- Email: [email protected]
Comparative Study Between Living and Cadaveric Donors in Pediatric Liver Transplantation
Comparative Study Between Living and Cadaveric Donors in Pediatric Liver Transplantation F. Hernández Oliveros, M. López Santamarı´a, M. Gámez, J. Murcia, N. Leal, E. Frauca, L. Hierro, C. Camarena, A. de la Vega, G. Bortolo, M.C. Dı´az, and P. Jara ABSTRACT We examined whether the results in living-related hepatic transplantation (LRLT) are better than those from a cadaveric donor (CDLT). Material and methods. The last 27 consecutive LRLT, performed from 1998 to 2005, were compared with 27 CDLT matched for age, weight, date, and diagnosis. Grafts in LRLT group were left lateral segment (n ⫽ 22), left lobe (n ⫽ 3), and right lobe (n ⫽ 2). In the CDLT group, the grafts were split in situ (n ⫽ 10), hepatic reduction (n ⫽ 9) and whole liver (n ⫽ 8). We analyzed the actuarial survivals (grafts and children), retransplantation, primary nonfunction, initial graft malfunction (liver enzymes ⬎2000 U/L), surgical complications, rejection, and resource consumption. Results. Patient survivals at 6 months, 1 year, and 5 years were 100%, 96%, and 96% in LRLT and 100%, 100%, and 100% in CDLT (P ⫽ NS). Graft survivals were 93%, 89%, and 89% versus 96%, 96%, and 96%, respectively (P ⫽ NS). Complications were biliary complications (LRLT, 25% vs CDLT, 3%; P ⫽ .021); portal vein thrombosis (LRLT, 7% vs CDLT, 3%; NS), and hepatic artery thrombosis (LRLT, 0% vs CDLT, 3%; NS). The overall incidence of acute rejection was slightly higher (NS) in LRLT (LRLT, 18% vs CDLT, 11%; NS). Liver enzyme levels were higher in the CDLT group, but initial malfunction rate was not statistically different. Regarding resource consumption: blood product needs were higher in LRLT (P ⬍ .05) and hospital stay and ICU stay were longer, although not significantly, among LRLT. Conclusions. The results in LRLT among children are similar to those obtained in CDLT. We found a trend towards less initial graft malfunction in LRLT. Blood product needs were higher in LRLT. Hospital and ICU stay were longer, but not significantly different in LRLT. The benefits of LRLT are saving a scarce resource: a cadaveric donor liver graft.
A
VAILABILITY of cadaveric organs is insufficient to meet the demands for liver transplantation even in Spain with its high donation rate.1 Thus, the need for living donor transplantation is beyond question. Furthermore, it has been demonstrated in recent studies that the results in living-related hepatic transplantation (LRLT) for small children are better than those in different modalities of cadaveric donors.2,3 Our aim was to compare the results between the groups in our series. MATERIAL AND METHODS The last 27 consecutive LRLT performed since 1998 were compared with 27 CDLT matched for age, weight, date, and diagnosis
group (cholestatic, cirrhosis, metabolic, and miscellaneous; Table 1). Noteworthy, 48% children in LRLT (0% in CDLT), were referred from abroad, most of them decompensated with end-stage liver disease. Grafts in the LRLT group were left lateral segments (n ⫽ 22),
From the Department of Pediatric Surgery (F.H.O., M.L.S., M.G., J.M., N.L.) and Department of Hepatology (E.F., L.H., C.C., A.d.l.V., G.B., M.C.D., P.J.), Hospital Universitario La Paz, Madrid, Spain. Address reprint requests to Dr. López-Santamarı´a, Manuel, Department of Pediatric Surgery, Hospital Universitario La Paz, Paseo de la Castellana 261, 28046 Madrid, Spain. E-mail: [email protected]
0041-1345/05/$–see front matter doi:10.1016/j.transproceed.2005.10.072
© 2005 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
3936
Transplantation Proceedings, 37, 3936 –3938 (2005)
LIVING VS CADAVERIC DONORS
3937
Table 1. Demographic and Outcome Data of Children in Both Groups—Living Donor and Cadaveric Donor Grafts Variable
Age (y) (mean ⫾ SD) Weight Group of diagnosis Cirrhosis Cholestatic Metabolic disease Miscelianeous Initial malfunction Patient survival 6 mo 1y 5y Graft survival 6 mo 1y 5y Retransplant (%) Biliary complications Acute rejection ICU stay (d), median Hospitalary stay Hemoderivates (cc) Platelets Plasma Red cells concentrate
Living Donor Organ
Cadaveric Donor Organs
2.3 11.7
2.8 12
1 21 0 5 3
3 14 6 4 7
93% 89% 89%
96% 96% 96%
100% 96% 96% 3 (10%) 7 (25%) 5 (18%) 16.1 78.6
100% 100% 100% 1 (3%) 1 (3%) 3 (11%) 10.9 56.6
95 1802 1526
28 1185 897
Statistic
NS NS
NS NS
NS
NS
NS NS NS P ⬍ .05 P ⬍ .05
NS, nonsignificant.
