early (within 1 month of transplantation) or late. Early strictures are usually due to technical errors, while strictures that appear later are often the result of vascular insufficiency [27].

In our experience, the most common biliary complication after liver transplantation is extrahepatic bile duct strictures [1] [2] [3] [4] [18] [19] [20]. Strictures in the proximity of the anastomosis are the most common type. Nonanastomotic proximal donor duct strictures have traditionally been more difficult to manage endoscopically and are thought to be secondary to vascular compromise such as hepatic artery thrombosis, prolonged cold ischemia time (more than 10 h from the organ harvest), and ABO blood type incompatibility [5] [6] [22] [23]. It is often difficult to distinguish, on the basis of cholangiography, between true anastomotic strictures and strictures just proximal to the anastomosis, except when the stricture extends to the hilum.

Anastomotic Strictures

Anastomotic strictures are usually the result of surgical technique in combination with local ischemia and fibrotic healing. In children, anastomotic strictures may occur due to the small-caliber bile ducts, especially when split-liver transplants are performed [16]. However, technical advances have reduced the incidence of biliary complications in children [28]. In some patients, a transient narrowing at a duct-to-duct connection appears within the first 30 - 60 days after transplantation, due to postoperative edema and inflammation. This type of stricture responds well to balloon dilation and temporary stent placement. After one or two therapeutic sessions separated by 2 - 3 months, the anastomosis often remains patent during the long-term follow-up. In our experience, anastomotic strictures that are identified within 1 year show an excellent response to short-term stenting (3 - 6 months), but these patients require long-term surveillance, as strictures may recur many years after the treatment.

Late-appearing anastomotic strictures (usually after 12 months) may respond well to initial balloon dilation and temporary stent placement (up to 3 months), but the response may be short-lived, with relapse rates of 30 - 40 %. These patients often require long-term stenting (12 - 24 months). We manage all strictures in the proximity of the anastomosis similarly with repetitive balloon dilation and multiple (two or three stents) large-diameter (10 - 12 Fr) parallel stenting. We prophylactically exchange stents at 3-month intervals, to avoid cholangitis due to stent occlusion. While this approach requires several endoscopic interventions, approximately 70 % of the patients respond to endoscopic management. Similar results have been observed in recipients of living-donor liver transplants [29].

In view of the minimal morbidity, we believe that endoscopic management should be considered the first choice before considering long-term percutaneous stenting or surgical reconstruction. The management of these strictures has developed from mostly surgical methods to mostly endoscopic methods over the past decade. It has been shown that prior nonsurgical intervention does not adversely influence the outcome of subsequent surgical reconstruction [15]. We therefore believe that endoscopic intervention should be attempted before percutaneous or surgical intervention in patients with extrahepatic duct strictures. However, surgical revision to a Roux-en-Y choledochojejunostomy may be an alternative in a stable patient with a resilient duct-to-duct stricture, since surgery eliminates the need for multiple procedures [16]. If endoscopic treatment fails, surgical repair or conversion to a Roux-en-Y choledochojejunostomy is necessary for successful long-term outcomes [27]. The short-term results with surgical and nonsurgical management of these strictures are comparable.

Strictures in patients with Roux-en-Y choledochojejunostomies respond to dilation, but usually require a percutaneous transhepatic approach. Roux-en-Y choledochojejunostomy strictures are managed by percutaneous balloon dilation followed by placement of a percutaneous transhepatic catheter. The catheter maintains the patency of the anastomosis and allows easy access to the stricture for repeated evaluation and dilation. Usually, percutaneous stents are periodically exchanged and left in place for approximately 1 year; a short trial period follows after the stent has been pulled proximal to the stricture, and if the liver enzymes remain normal, the percutaneous stent is then permanently removed.

Patients with bile duct strictures, irrespective of their nature, require lifelong surveillance, as these strictures have a tendency to recur. Periodic evaluation of liver enzymes, HIDA scanning, ultrasonography, or magnetic resonance cholangiography are used for surveillance, depending on the nature and duration of the stricture.

Nonanastomotic Strictures

The natural history of nonanastomotic (hilar and/or diffuse intrahepatic) strictures is less favorable, and these strictures are traditionally less responsive to nonsurgical therapies. Despite attempts at balloon dilation, debris removal, and stenting, some 30 - 50 % of patients undergo repeat transplantation or die as a result of this biliary complication [16]. These strictures are ischemic in nature, often involve the hilum, and are often associated with multiple strictures involving the intrahepatic ducts. Cast formation is also common with ischemic strictures [18] [19] [20]. In addition to ischemia (HAT, donor without heartbeat, vasculitis), other risk factors for the development of nonanastomotic strictures include chronic ductopenic rejection, postoperative cytomegalovirus (CMV) infection, ABO incompatibility (causing vasculitis), and a pretransplantation diagnosis of primary sclerosing cholangitis (PSC).

