World Journal of Surgery. Liver transplantation, the last measure in the treatment of bile duct Injuries.

Transcription

1 Liver transplantation, the last measure in the treatment of bile duct Injuries. Journal: Manuscript ID: Manuscript Type: Date Submitted by the Author: WJS R Original Scientific Report 0-Apr-00 Complete List of Authors: de Santibañes, Eduardo; Hospital Italiano de Buenos Aires, General Surgery and Liver Transplant Unit Ardiles, Victoria; Hospital Italiano de Buenos Aires, General Surgery and Liver Transplant Unit Gadano, Adrian; Hospital Italiano de Buenos Aires, Hepatology Palavecino, Martin; Hospital Italiano de Buenos Aires, General Surgery and Liver Transplant Unit Pekolj, Juan; Hospital Italiano de Buenos Aires, General Surgery and Liver Transplant Unit Ciardullo, Miguel; Hospital Italiano de Buenso Aires, Liver Transplant Unit Keywords: Gastrointestinal, Liver, Transplant

2 Page of Abstract: BACKGROUND: Bile duct injury (BDI) is a severe complication that may arise during the surgical treatment of a benign disease. A significant proportion of cases develops end-stage liver disease and liver transplant is required. The aim of this study is to analyze the indications and results of liver transplantation as treatment for BDI. PATIENTS AND METHODS: Between January and May 00, twenty patients with end-stage liver disease secondary to a BDI were included in the waiting list for consideration of transplantation. Retrospective charts were analyzed and survival was estimated by the Kaplan-Meier test. RESULTS: Four patients died on the waiting list and were transplanted. Injury to the bile duct occurred during a cholecystectomy in of patients with the main mechanism of lesion being duct division in patients and resection in. All patients had received some surgical treatment (median: procedures) prior to consideration of transplant. Transplantation was performed with cadaveric donors in all patients with a median time between BDI and liver transplant of 0 months. Two patients died in the postoperative period and had complications. Three patients died in the late postoperative period. Median follow-up was months (range, -). One,, and -year survival rates were %, % and %, respectively. CONCLUSIONS: Complex bile duct injuries and bile duct injuries with previous repair attempts can result in end-stage liver disease. In these cases, liver transplantation provides long- term survival.

3 Page of Introduction: Bile duct injury (BDI) may occur during any surgical procedure performed in the upper abdomen. The relatively higher frequency of cholecystectomy in the population results in this being the most common procedure leading to BDI []. BDI is associated with greater risk of perioperative morbidity and mortality, a reduction in the quality of life, and a decrease in the long-term survival [-]. This is of the utmost importance since, in most cases, injuries occur in young patients undergoing surgery for a benign disease []. Given that injuries are initially unsuspected in a high percentage of patients, the postoperative recovery may be prolonged and the possibility of a successful repair reduced [-]. Several surgical, endoscopic, and percutaneous procedures may be necessary to manage the lesions and to treat coexisting complications []. In spite of these options, a significant percentage of cases develop end-stage liver disease or present with complications that are intractable to common methods of management. Although liver transplantation may constitute the only solution available in these cases, very few papers have been published to address this issue [0-]. We have reported previously a series of patients who underwent liver transplantation following a BDI []. The aim of the present review of this larger group of patients is to analyze the indications and results of liver transplantation as a treatment for BDI. Patients and Methods: Medical records of hospital admissions and office visits were reviewed

4 Page of retrospectively. Analyzed data included: type of initial surgery, mechanism and type of biliary lesion, surgical repair procedures, postoperative outcome, symptoms determining indication for transplantation, time elapsed between occurrence of injury and indication for transplantation, time on the waiting list, transplant features and subsequent evolution. The need for transplantation was determined on a multidisciplinary basis, involving HPB surgeons, hepatologists and infectious disease specialists. Indications for transplantation included one or more of the following: end-stage liver disease with no other alternative treatment and associated with intractable ascites, progressive jaundice, repeated episodes of haemorrhage due to portal hypertension, recurrent episodes of cholangitis, intractable pruritus, and/or poor quality of life []. Patients meeting these criteria and with no contraindications for liver transplantation were included in the waiting list. Priority was considered in accordance with the categorical stratification system used in Argentina until the introduction of MELD scores in 00 (Table ). A pretransplant work-up was carried out in all cases. Multiple diagnostic methods were used to detect the type of bile duct injury and potential associated complications depending on the patients presentation [ultrasound, computed tomographic (CT)- scan, endoscopic retrograde cholangiopancreatography (ERCP), percutaneous transparietal cholangiography (PTC), MRI cholangiography, and intraoperative cholangiography]. Arterial damage was suspected from reports of the initial surgery, the mechanism of bile duct injury, Doppler ultrasound or CT-scan, and was finally confirmed by angiography. BDIs were described according to Strasberg s classification [].

