- Email: [email protected]
Biliary Complications after Orthotopic Liver Transplantation
Biliary Complications after Orthotopic Liver Transplantation David G. Buck, MD, and Albert B. Zajko, MD Liver transplantation has made many advances since its inception in the early 1970s. Despite volumes of basic science and clinical research related to liver transplantation, biliary complications continue to present the interventional radiologist with challenging cases in all transplant centers. Biliary complications can range from minor complications such as contained bile leaks to severe complications such as biliary necrosis resulting from hepatic artery thrombosis. Minor complications may require minimal or no intervention, whereas the more severe complications can require urgent surgery. To treat biliary complications such as anastomotic strictures, nonanastomotic strictures, biliary leaks, sludge or biliary necrosis, an accurate diagnosis must first be obtained. One must also be aware of how these complications can impair both allograft and transplant patient survival. With this information one can then plan a treatment knowing the potential success rates of specific treatments. Using proper technique with this information at hand can greatly increase the success rate in treating the spectrum of biliary complications. Interventional radiology serves a critical role in diagnosis and treatment of these liver transplant biliary complications and is important to the success of all transplant programs. Tech Vasc Interventional Rad 11:51-59 © 2008 Elsevier Inc. All rights reserved. Keywords liver transplantation, complications, biliary
B
iliary complications after liver transplantation continue to be a cause of morbidity and mortality despite advances in surgical techniques, immunosuppression, and postoperative management.1 Reports in recent literature indicate that biliary complications occur in 10 to 40% of all adult cases of liver transplantation,2,3 though some may not require intervention. The most common complications are bile leaks and anastomotic strictures. Biliary leaks are reported in 1 to 25% of all cases of liver transplantation.4,5 Anastomotic strictures are reported in 4 to 9% of adult orthotopic liver transplant (OLT) patients.6-9 Biliary strictures may also occur at locations other than the biliary anastomosis, called nonanastomotic strictures. The primary treatment for anastomotic biliary strictures is surgical repair, yet, with each subsequent repair, the failure rate increases.10 Nonanastomotic strictures can present a challenging problem also, as these are more difficult to treat, and surgical repair is not usually an option. Less common but significant biliary complications after liver transplantation include biliary leaks, retained internal biliary stents, biliary sludge/stones and biliary cast syndrome, and bile duct necrosis. University of Pittsburgh Medical Center, Department of Radiology, Division of Interventional Radiology, Pittsburgh, PA, USA. Address reprint requests to David G. Buck, MD, University of Pittsburgh Medical Center, Department of Radiology, Division of Interventional Radiology, 200 Lothrop Street, CMT-4886, Pittsburgh, PA 15213-2582. E-mail: [email protected].
1089-2516/08/$-see front matter © 2008 Elsevier Inc. All rights reserved. doi:10.1053/j.tvir.2008.05.006
No uniform algorithm for management of these biliary complications has been adopted by the transplant centers in the United States. Transplant patients are both surgically and medically complicated and therefore percutaneous methods for treatment of biliary complications have been used with increasing frequency.11 A survey in 1995 by Vallera and coworkers12 showed 22% of transplant centers in the United States reported the use of percutaneous transhepatic management, 29% opted for reoperation, and 45% used endoscopic treatment of these common biliary complications.
Anastomotic Strictures Anastomotic biliary strictures (AS) occur in 4 to 9% of transplanted patients.6,13-15 Biliary strictures at the site of bile duct anastomosis are thought to result from surgical technique and/or local ischemia.11 Other factors such as bile leakage have also been suggested as a risk factor in the development of anastomotic strictures.16 The majority of anastomotic strictures will present within the first 3 months after transplantation. In a study by Roumilhac and coworkers,17 the incidence of biliary strictures (diagnosed at a median time of 14 months) was not different between patients with choledochodochostomy and choledochojejunostomy anastomoses, or if a T-tube or trans-cystic tube was used, or if interrupted or continuous suture technique was used.17 Diagnosis of the stricture before percutaneous management can be sug51
52
D.G. Buck and A.B. Zajko
Figure 1 (A) PTC shows severe stenosis at the level of the choledochojejunostomy anastomosis in a patient with increasing serum bilirubin following orthotopic liver transplantation. Note filling of cystic duct stump. (B) Initial treatment consisted of placing an 8.5 French catheter across the stricture into the Roux-en-Y jejunal loop for internal/external drainage. Note drainage procedure was done from a left-sided approach. (C) The patient returned 1 week later for the first of two balloon dilations. For the first dilation, a 6-mm balloon was used. (D) Catheter cholangiogram after the second dilation of the stricture shows a normal anastomosis; the serum bilirubin had decreased to normal levels.
Biliary Complications after Liver Transplantation gested by noninvasive imaging such as ultrasound, CT, or MRI/MRCP, although most diagnoses are suggested by abnormal elevations in liver enzyme levels as these diagnostic studies have demonstrated false negative rates, which would lead one to pursue percutaneous evaluation. The technique for percutaneous treatment involves a standard right lateral intercostal access for whole liver and a subxyphoid access for split or partial liver transplants. After definitive diagnosis with transhepatic cholangiography and biliary drainage, dilation of the stricture is usually performed using standard angioplasty balloons over a 1- to 4-week period with up to three sessions of dilation required to treat the stricture (Figs. 1A-D). The balloon is sized to the normal duct adjacent to the stricture and then increased 1 to 2 mm at each successive session. A standard-sized (8.5 or 10 French) biliary catheter is placed to external drainage for 1 to 2 days after each dilation and then capped for internal drainage for a period of 4 to 6 weeks to allow for internal drainage before reevaluation.3 If the initial dilation is not successful, repeat dilation may be attempted. Otherwise, the patient is maintained with a biliary drainage catheter for an indefinite period or referred for surgical repair. Primary patency rates after balloon dilation of these strictures demonstrated by Zajko and coworkers18 in 1995 were 77% at 6 months and 66% at 6 years for anastomotic strictures. Although the previous method is the one used at the institution of the authors, alternative methods have been attempted to improve primary patency rates, such as balloon dilation of strictures and large profile catheters for maintenance after dilation19 or the use of combined cutting and conventional balloon catheters.18 These methods have resulted in minimal improvement in technical success and short-term patency rates in small study populations but require further evaluation with larger populations and midand long-term studies on an intent-to-treat basis to validate their utility.18,19 One might think that the use of a metallic stent in cases of anastomotic stenoses that are refractory to balloon dilation would be the next step. Early studies by Rieber and coworkers20 used Palmaz balloon expandable stents for AS and reported good results in five patients with follow-up between 19 and 43 months. Petersen and coworkers21 and Culp and coworkers11 reported success rates of expandable stents as 60 and 88%, respectively, at 60 months. The primary patency rates in these studies were low, 44% at 3 years and 0% at 5 years.11 The secondary patency results reached 88% in the study by Culp and coworkers.11 These studies and others suggest that the pitfall of metallic stents is the mucosal proliferation seen between the cells of the stent, which is responsible for recurrent bile duct obstruction and also can complicate any surgical intervention. Covered stents have also not proven successful, as the first results obtained with covered stents do not confirm the expectations of higher patency rates.22
Nonanastomotic Strictures Nonanastomotic or intrahepatic biliary strictures are a significant complication after OLT and cause increased morbidity and graft failure in the transplant patient.3,23 The reported incidence of nonanastomotic strictures (NAS) can range from
53
Figure 2 PTC shows multiple nonanastomotic central (hilar) biliary strictures in transplant patient with hepatic artery thrombosis.