Any ischemic injury that involves a large portion of the intrahepatic bile ducts is associated with poor graft survival and is best managed by repeat transplantation. The only exception is hilar strictures involving the right and left hepatic duct, where percutaneous management may be required if endoscopic stenting is not successful. As in anastomotic strictures, it is extremely important to have long-term follow-up of these patients, as the strictures can recur many years after a successful intervention. Ward et al. found that hilar strictures appear at a median of 10 weeks (range 4 - 112 weeks) after transplantation [30]. Strictures appearing within the first 3 months were more amenable to percutaneous balloon dilation and stenting than those developing later. Surgical revision is needed in many cases; if the initial biliary reconstruction was a duct-to-duct anastomosis, then a Roux-en-Y choledochojejunostomy is required, and if the patient had a Roux-en-Y choledochojejunostomy, it is redone by trimming the bile duct of the graft to an area that is well vascularized. A preoperatively placed stent can help guide the surgical dissection.

Diffuse disease in the smaller intrahepatic ducts is a reason for considering early repeat transplantation. These cases are usually associated with prolonged ischemia time before transplantation (e. g., in donors without heartbeat) or due to HAT. Although the short-term prognosis is good, the long-term prognosis is poor in our limited experience, due to frequent infections and liver abscesses. In one series, four of six patients who were managed conservatively developed liver abscesses (one died before and one died after repeat transplantation) and the other two had frequent infections, resulting in death in one patient [4]. Despite the reduced success in managing these strictures without repeat transplantation, radiotherapy techniques have offered reasonable palliation by lowering infection, reducing obstruction, and slowing progression to graft failure. These interventions may postpone the repeat transplantation and keep the patient free of infections while waiting for the repeat procedure. Repeat transplantation is indicated when the obstruction becomes progressive [16] [27].

Sludge, Stones, Casts, and Other Filling Defects

The differential diagnosis of filling defects in the bile duct after transplantation includes stones, blood clots, casts, and migrated stents. Most filling defects in our series were caused by stones [4]. Theoretically, stones can form in the post-transplantation setting due to increased lithogenicity of the bile or as a result of cyclosporine inhibition of bile flow, but in our experience they are most commonly seen in association with strictures. In most series, stones, debris, or casts were seen in about half of the cases in association with strictures of the bile duct. The stones or debris can be removed after sphincterotomy, and patients with strictures require dilation of the strictures before stone removal. Bile duct casts are seen in association with ischemic events and are often accompanied by strictures including diffuse stricturing of the hilum [31]. In one series, combined endoscopic and percutaneous methods were able to successfully clear the casts in 60 % of patients [31]. Although these casts can be removed endoscopically, the results are less favorable than with simple stones, and many patients are better managed with the percutaneous approach. Patients with Roux-en-Y choledochojejunostomy are treated using the transhepatic approach (PTC). Ursodeoxycholic acid may delay new formation of sludge and stones, although controlled data are not available.

Sphincter of Oddi Dysfunction and Distal Bile Duct Obstruction

Ampullary dysfunction or dyskinesia is reported to occur in 0 - 7 % of patients with a duct-to-duct anastomosis [7] [8]. The pathophysiology of sphincter of Oddi dysfunction (SOD) in the post-transplant setting is poorly understood, but it is probably related to denervation of the ampullary region of the native duct, resulting in abnormal ampullary relaxation. However, it is more likely that distal bile duct obstruction in the post-transplant setting is due to a combination of SOD, edema, or inflammatory stricturing due to long-term stenting with a T-tube or internal stent when the distal end protrudes into the sphincter. CMV and other opportunistic infections may also play a pathological role in post-transplant sphincter of Oddi dysfunction.

In most published series, the diagnosis of SOD is not always based on manometry, but on clinical suspicion and the response to biliary sphincterotomy. It is important to note that pain is not a part of the symptom complex in post-transplant patients [7] [8] [32]. The diagnosis is supported by improvements in liver tests with T-tube unclamping, by delayed drainage of contrast (> 15 min) after cholangiography, or by hepatobiliary scintigraphy and sphincter or T-tube manometry. Although manometry is essential to confirm the findings, it is rarely performed and instead patients are treated with endoscopic sphincterotomy. This was the least often encountered complication in our series, and required the fewest ERCs, with excellent response rates. Since there was a 100 % response to sphincterotomy, we do not believe that manometry is necessary in these patients.

