Original Clinical Science
Living Donor Liver Transplantation in Patients 70 Years or Older Arzu Oezcelik,1,2 Murat Dayangac,1 Necdet Guler,1 Onur Yaprak,1 Yalcin Erdogan,1 Murat Akyildiz,1 Zeynep Sevdik,1 Yildiray Yuzer,1 and Yaman Tokat1 Introduction. Previous published studies have shown that age is not a contraindication for deceased donor liver transplantation. The data about elderly recipient after living donor liver transplantation (LDLT) is unsatisfactory. The aim of this study was to evaluate the outcome of the LDLT with recipients aged 70 years or older. Patients and Methods. Between 2005 and 2013, 469 patients underwent LDLTs. The clinical characteristics, preoperative, intraoperative, and postoperative data, graft, and patients' survival of these patients were retrospectively analyzed. All recipients who were 70 years or older at the time of liver transplantation were indentified. The results were compared to the results of the patients younger than 70 years. Results. There were 12 patients (2%) 70 years or older. All patients received the right lobe of their donor in a standard technique. One patient died postoperatively because of pulmonary infection, and one patient died 6 months after the operation because of graft failure after cardiac infarction. The comorbidity score of these two patients were significantly higher compared to the other ten patients without any complications (8.5 vs. 4.6, P = 0.01). The 1-year and 3-year patient and graft survival was 84%. There were no significant differences in complications, hospital stay, perioperative mortality, or median survival compared to the younger group. Conclusion. Although the number of the patients is small, our study emphasizes that LDLTof patients 70 years or older can be performed safely in patients without major comorbidities. Elderly patients with increased risk for postoperative complications should be excluded from LDLT.
(Transplantation 2015;99: 1436–1440)
L
iver transplantation has become the accepted standard therapy of end-stage liver disease.1 Patients and graft survival rates of 86% have been reported.2 Improvements in outcome and survival are reflecting advances in surgical technique, anesthesia, critical care, infection management, and also immunosuppressant therapy. In some countries, the deceased donor liver transplantation (DDLT) is not a realistic option because of the lack of deceased donors based on cultural, religious, or political ideologies. In these countries, the living donor liver transplantation (LDLT) became the standard therapy for end-stage liver disease with similar outcome and survival rates. These improvements have led to the expansion of the recipient criteria to include patients previously considered as not suitable for liver transplantation Received 23 May 2014. Revision requested 22 June 2014. Accepted 6 October 2014. 1 Department of General and Transplantation Surgery, University Hospital of the Istanbul Science University, Istanbul, Turkey. 2
Department of General, Visceral and Transplantation Surgery, University Hospital of Duisburg-Essen, Essen, Germany. The authors declare no funding or conflicts of interest. A.O. designed the study, analyzed data and wrote the article. Y.Y. and Y.T. mentored the study and contributed important reagents. N.G., Z.S., and Y.E. collected data. M.D., O.Y., M.A. analyzed data. Correspondence: Arzu Oezcelik, MD, Department of General and Transplantation Surgery, University Hospital of the Istanbul Science University, Abide-i Hurriyet Cad. No: 164 Sisli, Istanbul, Turkey. ([email protected]). Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved. ISSN: 0041-1337/15/9907-1436 DOI: 10.1097/TP.0000000000000524
1436
www.transplantjournal.com
because of older age or comorbidities. If we consider that the population of the western world continues to live longer with health, this question of expanded recipient criteria will become even more important. Several previous published studies have shown that age alone is not a contraindication for DDLT.3-10 However, there are not enough data in the literature about older recipients of LDLT. The aim of this study is to evaluate the outcome of patients with age of 70 years or older, who underwent a LDLT for end-stage liver disease. RESULTS There were 16 patients in the age of 70 years or older, who were discussed for LDLT. Of these patients, two patients canceled the operation, and one patient was excluded because of portal vein thrombosis. Another patient was, in addition to his age, in a poor general condition with multiple comorbidities. Considering all these cofactors this patient was evaluated as not suitable for LDLT. The remaining 12 patients in the age of 70 years or older underwent LDLT at our center, six women (50%) and six men (50%). The causes of the liver cirrhoses were hepatitis B or C in seven patients (58%), cryptogenic in four (34%), and alcoholic in one (8%). All of the patients had at least one complication of their liver cirrhosis, such as hepatic encephalopathy, variceal bleeding, or spontaneous bacterial peritonitis. The median model for end-stage liver disease (MELD) score was 13 (interquartile range [IQR], 11‐17) and the median World Health Organization (WHO) performance status was preoperatively three (IQR, 3‐3.5). The measured median skeletal muscle area, using preoperative computed tomography scan, was 98 cm2 (IQR, 95‐125) in Transplantation