5 Page of All transplants were performed with whole liver grafts from cadaveric donors following the standard technique for vascular reconstruction reconstruction with or without piggy back technique, depending on the clinical condition of the patient. Biliary reconstruction was undertaken with a Roux-en-Y hepaticojejunostomy using polypropylene /0 suture. A multidisciplinary team was responsible for the postoperative care. All patients received a standardized immunosuppressive regimen (table ). Antibiotic and antifungal prophylaxis was administered to all recipients. Postoperative complications were classified according to the criteria proposed by Dindo et al []. Follow-up was carried out until submission of this manuscript or patient death. Kaplan-Meier test was used for survival analysis. Results: Between January and May 00, liver transplants were performed at Hospital Italiano de Buenos Aires, Argentina, with of these being adult recipients. Of these, 0 patients with BDI as an indication for transplantation were included in this study. Nineteen of these 0 patients were referred from other centres. Four patients (0%) died while on the waiting list due to septic or hemorrhagic complications and underwent transplantation. These 0 patients represent.% of all the liver transplants performed in adult recipients and.% of all the bile duct injuries treated during the same period (n=).

6 Page of The sixteen recipients of liver transplantation comprised men and women, with a median age of years (range, - yr). The most common surgery during which BDI occurred was cholecystectomy (n=), while the most frequent mechanisms of injury were bile duct division ( cases); and resection of the duct ( cases). The right hepatic artery was injured in cases, while in one patient the right portal vein was also damaged. According to the Strasberg classification, lesions included E, patients; E, patients; and E, patients. This classification was not applied in two patients because one presented with complete stenosis of the biliary duct due to formaldehyde injection, and the remaining patient presented with a lesion in the left hepatic duct that occurred during a right hepatectomy. In cases the lesion was identified during surgery and was repaired immediately. In cases, it was detected during the first week postoperatively and was repaired at the primary centre during that admission. In the remaining five patients, the lesion was detected in the late postoperative period (due to alteration of hepatic enzymes and cholangitis). All patients except for one underwent previous surgical procedures at the primary centre before referral. Table records lesion features, immediate surgical intervention and other procedures performed. Thirteen patients were demonstrated to have oesophageal varices on endoscopy. A transjugular intrahepatic portosystemic shunt (TIPS) was placed in one patient because of recurrent variceal bleeding non-responsive to pharmacological and endoscopic therapy. The main symptoms leading to transplantation were repeated upper gastrointestinal bleeding ( patients); recurrent episodes of cholangitis ( patients - with hepatic abscess in cases); intractable pruritus (); and refractory

7 Page of ascites (). Patient pre-transplantation characteristics are recorded in Table. Median time elapse between lesional surgery and transplantation was 0 months (range, - mo) and median time between the last surgery performed and transplantation was months (range, - mo). The median time on the waiting list was months (range, -0 mo). At the moment of transplantation, patients had a patent hepaticojejunostomy confirmed on a HIDA scintigraphy. Six patients were placed on the waiting list on an elective basis, whereas the remaining 0 were considered urgent. Extracorporeal circulation was used in three patients. Median cold ischemia time and operative time were minutes (range, 0-0 min) and minutes (range, 0-0 min) respectively. Median red blood cell usage was units (range, 0- units). Intraoperative injuries included a diaphragmatic laceration requiring pleural drainage, and a small bowel perforation requiring local resection both following division of dense adhesions. No intraoperative mortality occurred. Median intensive care unit and hospital stay were (range, -) days and 0 (range, -) days respectively. Nine of the patients had postoperative complications (table ). There were no early complications related to the biliary anastomosis. According to Dindos classification, complications were grade IIIb and were grade II. Two patients died during the postoperative period. One died at postoperative day due to bacterial pneumonia with no abnormality of the transplanted organ observed at autopsy. The other deceased patient underwent relaparotomy due to intraperitoneal bleeding. He also required percutaneous drainage of abdominal