5 to 15%.3,24 NAS can result in a graft loss rate up to 46% after 2 years,25 can occur at multiple locations in the biliary tree, and are frequently resistant to therapy.24,26 Initial reports of NAS after OLT were described in association with hepatic artery thrombosis resulting in bile duct ischemia (Fig. 2).9 Later reports described intrahepatic strictures and dilations in patients without hepatic artery thrombosis,27 suggesting that several mechanisms may cause intrahepatic biliary strictures. The exact mechanisms resulting in NAS are not understood, but several studies have suggested risk factors associated with two groups that have shown increased incidence of NAS. The two groups are patients with preservation injury (prolonged cold and warm ischemia times) and also patients with complications related to immunological processes.28,29 Other factors implicated in NAS include a rapid increase in hydrophobic bile salt secretion seen after transplantation.30 Additionally, recurrent pretransplant diseases, chronic rejection, and recurrent infection may be issues that are difficult to separate from these factors. Several studies have shown that a higher incidence of NAS is seen in patients transplanted for primary sclerosing cholangitis (PSC)26 and in patients with postoperative cytomegalovirus (CMV) infections.31 This finding may also be in part due to the fact that most patients with PSC undergo a choledochojejunostomy anastomosis and this has been shown as an independent risk factor for the development of NAS and cholangitis.14 In addition, some investigators have shown that patients who present with NAS early after transplantation have a more severe course of disease.24 Those with lesions that are within the segmental and subsegmental zones of the liver result in more long-term damage than those with central lesions.14 It is safe to say that NAS is a single disease with many different pathogenesis. Depending on how one
D.G. Buck and A.B. Zajko
54
portion of these patients eventually required retransplantation. Several authors have described successful treatment of NAS with different modalities.18,32 The authors’ institution is similar to most major transplant centers in the use of both endoscopic and percutaneous methods to treat NAS lesions. Percutaneous dilation protocols for treatment of NAS are similar to those used for AS with the use of progressively larger balloon catheters over a short interval with repeated dilations. The treatment of NAS differs from AS in that multiple strictures may need to be treated and more than one drainage catheter and access route may be required. In most patients, a short-term improvement in liver function is seen, though these results do not translate into durable long-term results.
Biliary Leaks Biliary leaks after orthotopic whole liver transplantation usually occur within 1 to 3 months after transplantation4,5 and occur in 1 to 25% of liver transplantations.5,33 The majority of these postoperative leaks will occur either at the site of anastomosis or the T-tube insertion site (Figs. 3, 4, and 5). Other sources may include leaks due to hepatic artery thrombosis (which tend to occur relatively late) (Fig. 6), leaks from an aberrant duct, or leaks as a result of liver biopsy (Fig. 7). Anastomotic leaks may suggest a technical problem with the
Figure 3 (A) Catheter cholangiogram after transhepatic biliary drainage shows a contained bile leak at the choledochocholedochostomy anastomosis. This was treated with transhepatic external biliary drainage. (B) Ten days after external catheter drainage, follow-up catheter cholangiogram shows resolution of the anastomotic leak.
classifies NAS, the severity can also range from mild mural irregularity to diffuse intrahepatic biliary strictures. NAS can have severe clinical consequences. NAS, untreated, can progress to recurrent cholangitis or even to the endpoint of biliary cirrhosis. In a study by Verdonk and coworkers,14 biliary cirrhosis or even severe fibrosis was found in 28% of the cases of NAS that were followed. A large
Figure 4 T-tube cholangiogram shows a contained leak at the T-tube insertion site.
Biliary Complications after Liver Transplantation
55
anastomosis, infection, or evidence of bile duct ischemia, whereas leaks at the T-tube site may occur either due to a technical problem with insertion at surgery or after removal of the T-tube.34 Most transplant centers perform a duct-toduct choledochocholedochostomy biliary anastomosis, leaving a biliary T-tube in place to inhibit stricture formation. A choledochojejunostomy biliary anastomosis is suggested for patients with PSC or when there is a significant size discrepancy between the donor and recipient.35 A biliary leak is suggested after transplantation if there is a high clinical suspicion and symptoms of fever and upper abdominal pain with an elevation in cholestatic liver enzyme levels (gammaglutamyl transferase, bilirubin, and serum alkaline phosphatase). Indirect confirmatory diagnosis can be obtained with ultrasound, radionuclide imaging, CT, or MRI/
Figure 6 Catheter cholangiogram shows diffuse intrahepatic bile duct necrosis with multiple intrahepatic bilomas and a hilar biliary stricture in transplant patient with hepatic artery thrombosis.
MRCP or direct diagnosis with T-tube cholangiography or percutaneous/endoscopic cholangiography. Treatment of biliary leaks is dependent on the severity and the location of the leak. T-tube insertion site leaks can be treated by external drainage, drainage through the T-tube, or endoscopic temporary stent placement.36 It is important to note that half of T-tube leaks are reported to seal spontaneously; the remainder may require endoscopic or percutaneous management. Surgical revision is reserved for anastomotic leaks in which the anastomosis is severely disrupted or there is extensive leakage.37 If the anastomosis is intact and
Figure 5 (A) T-tube cholangiogram shows leak from choledochocholedochostomy anastomosis resulting in a large biloma. (B) The biloma was treated with CT-guided placement of an external pigtail drainage catheter with complete resolution of the collection.
Figure 7 PTC shows leak from a right segmental bile duct after recent percutaneous liver biopsy. Note obstruction at the hepaticojejunostomy, which aided in keeping the leak open.
56
D.G. Buck and A.B. Zajko mortality as a result of biliary sludge and casts caused by recurrent cholangitis, multiple surgeries, graft loss, and death.43 Multiple factors can contribute to bile duct filling defect formation, including ischemia, infection, and preservation injuries28,29 An early report suggested that ischemic necrosis of the mucosa and duct wall in conjunction with infection is the mechanism for sludge formation.45 Bile duct edema during the perioperative period causing decreased bile flow or later development of bile duct obstruction or stricture were also suggested in that study to cause formation of biliary sludge. As seen in biliary strictures, it is also important to note that bile duct filling defects occur more frequently in patients with a choledochojejunostomy than in those with a choledochodochostomy.46 Biliary sludge may progress to biliary stones given enough time. This has been postulated in several studies that note that the interval between transplantation and diagnosis of sludge was significantly shorter than for the diagnosis of stones.46 It may be impossible to distinguish the difference between stones and sludge with cholangiography but, if stones are identified, a surgical approach for treatment may be indicated. The clinical presentation of transplant patients with bile duct filling defects is similar to patients with other biliary complications. Cholangitis is the most frequent presentation,
Figure 8 PTC demonstrates multiple filling defects in the extrahepatic bile duct, presumed to be sludge. A biliary leak is also seen at the choledochojejunostomy anastomosis.
there is minimal leakage, the biliary leak can be managed with endoscopic placement of a temporary stent, sphincterotomy, or percutaneous treatment (Fig. 3) and achieve success rates near 90% for anastomotic leaks.38 Other percutaneous methods have been suggested in anecdotal reports for treating segmental and subsegmental bile duct leaks, such as using cyanoacrylate glue39 to seal an aberrant duct, selective portal vein embolization,40 and acetic acid41 or ethanol42 injections. The utility of these methods has not been tested in the transplant patient, and percutaneous or endoscopic treatments remain the first options.