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
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© 2015 Wolters Kluwer
men and 68 cm2 (IQR, 61‐87) in women. There was no significant difference between the 12 patients regarding the skeletal muscle area. The median comorbidity score of all 12 patients was 7.2 (IQR, 3‐6). However, the comorbidity score in two patients was significantly higher compared to the other 10 patients (8.5 vs. 4.6; P = 0.01). All patients received the right lobe of their donor in a standard technique. There were no significant differences in the donor criteria, MELD score, or time of ischemia (Table 1). There were no intraoperative complications. The median blood transfusion was three units (IQR, 3‐6). There were no major anatomic vascular variations requiring vascular reconstructions. The anastomosis of the bile duct was duct to duct in all cases with placement of a catheter transanastomotic as external bile drainage. The median initial intensive care unit (ICU) stay, after the transplantation, was 3 days (IQR, 2‐6). All patients received tacrolimus-based immunosuppressant therapy in combination with prednisone, which was supplemented with mycophenolat mofetil. There was no acute rejection after liver transplantation. In the second postoperative week after transplantation, one (8%) of the 12 patients developed severe pulmonary infection, which required readmission to the ICU and reintubation. Despite extensive treatment on ICU she died because of multiorgan failure based on the infection within a month after surgery. Another patient (8%) suffered cardiac infarction 3 months after LDLT and had to be readmitted to the hospital. The cardiac infarction could be treated successfully with recovery of her cardiac function. However, after cardiac dysfunction, the patient developed a failure of the liver graft and died 6 months after the transplantation because of liver failure. These two patients had a significantly higher comorbidity score preoperatively compared to the remaining 10 patients (8.5 vs. 4.6; P = 0.01). In addition to the age, one patient had diabetes mellitus, cardiac and kidney disease, and the other patient had chronic pulmonary disease and diabetes mellitus. In the remaining 10 patients, biliary leakage was seen in two patients (16%), which could be treated successfully by interventional placement of a drain. There were no other major postoperative complications. Two patients (16%) were readmitted to the hospital 4 and 7 months after transplantation due to cholangitis, which could be treated successfully with antibiotics. One patient (8%) was readmitted to the hospital 3 months after surgery because of enteritis and hypovolemia, which could be treated with antibiotics and intravenous fluid substitution. The
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TABLE 2.
Serum levels of the patients three years after liver transplantation Values in median and IQR
n Total bilirubin, mg/dL AST/GOT, U/L ALT/GPT, U/L INR Serum creatinine, mg/dL Serum albumin, g/dL
10 0.8 (0.3-1.0) 24 (15-31) 22 (14-43) 0.9 (0.9-1.0) 1.1 (0.8-1.3) 4.1 (3.4-4.4)
ALT, alanine aminotransferase; AST, aspartate aminotransferase; GOT, glutamate-oxaloacetatetransaminase; GPT, glutamate-pyruvate-transaminase; INR, international normalized ratio.
median postoperative WHO performance status was 1 (IQR, 1‐2), which was significantly improved compared to the preoperative status (P = 0.0002). The patients had a follow-up for at least 3 years. The median survival rate was 37 months (IQR, 36‐52). Three years after transplantation, all 10 patients (84%) had a good liver function with normal blood values (Table 2). The median age of the donor was 40 years. The ICU stay was 1 day. There were no intraoperative or postoperative complications. All donors had a normal postoperative course and could be discharged 7 days after the operation. There were 422 patients younger than 70 years, who underwent LDLT at our center. The median age was 53 years (IQR, 45‐58). The cause was hepatitis B in 180 (43%), cryptogenic in 66 (16%), hepatitis C in 64 (14%), alcoholic in 58 (14%), non-alcoholic stereohepatitis in 34 (8%), and primary bilary cirrhosis or primary sclerosing cholangitis in 22 patients (5%). The median MELD score was 16 (IQR, 12‐20). All patients received the right lobe of their donor in a standard technique. The results of the patients 70 years or older were compared with the results of the patients younger than 70 years. There were no significant differences between the two groups in MELD score, complications rate, perioperative mortality, hospital stay or median survival (Tables 1 and 3). DISCUSSION The outcome and survival of the LDLT is significantly improved in the last years, especially in those centers performing mainly LDLT because of the lack of deceased donors.11,12 In these countries, the LDLT became the accepted
TABLE 1.