left lobe (n ⫽ 3), and right lobe (n ⫽ 2). In the CDLT group, grafts were split in situ (n ⫽ 10), or hepatic reduction (n ⫽ 9), or whole liver (n ⫽ 8). Indications for transplantation in LRLT group were biliary atresia (n ⫽ 19), tumor (n ⫽ 3), Alagille syndrome (n ⫽ 1), cryptogenetic (n ⫽ 1), neonatal hepatitis (n ⫽ 1), acute hepatic failure (n ⫽ 1), and sequential transplantation for intestinal failure because of Hirschsprung disease (n ⫽ 1). Indications for transplantation in the CDLT group were metabolic diseases (n ⫽ 6), Byler disease (n ⫽ 3), cryptogenetic (n ⫽ 3), biliary atresia (n ⫽ 2), tumor (n ⫽ 2), Alagille syndrome (n ⫽ 2), neonatal hepatitis (n ⫽ 1), and acute hepatic failure (n ⫽ 1). The analyzed variables were actuarial survival (grafts and children), retransplantation, primary nonfunction, initial graft malfunction (liver enzymes ⬎2000 U/L), surgical complications, rejection, and resource consumption.
RESULTS
The median hospital stay for donors was 6 days (range 5 to 21). Morbidity among the donors included: abdominal wall anesthesia (92%), biliary fistula (3%) that closed spontaneously, right pleural effusion in a right lobe donor (3%), prothrombin activity less than 40% in a right lobe donor (3%), laparotomy for wound effusion (3%), and safenectomy wound infection (3%). Patient survivals at 6 months, 1 year, and 5 years were 100%, 96%, and 96% in LRLT and 100%, 100%, and 100% for CDLT (NS). The global survivals of the series from 1998 among 142 children were 98%, 97%, and 96%. There were
no biases in the selection procedure for CDLT group. The patient who died in the LRLT group was a child with extensive intestinal aganglionism listed for hepatointestinal transplantation. LRLT was performed as a sequential transplantation; the boy died during the procedure of multivisceral transplantation 8 months later. Graft survivals were 93%, 89%, and 89% versus 96%, 96%, and 96%, respectively (NS). For the global series since 1998, including 151 grafts, the values were 93%, 91%, and 88%, respectively. Complications were biliary (LRLT, 25% versus CDLT, 3%; P ⫽ .021) portal vein thrombosis (LRLT, 7% versus CDLT, 3%; NS); hepatic artery thrombosis (LRLT, 0% versus CDLT, 3%; NS). The overall incidence of acute rejection episodes was slightly but not significantly higher among LRLT (LRLT, 18% versus CDLT, 11%, NS). We did not demonstrate significant differences in initial graft malfunction, but the liver enzymes levels were higher among the CDLT group (GOT, LRLT, 1849 versus CDLT, 3176; NS; GPT, LRLT, 1370 versus CDLT, 2770; NS). Blood product needs in both groups were red cell concentrates (LRLT, 1523 versus CDLT, 897 cc; P ⬍ .05), plasma (LRLT, 1802 cc versus CDLT, 1185 cc; P ⬍ .05), platelets (LRLT, 95 cc versus CDLT, 28; NS). Mean hospital stay was 78.6 days for LRLT and 56.6 days for CDLT (NS). ICU stay was 16.1 and 10.9 days (NS), respectively. DISCUSSION