Mucocele

An obstructing mucocele in the cystic duct remnant is a very rare complication of liver transplant surgery. It forms when the secretions from the cells lining the cystic duct remnant accumulate, causing extrinsic obstruction of the bile duct [24]. As the mucocele grows, it can compress and obstruct the adjacent bile duct, and it may take several weeks to years before the diagnosis is made. Computed tomography and ultrasonography will reveal the mucocele as a fluid collection in the porta hepatis, which has to be differentiated from other conditions, including hepatic artery pseudoaneurysm, biloma, loculated ascites, abscess, liquefied hematoma, tumor, adenopathy, and a fluid-filled Roux-en-Y loop of jejunum. Surgical excision or drainage of the cystic duct remnant by enteric anastomosis is curative [16].

Recipient and Donor Complications after Live Donor Liver Transplantation

Recipient Complications

Biliary complications are more common after adult-to-adult live-donor liver transplantation (LDLT). The incidence of biliary leaks and strictures has been reported to be as high as 30 %, and these complications are attributed to difficulties in defining the dissection plane around the right hepatic duct. In one series, early bile duct complications, consisting of leakage from the anastomotic site or cut surface, occurred in 23.9 % of cases, and late complications (at a mean of 6.7 months), consisting primarily of anastomotic structures, occurred in 32.6 %. In this series, early complications were managed surgically and late complications were managed with nonsurgical methods [33]. In another series of 391 patients in Japan, biliary complications were reported in 18.2 % of cases; more than half of the complications were due to bile leaks, and the rest were due to strictures [34]. Although there was a higher incidence of biliary complications, these studies showed that the types of bile duct complication occurring are similar in cadaver and live-donor liver transplantation, with the exception of leaks from the cut surface after LDLT. It is probable that increased surgical experience will reduce the rate of biliary complications in LDLT. Although LDLT presently appears to result in larger numbers of biliary complications, endoscopic treatment of the complications is equally efficacious in both LDLT and cadaver transplant recipients and should continue to be the first line of therapy [29].

At present, it is still unclear which type of biliary reconstruction is better after LDLT. In one center in which both duct-to-duct anastomosis (40.6 %) and Roux-en-Y reconstruction (55.2 %) were used for right-lobe LDLT, the incidence of complications was similar [35]. In this study, 40.6 % of the patients (39 of 96; 21 bile leaks, 22 strictures, four patients with both) had bile duct complications, with a higher incidence of bile leaks in those with multiple bile duct anastomoses (5.3 % with one duct, 14.9 % with two ducts, and 40 % with three ducts). The 2-year patient survival (76 % vs. 89 %) and graft survival (77 % vs. 85 %) rates were lower (P = 0.07) in patients who had bile leaks [35].

Donor Complications

In addition to the recipients, donors also may experience biliary complications. In a series of 200 consecutive right-lobe grafts, Ito et al. [36] reported biliary complications, consisting of 26 bile leaks (13 %) and three strictures (1.5 %), in 27 donors during a median surveillance period of 28.7 months. In a survey of 1508 donors in Asia, complications were seen more commonly with right-lobe as compared to left-lobe or left lateral segment transplantation; among 561 right-lobe donors, 6.1 % had bile leaks and 1.1 % developed strictures [37]. In another series, nine of 74 donors (11.2 %) had bile leaks, three of whom required surgical revision; the remainder were treated by endoscopic stent placement [38].

Management

The general principles of management discussed earlier apply to both donors and recipients with bile duct complications. In one series, 14 of 19 (73.7 %) recipients were treated endoscopically by internal stents, with a successful outcome in 13 patients [39]. Similar results have been reported for donors with bile duct complications [29] [38]. However, surgical revision is carried out more frequently in both donors and recipients after LDLT; this may be due to larger leaks after LDLT.

Impact of Biliary Complications on Graft and Patient Survival

There are conflicting data in the literature on the effect of biliary complications on survival. In one study, Stratta et al. [1] found no difference in graft survival rates in patients with or without biliary complication; in another, Rizk et al. [17] reported that endoscopic management of biliary complications following OLT did not adversely affect the patient or graft survival. By contrast, Kuo et al. [14] found a significantly higher 1-year mortality rate in patients with biliary complications. Similarly, lower graft and patient survival rates have been reported in adult LDLT patients who had biliary complications [35]. The differences in these reports may well be related to the type of bile duct complications and numerous other confounding factors. In our experience, only hilar or diffuse stricturing due to hepatic artery thrombosis appears to have an adverse outcome on graft or patient survival after cadaver transplantation. The limited data on LDLT indicate that biliary complications, especially bile leaks, may have an adverse outcome on graft survival.