Bile Duct Filling Defects Biliary stones, sludge, and casts are a spectrum of intraductal bile duct filling defects which are recognized complications after liver transplantation but are not as well known (Figs. 8 and 9). These complications are relatively infrequent compared with biliary strictures and leaks. In the initial experience with liver transplantation (reported in 1977), the prevalence of sludge was reported as ranging from 26 to 42%.43 The prevalence significantly decreased to 13% in a report 14 to 15 years later44 and Sheng and coworkers45 in 1996 reported a prevalence of 5.7% in a total of 1650 transplanted livers at the authors institution. Despite the relative infrequency, studies have shown an increased morbidity and
Figure 9 T-tube cholangiogram shows a large biliary stone within the allograft common hepatic duct.
Biliary Complications after Liver Transplantation
57
with only a small percentage presenting with abdominal pain.46 Bile duct filling defects may be treated using percutaneous, endoscopic, or surgical methods. The treatment option is often dictated by the clinical condition and the surgical anatomy. At the authors’ institution, there are no indications for use of a specific method. Percutaneous transhepatic biliary treatment is advantageous in that it can be used for both biliary drainage and treatment of any underlying strictures. Treatments may include stone/sludge removal or extraction using balloon catheters or basket retrieval or even chemolysis. The use of oral ursodiol (Summit Pharmaceuticals, Summit, NJ) or transhepatic infusions of N-acetyl-cysteine (Apothecon, Princeton, NJ) for chemolysis have been used with limited success. Although, there are selected reports showing chemolysis to result in complete disappearance of biliary sludge in 40% of treated patients.47 Two other entities should be considered when discussing filling defects, biliary cast syndrome and retained internal biliary stents. Biliary cast syndrome was described over three decades ago.43 It is characterized by multiple intrahepatic biliary strictures, ductal dilation, intrahepatic abscesses, and biliary anastomotic leakage and has a characteristic cholangiographic appearance and can be seen in association with CMV cholangitis.31 The prevalence has significantly decreased over three decades with improvements in graft harvesting and preservation. The casts are treated with percutaneous or endoscopic extraction but may require surgical intervention. Retained internal biliary stents can also cause filling defects and/or biliary obstruction. The biliary anastomoses are constructed over small silastic stents or externalized T-tubes. These internal stents are designed to pass into the small bowel once the biliary sutures dissolve.48 These stents can occasionally fail to pass. If the endoscopist is unable to retrieve the stent (which is often the case since they are within a Roux loop), a percutaneous approach with snare retrieval is used. The stent is then removed via the percutaneous tract or advanced into the adjacent bowel (Fig. 10).
Biliary Complications and Hepatic Artery Thrombosis Hepatic artery thrombosis is a complication that deserves discussion when addressing biliary complications. All native arterial vascular connections to the donor bile ducts are severed at donor hepatectomy.49 Many patients with thrombosis are retransplanted, when the diagnosis is made early. These patients usually present with liver failure, hepatic necrosis, or nonanastomotic bile leaks.50 A study by Tzakis and coworkers50 documented seven patients with extrahepatic bile leaks and hepatic artery thrombosis. All of the patients showed common duct necrosis at laparotomy. Bile duct necrosis at cholangiography is characterized by confluent intruductal filling defects within irregular dilated or strictured bile ducts. At the authors’ institution, biliary necrosis has been shown in up to 58% of patients and abnormal cholangiograms have been found in more than 80% of patients with hepatic artery thrombosis (Fig. 11) and is frequently associated with intrahepatic bile leak and biloma formation (Fig. 12).9 Therefore,
Figure 10 (A) Catheter cholangiogram after transhepatic drainage shows a retained internal biliary stent associated with obstruction of the hepaticojejunostomy due to anastomotic edema. Note thickened jejunal folds also due to edema. The stent was snared and advanced into the jejunum. (B) After a week of external drainage, catheter cholangiogram shows a patent hepaticojejunostomy anastomosis after resolution of the edema. The biliary catheter was removed.
D.G. Buck and A.B. Zajko
58 perioperative hilar or intrahepatic bilomas should raise the suspicion of thrombosis and should also be treated to prevent secondary infection and sepsis. In comparison, hepatic artery stenosis has a variable presentation, though some will have nonanstomotic biliary strictures. Many patients with hepatic artery stenosis will present with nonspecific elevation in liver enzyme levels. The cause of elevated liver enzyme levels can be attributed to many factors, including rejection, infection, or ischemia, and are not predictive of specific abnormal cholangiographic findings. But abnormal cholangiograms will be present in up to
Figure 12 Enhanced CT scan of the liver shows extensive intrahepatic bilomas due to biliary necrosis resulting from hepatic artery thrombosis.
67% of patients with hepatic artery stenosis.51 In fact, a study by Orons and coworkers51 demonstrated the importance of cholangiographic evaluation, as the majority of patients with hepatic artery stenosis demonstrated findings that were not evident by ultrasound examination. Another important point of this study was the critical point of early identification of hepatic artery stenosis. Complications such as intrahepatic strictures and the resultant increased risk of cholangitis may be avoided by early detection. With detection, permanent allograft damage is avoided. In 1995, Orons and coworkers52 found that the treatment of hepatic artery stenosis with balloon angioplasty is of limited benefit once significant allograft dysfunction is present.
References
Figure 11 (A) Catheter cholangiogram after transhepatic drainage shows a large area of hilar biliary necrosis in a patient with hepatic artery thrombosis. (B) PTC shows left lobe biliary necrosis, necrotic debris within the right hepatic duct, and a severe hilar stricture in another patient with hepatic artery thrombosis. Note, however, that the hepaticojejunostomy biliary anastomosis is normal. An internal stent is also in place.
1. Ward EM, Kiely MJ, Maus TP, et al: Hilar biliary strictures after liver transplantation: Cholangiography and percutaneous management. Radiology 177:259-263, 1999 2. Zajko AB, Campbell WL, Bron KM, et al: Cholangiography and interventional radiology in adult liver transplantation. Am J Roentgenol 144:127-133, 1985 3. Thethy S, Thomson B, Pleass H, et al: Management of biliary tract complications after orthotopic liver transplantation. Clin Transplant 18:647-653, 2004 4. Tung BY, Kimmey MB: Biliary complications of orthotopic liver transplantation. Dig Dis 17:133, 1999 5. Jagganath S, Kaloo AN: Biliary complications after liver transplantation. Curr Treat Options Gastroenterol 5:101, 2002 6. Greif F, Bronsther OL, Van Thiel DH, et al: The incidence, timing and management of biliary complications after orthotopic liver transplantation. Ann Surg 219:40-45, 1994 7. Campbell WL, Sheng R, Zajko AB, et al: Intrahepatic biliary strictures after liver transplantation. Radiology 191:735-740, 1994 8. Evans RA, Raby ND, O’Grady JG, et al: Biliary complications following liver transplantation. Clin Radiology 41:190-194, 1990 9. Zajko AB, Campbell WL, Logsdon GA, et al: Cholangiographic findings in hepatic artery occlusion after liver transplantation. Am J Radiol 149: 485-489, 1987 10. Pitt HA, Miyamoto T, Parppatis SK, et al: Factors influencing outcome in patients with postoperative biliary strictures. Am J Surg 144:14-21, 1982 11. Culp W, McCowan T, Lieberman R, et al: Biliary strictures in liver transplant recipients: treatment with metal stents. Radiology 199:339346, 1996 12. Vallera RA, Cotton PB, Clavien PA: Biliary reconstruction for liver transplantation and management of biliary complications overview and
Biliary Complications after Liver Transplantation
13.
