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Outcome after liver transplantation for primary sclerosing cholangitis
Outcome After Liver Transplantation for Primary Sclerosing Cholangitis H. Lide´n, J. Norrby, M. Ga¨bel, S. Friman, and M. Olausson
P
RIMARY SCLEROSING CHOLANGITS (PSC) is one of the major indications for liver transplantation in Scandinavia. During the period from 1985 to 1998, 419 liver transplantations were performed at our center. PSC patients received 17% of these grafts. PSC is predominantly a disease of men and is often associated with inflammatory bowel disease (approximately 70%). There is an increased risk of developing cholangiocellular carcinoma that significantly affects outcome.1 Medical and surgical therapies for PSC are limited, and the natural course of PSC is hard to predict but it has been established that carefully selected patients clearly benefit from OLT.2 After transplantation the possibility of recurrence of PSC has been debated. It has been argued that the pathological findings that suggest recurrence are indistinguishable from other events such as chronic rejection and bile duct damage due to poor arterial blood flow.3 The aim of this study was to (a) analyze the outcome of liver transplantations for primary sclerosing cholangitis at our center, (b) review vascular and biliary complications, and (c) identify possible recurrent disease. MATERIALS AND METHODS The study population consisted of all 61 patients transplanted during the period from 1985 to 1998 for end-stage liver disease due to PSC. We have retrospectively reviewed their medical records and collected data on biliary complications, vascular complications, cause of retransplantation, indicators of recurrent disease, and survival. Indicators of recurrent disease were histology and biliary strictures on cholangiogram. Kaplan-Meier survival with CoxMantel log-rank tests were performed on patients transplanted from 1985 to 1993 versus 1994 to 1998.
RESULTS
Sixtyone patients were liver-transplanted for PSC during the study period. Mean age at transplantation was 43 years (range 11 to 70) and the female-male ratio was 22-39. Patient survival was 82% at 1 year, 73% at 5 years, and 64% at 10 years. Patients transplanted during the period from 1994 to 1998 (n ⫽ 38) had a significantly better(P ⬍ .05) 1-year (90% vs 60.9%) and 5-year (83.3% vs 47.8%) patient survival than those transplanted during the period from 1985 to 1993 (n ⫽ 23). Seven patients were retransplanted (two due to artery thrombosis, one to primary graft non-
function and four to late graft dysfunction). Two of these patients were again retransplanted due to primary graft nonfunction. Five of the retransplanted patients are currently alive. Biliary complications that needed intervention were seen in 12 patients (20%). Four patients needed open surgical intervention. Anastomotic and nonanastomotic bile duct strictures of clinical significance were seen in nine and seven cases, respectively. Indications of recurrent disease (histology and cholangiogram) developed in five patients. None of them needed retransplantation and all five are alive with a follow-up of 4 to 10 years. Cholangiocellular carcinoma was found in six explanted livers. Two died in the early postoperative period (one of portal thrombosis and one of multiple organ failure). Three succumbed to disseminated cancer after 10, 10, and 12 months. One patient is currently alive after 24 months with no sign of cancer recurrence. DISCUSSION
The results of liver transplantation for PSC are comparable to those of other benign indications for liver transplantation at our center. Since the start of our program 15 years ago results have improved and are comparable to those of other centers.4 This improvement is probably explained by a learning curve and the fact that PSC patients were transplanted at more advanced stages of the disease in the early era. Biliary complications that required intervention were seen in 20% of cases. One of the cases was a patient who originally had a duct-to-duct anastomosis but had to have it converted to a Roux-en-Y after 6 years. The rate of biliary complications is comparable to those reported from other centers.5 Cholangiocellular carcinoma undetectable before transplantation was found in six explanted livers and resulted in patient death due to disseminated disease within a year for three patients. Two patients were lost in the early postoperative period because of multiple organ failure and From the Department of Transplantation and Liver Surgery, Sahlgrenska University Hospital, Gothenburg, Sweden. Address reprint requests to Dr M. Olausson, Sahlgrenska University Hospital, Department of Transplantation and Liver Surgery, Gothenburg, Sweden.