The scarcity of donors and deaths of candidates while on the waiting list remains a big problem for transplant programs. The use of alternative techniques (split) and the high donation rate in our country (the highest in the world) are of great help in alleviating this problem. However, the availability of cadaveric organs is still insufficient to meet the demand. The probability of access to liver transplantation remains low (near 50%) and the mortality rate significant (9%).2,4 – 6 We agree with several authors that a pediatric transplantation group should be able to offer every alternative of liver transplantation, including LRLT.6 In our mind, living donation will be necessary until pretransplant mortality is zero; even in that case LRLT will be an essential tool for some indications: such as tumours and acute liver failure. Unfortunately, liver transplantation is not available in many countries. LRLT programs give developed countries a chance to help these children without interfering with their own waiting list. In our series, children coming from abroad accounted for 48% of LRLT group. In our series, we observed a lower rate of primary malfunction among the LRLT group. Elective surgery and shorter ischemia time are features of LRLT that contribute to this finding. Like other authors we did not find a lower rejection rate among LRLT.7 With respect to resource consumption, blood product needs were significantly higher among the LRLT group, a finding that can be attributed to the differences in primary diseases: biliary atresia accounted for 70% of children in the LRLT group; while children in
3938
CDLT were mostly nonoperated and suffered from less decompensated hepatopathy. Longer hospital and ICU stays may be understood in the same way. Finally, biliary complications have been reported to be frequent in LRLT.7–9 Our series included 7 of 27 cases (25%), including bile leaks (n ⫽ 4) and strictures (n ⫽ 3). Regarding the ethical justification of living donors, the issue in children is clearly different from adults, as LRLT in children is curative with only a few exceptions. Another advantage in children is the use of the left lateral segment that provides a lower complication rate than the right lobe, which is used for adults. Additionally, psychological effects of donation are important; for young parents it offers the only direct action to affect the course of their children’s disease.10 In conclusion, our results in LRLT in children were similar to those obtained in cadaveric liver transplantation. In our series we observed a trend toward less initial graft malfunction among LRLT. However, blood product needs were higher and hospitalization tended to be longer in LRLT. The benefits of LRLT are avoiding pretransplant mortality on the waiting list without significant morbidity for the donor.