14.
15.
16. 17.
18.
19.
20.
21.
22.
23.
24.
25.
26.
27.
28.
29.
30.
31.
survey of current practices in the United States. Liver Transpl Surg 1:143-152, 1995 Diamond N, Lee S, Niblett R, et al: Metallic stents for the treatment of intrahepatic biliary strictures after liver transplantation. J Vasc Interv Radiol 6:755-761, 1995 Verdonk RC, Buis CI, Porte RJ, et al: Anastomotic biliary strictures after liver transplantation: Causes and consequences. Liver Transpl 12:726735, 2006 Mosca S. Militerno G, Guardascione MA, et al: Late biliary tract complications after orthotopic liver transplantation: Diagnostic and therapeutic role of endoscopic retrograde cholangiopancreatography. J Gastroenterol Hepatol 15:654-660, 2000 Ostroff JW: Post-transplant biliary problems. Gastrointest Endosc Clin N Am 11:163-183, 2001 Roumilhac D, Poyet G, Sergent G, et al: Long-term results of percutaneous management for anastomotic biliary stricture after orthotopic liver transplantation. Liver Transplantation 9:394-400, 2003 Zajko AB, Sheng R, Zetti GM, et al: Transhepatic balloon dilation of biliary strictures in liver transplant patients: A 10-year experience. J Vasc Interv Radiol 6:79-83, 1995 Thuluvath PJ, Atassi T, Lee J: An endoscopic approach to biliary complications following orthotopic liver transplantation. Liver Int 23:156162, 2003 Rieber A, Brambs HJ, Lauchart W: The radiological management of biliary complications following liver transplantation. Cardiovasc Intervent Radiol 19:242-247, 1996 Petersen BD, Maxfield SR, Ivancev K, et al: Biliary strictures in hepatic transplantation: Treatment with self-expanding Z stents. J Vasc Interv Radiol 7:221-228, 1996 Righi D, Cesarini F, Muraro E, et al: Role of interventional radiology in the treatment of biliary strictures following orthotopic liver transplantation. Cardiovasc Intervent Radiol 25:30-35, 2002 Choo SW, Shin SW, Do YS, et al: The balloon dilation and large profile catheter maintenance method for the management of the bile duct stricture following liver transplantation. Korean J Radiol 7:41-49, 2006 Sanchez-Urdazpal L, Gores GJ, Ward EM, et al: Diagnostic features and clinical outcome of ischemic-type biliary strictures. Hepatology 17: 605-609, 1993 Saad WEA, Davies MG, Saad NEA, et al: Transhepatic dilation of anastomotic biliary strictures in liver transplant recipients with use of a combined cutting and conventional balloon protocol: Technical safety and efficacy. J Vasc Interv Radiol 17:837-843, 2006 Guichelaar MM, Benson JT, Malinchoc M, et al: Risk factors for and clinical course of non-anastomotic biliary strictures after liver transplantation. Am J Transplant 3:885-890, 2003 Sanchez-Urdazpal L, Sterioff S, Janes C, et al: Increased bile duct complications in ABO incompatable liver transplant recipients. Transplant Proc 23:1440-1441, 1991 Buis CI, Hoekstra H, Verdonk RC, et al: Causes and consequences of ischemic-type biliary lesions after liver transplantation. J Hepatobiliary Pancreat Surg 13:517-524, 2006 Sankary HN, McChesney L, Hart M, et al: Identification of donor and recipient risk factors associated with non-anastomotic biliary strictures in human hepatic allografts. Transpl Proc 25:1964-1967, 1993 Gueken E, Visser D, Kuipers F, et al: Rapid increase of bile salt associated with bile duct injury after human liver transplantation. J Hepatol 41:1017-1025, 2004 Halme L, Hockerstedt K, Lautenschlager I: Cytomegalovirus infection and development of biliary complications after liver transplantation. Transplantation 75:1853-1858, 2003
59 32. Sung RS, Campbell DA Jr, Rudich SM, et al: Long-term follow-up of percutaneous transhepatic balloon cholangiography in the management of biliary strictures after liver transplantation. Transplantation 77:110-115, 2004 33. Tung BY, Kimmey MB: Biliary complications of orthotopic liver transplantation. Dig Dis 17:133, 1999 34. Lake JR: Long-term management of biliary tract complications. Liver Transpl Surg 1:45, 1998 35. Hampe T, Dogan A, Enche J, et al: Biliary complications after liver transplantation. Clin Transplant 20:93-96, 2006 (suppl 17) 36. Rerknimitr R, Sherman S, Fogel EL, et al: Biliary tract complications after orthotopic liver transplantation with choledochocholedochostomy anastomosis: Endoscopic findings and results of therapy. Gastrointest Endosc 55:224, 2002 37. Sheng R, Sammon JK, Zajko AB, et al: Bile leak after hepatic transplantation: Cholangiographic features, prevalence, and clinical outcome. Radiology 192:413, 1994 38. Moser MA, Wall WJ: Management of biliary problems after liver transplantation. Liver Transpl 7:S46, 2001 (suppl 2) 39. Kiltz U, Baier J, Adamek RJ: Selective embolization of a bile leak after operative resection of an echinococcal cyst. Dtsch Med Wochenschr 124:650-652, 1999 40. Yamakado K, Atsuhiro N, Iwata M, et al: Refractory biliary leak from intrahepatic biliary-enteric anastomosis treated by selective portal vein embolization. J Vasc Interv Radiol 13:1279-181, 2002 41. Park J, Oh JH, Yoon Y, et al: Acetic acid sclerotherapy for the treatment of a biliary leak from an isolated bile duct after hepatic surgery. J Vasc Interv Radiol 16:885-888, 2005 42. Kyokane T, Nagino M, Sano T, et al: Ethanol ablation for segmental bile duct leakage after hepatobiliary resection. Surgery 131:111-113, 2002 43. Starzl TE, Putman CW, Hansbrough JF, et al: Biliary complications after liver transplantation; with special reference to the biliary cast syndrome and techniques of secondary duct repair. Surgery 81:212221, 1977 44. Barton PP, Maier A, Steininger R, et al: Biliary sludge after liver transplantation. 1. Imaging findings and efficacy of various imaging procedures. Am J Roentgenol 164:859-864, 1995 45. McMaster P, Herbertson BM, Cusick C, et al: Biliary sludging following liver transplantation in man. Transplantation 25:56-62, 1978 46. Sheng R, Ramirez CB, Zajko AB, et al: Biliary stones and sludge in liver transplant patients: A 13-year experience. Radiology 198:243-247, 1996 47. Barton PP, Maier A, Steininger R, et al: Biliary sludge after liver transplantation. 2. Treatment with interventional techniques versus surgery and/or oral chemolysis. Am J Roentgenol 164:865-869, 1995 48. Zajko AB, Campbell WL, Bron KM, et al: Diagnostic and interventional radiology in liver transplantation. Gastroenterol Clin N Am 17:105143, 1988 49. Cho KJ, Lunderquist A: The peribiliary vascular plexus: The microvascular architecture of the bile duct in the rabbit and in clinical cases. Radiology 41:357-364, 1983 50. Tzakis AG, Gordon RD, Shaw BW Jr, et al: Clinical presentation of hepatic artery thrombosis after liver transplantation in the cyclosporine era. Transplantation 40:667-671, 1985 51. Orons PD, Sheng R, Zajko AB: Hepatic artery stenosis in liver transplant recipients: Prevalence and cholangiographic appearance of associated biliary complications. Am J Roentgenol 165:1145-1149, 1995 52. Orons PD, Zajko AB, Bron KM, et al: Hepatic artery stenosis after liver transplantation: Experience in 21 allografts. J Vasc Interv Radiol 6:523529, 1995
B
iliary complications after liver transplantation continue to be a cause of morbidity and mortality despite advances in surgical techniques, immunosuppression, and postoperative management.1 Reports in recent literature indicate that biliary complications occur in 10 to 40% of all adult cases of liver transplantation,2,3 though some may not require intervention. The most common complications are bile leaks and anastomotic strictures. Biliary leaks are reported in 1 to 25% of all cases of liver transplantation.4,5 Anastomotic strictures are reported in 4 to 9% of adult orthotopic liver transplant (OLT) patients.6-9 Biliary strictures may also occur at locations other than the biliary anastomosis, called nonanastomotic strictures. The primary treatment for anastomotic biliary strictures is surgical repair, yet, with each subsequent repair, the failure rate increases.10 Nonanastomotic strictures can present a challenging problem also, as these are more difficult to treat, and surgical repair is not usually an option. Less common but significant biliary complications after liver transplantation include biliary leaks, retained internal biliary stents, biliary sludge/stones and biliary cast syndrome, and bile duct necrosis. University of Pittsburgh Medical Center, Department of Radiology, Division of Interventional Radiology, Pittsburgh, PA, USA. Address reprint requests to David G. Buck, MD, University of Pittsburgh Medical Center, Department of Radiology, Division of Interventional Radiology, 200 Lothrop Street, CMT-4886, Pittsburgh, PA 15213-2582. E-mail: [email protected].
