How to prevent and manage biliary complications in living donor liver transplantation?

Transcription

1 22 Forum on Liver Transplantation / Journal of Hepatology 43 (2005) [24] Calne RY. A new technique for biliary drainage in orthotopic liver transplantation utilizing the gall bladder as a pedicle graft conduit between the donor and recipient common bile ducts. Ann Surg 1976; 184: [25] Vallera RA, Cotton PB, Clavien PA. Biliary reconstruction for liver transplantation and management of biliary complications: overview and survey of current practices in the United States. Liver Transpl Surg 1995;1: [26] Wachs ME, Bak TE, Karrer FM, Everson GT, Shrestha R, Trouillot TE, et al. Adult living donor liver transplantation using a right hepatic lobe. Transplantation 1998;66: [27] Grewal HP, Shokouh-Amiri MH, Vera S, Stratta R, Bagous W, Gaber AO. Surgical technique for right lobe adult living donor liver transplantation without venovenous bypass or portocaval shunting and with duct-to-duct biliary reconstruction. Ann Surg 2001;233: [28] Liu CL, Lo CM, Chan SC, Fan ST, Wong J. Internal hernia of the small bowel after right-lobe live donor liver transplantation. Clin Transplant 2004;18: [29] Malago M, Testa G, Hertl M, Lang H, Paul A, Frilling A, et al. Biliary reconstruction following right adult living donor liver transplantation end-to-end or end-to-side duct-to-duct anastomosis. Langenbecks Arch Surg 2002;387: [30] Miller CM, Gondolesi GE, Florman S, Matsumoto C, Munoz L, Yoshizumi T, et al. One hundred nine living donor liver transplants in adults and children: a single-center experience. Ann Surg 2001;234: [31] Shokouh-Amiri MH, Grewal HP, Vera SR, Stratta RJ, Bagous W, Gaber AO. Duct-to-duct biliary reconstruction in right lobe adult living donor liver transplantation. J Am Coll Surg 2001;192: [32] Ishiko T, Egawa H, Kasahara M, Nakamura T, Oike F, Kaihara S, et al. Duct-to-duct biliary reconstruction in living donor liver transplantation utilizing right lobe graft. Ann Surg 2002;236: [33] Liu CL, Lo CM, Chan SC, Fan ST. Safety of duct-to-duct biliary reconstruction in right-lobe live-donor liver transplantation without biliary drainage. Transplantation 2004;77: [34] Kawachi S, Shimazu M, Wakabayashi G, Hoshino K, Tanabe M, Yoshida M, et al. Biliary complications in adult living donor liver transplantation with duct-to-duct hepaticocholedochostomy or Rouxen-Y hepaticojejunostomy biliary reconstruction. Surgery 2002;132: [35] Dulundu E, Sugawara Y, Sano K, Kishi Y, Akamatsu N, Kaneko J, et al. Duct-to-duct biliary reconstruction in adult living-donor liver transplantation. Transplantation 2004;78: [36] Scatton O, Meunier B, Cherqui D, Boillot O, Sauvanet A, Boudjema K, et al. Randomized trial of choledochocholedochostomy with or without a T tube in orthotopic liver transplantation. Ann Surg 2001;233: [37] Ben Ari Z, Neville L, Davidson B, Rolles K, Burroughs AK. Infection rates with and without T-tube splintage of common bile duct anastomosis in liver transplantation. Transpl Int 1998;11: [38] Fan ST, Lo CM, Liu CL, Tso WK, Wong J. Biliary reconstruction and complications of right lobe live donor liver transplantation. Ann Surg 2002;236: How to prevent and manage biliary complications in living donor liver transplantation? Satoru Todo*, Hiroyuki Furukawa, Toshiya Kamiyama The First Department of Surgery, Hokkaido University School of Medicine, N-15, W-7, Kita-ku, Sapporo , Japan Ever since the introduction of deceased donor (DD) liver transplantation, biliary complications have been the Achilles heel of the procedure [1]. Certain techniques used in early series (e.g. cholecysto-duodenostomy, cholecysto-jejunostomy) were associated with high complication rates of approximately 50%, and thus were rapidly abandoned. Currently, choledocho-jejunostomy or choledocho-choledochostomy are the standard methods for biliary reconstruction in liver transplantation, but complications still occur in 5 20% of recipients. For