0041-1345/01/$–see front matter PII S0041-1345(01)02043-7
© 2001 by Elsevier Science Inc. 655 Avenue of the Americas, New York, NY 10010
2452
Transplantation Proceedings, 33, 2452–2453 (2001)
PRIMARY SCLEROSING CHOLANGITIS
portal thrombosis. Timing of transplantation is crucial as outcome is severely affected by the presence of cholangiocellular carcinoma at the time of transplantation.6 During the study period, seven patients were taken off the waiting list due to detection of cholangiocellular carcinoma before transplantation. A cause of concern is the signs of late disease recurrence, which may be as high as 8% in our material. The possibility of recurrent disease is controversial,3 but we have seen both histology and cholangiograms suggestive of recurrence in five patients without impaired blood flow as measured with Duplex ultrasonography. This is also reported from other centers.5 In conclusion, patients with end-stage liver disease due to PSC can be offered an effective treatment with liver transplantation with results comparable to those of other benign indications. Timing is crucial as a biliary malignancy discovered at the time of transplantation significantly worsens outcome.
2453
ACKNOWLEDGMENTS This work was supported by grants from the Medical Faculty of the University of Gothenburg (L.U.A.) and the Medical Research Council (K1999-73X-012228-03A).
REFERENCES 1. Abu Elmagd KM, Selby R, Iwatsuki S, et al: Transplant Proc 25:1124, 1993 2. Abu-Elmagd KM, Malinchoc M, Dickson ER, et al: Surg Gynecol Obstet 177:335, 1993 3. Boyer TD: Liver Transpl Surg 3(Suppl 1):24, 1997 4. Goss JA, Schacleton CR, Farmer DG, et al: Ann Surg 225:472, 1997 5. Mylene S, Farges O, Kalil A, et al: Am J Surg Pathol 19:81, 1995 6. Narumi S, Roberts JP, Emond JC, et al: Hepatology 22:451, 1995
P
RIMARY SCLEROSING CHOLANGITS (PSC) is one of the major indications for liver transplantation in Scandinavia. During the period from 1985 to 1998, 419 liver transplantations were performed at our center. PSC patients received 17% of these grafts. PSC is predominantly a disease of men and is often associated with inflammatory bowel disease (approximately 70%). There is an increased risk of developing cholangiocellular carcinoma that significantly affects outcome.1 Medical and surgical therapies for PSC are limited, and the natural course of PSC is hard to predict but it has been established that carefully selected patients clearly benefit from OLT.2 After transplantation the possibility of recurrence of PSC has been debated. It has been argued that the pathological findings that suggest recurrence are indistinguishable from other events such as chronic rejection and bile duct damage due to poor arterial blood flow.3 The aim of this study was to (a) analyze the outcome of liver transplantations for primary sclerosing cholangitis at our center, (b) review vascular and biliary complications, and (c) identify possible recurrent disease. MATERIALS AND METHODS The study population consisted of all 61 patients transplanted during the period from 1985 to 1998 for end-stage liver disease due to PSC. We have retrospectively reviewed their medical records and collected data on biliary complications, vascular complications, cause of retransplantation, indicators of recurrent disease, and survival. Indicators of recurrent disease were histology and biliary strictures on cholangiogram. Kaplan-Meier survival with CoxMantel log-rank tests were performed on patients transplanted from 1985 to 1993 versus 1994 to 1998.