8 Page of abscess in the postoperative period and finally died on day 0 due to sepsis with a normal functional graft. Three patients died in the late postoperative period. One developed, at month, a stenosis of the hepaticojejunostomy that required a revisional anastomosis. During the surgical exposure of the hepatic pedicle, a hepatic arterial thrombosis was evident. As all the remaining arterial blood supply was compromised, the patient developed fulminant hepatic failure secondary to liver devascularization, and required an emergency transplantation. He died at day due to a rupture of a cerebral mycotic aneurysm. The second patient died at months due to a lung carcinoma with bone metastasis, whereas the third patient died at 0 months due to endometrial cancer. The remaining eleven patients reported good quality of life on follow up and liver functional tests were within the normal range. Median follow-up was months (range -). Survival at, and years was %, % and %, respectively (Fig. ). Discussion: BDI is considered the most serious surgical complication associated with cholecystectomy [0]. According to different reports, its incidence has remained constant over the years, ranging from 0.% to 0.% [,]. Together with the introduction of laparoscopy, BDI increased to 0.-.0% and at most centres did not

9 Page of decrease upon completion of the learning curve, as it would have been expected [-]. Moreover, lesions occurring during laparoscopic cholecystectomy result in more serious injury due to the more proximal location of the injury in the biliary tree and the frequent association with vascular injury [,,]. Bile duct injuries occur less frequently during surgery for hydatid cysts [0,]. In our series, only out of the patients (.%) treated for bile duct injuries were operated on for this disease. In one case, the therapeutic injection of formaldehyde into a hydatid cyst that communicated inadvertently with the bile duct caused complete necrosis of the biliary tree. Hepatic resection surgery, injection of sclerosing agents into the liver and interventional radiology account for % of all the BDIs. Only % to % of bile duct injuries are diagnosed at the moment of the initial surgery [-,0,]. In the present series, intraoperative diagnosis was made in % of the cases. The best repair option for patients with complex lesions is a Roux-en-Y hepaticojejunostomy [,0]. It is particularly demanding surgery because the biliary ducts are thin and it is sometimes necessary to perform a deep resection in the hepatic pedicle. Additionally, when reparative surgery is intended in the few days after the occurrence of injury, local inflammation and fibrosis may make it difficult to determine the precise extent of the lesion and negatively affect the outcome of the anastomosis. The presence of biliary peritonitis has been described as an independent factor of poor outcome. In our series, seven of the lesions were diagnosed due to such a presentation. A non-diagnosed arterial lesion, the incidence of which is reported at

10 Page of % to %, can result in a poor outcome of primary treatment [,0,-]. Koffron et al showed that the percentage of vascular lesions is related to the level of the lesion []. This incidence reaches % in E lesions, % in E lesions, and % in E lesions []. We cannot confirm these findings from our data because only patients presented with associated vascular lesions (E, ; E, ; E, ; Not-classified, ). Regardless of the level of the lesion, vascular injuries are associated with a greater mortality and morbidity []. The inexperience of the surgeon performing the operation is another factor associated with the poor evolution of primary repair [-]. In - % of cases, primary repair is performed at the same centre where the lesion occurred [,,,,,]. In our series, all the patients except for one underwent attempted repair of the biliary tract at the primary centre. Patients with complex BDI often undergo several repair attempts before successful resolution. This affects their quality of life and represents a high psychological, physical and mental impact due to the prolonged, complicated and unexpected nature of the injury [,0]. Successive failures of therapeutic procedures or the application of inappropriate treatments may determine the manifestation of late complications, such as portal hypertension and secondary biliary cirrhosis[,,,]. Because of such late complications, - 0% of the patients with complex lesions should enter the waiting list for liver transplantation as the only possible treatment [-,0]. Prolonged biliary obstruction can lead to progressive liver fibrosis and secondary biliary cirrhosis. Duration of obstruction is the most important predictor of advanced