example, in 1792 consecutive liver transplantations at the University of Pittsburgh [2], 11.5% of the recipients suffered various biliary complications including strictures (42.8%), leaks * Corresponding author. Tel.: C ; fax: C address: stodo@med.hokudai.ac.jp (S. Todo). Abbreviations: DD; deceased donor; LDLT; living donor liver transplantation; HJ; hepatico-jejunostomy, duct-to-duct anastomosis; MRCP; magnetic resonance cholangio pancreaticography. (26.7%), ampullary dysfunction (6.6%), and obstruction (13.8%), leading to death in 21 patients. Although patient and graft survival rates after living donor liver transplantation (LDLT) have approached those after DD liver transplantation, biliary complications have been again identified as the Achilles heel of this newer procedure, affecting approximately 20 30% of recipients (Tables 1 and 2) (see previous article by CL Liu, CM Lo, and ST Fan in this forum). Initially, LDLT was undertaken to reduce mortality among children waiting for a cadaveric organ, by grafting the left lateral segment with a Roux-en Y hepatico-jejunostomy. Now, LDLT are mostly offered to adult recipients. The first adult recipient of a living donor graft successfully received the left hemiliver with a hepatico-jejunostomy reconstruction [3]. Currently, right hemiliver transplants are preferred in most centers often choosing a duct-to-duct biliary reconstruction in the hope of offering sufficient liver mass and preventing events associated with a hepatico-jejunostomy. Problems after /$30.00 q 2005 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved. doi: /j.jhep

2 Forum on Liver Transplantation / Journal of Hepatology 43 (2005) Table 1 Biliary complication in pediatric LDLT Center Year Cases Biliary complication (%) Reference All Anastomotic leakage Anastomotic stricture UCSF, USA (18.8) 6 (18.8) 0 (0) [5] Brussels, Belgium (34) 3 (7) 10 (24) [6] Kyoto, Japan a 71 (18.2) 45 (11.5) 35 (9.0) [7] Hamburg, Germany (4.6) NA NA [8] Johns Hopkins, USA (33.3) 10 (20.8) 2 (4.2) [9] a Includes 55 adult cases. duct-to-duct reconstruction in LDLT became already apparent with the first case [4]. The patient developed an anastomotic stricture 4 weeks later, and subsequently required conversion to a hepatico-jejunostomy. 1. Incidence of biliary complications after living donor liver transplantation Biliary complications after LDLT include leakage (anastomosis, cut-surface, T-tube exit), stricture (anastomosis, biliary tract), sludge, choledocholithiasis, biliary sepsis, and others. Major anastomotic leakage and multiple or diffuse stenosis of the biliary tree most are the source of significant morbidity, resulting in fatal outcomes in 1 3% of the recipients. The reported incidence of such complications differs considerably among centers. Overall incidences of biliary complications in pediatric recipients range from 5 to 34% [5 9]. The rates of anastomotic leakage and stricture are between 7.0 and 21%, and 0 24%, respectively (Table 1). Regardless of the type of segmental graft and biliary reconstruction, the overall incidence of biliary complication in adult LDLT patients ranges from 0 to 60% [10 20], with anastomotic leakage occurring in 0 37% and stricture in 0 40% (Table 2). 2. Risk factors for biliary complications The etiology of biliary complications is multifactorial. Risk factors include age and gender of recipients, severity of original disease, variations in the biliary tract anatomy, number and size of reconstructed bile dust(s), techniques in graft procurement and diseased liver removal, ischemic damage to bile duct (hepatic artery complication, warm/cold ischemia, bile duct blood supply), method of biliary reconstruction (type, suture methods, suture material, stent, or T-tube use), immunological issues (ABO incompatibility, preformed antibody), infection (biliary Table 2 Biliary complication in adult right hemiliver LDLT Center Year Case Anastomosis Biliary complication (%) Reference H J D D All Automatic leakage Automatic stricture Tennessee, USA a 8 5 (62.5) 3 (37.5) 0 [10] 6 4 (66.7) 0 (0) 0 (0) Paul-Brusse, a 3 0 (0) 0 (0) 0 (0) [11] France 7 1 (14.2) 0 (0) 0 (0) Essen, Germany (26.7) 4 (13.3) 1 (3.3) [12] NA NA 17 (23) 7 (9.5) 5 (6.8) [13] Hong Kong (43.2) 5 (13.5) 10 (27) [14] 37 b 3 (8.1) 0 (0) 3 (8.1) Hong Kong (24.3) 3 (7.3) 10 (24.3) [15] Keio U., Japan (20) 1 (10) 0 (0) [16] 10 8 (80) 2 (20) 4 (40) Kyoto, Japan (32.6) 5 (9.6) 12 (23) [17] Tokyo, Japan c (32) 2 (2.5) 10 (12.3) [18] Mt Sinai, USA (34.3) 13 (13.5) 20 (20.8) [19] Samsung, Korea d 31 5 (16.1) 0 (0) 3 (9.7) [20] a With hilar blood supply preservation. b By modified methods. c Includes 29 left lobes. d By high hilar dissection.

3 24 Forum on Liver Transplantation / Journal of Hepatology 43 (2005) sepsis, cytomegalovirus). In 400 LDLT cases reported by the Kyoto group [4] including 55 adult recipients, biliary complications occurred in 11.5% of the patients. Biliary stent, intrapulmonary shunting, and female recipients were at higher risk for leakage. Risk factors for stricture were anastomotic leak, cytomegatovirus infection, hepatic artery complication, and female recipient. 3. Prevention of biliary complications Issues that must be considered in order to prevent biliary complications after LDLT fall into two categories: anatomical and technical Anatomical consideration Anatomy of the bile duct Accurate knowledge of bile duct anatomy is critical to secure donor safety and to minimize complications in the recipients. According to Couinaud [21], patterns of the hepatic duct confluence are classified into six groups; (A) typical anatomy (57%), (B) triple confluence (12%), (C) ectopic drainage of a right duct (anterior or posterior) into the common hepatic duct (20%), (D) ectopic drainage of a right duct (anterior or posterior) into the left hepatic duct (6%), (E) absence of the hepatic duct confluence (3%), and (F) absence of the right hepatic duct and ectopic drainage of the right posterior duct into the cystic duct (2%). The type and the rate of these hepatic duct anomalies are similar to those observed during hepatic [22] and LDLT donor surgery [23]. Choi et al. [24] found a peculiar anomaly among 300 consecutive intraoperative cholangiograms. One live donor had a total drainage of the right hepatic duct into the cystic duct. When the right graft is to be removed, precise investigation of these anomalies is paramount to minimize the number of duct reconstructions and to avoid injury to the donor bile duct near the confluence. During procurement of the left lateral segment or the left hemiliver, particular caution must be taken to recognize separate drainage of the segment II and III ducts into the hepatic confluence, or whether the left hepatic duct is absent (type E, 3%). One of these segmental ducts was accidentally ligated in three of the 400 LDLT in the Kyoto series [4]. Recent advances in imaging technology, particularly of multiphase three-dimensional analyses, have allowed precise information to be obtained preoperatively on the graft volume and the vascular structures (hepatic artery, portal vein, and hepatic veins). However, imaging studies of the biliary tree are less reliable [25,26]. Using the sensitive mangafodipir trisodium enhanced magnetic resonance cholangiography, the accuracy of depicting the pattern of bile duct bifurcation was 88% (22/25). Patients with multiple left hepatic ducts, a trifurcation pattern, or ectopic drainage of hight hepatic duct into the cystic duct were not identified properly. Therefore, it is essential to perform intraoperative cholangiography at every donor hepatpectomy in LDLT. A C-arm fluoroscopy is particularly useful in confirming the bile duct anatomy and a point of bile duct(s) transection Blood supply to the bile duct The bile duct is divided into three segments: hilar, supraduodenal, and retropancreatic. The supraduodenal segment of the bile duct