1089-2516/08/$-see front matter © 2008 Elsevier Inc. All rights reserved. doi:10.1053/j.tvir.2008.05.006
No uniform algorithm for management of these biliary complications has been adopted by the transplant centers in the United States. Transplant patients are both surgically and medically complicated and therefore percutaneous methods for treatment of biliary complications have been used with increasing frequency.11 A survey in 1995 by Vallera and coworkers12 showed 22% of transplant centers in the United States reported the use of percutaneous transhepatic management, 29% opted for reoperation, and 45% used endoscopic treatment of these common biliary complications.
Anastomotic Strictures Anastomotic biliary strictures (AS) occur in 4 to 9% of transplanted patients.6,13-15 Biliary strictures at the site of bile duct anastomosis are thought to result from surgical technique and/or local ischemia.11 Other factors such as bile leakage have also been suggested as a risk factor in the development of anastomotic strictures.16 The majority of anastomotic strictures will present within the first 3 months after transplantation. In a study by Roumilhac and coworkers,17 the incidence of biliary strictures (diagnosed at a median time of 14 months) was not different between patients with choledochodochostomy and choledochojejunostomy anastomoses, or if a T-tube or trans-cystic tube was used, or if interrupted or continuous suture technique was used.17 Diagnosis of the stricture before percutaneous management can be sug51
52
D.G. Buck and A.B. Zajko
Figure 1 (A) PTC shows severe stenosis at the level of the choledochojejunostomy anastomosis in a patient with increasing serum bilirubin following orthotopic liver transplantation. Note filling of cystic duct stump. (B) Initial treatment consisted of placing an 8.5 French catheter across the stricture into the Roux-en-Y jejunal loop for internal/external drainage. Note drainage procedure was done from a left-sided approach. (C) The patient returned 1 week later for the first of two balloon dilations. For the first dilation, a 6-mm balloon was used. (D) Catheter cholangiogram after the second dilation of the stricture shows a normal anastomosis; the serum bilirubin had decreased to normal levels.
Biliary Complications after Liver Transplantation gested by noninvasive imaging such as ultrasound, CT, or MRI/MRCP, although most diagnoses are suggested by abnormal elevations in liver enzyme levels as these diagnostic studies have demonstrated false negative rates, which would lead one to pursue percutaneous evaluation. The technique for percutaneous treatment involves a standard right lateral intercostal access for whole liver and a subxyphoid access for split or partial liver transplants. After definitive diagnosis with transhepatic cholangiography and biliary drainage, dilation of the stricture is usually performed using standard angioplasty balloons over a 1- to 4-week period with up to three sessions of dilation required to treat the stricture (Figs. 1A-D). The balloon is sized to the normal duct adjacent to the stricture and then increased 1 to 2 mm at each successive session. A standard-sized (8.5 or 10 French) biliary catheter is placed to external drainage for 1 to 2 days after each dilation and then capped for internal drainage for a period of 4 to 6 weeks to allow for internal drainage before reevaluation.3 If the initial dilation is not successful, repeat dilation may be attempted. Otherwise, the patient is maintained with a biliary drainage catheter for an indefinite period or referred for surgical repair. Primary patency rates after balloon dilation of these strictures demonstrated by Zajko and coworkers18 in 1995 were 77% at 6 months and 66% at 6 years for anastomotic strictures. Although the previous method is the one used at the institution of the authors, alternative methods have been attempted to improve primary patency rates, such as balloon dilation of strictures and large profile catheters for maintenance after dilation19 or the use of combined cutting and conventional balloon catheters.18 These methods have resulted in minimal improvement in technical success and short-term patency rates in small study populations but require further evaluation with larger populations and midand long-term studies on an intent-to-treat basis to validate their utility.18,19 One might think that the use of a metallic stent in cases of anastomotic stenoses that are refractory to balloon dilation would be the next step. Early studies by Rieber and coworkers20 used Palmaz balloon expandable stents for AS and reported good results in five patients with follow-up between 19 and 43 months. Petersen and coworkers21 and Culp and coworkers11 reported success rates of expandable stents as 60 and 88%, respectively, at 60 months. The primary patency rates in these studies were low, 44% at 3 years and 0% at 5 years.11 The secondary patency results reached 88% in the study by Culp and coworkers.11 These studies and others suggest that the pitfall of metallic stents is the mucosal proliferation seen between the cells of the stent, which is responsible for recurrent bile duct obstruction and also can complicate any surgical intervention. Covered stents have also not proven successful, as the first results obtained with covered stents do not confirm the expectations of higher patency rates.22
Nonanastomotic Strictures Nonanastomotic or intrahepatic biliary strictures are a significant complication after OLT and cause increased morbidity and graft failure in the transplant patient.3,23 The reported incidence of nonanastomotic strictures (NAS) can range from
53
Figure 2 PTC shows multiple nonanastomotic central (hilar) biliary strictures in transplant patient with hepatic artery thrombosis.