RESULTS
Sixtyone patients were liver-transplanted for PSC during the study period. Mean age at transplantation was 43 years (range 11 to 70) and the female-male ratio was 22-39. Patient survival was 82% at 1 year, 73% at 5 years, and 64% at 10 years. Patients transplanted during the period from 1994 to 1998 (n ⫽ 38) had a significantly better(P ⬍ .05) 1-year (90% vs 60.9%) and 5-year (83.3% vs 47.8%) patient survival than those transplanted during the period from 1985 to 1993 (n ⫽ 23). Seven patients were retransplanted (two due to artery thrombosis, one to primary graft non-
function and four to late graft dysfunction). Two of these patients were again retransplanted due to primary graft nonfunction. Five of the retransplanted patients are currently alive. Biliary complications that needed intervention were seen in 12 patients (20%). Four patients needed open surgical intervention. Anastomotic and nonanastomotic bile duct strictures of clinical significance were seen in nine and seven cases, respectively. Indications of recurrent disease (histology and cholangiogram) developed in five patients. None of them needed retransplantation and all five are alive with a follow-up of 4 to 10 years. Cholangiocellular carcinoma was found in six explanted livers. Two died in the early postoperative period (one of portal thrombosis and one of multiple organ failure). Three succumbed to disseminated cancer after 10, 10, and 12 months. One patient is currently alive after 24 months with no sign of cancer recurrence. DISCUSSION
The results of liver transplantation for PSC are comparable to those of other benign indications for liver transplantation at our center. Since the start of our program 15 years ago results have improved and are comparable to those of other centers.4 This improvement is probably explained by a learning curve and the fact that PSC patients were transplanted at more advanced stages of the disease in the early era. Biliary complications that required intervention were seen in 20% of cases. One of the cases was a patient who originally had a duct-to-duct anastomosis but had to have it converted to a Roux-en-Y after 6 years. The rate of biliary complications is comparable to those reported from other centers.5 Cholangiocellular carcinoma undetectable before transplantation was found in six explanted livers and resulted in patient death due to disseminated disease within a year for three patients. Two patients were lost in the early postoperative period because of multiple organ failure and From the Department of Transplantation and Liver Surgery, Sahlgrenska University Hospital, Gothenburg, Sweden. Address reprint requests to Dr M. Olausson, Sahlgrenska University Hospital, Department of Transplantation and Liver Surgery, Gothenburg, Sweden.
0041-1345/01/$–see front matter PII S0041-1345(01)02043-7
© 2001 by Elsevier Science Inc. 655 Avenue of the Americas, New York, NY 10010
2452
Transplantation Proceedings, 33, 2452–2453 (2001)
PRIMARY SCLEROSING CHOLANGITIS
portal thrombosis. Timing of transplantation is crucial as outcome is severely affected by the presence of cholangiocellular carcinoma at the time of transplantation.6 During the study period, seven patients were taken off the waiting list due to detection of cholangiocellular carcinoma before transplantation. A cause of concern is the signs of late disease recurrence, which may be as high as 8% in our material. The possibility of recurrent disease is controversial,3 but we have seen both histology and cholangiograms suggestive of recurrence in five patients without impaired blood flow as measured with Duplex ultrasonography. This is also reported from other centers.5 In conclusion, patients with end-stage liver disease due to PSC can be offered an effective treatment with liver transplantation with results comparable to those of other benign indications. Timing is crucial as a biliary malignancy discovered at the time of transplantation significantly worsens outcome.
2453
ACKNOWLEDGMENTS This work was supported by grants from the Medical Faculty of the University of Gothenburg (L.U.A.) and the Medical Research Council (K1999-73X-012228-03A).
REFERENCES 1. Abu Elmagd KM, Selby R, Iwatsuki S, et al: Transplant Proc 25:1124, 1993 2. Abu-Elmagd KM, Malinchoc M, Dickson ER, et al: Surg Gynecol Obstet 177:335, 1993 3. Boyer TD: Liver Transpl Surg 3(Suppl 1):24, 1997 4. Goss JA, Schacleton CR, Farmer DG, et al: Ann Surg 225:472, 1997 5. Mylene S, Farges O, Kalil A, et al: Am J Surg Pathol 19:81, 1995 6. Narumi S, Roberts JP, Emond JC, et al: Hepatology 22:451, 1995