receives 60% of the blood supply via axial 3 O clock and 9 O clock arteries that arise from the posterior superior pancreatico-duodenal artery and the gastro-duodenal artery. The bile duct receives 2% of transversal blood supply from the proper hepatic artery. A fine arterial plexus formed by these marginal arteries ascends to the confluence at the hepatic hilum and nourishes the common bile duct. The right and left hepatic arteries account for 38% of the arterial blood supply of the biliary system; they nourish the confluence and both hepatic ducts via the hilar plexus at inferior aspect of the hilar plate [27,28]. Thus, as stressed by others [10,11] interruption of blood supply to the hilar plate during donor hepatectomy and that to the supra-duodenal segment during recipient liver removal should be avoided. Injury to the duct blood supply may lead to bile duct ischemia, resulting in anastomotic leakage, stricture, or even necrosis of the bile duct Technical considerations Graft removal Standard techniques of graft removal, learned from partial hepatectomies and whole liver or split-liver transplantations, have well been described elsewhere with minor variations. Particular attention is needed to confirm the plane of intrahepatic bile duct division using intraoperative cholangiography or fluoroscopy. Dissection between the hepatic duct and the hepatic artery beyond the transection should be avoided to maintain a viable blood supply to the hepatic duct(s). The stump, at least 2 mm apart from the confluence, should be left for safe closure. Any damage to the graft bile duct(s) by a cautery, clips or blunt trauma should be strictly avoided. Any tiny bleeding at bile duct openings requires suture ligation with fine needles Recipient hepatectomy Similarly, methods of native liver removal in recipients are essentially the same as those applied in DD liver transplantation. When a duct duct reconstruction is planned, however, care should be taken not to interrupt the arterial blood supply to the biliary tract and to leave enough length of the bile duct for a tension-free anastomosis. Toward this end, the connective tissue around the hepatic artery and the bile duct should be kept intact as high as possible in the hilum. Using these modifications, Shokouh-Amiri et al. [10] and Azoulay et al. [11] experienced no anastomotic leakage and stricture after duct duct reconstruction in consecutive series of 6 and 7

4 Forum on Liver Transplantation / Journal of Hepatology 43 (2005) patients, respectively. Recently, Lee et al. [20] proposed a new intrahepatic Glissonian approach for recipient hepatectomy to reduce biliary complications. The high hilar dissection method, in which intrahepatic pedicles are divided at the third level or beyond, allowed tension-free duct duct anastomosis with good preservation of blood supply to the bile duct. No anastomotic leakage occurred in 33 consecutive adult DD liver transplantation patients, and none required a hepatico-jejunostomy conversion, although three anastomotic strictures occurred during a mean followup of 11 months Type of biliary reconstruction Hepatico-jejunostomy is inevitable for biliary reconstruction in pediatric LDLT, as well as in patients with bile duct diseases, prior biliary surgery, re-transplantation, significant duct size discrepancy, and the presence of multiple or small bile ducts. Although the superiority of either hepatico-jejunostomy or duct to duct for biliary reconstruction in adult LDTT has been a debate (see previous article by CL Liu, CM Lo, and ST Fan in this forum and Table 2), surgeons should follow the principle of tension-free and viable anastomosis, and be accustomed to both procedures Number and size of bile duct(s) When the left hemiliver is used, bile duct reconstruction is generally straight forward, except in the presence of separate segmental II and III ducts or a segment IV duct draining into the confluence. Very small caudate lobe ducts