5 to 15%.3,24 NAS can result in a graft loss rate up to 46% after 2 years,25 can occur at multiple locations in the biliary tree, and are frequently resistant to therapy.24,26 Initial reports of NAS after OLT were described in association with hepatic artery thrombosis resulting in bile duct ischemia (Fig. 2).9 Later reports described intrahepatic strictures and dilations in patients without hepatic artery thrombosis,27 suggesting that several mechanisms may cause intrahepatic biliary strictures. The exact mechanisms resulting in NAS are not understood, but several studies have suggested risk factors associated with two groups that have shown increased incidence of NAS. The two groups are patients with preservation injury (prolonged cold and warm ischemia times) and also patients with complications related to immunological processes.28,29 Other factors implicated in NAS include a rapid increase in hydrophobic bile salt secretion seen after transplantation.30 Additionally, recurrent pretransplant diseases, chronic rejection, and recurrent infection may be issues that are difficult to separate from these factors. Several studies have shown that a higher incidence of NAS is seen in patients transplanted for primary sclerosing cholangitis (PSC)26 and in patients with postoperative cytomegalovirus (CMV) infections.31 This finding may also be in part due to the fact that most patients with PSC undergo a choledochojejunostomy anastomosis and this has been shown as an independent risk factor for the development of NAS and cholangitis.14 In addition, some investigators have shown that patients who present with NAS early after transplantation have a more severe course of disease.24 Those with lesions that are within the segmental and subsegmental zones of the liver result in more long-term damage than those with central lesions.14 It is safe to say that NAS is a single disease with many different pathogenesis. Depending on how one
D.G. Buck and A.B. Zajko
54
portion of these patients eventually required retransplantation. Several authors have described successful treatment of NAS with different modalities.18,32 The authors’ institution is similar to most major transplant centers in the use of both endoscopic and percutaneous methods to treat NAS lesions. Percutaneous dilation protocols for treatment of NAS are similar to those used for AS with the use of progressively larger balloon catheters over a short interval with repeated dilations. The treatment of NAS differs from AS in that multiple strictures may need to be treated and more than one drainage catheter and access route may be required. In most patients, a short-term improvement in liver function is seen, though these results do not translate into durable long-term results.
Biliary Leaks Biliary leaks after orthotopic whole liver transplantation usually occur within 1 to 3 months after transplantation4,5 and occur in 1 to 25% of liver transplantations.5,33 The majority of these postoperative leaks will occur either at the site of anastomosis or the T-tube insertion site (Figs. 3, 4, and 5). Other sources may include leaks due to hepatic artery thrombosis (which tend to occur relatively late) (Fig. 6), leaks from an aberrant duct, or leaks as a result of liver biopsy (Fig. 7). Anastomotic leaks may suggest a technical problem with the
Figure 3 (A) Catheter cholangiogram after transhepatic biliary drainage shows a contained bile leak at the choledochocholedochostomy anastomosis. This was treated with transhepatic external biliary drainage. (B) Ten days after external catheter drainage, follow-up catheter cholangiogram shows resolution of the anastomotic leak.
classifies NAS, the severity can also range from mild mural irregularity to diffuse intrahepatic biliary strictures. NAS can have severe clinical consequences. NAS, untreated, can progress to recurrent cholangitis or even to the endpoint of biliary cirrhosis. In a study by Verdonk and coworkers,14 biliary cirrhosis or even severe fibrosis was found in 28% of the cases of NAS that were followed. A large
Figure 4 T-tube cholangiogram shows a contained leak at the T-tube insertion site.
Biliary Complications after Liver Transplantation
55
anastomosis, infection, or evidence of bile duct ischemia, whereas leaks at the T-tube site may occur either due to a technical problem with insertion at surgery or after removal of the T-tube.34 Most transplant centers perform a duct-toduct choledochocholedochostomy biliary anastomosis, leaving a biliary T-tube in place to inhibit stricture formation. A choledochojejunostomy biliary anastomosis is suggested for patients with PSC or when there is a significant size discrepancy between the donor and recipient.35 A biliary leak is suggested after transplantation if there is a high clinical suspicion and symptoms of fever and upper abdominal pain with an elevation in cholestatic liver enzyme levels (gammaglutamyl transferase, bilirubin, and serum alkaline phosphatase). Indirect confirmatory diagnosis can be obtained with ultrasound, radionuclide imaging, CT, or MRI/
Figure 6 Catheter cholangiogram shows diffuse intrahepatic bile duct necrosis with multiple intrahepatic bilomas and a hilar biliary stricture in transplant patient with hepatic artery thrombosis.
MRCP or direct diagnosis with T-tube cholangiography or percutaneous/endoscopic cholangiography. Treatment of biliary leaks is dependent on the severity and the location of the leak. T-tube insertion site leaks can be treated by external drainage, drainage through the T-tube, or endoscopic temporary stent placement.36 It is important to note that half of T-tube leaks are reported to seal spontaneously; the remainder may require endoscopic or percutaneous management. Surgical revision is reserved for anastomotic leaks in which the anastomosis is severely disrupted or there is extensive leakage.37 If the anastomosis is intact and
Figure 5 (A) T-tube cholangiogram shows leak from choledochocholedochostomy anastomosis resulting in a large biloma. (B) The biloma was treated with CT-guided placement of an external pigtail drainage catheter with complete resolution of the collection.
Figure 7 PTC shows leak from a right segmental bile duct after recent percutaneous liver biopsy. Note obstruction at the hepaticojejunostomy, which aided in keeping the leak open.
56
D.G. Buck and A.B. Zajko mortality as a result of biliary sludge and casts caused by recurrent cholangitis, multiple surgeries, graft loss, and death.43 Multiple factors can contribute to bile duct filling defect formation, including ischemia, infection, and preservation injuries28,29 An early report suggested that ischemic necrosis of the mucosa and duct wall in conjunction with infection is the mechanism for sludge formation.45 Bile duct edema during the perioperative period causing decreased bile flow or later development of bile duct obstruction or stricture were also suggested in that study to cause formation of biliary sludge. As seen in biliary strictures, it is also important to note that bile duct filling defects occur more frequently in patients with a choledochojejunostomy than in those with a choledochodochostomy.46 Biliary sludge may progress to biliary stones given enough time. This has been postulated in several studies that note that the interval between transplantation and diagnosis of sludge was significantly shorter than for the diagnosis of stones.46 It may be impossible to distinguish the difference between stones and sludge with cholangiography but, if stones are identified, a surgical approach for treatment may be indicated. The clinical presentation of transplant patients with bile duct filling defects is similar to patients with other biliary complications. Cholangitis is the most frequent presentation,
Figure 8 PTC demonstrates multiple filling defects in the extrahepatic bile duct, presumed to be sludge. A biliary leak is also seen at the choledochojejunostomy anastomosis.
there is minimal leakage, the biliary leak can be managed with endoscopic placement of a temporary stent, sphincterotomy, or percutaneous treatment (Fig. 3) and achieve success rates near 90% for anastomotic leaks.38 Other percutaneous methods have been suggested in anecdotal reports for treating segmental and subsegmental bile duct leaks, such as using cyanoacrylate glue39 to seal an aberrant duct, selective portal vein embolization,40 and acetic acid41 or ethanol42 injections. The utility of these methods has not been tested in the transplant patient, and percutaneous or endoscopic treatments remain the first options.
Bile Duct Filling Defects Biliary stones, sludge, and casts are a spectrum of intraductal bile duct filling defects which are recognized complications after liver transplantation but are not as well known (Figs. 8 and 9). These complications are relatively infrequent compared with biliary strictures and leaks. In the initial experience with liver transplantation (reported in 1977), the prevalence of sludge was reported as ranging from 26 to 42%.43 The prevalence significantly decreased to 13% in a report 14 to 15 years later44 and Sheng and coworkers45 in 1996 reported a prevalence of 5.7% in a total of 1650 transplanted livers at the authors institution. Despite the relative infrequency, studies have shown an increased morbidity and
Figure 9 T-tube cholangiogram shows a large biliary stone within the allograft common hepatic duct.