Comparison of the preoperative data between younger and older patients group Younger patients
Older patients
P
n 422 12 Age, yr 53 (IQR, 45-58) 70 (IQR, 70-72) /=70 years) recipients? A case-controlled analysis. HPB (Oxford). 2014;12:1088.
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
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19. Yoshizumi T, Shirabe K, Soejima Y, et al. Living donor liver transplantation in patients older than 60 years. Transplantation. 2010;90:433. 20. Olthoff KM, Merion RM, Ghobrial RM, et al. Outcomes of 385 adult-toadult living donor liver transplant recipients: a report from the A2ALL Consortium. Ann Surg. 2005;242:314, discussion 323–315. 21. Suehiro T, Shimada M, Kishikawa K, et al. Is an elderly recipient a risk for living donor adult liver transplantation? Hepatogastroenterology. 2008;55:653.
www.transplantjournal.com
22. Taner CB, Ung RL, Rosser BG, et al. Age is not a contraindication for orthotopic liver transplantation: a single institution experience with recipients older than 75 years. Hepatol Int. 2011. 23. Ikegami T, Bekki Y, Imai D, et al. Clinical outcomes of living donor liver transplantation for patients 65 years old or older with preserved performance status. Liver Transpl. 2014;20:408. 24. Guler N, Dayangac M, Yaprak O, et al. Anatomical variations of donor portal vein in right lobe living donor liver transplantation: the safe use of variant portal veins. Transpl Int. 2013;26:1191.
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Living Donor Liver Transplantation in Patients 70 Years or Older Arzu Oezcelik,1,2 Murat Dayangac,1 Necdet Guler,1 Onur Yaprak,1 Yalcin Erdogan,1 Murat Akyildiz,1 Zeynep Sevdik,1 Yildiray Yuzer,1 and Yaman Tokat1 Introduction. Previous published studies have shown that age is not a contraindication for deceased donor liver transplantation. The data about elderly recipient after living donor liver transplantation (LDLT) is unsatisfactory. The aim of this study was to evaluate the outcome of the LDLT with recipients aged 70 years or older. Patients and Methods. Between 2005 and 2013, 469 patients underwent LDLTs. The clinical characteristics, preoperative, intraoperative, and postoperative data, graft, and patients' survival of these patients were retrospectively analyzed. All recipients who were 70 years or older at the time of liver transplantation were indentified. The results were compared to the results of the patients younger than 70 years. Results. There were 12 patients (2%) 70 years or older. All patients received the right lobe of their donor in a standard technique. One patient died postoperatively because of pulmonary infection, and one patient died 6 months after the operation because of graft failure after cardiac infarction. The comorbidity score of these two patients were significantly higher compared to the other ten patients without any complications (8.5 vs. 4.6, P = 0.01). The 1-year and 3-year patient and graft survival was 84%. There were no significant differences in complications, hospital stay, perioperative mortality, or median survival compared to the younger group. Conclusion. Although the number of the patients is small, our study emphasizes that LDLTof patients 70 years or older can be performed safely in patients without major comorbidities. Elderly patients with increased risk for postoperative complications should be excluded from LDLT.