can be joined successfully to a jejunal loop by non-anatomotic reconstruction [29]. However, in right hemiliver LDLT, all grafts, except for those with typical biliary anatomy (type A by Cuinaud s classification), will require a ductoplasty (type B), or two or more anastomoses (types C F) [30] Stent or T-tube use Risks associated with the use of stents or T-tubes have been controversial. Many centers prefer them to ease postoperative patient management because they provide early information on graft function, biliary imaging, and easy access. As highlighted in the previous article by CL Liu, CM Lo, and ST Fan in this forum a prospective randomized trial is needed to definitively settle the controversy Suture and suture material Here also no consensus has been reached; for example the Kyoto group recommends that the biliary anastomosis be constructed with continuous absorbable sutures [17], while the Hong Kong group prefers interrupted sutures with non-absorbable monofilaments [15] ABO incompatibility ABO incompatibility is a relative contraindication to DD liver transplantation, but faced with a shortage of both deceased donors and blood type compatible living donors, blood type incompatible LDLT has been attempted under sophisticated preoperative and postoperative patient management protocols [31]. Among 66 reported cases, 21 patients less than 1 year of age had no significant problem, but 12 of the 45 adult patients developed biliary complications which were the major causes of deaths in 11 patients (24%). Longer follow-up is necessary to determine the efficacy of blood type incompatible adult LDLT. 4. Management of biliary complications The clinical manifestations of biliary complications after liver transplantation vary considerably. Patients may have no symptoms or may present with fulminant biliary sepsis. Thus, any abnormal liver function test must be carefully followed, and, if it persists, the recipient needs to be thoroughly examined to identify whether the problem is related to technical errors (hepatic artery, portal vein, hepatic vein, and biliary tract), small-for-size graft syndrome, rejection, infection, or recurrence of the original liver disease. Cholangiography via external stent, T-tube, endoscopy or percutaneous approach is often necessary for a accurate biliary analysis. Although ultrasonography is less sensitive, it can convincingly identify bile duct dilation related to an anastomotic stricture. Additionally, Doppler ultrasonography may detect hepatic artery problems. Magnetic resonance cholangio pancreaticography (MRCP) and hepatobiliary iminodiacetic acid scan are occasionally employed when cholangiography through a T-tube, stent or endoscope is inadequate. Others may use MRCP as the first line of investigation. Causes and management of biliary complication are timedependent. The majority of complications develop within a few days to 3 months as early complications. Bile leak at the cut surface is usually successfully managed by fine-needle aspiration and drainage, while an endoscopic nasal biliary drainage maneuver is usually successful for T-tube exit leakage, which formerly was treated by suture closure upon laparotomy. If anastomotic leakage is minor, endoscopic or percutaneous biliary stent placement is sometimes sufficient [32 34]. Re-do of the biliary anastomosis, conversion from duct to duct to hepatico-jejunostomy anastomosis, or regrafting of the liver is required when major leakage or bile duct necrosis has occurred. With regard to biliary stricture, the majority (80 90%) occurs at an anastomotic site. Percutaneous balloon dilation and stent placement or stents placed by endoscope with or without papillotomy are usually successful. In one report, of 19 recipients who developed stricture between 22 and 449 days after receiving the right hemiliver with duct to duct reconstruction, 14 (74%) were treated endoscopically with insertion of stents, three underwent anastomotic conversion, and two were followed conservatively [32]. In contrast, management of late biliary