Conclusion

Biliary complications are common after liver transplantation, and prompt recognition and management of these complications enhances complete and definitive treatment in most cases. ERC is safe and effective in the diagnosis and management of biliary complications after cadaveric liver transplantation and avoids the need for surgical or percutaneous transhepatic approaches in the majority of cases. Percutaneous or surgical approaches should be reserved for patients in whom endoscopic treatment fails and for those with multiple intrahepatic strictures or Roux-en-Y choledochojejunostomy anastomoses. The limited experience with LDLT suggests that biliary strictures can be managed by either endoscopic or percutaneous methods, but a significant number of bile leaks may require surgical revision. Although there are conflicting data, biliary complications do not have a major impact on graft or patient survival with cadaveric transplantation, except in patients with diffuse intrahepatic ischemic strictures. However, bile leakage may reduce graft survival in patients who receive LDLT.

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• 36 Ito T, Kiuchi T, Egawa H. et al . Surgery related morbidity in living donors of right lobe liver graft: lesions from the first 200 cases.  Transplantation. 2003;  76 158-163
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• 39 Hisatsune H, Yazumi S, Egawa H. et al . Endoscopic management of biliary strictures after duct to duct biliary reconstruction in right lobe living donor liver transplantation.  Transplantation. 2003;  76 810-815
  PubMedSearch in Google Scholar

P. J. Thuluvath, M.D., F.R.C.P.

The Johns Hopkins University School of Medicine

1830 East Monument Street · Baltimore, MD 21205 · USA

Fax: +1-410-614-9612

Email: pjthuluv@jhmi.edu

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• 26 Saab S, Martin P, Soliman G Y. et al . Endoscopic management of biliary leaks after T-tube removal in liver transplant recipients: nasobiliary drainage versus biliary stenting.  Liver Transpl. 2000;  6 627-632
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  CrossrefPubMedSearch in Google Scholar
• 28 Heffron T G, Pillen T, Welch D. et al . Biliary complications after pediatric liver transplantation revisited.  Transplant Proc.. 2003;  35 1461-1462
  CrossrefPubMedSearch in Google Scholar
• 29 Shah J N, Ahmad N A, Shetty K. et al . Endoscopic management of biliary complications after adult living donor liver transplantation.  Am J Gastroenterol. 2004;  99 1291-1295
  CrossrefPubMedSearch in Google Scholar
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  PubMedSearch in Google Scholar
• 31 Shah J N, Haigh W G, Lee S P. et al . Biliary casts after orthotopic liver transplantation: clinical factors, treatment, biochemical analysis.  Am J Gastroenterol. 2003;  98 1861-1867
  CrossrefPubMedSearch in Google Scholar
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  PubMedSearch in Google Scholar
• 33 Fondevila C, Ghobrial R M, Fuster J. et al . Biliary complications after adult living donor liver transplantation.  Transplant Proc. 2003;  35 1902-1903
  CrossrefPubMedSearch in Google Scholar
• 34 Egawa H, Inomata Y, Uemoto S. et al . Biliary anastomotic complications in 400 living related liver transplantations.  World J Surg. 2001;  25 1300-1307
  CrossrefPubMedSearch in Google Scholar
• 35 Gondolesi G E, Varotti G, Florman S S. et al . Biliary complications in 96 consecutive right lobe living donor transplant recipients.  Transplantation. 2004;  77 1842-1848
  CrossrefPubMedSearch in Google Scholar
• 36 Ito T, Kiuchi T, Egawa H. et al . Surgery related morbidity in living donors of right lobe liver graft: lesions from the first 200 cases.  Transplantation. 2003;  76 158-163
  PubMedSearch in Google Scholar
• 37 Lo C M. Complications and long-term outcome of living liver donors: a survey of 1,508 cases in five Asian centers.  Transplantation. 2003;  75 (3 Suppl) S12-S15
  PubMedSearch in Google Scholar
• 38 Malago M, Testa G, Frilling A. et al . Right living donor liver transplantation: an option for adult patients.  Ann Surg. 2003;  238 853-863
  PubMedSearch in Google Scholar
• 39 Hisatsune H, Yazumi S, Egawa H. et al . Endoscopic management of biliary strictures after duct to duct biliary reconstruction in right lobe living donor liver transplantation.  Transplantation. 2003;  76 810-815
  PubMedSearch in Google Scholar

P. J. Thuluvath, M.D., F.R.C.P.

The Johns Hopkins University School of Medicine

1830 East Monument Street · Baltimore, MD 21205 · USA

Fax: +1-410-614-9612

Email: pjthuluv@jhmi.edu