11 Page 0 of fibrosis []. Johnson et al. reported that development of hepatic fibrosis is associated with a delay in the implementation of adequate therapeutic procedures for the treatment of biliary stenosis []. Negi et al. found that the mean duration of biliary obstruction before onset of portal and periportal fibrosis was. months, for the development of severe fibrosis. months, and for cirrhosis months []. The presence of cirrhosis at the time of surgery increases postoperative morbidity and mortality, worsens repair outcome and results in a greater late mortality, even in patients with patent hepaticojejunostomy [-]. The presence of marked fibrosis, with consequent resistance in the hepatic microcirculation, together with hepatocyte hyperplasia, leads to portal hypertension. In fact, of the patients in our series had grade II-III esophageal varices and of them were included for transplantation due to repeated episodes of variceal bleeding. While portal hypertension accounts for.% of all the bile duct injuries treated in our institution, other authors report higher rates [0,,], with a global mortality rate of % [0]. In our series, of the 0 patients that died on the waiting list had severe portal hypertension resulting in multiple episodes of variceal bleeding. It has also been observed that portal hypertension is an independent factor associated with hospital mortality. Chapman et al. observed a mortality rate of % and % for patients undergoing surgery with or without portal hypertension, respectively [0]. Main indications for liver transplantation are advanced chronic liver disease with no alternative form of therapy. Other indicators for liver replacement include intractable ascites, progressive jaundice, repeated episodes of variceal bleeding, repeated episodes of cholangitis, intractable pruritus, and poor quality of life [].

12 Page of There are few publications on liver transplantation secondary to a bile duct injury. Some report a small series of cases in which the indication for transplantation was fulminant hepatic failure secondary to an associated vascular lesion [-]. However, cases published on the development of biliary cirrhosis secondary to a BDI are uncommon [0-]. According to the European Liver Transplantation Registry, secondary biliary cirrhosis accounts for % of all the indications for transplantation ( patients) [0], whereas in Argentina it accounts for % []. Previous surgical procedures may adversely affect liver transplantation by increasing both its technical complexity and the risk for complications0. In 00, we published a comparative study between patients undergoing liver transplantation for bile duct injury with a control group. In this series, we found that patients with bile duct injury had more prolonged and demanding surgery, and required more blood transfusion, although the postoperative morbidity and the long term results were similar in both groups []. In the present work, the postoperative complication rate, the mortality rate, and the -year survival rate were.%,.% and %, respectively, resulting equivalent to those observed for transplants undertaken for other diseases. Interestingly enough, two of the three deaths that occurred during follow-up were due to cancer. Similar results were observed by other investigators, who showed an increased incidence of malignant diseases in immunosuppressed patients [,]. In general, this is a group of young patients who were initially operated on for a benign condition []. In summary, according to literature, bile duct injury continues to occur worldwide with a frequency that is not decreasing [,]. Correct management is essential to

13 Page of ensure long-term survival of patients because inadequate procedures, multiple interventions performed by inexperienced surgeons, and delayed referrals to specialized centres may result in late complications. Secondary biliary cirrhosis and portal hipertensión cause significant morbidity and mortality rates, requiring liver transplantation as the only possible treatment. This procedure, for end-stage complicated BDI, is extremely difficult with a significant postoperative morbidity. Although it provides long-term survival and a good quality of life, it represents a high biological price for the patient with a benign disease. Acknowledgment: We would sincerely like to thanks Isabel Millicay for her help with the language, and Sung Ho Hyon and James Garden for correcting this manuscript. References:. Huang ZQ, Huang XQ. Changing patterns of traumatic bile duct injuries: a review of forty years experience. World J Gastroenterol 00;:-.. Savader SJ, Lillemoe KD, Prescott CA, et al. Laparoscopic cholecystectomyrelated bile duct injuries: a health and financial disaster. Ann Surg ;:-.. Moossa AR, Mayer AD, Stabile B. Iatrogenic injury to the bile duct. Who, how, where? Arch Surg 0;:0-0.. Flum DR, Cheadle A, Prela C, et al. Bile duct injury during cholecystectomy and survival in Medicare beneficiaries. JAMA 00 ;0:-.. Cooper AD, Young HS Pathophysiology and treatment of gallstones. Med Clin