(Transplantation 2015;99: 1436–1440)
L
iver transplantation has become the accepted standard therapy of end-stage liver disease.1 Patients and graft survival rates of 86% have been reported.2 Improvements in outcome and survival are reflecting advances in surgical technique, anesthesia, critical care, infection management, and also immunosuppressant therapy. In some countries, the deceased donor liver transplantation (DDLT) is not a realistic option because of the lack of deceased donors based on cultural, religious, or political ideologies. In these countries, the living donor liver transplantation (LDLT) became the standard therapy for end-stage liver disease with similar outcome and survival rates. These improvements have led to the expansion of the recipient criteria to include patients previously considered as not suitable for liver transplantation Received 23 May 2014. Revision requested 22 June 2014. Accepted 6 October 2014. 1 Department of General and Transplantation Surgery, University Hospital of the Istanbul Science University, Istanbul, Turkey. 2
Department of General, Visceral and Transplantation Surgery, University Hospital of Duisburg-Essen, Essen, Germany. The authors declare no funding or conflicts of interest. A.O. designed the study, analyzed data and wrote the article. Y.Y. and Y.T. mentored the study and contributed important reagents. N.G., Z.S., and Y.E. collected data. M.D., O.Y., M.A. analyzed data. Correspondence: Arzu Oezcelik, MD, Department of General and Transplantation Surgery, University Hospital of the Istanbul Science University, Abide-i Hurriyet Cad. No: 164 Sisli, Istanbul, Turkey. ([email protected]). Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved. ISSN: 0041-1337/15/9907-1436 DOI: 10.1097/TP.0000000000000524
1436
www.transplantjournal.com
because of older age or comorbidities. If we consider that the population of the western world continues to live longer with health, this question of expanded recipient criteria will become even more important. Several previous published studies have shown that age alone is not a contraindication for DDLT.3-10 However, there are not enough data in the literature about older recipients of LDLT. The aim of this study is to evaluate the outcome of patients with age of 70 years or older, who underwent a LDLT for end-stage liver disease. RESULTS There were 16 patients in the age of 70 years or older, who were discussed for LDLT. Of these patients, two patients canceled the operation, and one patient was excluded because of portal vein thrombosis. Another patient was, in addition to his age, in a poor general condition with multiple comorbidities. Considering all these cofactors this patient was evaluated as not suitable for LDLT. The remaining 12 patients in the age of 70 years or older underwent LDLT at our center, six women (50%) and six men (50%). The causes of the liver cirrhoses were hepatitis B or C in seven patients (58%), cryptogenic in four (34%), and alcoholic in one (8%). All of the patients had at least one complication of their liver cirrhosis, such as hepatic encephalopathy, variceal bleeding, or spontaneous bacterial peritonitis. The median model for end-stage liver disease (MELD) score was 13 (interquartile range [IQR], 11‐17) and the median World Health Organization (WHO) performance status was preoperatively three (IQR, 3‐3.5). The measured median skeletal muscle area, using preoperative computed tomography scan, was 98 cm2 (IQR, 95‐125) in Transplantation
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
■
July 2015
■
Volume 99
■
Number 7
Oezcelik et al
© 2015 Wolters Kluwer
men and 68 cm2 (IQR, 61‐87) in women. There was no significant difference between the 12 patients regarding the skeletal muscle area. The median comorbidity score of all 12 patients was 7.2 (IQR, 3‐6). However, the comorbidity score in two patients was significantly higher compared to the other 10 patients (8.5 vs. 4.6; P = 0.01). All patients received the right lobe of their donor in a standard technique. There were no significant differences in the donor criteria, MELD score, or time of ischemia (Table 1). There were no intraoperative complications. The median blood transfusion was three units (IQR, 3‐6). There were no major anatomic vascular variations requiring vascular reconstructions. The anastomosis of the bile duct was duct to duct in all cases with placement of a catheter transanastomotic as external bile drainage. The median initial intensive care unit (ICU) stay, after the transplantation, was 3 days (IQR, 2‐6). All patients received tacrolimus-based immunosuppressant therapy in combination with prednisone, which was supplemented with mycophenolat mofetil. There was no acute rejection after liver transplantation. In the second postoperative week after transplantation, one (8%) of the 12 patients developed severe pulmonary infection, which required readmission to the ICU and reintubation. Despite extensive treatment on ICU she died because of multiorgan failure based on the infection within a month after surgery. Another patient (8%) suffered cardiac infarction 3 months after LDLT and had to be readmitted to the hospital. The cardiac infarction could be treated successfully with recovery of her cardiac function. However, after cardiac dysfunction, the patient developed a failure of the liver graft and died 6 months after the transplantation because of liver failure. These two patients had a significantly higher comorbidity score preoperatively compared to the remaining 10 patients (8.5 vs. 4.6; P = 0.01). In addition to the age, one patient had diabetes mellitus, cardiac and kidney disease, and the other patient had chronic pulmonary disease and diabetes mellitus. In the remaining 10 patients, biliary leakage was seen in two patients (16%), which could be treated successfully by interventional placement of a drain. There were no other major postoperative complications. Two patients (16%) were readmitted to the hospital 4 and 7 months after transplantation due to cholangitis, which could be treated successfully with antibiotics. One patient (8%) was readmitted to the hospital 3 months after surgery because of enteritis and hypovolemia, which could be treated with antibiotics and intravenous fluid substitution. The
1437
TABLE 2.