5 26 Forum on Liver Transplantation / Journal of Hepatology 43 (2005) complications is generally difficult and time-consuming. In particular, management of diffuse and multiple strictures of the bile duct is complex due to systemic, rather than a local nature of the cause. Early replacement of the liver graft is often warranted to avoid fatal outcome. 5. Biliary complications in the donors Among 100 LDLT in Chicago [35], minor complications developed in 20% of donors, while 14% of patients encountered major complications, including five bile duct injuries and two cut edge bile leaks. Of the 1508 living donors of partial liver grafts at five Asian centers [36], 15.8% developed various complications, in which bile leakage was documented in 6.1%, and biliary stricture in 1.1%. Six patients (0.4%) required subsequent surgical repairs. According to a recent survey of 1852 donors in Japan [37], there were 244 postoperative complications in 228 donors (12%). Biliary leaks and stricture accounted for 11% of the morbidity. Biliary complications occurred in 10% of patients after right hemiliver resections, compared to only 3.6% with the left hemiliver, and 1.9% with a bisegment II III. Ten donors required re-operation for biliary complications. References [1] Starzl TE, Demetris AJ. Liver transplantation. Chicago: Yearbook Medical Publishers Inc.; [2] Greif F, Bronsther OL, Van Thiel DH, Casavilla A, Iwatsuki S, Tzakis A, et al. The incidence, timing, and management of biliary tract complications after orthotopic liver transplantation. Ann Surg 1994;219: [3] Hashikura Y, Makuuchi M, Kawasaki S, Matsunami H, Ikegami T, Nakazawa Y, et al. Successful living-related partial liver transplantation to an adult patient. Lancet 1994;343: [4] Wachs ME, Bak TE, Karrer FM, Everson GT, Shrestha R, Trouillot TE, et al. Adult living donor liver transplantation using a right hepatic lobe. Transplantation 1998;66: [5] Reichert PR, Renz JF, Rosenthal P, Bacchetti P, Lim RC, Roberts JP, et al. Biliary complications of reduced-organ liver transplantation. Liver Transpl Surg 1998;4: [6] Reding R, de Goyet Jde V, Delbeke I, Sokal E, Jamart J, Janssen M, et al. Pediatric liver transplantation with cadaveric or living related donors: comparative results in 90 elective recipients of primary grafts. Pediatrics 1999;134: [7] Egawa H, Inomata Y, Uemoto S, Asonuma K, Kiuchi T, Fujita S, et al. Biliary anastomotic complications in 400 living related liver transplantations. World J Surg 2001;25: [8] Broering DC, Kim JS, Mueller T, Fischer L, Ganschow R, Bicak T, et al. One hundred thirty-two consecutive pediatric liver transplants without hospital mortality: lessons learned and outlook for the future. Ann Surg 2004;240: [discussion 1012]. [9] Kling K, Lau H, Colombani P. Biliary complications of living related pediatric liver transplant patients. Pediatr Transplant 2004;8: [10] Shokouh-Amiri MH, Grewal HP, Vera SR, Stratta RJ, Bagous W, Gaber AO. Duct-to-duct biliary reconstruction in right lobe adult living donor liver transplantation. J Am Coll Surg 2001;192: [11] Azoulay D, Marin-Hargreaves G, Castaing D, ReneAdam, Bismuth H. Duct-to-duct biliary anastomosis in living related liver transplantation: the Paul Brousse technique. Arch Surg 2001;136: [12] Testa G, Malago M, Valentin-Gamazo C, Lindell G, Broelsch CE. Biliary anastomosis in living related liver transplantation using the right liver lobe: techniques and complications. Liver Transpl 2000;6: [13] Malago M, Testa G, Frilling A, Nadalin S, Valentin-Gamazo C, Paul A, et al. Right living donor liver transplantation: an option for adult patients: single institution experience with 74 patients. Ann Surg 2003;238: [discussion 862 3]. [14] Fan ST, Lo CM, Liu CL, Tso WK, Wong J. Biliary reconstruction and complications of right lobe live donor liver transplantation. Ann Surg 2002;236: [15] Liu