14 Page of North Am ;():-.. Carroll BJ, Birth M, Phillips EH. Common bile duct injuries during laparoscopic cholecystectomy that result in litigation. Surg Endosc ;:0-. De Wit LT, Rauws EA, Gouma DJ. Surgical management of iatrogenic bile duct injury. Scand J Gastroenterol Suppl ;0:-.. Johnson SR, Koehler A, Pennington LK, et al. Long-term results of surgical repair of bile duct injuries following laparoscopic cholecystectomy. Surgery 000;:-.. al-karawi MA, Sanai FM. Endoscopic management of bile duct injuries in 0 patients: experience of a Saudi referral centre. Hepatogastroenterology 00;: Loinaz C, Gonzalez EM, Jimenez C, et al. A. Long-term biliary complications after liver surgery leading to liver transplantation. World J Surg 00;:0-.. Oncel D, Ozden I, Bilge O, et al. Bile duct injury during cholecystectomy requiring delayed liver transplantation: a case report and literature review. Tohoku J Exp Med 00;0:-. Schmidt SC, Langrehr JM, Hintze RE, et al. Long-term results and risk factors influencing outcome of major bile duct injuries following cholecystectomy. Br J Surg 00;:-. Nordin A, Makisalo H, Isoniemi H, et al. Iatrogenic lesion at cholecystectomy resulting in liver transplantation. Transplant Proc 00;:-00. Robertson AJ, Rela M, Karani J, et al. Laparoscopic cholecystectomy injury: an unusual indication for liver transplantation. Transpl Int ;:-

15 Page of de Santibanes E, Palavecino M, Ardiles V, et al. Bile duct injuries: management of late complications. Surg Endosc 00;0:-.. de Santibañes E, Pekolj J, Mc Cormack L, et al. Liver transplantation for the sequelae of intra-operative bile duct injury. HPB 00;:-. Keeffe EB. Selection of patients for liver transplantation. In: Maddrey WC, Schiff ER, Sorrel MF Eds. Transplantation of the Liver. ed. Philadelphia, PA: Lippincott Williams &Wilkins, 00, pp-. Strasberg SM, Hertl M, Soper NJ. An analysis of the problem of biliary injury during laparoscopic cholecystectomy. J Am Coll Surg ;0:0-.. Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of patients and results of a survey. Ann Surg. 00;0(): Chapman WC, Halevy A, Blumgart LH, et al. Postcholecystectomy bile duct strictures. Management and outcome in 0 patients. Arch Surg ;0:- 0.. Roslyn JJ, Binns GS, Hughes EF, et al. Open cholecystectomy. A contemporary analysis of, patients. Ann Surg ;:-.. Ahrendt SA, Pitt HA. Surgical therapy of iatrogenic lesions of biliary tract. World J Surg 00;:0-.. Fletcher DR, Hobbs MS, Tan P, et al. Complications of cholecystectomy: risks of the laparoscopic approach and protective effects of operative cholangiography: a population-based study. Ann Surg ;:-.

16 Page of MacFadyen BV Jr, Vecchio R, Ricardo AE, et al.bile duct injury after laparoscopic cholecystectomy. The United States experience. Surg Endosc ;:-..Gigot J, Etienne J, Aerts R, et al. The dramatic reality of biliary tract injury during laparoscopic cholecystectomy. An anonymous multicenter Belgian survey of patients. Surg Endosc ;:-.. Lillemoe KD, Melton GB, Cameron JL, et al.postoperative bile duct strictures: management and outcome in the 0s. Ann Surg 000;:0-.. Shah SR, Mirza DF, Afonso R, et al. Changing referral pattern of biliary injuries sustained during laparoscopic cholecystectomy. Br J Surg 000;:0-.. Vicente E, Meneu JC, Hervás PL, et al. Management of biliary duct confluence injuries produced by hepatic hydatidosis. World J Surg 00;:-.. Bismuth H, Franco D, Corlette MB, et al.long term results of Roux-en-Y hepaticojejunostomy. Surg Gynecol Obstet ;:-. 0. Strasberg SM, Picus DD, Drebin JA. Results of a new strategy for reconstruction of biliary injuries having an isolated right-sided component. J Gastrointest Surg 00;:-.. Stewart L, Way LW. Bile duct injuries during laparoscopic cholecystectomy. Factors that influence the results of treatment. Arch Surg ;0:-. Buell JF, Cronin DC, Funaki B, et al..devastating and fatal complications associated with combined vascular and bile duct injuries during cholecystectomy. Arch Surg 00;:0-.