Biliary Complications after Liver Transplantation
57
with only a small percentage presenting with abdominal pain.46 Bile duct filling defects may be treated using percutaneous, endoscopic, or surgical methods. The treatment option is often dictated by the clinical condition and the surgical anatomy. At the authors’ institution, there are no indications for use of a specific method. Percutaneous transhepatic biliary treatment is advantageous in that it can be used for both biliary drainage and treatment of any underlying strictures. Treatments may include stone/sludge removal or extraction using balloon catheters or basket retrieval or even chemolysis. The use of oral ursodiol (Summit Pharmaceuticals, Summit, NJ) or transhepatic infusions of N-acetyl-cysteine (Apothecon, Princeton, NJ) for chemolysis have been used with limited success. Although, there are selected reports showing chemolysis to result in complete disappearance of biliary sludge in 40% of treated patients.47 Two other entities should be considered when discussing filling defects, biliary cast syndrome and retained internal biliary stents. Biliary cast syndrome was described over three decades ago.43 It is characterized by multiple intrahepatic biliary strictures, ductal dilation, intrahepatic abscesses, and biliary anastomotic leakage and has a characteristic cholangiographic appearance and can be seen in association with CMV cholangitis.31 The prevalence has significantly decreased over three decades with improvements in graft harvesting and preservation. The casts are treated with percutaneous or endoscopic extraction but may require surgical intervention. Retained internal biliary stents can also cause filling defects and/or biliary obstruction. The biliary anastomoses are constructed over small silastic stents or externalized T-tubes. These internal stents are designed to pass into the small bowel once the biliary sutures dissolve.48 These stents can occasionally fail to pass. If the endoscopist is unable to retrieve the stent (which is often the case since they are within a Roux loop), a percutaneous approach with snare retrieval is used. The stent is then removed via the percutaneous tract or advanced into the adjacent bowel (Fig. 10).
Biliary Complications and Hepatic Artery Thrombosis Hepatic artery thrombosis is a complication that deserves discussion when addressing biliary complications. All native arterial vascular connections to the donor bile ducts are severed at donor hepatectomy.49 Many patients with thrombosis are retransplanted, when the diagnosis is made early. These patients usually present with liver failure, hepatic necrosis, or nonanastomotic bile leaks.50 A study by Tzakis and coworkers50 documented seven patients with extrahepatic bile leaks and hepatic artery thrombosis. All of the patients showed common duct necrosis at laparotomy. Bile duct necrosis at cholangiography is characterized by confluent intruductal filling defects within irregular dilated or strictured bile ducts. At the authors’ institution, biliary necrosis has been shown in up to 58% of patients and abnormal cholangiograms have been found in more than 80% of patients with hepatic artery thrombosis (Fig. 11) and is frequently associated with intrahepatic bile leak and biloma formation (Fig. 12).9 Therefore,
Figure 10 (A) Catheter cholangiogram after transhepatic drainage shows a retained internal biliary stent associated with obstruction of the hepaticojejunostomy due to anastomotic edema. Note thickened jejunal folds also due to edema. The stent was snared and advanced into the jejunum. (B) After a week of external drainage, catheter cholangiogram shows a patent hepaticojejunostomy anastomosis after resolution of the edema. The biliary catheter was removed.
D.G. Buck and A.B. Zajko
58 perioperative hilar or intrahepatic bilomas should raise the suspicion of thrombosis and should also be treated to prevent secondary infection and sepsis. In comparison, hepatic artery stenosis has a variable presentation, though some will have nonanstomotic biliary strictures. Many patients with hepatic artery stenosis will present with nonspecific elevation in liver enzyme levels. The cause of elevated liver enzyme levels can be attributed to many factors, including rejection, infection, or ischemia, and are not predictive of specific abnormal cholangiographic findings. But abnormal cholangiograms will be present in up to
Figure 12 Enhanced CT scan of the liver shows extensive intrahepatic bilomas due to biliary necrosis resulting from hepatic artery thrombosis.
67% of patients with hepatic artery stenosis.51 In fact, a study by Orons and coworkers51 demonstrated the importance of cholangiographic evaluation, as the majority of patients with hepatic artery stenosis demonstrated findings that were not evident by ultrasound examination. Another important point of this study was the critical point of early identification of hepatic artery stenosis. Complications such as intrahepatic strictures and the resultant increased risk of cholangitis may be avoided by early detection. With detection, permanent allograft damage is avoided. In 1995, Orons and coworkers52 found that the treatment of hepatic artery stenosis with balloon angioplasty is of limited benefit once significant allograft dysfunction is present.
References
Figure 11 (A) Catheter cholangiogram after transhepatic drainage shows a large area of hilar biliary necrosis in a patient with hepatic artery thrombosis. (B) PTC shows left lobe biliary necrosis, necrotic debris within the right hepatic duct, and a severe hilar stricture in another patient with hepatic artery thrombosis. Note, however, that the hepaticojejunostomy biliary anastomosis is normal. An internal stent is also in place.
1. Ward EM, Kiely MJ, Maus TP, et al: Hilar biliary strictures after liver transplantation: Cholangiography and percutaneous management. Radiology 177:259-263, 1999 2. Zajko AB, Campbell WL, Bron KM, et al: Cholangiography and interventional radiology in adult liver transplantation. Am J Roentgenol 144:127-133, 1985 3. Thethy S, Thomson B, Pleass H, et al: Management of biliary tract complications after orthotopic liver transplantation. Clin Transplant 18:647-653, 2004 4. Tung BY, Kimmey MB: Biliary complications of orthotopic liver transplantation. Dig Dis 17:133, 1999 5. Jagganath S, Kaloo AN: Biliary complications after liver transplantation. Curr Treat Options Gastroenterol 5:101, 2002 6. Greif F, Bronsther OL, Van Thiel DH, et al: The incidence, timing and management of biliary complications after orthotopic liver transplantation. Ann Surg 219:40-45, 1994 7. Campbell WL, Sheng R, Zajko AB, et al: Intrahepatic biliary strictures after liver transplantation. Radiology 191:735-740, 1994 8. Evans RA, Raby ND, O’Grady JG, et al: Biliary complications following liver transplantation. Clin Radiology 41:190-194, 1990 9. Zajko AB, Campbell WL, Logsdon GA, et al: Cholangiographic findings in hepatic artery occlusion after liver transplantation. Am J Radiol 149: 485-489, 1987 10. Pitt HA, Miyamoto T, Parppatis SK, et al: Factors influencing outcome in patients with postoperative biliary strictures. Am J Surg 144:14-21, 1982 11. Culp W, McCowan T, Lieberman R, et al: Biliary strictures in liver transplant recipients: treatment with metal stents. Radiology 199:339346, 1996 12. Vallera RA, Cotton PB, Clavien PA: Biliary reconstruction for liver transplantation and management of biliary complications overview and
Biliary Complications after Liver Transplantation
13.
14.
15.
16. 17.
18.
19.
20.
21.
22.
23.
24.
25.
26.
27.
28.
29.
30.