Serum levels of the patients three years after liver transplantation Values in median and IQR
n Total bilirubin, mg/dL AST/GOT, U/L ALT/GPT, U/L INR Serum creatinine, mg/dL Serum albumin, g/dL
10 0.8 (0.3-1.0) 24 (15-31) 22 (14-43) 0.9 (0.9-1.0) 1.1 (0.8-1.3) 4.1 (3.4-4.4)
ALT, alanine aminotransferase; AST, aspartate aminotransferase; GOT, glutamate-oxaloacetatetransaminase; GPT, glutamate-pyruvate-transaminase; INR, international normalized ratio.
median postoperative WHO performance status was 1 (IQR, 1‐2), which was significantly improved compared to the preoperative status (P = 0.0002). The patients had a follow-up for at least 3 years. The median survival rate was 37 months (IQR, 36‐52). Three years after transplantation, all 10 patients (84%) had a good liver function with normal blood values (Table 2). The median age of the donor was 40 years. The ICU stay was 1 day. There were no intraoperative or postoperative complications. All donors had a normal postoperative course and could be discharged 7 days after the operation. There were 422 patients younger than 70 years, who underwent LDLT at our center. The median age was 53 years (IQR, 45‐58). The cause was hepatitis B in 180 (43%), cryptogenic in 66 (16%), hepatitis C in 64 (14%), alcoholic in 58 (14%), non-alcoholic stereohepatitis in 34 (8%), and primary bilary cirrhosis or primary sclerosing cholangitis in 22 patients (5%). The median MELD score was 16 (IQR, 12‐20). All patients received the right lobe of their donor in a standard technique. The results of the patients 70 years or older were compared with the results of the patients younger than 70 years. There were no significant differences between the two groups in MELD score, complications rate, perioperative mortality, hospital stay or median survival (Tables 1 and 3). DISCUSSION The outcome and survival of the LDLT is significantly improved in the last years, especially in those centers performing mainly LDLT because of the lack of deceased donors.11,12 In these countries, the LDLT became the accepted
TABLE 1.
Comparison of the preoperative data between younger and older patients group Younger patients
Older patients
P
n 422 12 Age, yr 53 (IQR, 45-58) 70 (IQR, 70-72) /=70 years) recipients? A case-controlled analysis. HPB (Oxford). 2014;12:1088.
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
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Number 7
19. Yoshizumi T, Shirabe K, Soejima Y, et al. Living donor liver transplantation in patients older than 60 years. Transplantation. 2010;90:433. 20. Olthoff KM, Merion RM, Ghobrial RM, et al. Outcomes of 385 adult-toadult living donor liver transplant recipients: a report from the A2ALL Consortium. Ann Surg. 2005;242:314, discussion 323–315. 21. Suehiro T, Shimada M, Kishikawa K, et al. Is an elderly recipient a risk for living donor adult liver transplantation? Hepatogastroenterology. 2008;55:653.
www.transplantjournal.com
22. Taner CB, Ung RL, Rosser BG, et al. Age is not a contraindication for orthotopic liver transplantation: a single institution experience with recipients older than 75 years. Hepatol Int. 2011. 23. Ikegami T, Bekki Y, Imai D, et al. Clinical outcomes of living donor liver transplantation for patients 65 years old or older with preserved performance status. Liver Transpl. 2014;20:408. 24. Guler N, Dayangac M, Yaprak O, et al. Anatomical variations of donor portal vein in right lobe living donor liver transplantation: the safe use of variant portal veins. Transpl Int. 2013;26:1191.
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