17 Page of Koffron A, Ferrario M, Parsons W, eta l. Failed primary management of iatrogenic biliary injury: incidence and significance of concomitant hepatic arterial disruption. Surgery 00;0:-. Connor S, Garden OJ. Bile duct injury in the era of laparoscopic cholecystectomy. Br J Surg 00;:-.. Davidoff AM, Pappas TN, Murray EA, et al. Mechanisms of major biliary injury during laparoscopic cholecystectomy. Ann Surg ;:-0.. Mirza DF, Narsimhan KL, Ferraz Neto BH, et al. Bile duct injury following laparoscopic cholecystectomy: referral pattern and management. Br J Surg ;:-0.. Huang CS, Lein HH, Tai FC, et al Long-term results of major bile duct injury associated with laparoscopic cholecystectomy. Surg Endosc 00;:-.. Doctor N, Dooley JS, Dick R, et al. Multidisciplinary approach to biliary complications of laparoscopic cholecystectomy. Br J Surg ;:-.. Melton GB, Lillemoe KD, Cameron JL, et al. Major bile duct injuries associated with laparoscopic cholecystectomy: effect of surgical repair on quality of life. Ann Surg 00 ;:-. 0. Mercado MA, Orozco H, López-Martínez LM; et al. Survival and quality of life after bile duct reconstruction for iatrogenic injury. HPB 000;:-.. Braasch JW, Bolton JS, Rossi RL. A technique of biliary tract reconstruction with complete follow-up in consecutive cases. Ann Surg ;:-.. Negi SS, Sakhuja P, Malhotra V, et al. Factors predicting advanced hepatic fibrosis in patients with postcholecystectomy bile duct strictures. Arch Surg 00;:-0.

18 Page of Pellegrini CA, Thomas MJ, Way LW. Recurrent biliary stricture. Patterns of recurrence and outcome of surgical therapy. Am J Surg ;:-0.. Röthlin MA, Löpfe M, Schlumpf R, et al. Long-term results of hepaticojejunostomy for benign lesions of the bile ducts. Am J Surg ;:-.. Raute M, Podlech P, Jaschke W, et al. Management of bile duct injuries and strictures following cholecystectomy. World J Surg ;:-.. Fernández JA, Robles R, Marín C, et al. Laparoscopic iatrogeny of the hepatic hilum as an indication for liver transplantation. Liver Transpl 00;0:-.. Madariaga JR, Dodson SF, Selby R, et al. Corrective treatment and anatomic considerations for laparoscopic cholecystectomy injuries. J Am Coll Surg ;:-.. Bacha EA, Stieber AC, Galloway JR, et al. Non-biliary complication of laparoscopic cholecystectomy. Lancet ;:-.. Thomson B.N.J.; Parks R.W.; Madhavan K.K.; Garden O.J. Liver resection and transplantation in the management of iatrogenic biliary injury. World J Surg 00;:-. 0. The European Liver Transplantation Registry. Available at: Accessed july, 00. Incucai- CRESI. Available at: Accessed July, 00. Penn I. Post transplant malignancy: the role of immunosupperssion. Drug Sof 000;:0-.

19 Page of Table : Categorical stratification system used in Argentina until 00 to prioritise patients for liver transplantation. EMERGENCY Fulminant hepatic failure or subfulminant hepatic failure with encephalopathy grade III IV, retransplantation for primary nonfunction or vascular thrombosis with hepatic gangrene. URGENCY Fulminant hepatic failure or subfulminant hepatic failure with encephalopathy grade I II or Hepatopulmonary Syndrome with PO < 0 mmhg or hepatocellular disease meeting two of the following three criteria: creatinine >.mg/dl, total bilirubin (TB) > mg/dl, prothrombin time (PT)< % or chronic cholestatic disease with TB > 0 mg/dl or PT< 0%. ELECTIVE

20 Page of Table : Inmunosupression regimen. Cyclosporin A Azathioprin Prednisone Mycophenolate mofetil Tacrolimus patients X X X patients X X X patients X X X patients X X 0