CL, Lo CM, Chan SC, Fan ST. Safety of duct-to-duct biliary reconstruction in right-lobe live-donor liver transplantation without biliary drainage. Transplantation 2004;77: [16] Kawachi S, Shimazu M, Wakabayashi G, Hoshino K, Tanabe M, Yoshida M, et al. Biliary complications in adult living donor liver transplantation with duct-to-duct hepaticocholedochostomy or Rouxen-Y hepaticojejunostomy biliary reconstruction. Surgery 2002;132: [17] Ishiko T, Egawa H, Kasahara M, Nakamura T, Oike F, Kaihara S, et al. Duct-to-duct biliary reconstruction in living donor liver transplantation utilizing right lobe graft. Ann Surg 2002;236: [18] Dulundu E, Sugawara Y, Sano K, Kishi Y, Akamatsu N, Kaneko J, et al. Duct-to-duct biliary reconstruction in adult living-donor liver transplantation. Transplantation 2004;78: [19] Gondolesi GE, Varotti G, Florman SS, Munoz L, Fishbein TM, Emre SH, et al. Biliary complications in 96 consecutive right lobe living donor transplant recipients. Transplantation 2004;77: [20] Lee KW, Joh JW, Kim SJ, Choi SH, Heo JS, Lee HH, et al. High hilar dissection: new technique to reduce biliary complication in living donor liver transplantation. Liver Transpl 2004;10: [21] Couinau C. Etudes anatomiques et chirurgicales. vol. 1. Paris: Masson; [22] Ohkubo M, Nagino M, Kamiya J, Yuasa N, Oda K, Arai T, et al. Surgical anatomy of the bile ducts at the hepatic hilum as applied to living donor liver transplantation. Ann Surg 2004;239: [23] Varotti G, Gondolesi GE, Goldman J, Wayne M, Florman SS, Schwartz ME, et al. Anatomic variations in right liver living donors. J Am Coll Surg 2004;198: [24] Choi JW, Kim TK, Kim KW, Kim AY, Kim PN, Ha HK, et al. Anatomic variation in intrahepatic bile ducts: an analysis of intraoperative cholangiograms in 300 consecutive donors for living donor liver transplantation. Korean J Radiol 2003;4: [25] Ayuso JR, Ayuso C, Bombuy E, De Juan C, Llovet JM, De Caralt TM, et al. Preoperative evaluation of biliary anatomy in adult live liver donors with volumetric mangafodipir trisodium enhanced magnetic resonance cholangiography. Liver Transpl 2004;10: [26] Yeh BM, Breiman RS, Taouli B, Qayyum A, Roberts JP, Coakley FV. Biliary tract depiction in living potential liver donors: comparison of conventional MR, mangafodipir trisodium-enhanced excretory MR, and multi-detector row CT cholangiography initial experience. Radiology 2004;230: [27] Northover JM, Terblanche J. A new look at the arterial supply of the bile duct in man and its surgical implications. Br J Surg 1979;66: [28] Terblanche J, Allison HF, Northover JM. An ischemic basis for biliary strictures. Surgery 1983;94: [29] Kubota K, Takayama T, Sano K, Hasegawa K, Aoki T, Sugawara Y, Makuuchi M. Small bile duct reconstruction of the caudate lobe in living-related liver transplantation. Ann Surg 2002;235:

6 Forum on Liver Transplantation / Journal of Hepatology 43 (2005) [30] Nakamura T, Tanaka K, Kiuchi T, Kasahara M, Oike F, Ueda M, et al. Anatomical variations and surgical strategies in right lobe living donor liver transplantation: lessons from 120 cases. Transplantation 2002;73: [31] Egawa H, Oike F, Buhler L, Shapiro AM, Minamiguchi S, Haga H, et al. Impact of recipient age on outcome of ABO-incompatible livingdonor liver transplantation. Transplantation 2004;77: [32] Hisatsune H, Yazumi S, Egawa H, Asada M, Hasegawa K, Kodama Y, et al. Endoscopic management of biliary strictures after duct-to-duct biliary reconstruction in right-lobe living-donor liver transplantation. Transplantation 2003;76: [33] Shah JN, Ahmad NA, Shetty K, Kochman ML, Long WB, Brensinger CM, et al. Endoscopic management of biliary complications after adult living donor liver transplantation. Am J Gastroenterol 2004;99: [34] Park JS, Kim MH, Lee SK, Seo DW, Lee SS, Han J, et al. Efficacy of endoscopic and percutaneous treatments for biliary complications after cadaveric and living donor liver transplantation. Gastrointest Endosc 2003;57: [35] Grewal