31.
survey of current practices in the United States. Liver Transpl Surg 1:143-152, 1995 Diamond N, Lee S, Niblett R, et al: Metallic stents for the treatment of intrahepatic biliary strictures after liver transplantation. J Vasc Interv Radiol 6:755-761, 1995 Verdonk RC, Buis CI, Porte RJ, et al: Anastomotic biliary strictures after liver transplantation: Causes and consequences. Liver Transpl 12:726735, 2006 Mosca S. Militerno G, Guardascione MA, et al: Late biliary tract complications after orthotopic liver transplantation: Diagnostic and therapeutic role of endoscopic retrograde cholangiopancreatography. J Gastroenterol Hepatol 15:654-660, 2000 Ostroff JW: Post-transplant biliary problems. Gastrointest Endosc Clin N Am 11:163-183, 2001 Roumilhac D, Poyet G, Sergent G, et al: Long-term results of percutaneous management for anastomotic biliary stricture after orthotopic liver transplantation. Liver Transplantation 9:394-400, 2003 Zajko AB, Sheng R, Zetti GM, et al: Transhepatic balloon dilation of biliary strictures in liver transplant patients: A 10-year experience. J Vasc Interv Radiol 6:79-83, 1995 Thuluvath PJ, Atassi T, Lee J: An endoscopic approach to biliary complications following orthotopic liver transplantation. Liver Int 23:156162, 2003 Rieber A, Brambs HJ, Lauchart W: The radiological management of biliary complications following liver transplantation. Cardiovasc Intervent Radiol 19:242-247, 1996 Petersen BD, Maxfield SR, Ivancev K, et al: Biliary strictures in hepatic transplantation: Treatment with self-expanding Z stents. J Vasc Interv Radiol 7:221-228, 1996 Righi D, Cesarini F, Muraro E, et al: Role of interventional radiology in the treatment of biliary strictures following orthotopic liver transplantation. Cardiovasc Intervent Radiol 25:30-35, 2002 Choo SW, Shin SW, Do YS, et al: The balloon dilation and large profile catheter maintenance method for the management of the bile duct stricture following liver transplantation. Korean J Radiol 7:41-49, 2006 Sanchez-Urdazpal L, Gores GJ, Ward EM, et al: Diagnostic features and clinical outcome of ischemic-type biliary strictures. Hepatology 17: 605-609, 1993 Saad WEA, Davies MG, Saad NEA, et al: Transhepatic dilation of anastomotic biliary strictures in liver transplant recipients with use of a combined cutting and conventional balloon protocol: Technical safety and efficacy. J Vasc Interv Radiol 17:837-843, 2006 Guichelaar MM, Benson JT, Malinchoc M, et al: Risk factors for and clinical course of non-anastomotic biliary strictures after liver transplantation. Am J Transplant 3:885-890, 2003 Sanchez-Urdazpal L, Sterioff S, Janes C, et al: Increased bile duct complications in ABO incompatable liver transplant recipients. Transplant Proc 23:1440-1441, 1991 Buis CI, Hoekstra H, Verdonk RC, et al: Causes and consequences of ischemic-type biliary lesions after liver transplantation. J Hepatobiliary Pancreat Surg 13:517-524, 2006 Sankary HN, McChesney L, Hart M, et al: Identification of donor and recipient risk factors associated with non-anastomotic biliary strictures in human hepatic allografts. Transpl Proc 25:1964-1967, 1993 Gueken E, Visser D, Kuipers F, et al: Rapid increase of bile salt associated with bile duct injury after human liver transplantation. J Hepatol 41:1017-1025, 2004 Halme L, Hockerstedt K, Lautenschlager I: Cytomegalovirus infection and development of biliary complications after liver transplantation. Transplantation 75:1853-1858, 2003
59 32. Sung RS, Campbell DA Jr, Rudich SM, et al: Long-term follow-up of percutaneous transhepatic balloon cholangiography in the management of biliary strictures after liver transplantation. Transplantation 77:110-115, 2004 33. Tung BY, Kimmey MB: Biliary complications of orthotopic liver transplantation. Dig Dis 17:133, 1999 34. Lake JR: Long-term management of biliary tract complications. Liver Transpl Surg 1:45, 1998 35. Hampe T, Dogan A, Enche J, et al: Biliary complications after liver transplantation. Clin Transplant 20:93-96, 2006 (suppl 17) 36. Rerknimitr R, Sherman S, Fogel EL, et al: Biliary tract complications after orthotopic liver transplantation with choledochocholedochostomy anastomosis: Endoscopic findings and results of therapy. Gastrointest Endosc 55:224, 2002 37. Sheng R, Sammon JK, Zajko AB, et al: Bile leak after hepatic transplantation: Cholangiographic features, prevalence, and clinical outcome. Radiology 192:413, 1994 38. Moser MA, Wall WJ: Management of biliary problems after liver transplantation. Liver Transpl 7:S46, 2001 (suppl 2) 39. Kiltz U, Baier J, Adamek RJ: Selective embolization of a bile leak after operative resection of an echinococcal cyst. Dtsch Med Wochenschr 124:650-652, 1999 40. Yamakado K, Atsuhiro N, Iwata M, et al: Refractory biliary leak from intrahepatic biliary-enteric anastomosis treated by selective portal vein embolization. J Vasc Interv Radiol 13:1279-181, 2002 41. Park J, Oh JH, Yoon Y, et al: Acetic acid sclerotherapy for the treatment of a biliary leak from an isolated bile duct after hepatic surgery. J Vasc Interv Radiol 16:885-888, 2005 42. Kyokane T, Nagino M, Sano T, et al: Ethanol ablation for segmental bile duct leakage after hepatobiliary resection. Surgery 131:111-113, 2002 43. Starzl TE, Putman CW, Hansbrough JF, et al: Biliary complications after liver transplantation; with special reference to the biliary cast syndrome and techniques of secondary duct repair. Surgery 81:212221, 1977 44. Barton PP, Maier A, Steininger R, et al: Biliary sludge after liver transplantation. 1. Imaging findings and efficacy of various imaging procedures. Am J Roentgenol 164:859-864, 1995 45. McMaster P, Herbertson BM, Cusick C, et al: Biliary sludging following liver transplantation in man. Transplantation 25:56-62, 1978 46. Sheng R, Ramirez CB, Zajko AB, et al: Biliary stones and sludge in liver transplant patients: A 13-year experience. Radiology 198:243-247, 1996 47. Barton PP, Maier A, Steininger R, et al: Biliary sludge after liver transplantation. 2. Treatment with interventional techniques versus surgery and/or oral chemolysis. Am J Roentgenol 164:865-869, 1995 48. Zajko AB, Campbell WL, Bron KM, et al: Diagnostic and interventional radiology in liver transplantation. Gastroenterol Clin N Am 17:105143, 1988 49. Cho KJ, Lunderquist A: The peribiliary vascular plexus: The microvascular architecture of the bile duct in the rabbit and in clinical cases. Radiology 41:357-364, 1983 50. Tzakis AG, Gordon RD, Shaw BW Jr, et al: Clinical presentation of hepatic artery thrombosis after liver transplantation in the cyclosporine era. Transplantation 40:667-671, 1985 51. Orons PD, Sheng R, Zajko AB: Hepatic artery stenosis in liver transplant recipients: Prevalence and cholangiographic appearance of associated biliary complications. Am J Roentgenol 165:1145-1149, 1995 52. Orons PD, Zajko AB, Bron KM, et al: Hepatic artery stenosis after liver transplantation: Experience in 21 allografts. J Vasc Interv Radiol 6:523529, 1995