21 Page 0 of Table : Characteristics of the lesion sex age Initial Surgery Lesion Mechanism Strasberg Immediate surgery Other procedures M OC Resection E Non recognised BDI PBD M OC Thermal lesion E Non recognised BDI )Bile duct resection +HJ, )PBD + PD F OC Ligature, RHA lesion E + vascular Non recognised BDI )choleperitoneum- abdominal drainage, HJ 0 ) PBD F OC Ligature E HJ PBD M OC Section E Repair after T-Tube placement )HJ )PBD M OC Section, RHA Lesion E+ vascular Non recognised BDI ) T- tube placement, )HJ, ) PBD + metallic stent M 0 OC Section E )HJ, )PBD Repair after T-Tube placement F OC Section E HJ )PBD ) re- HJ 0 M OC Resection E Non recognised BDI )HJ )percutaneous drainage of hepatic abscess)pbd 0 M OC Stenosis post T-Tube placement E Non recognised BDI )T-Tube replacement )PBD F LC Clippage, section and right pedicle thermal lesion E+ vascular Conversion. Right portal vein ligation. Non recognised BDI ) Choleperitoneum- abdominal drainage, )PBD, )HJ M LC Converted for BDE Stenosis post T-Tube placement, RHA lesion E+ vascular Non recognised BDI ) T-Tube replacement )HJ, )PBD)several replacements due to haemobilia F 0 LC Resection, termal lesion E Non recognised BDI )HJ, )PBD,) PD with extraction of intrahepatic stones F RH Left bile duct section, LHA lesion N/C +vascular Non recognised BDI ) HJ, )PBD 0 F HC Formaldehyde injection N/C Non recognised BDI ) choleperitoneum- abdominal drainage F HC Resection E Non recognised BDI ) HJ )re-hj Patients that died on the waiting list F 0 OC Resection E Non recognised BDI PBD M OC Resection E Non recognised BDI PBD M OC Stenosis post T-Tube placement E Non recognised BDI PBD 0 M OC Resection E HJ PBD 0 OC,open cholecystectomy; LC, laparoscopic cholecystectomy; BDE, bile duct exploration; RH, right hepatectomy; HC, hydatid cyst resection; HA, right hepatic artery; LHA, left hepatic artery; PBD, percutaneous biliary drainage; HJ, hepaticojejunstomy; PD, percutaneous dilatation; N/C, not classified.

22 Page of Table : Pre-transplantation features Main Symptoms TB DB ALP PT Child Meld Score UGB, cholangitis, refractory ascites, pruritus..0 0 B 0 UGB, cholangitis,. 0 0 A Refractory ascites, pruritus, hypersplenism A Cholangitis, pruritus, intrahepatic lithiasis.. 0 B UGB, cholangitis, hepatic abscess.. 0 B Cholangitis, pruritus.. A Cholangitis B UGB, cholangitis, pruritus, hypersplenism B UGB, cholangitis, hepatic abscess, refractory.. 0 B ascites 0 UGB, cholangitis, refractory ascites, pruritus B UGB, refractory ascites.. 0 B Cholangitis, intrahepatic lithiasis, haemobilia C UGB, intrahepatic lithiasis 0. 0,. 00 A Cholangitis, refractory ascites, pruritus.. 00 B Cholangitis. 0 B UGB, cholangitis, refractory ascites, pruritus, recurrent SBP.. 00 A UGB, upper gastrointestinal bleeding; SBP, spontaneous bacterial peritonitis; TB, total bilirubin; DB, direct bilirubin; ALP, alkaline phosphatase; PT, prothrombin time.

23 Page of Table : Postoperative complication Postoperative Complication Number of patients Treatment Dindo s classification Intraabdominal Percutaneous IIIb Abscess drainage Haemoperitoneum Relaparotomy IIIB Wound infection Drainage () Surgical toilette () II IIIB Acute rejection episodes moderate severe Methylprednisone II I.V. bolus

24 Page of Fig : Survival rate after liver transplantation Overall Survival Survival,000 0,0 year 0,00 % years years % % 0,0 0,000 0,0,0, 0 0, 0,0 Month Months Time Patients at risk months months months months 0 months