HP, Thistlewaite Jr JR, Loss GE, Fisher JS, Cronin DC, Siegel CT, et al. Complications in 100 living-liver donors. Ann Surg 1998;228: [36] Lo CM. Complications and long-term outcome of living liver donors: a survey of 1508 cases in five Asian centers. Transplantation 2003;75: S12 S15. [37] Umeshita K, Fujiwara K, Kiyosawa K, Makuuchi M, Satomi S, Sugimachi K, et al. Operative morbidity of living liver donors in Japan. Lancet 2003;362: Is living donor liver transplantation cost-effective? Markus Sagmeister 1,2, Beat Müllhaupt 1, * 1 Division of Gastroenterology and Hepatology, University Hospital Zürich, Rämistrasse 100, 8091 Zurich, Switzerland 2 Division of Gastroenterology and Hepatology, Kantonsspital St Gallen, 9007 St Gallen, Switzerland Deceased donor (DD) liver transplantation has been accepted as the standard of care for patients with end stage liver disease. With the growing discrepancy between the numbers of donors and recipients, the median waiting time for liver transplantation has increased dramatically, exceeding in some countries one to two years [1]. Strategies to expand the donor pool include increasing the donor consent rate, the use of marginal donors, split liver and most recently living donor liver transplantation (LDLT) [2]. Initial studies focused on the efficacy and safety of LDLT compared to DD liver transplantation. While multiple studies have now demonstrated excellent patient and graft survival rates with LDLT, the first studies on cost and cost-effectiveness are only emerging. In addition to ethical concerns, there is an ongoing debate in the medical community about the ability to afford expensive life saving techniques such as cadaveric and living donor liver transplantation and there is concern about a gap between scarce financial resources in medicine and a growing availability of expensive health related interventions. Therefore studies on cost and cost-effectiveness are increasingly important in this era of financial pressures. This article focuses on economic aspects of liver transplantation and aims to give an insight into the financial aspects of liver transplantation. First the most recent data for * Corresponding author. Tel.: C ; fax: C address: beat.muellhaupt@usz.ch (B. Müllhaupt). Abbreviations: DD, deceased donor liver transplantation; LDLT, living donor liver transplantation; QUALY, quality adjusted live years gained. DD liver transplantation will be reviewed and finally the data for LDLT. An economic assessment of liver transplantation should include the costs of the pretransplant care including the initial work-up, the transplantation itself and the posttransplant care. However, the study design of the published studies and the follow-up period considered in the cost analysis is highly variable and comparisons are therefore difficult. Nevertheless it gives the reader some ideas about the cost and cost-effectiveness of DD liver transplantation and LDLT. A glossary of the most important economic definitions is given in Table 1. For easier comparisons the different national cost are compared in Euro (exchange rate November 2004; 1 USDZ0.76V). 1. Cost studies Early assessment of the costs of liver transplantation in the late 1980s and early 1990s probably overestimated the costs of liver transplantation (Table 2). As reviewed by O Grady in a retrospective cost (charges) analysis of DD liver transplantation in the UK there is a variance of 40 45% per unit charge between the different centers [3]. The average charges for one liver transplantation ranged from V. High costs were observed at the beginning of a new program, followed by a trend towards reduced cost as the number of transplants increased. Several factors such as cytomegalovirus (CMV) disease, the number of units of blood products administered during transplantation, bacteraemia, pretransplant renal dysfunction, and /$30.00 q 2005 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved. doi: /j.jhep