HERNÁNDEZ OLIVEROS, LÓPEZ SANTAMARÍA, GÁMEZ ET AL
REFERENCES 1. ONT, Transplante Hepático en España 2002. 2002. 2. Otte JB, et al: Pediatric liver transplantation: from the full-size liver graft to reduced, split, and living related liver transplantation. Pediatr Surg Int 13:308, 1998 3. Roberts JP, et al: Influence of graft type on outcomes after pediatric liver transplantation. Am J Transplant 4:373, 2004 4. Lopez-Santamaria M, et al: Pediatric living donor liver transplantation. Transplant Proc 35:1808, 2003 5. Lopez-Santamaria M, et al: Do the results justify living donor and split liver transplant for children in Spain? Transplant Proc 34:239, 2002 6. Testa G, Malago M, Broelsch CE: From living related to in-situ split liver transplantation: how to reduce waiting-list mortality. Pediatr Transplant 5:16, 2001 7. Reding R, et al: Pediatric liver transplantation with cadaveric or living related donors: comparative results in 90 elective recipients of primary grafts. J Pediatr 134:280, 1999 8. de Ville, de Goyet J, et al: Related living donor for liver transplantation in children: results and impact. Chirurgie 122:83, 1997 9. Egawa H, et al: Biliary complications in pediatric living related liver transplantation. Surgery 124:901, 1998 10. Otte JB, et al: Parental experience with living-related donor liver transplantation. Pediatr Transplant 8:317, 2004
A
VAILABILITY of cadaveric organs is insufficient to meet the demands for liver transplantation even in Spain with its high donation rate.1 Thus, the need for living donor transplantation is beyond question. Furthermore, it has been demonstrated in recent studies that the results in living-related hepatic transplantation (LRLT) for small children are better than those in different modalities of cadaveric donors.2,3 Our aim was to compare the results between the groups in our series. MATERIAL AND METHODS The last 27 consecutive LRLT performed since 1998 were compared with 27 CDLT matched for age, weight, date, and diagnosis
group (cholestatic, cirrhosis, metabolic, and miscellaneous; Table 1). Noteworthy, 48% children in LRLT (0% in CDLT), were referred from abroad, most of them decompensated with end-stage liver disease. Grafts in the LRLT group were left lateral segments (n ⫽ 22),
From the Department of Pediatric Surgery (F.H.O., M.L.S., M.G., J.M., N.L.) and Department of Hepatology (E.F., L.H., C.C., A.d.l.V., G.B., M.C.D., P.J.), Hospital Universitario La Paz, Madrid, Spain. Address reprint requests to Dr. López-Santamarı´a, Manuel, Department of Pediatric Surgery, Hospital Universitario La Paz, Paseo de la Castellana 261, 28046 Madrid, Spain. E-mail: [email protected]
0041-1345/05/$–see front matter doi:10.1016/j.transproceed.2005.10.072
© 2005 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
3936
Transplantation Proceedings, 37, 3936 –3938 (2005)
LIVING VS CADAVERIC DONORS
3937
Table 1. Demographic and Outcome Data of Children in Both Groups—Living Donor and Cadaveric Donor Grafts Variable
Age (y) (mean ⫾ SD) Weight Group of diagnosis Cirrhosis Cholestatic Metabolic disease Miscelianeous Initial malfunction Patient survival 6 mo 1y 5y Graft survival 6 mo 1y 5y Retransplant (%) Biliary complications Acute rejection ICU stay (d), median Hospitalary stay Hemoderivates (cc) Platelets Plasma Red cells concentrate
Living Donor Organ
Cadaveric Donor Organs
2.3 11.7
2.8 12
1 21 0 5 3
3 14 6 4 7
93% 89% 89%
96% 96% 96%
100% 96% 96% 3 (10%) 7 (25%) 5 (18%) 16.1 78.6
100% 100% 100% 1 (3%) 1 (3%) 3 (11%) 10.9 56.6
95 1802 1526
28 1185 897
Statistic
NS NS
NS NS
NS
NS
NS NS NS P ⬍ .05 P ⬍ .05
NS, nonsignificant.
left lobe (n ⫽ 3), and right lobe (n ⫽ 2). In the CDLT group, grafts were split in situ (n ⫽ 10), or hepatic reduction (n ⫽ 9), or whole liver (n ⫽ 8). Indications for transplantation in LRLT group were biliary atresia (n ⫽ 19), tumor (n ⫽ 3), Alagille syndrome (n ⫽ 1), cryptogenetic (n ⫽ 1), neonatal hepatitis (n ⫽ 1), acute hepatic failure (n ⫽ 1), and sequential transplantation for intestinal failure because of Hirschsprung disease (n ⫽ 1). Indications for transplantation in the CDLT group were metabolic diseases (n ⫽ 6), Byler disease (n ⫽ 3), cryptogenetic (n ⫽ 3), biliary atresia (n ⫽ 2), tumor (n ⫽ 2), Alagille syndrome (n ⫽ 2), neonatal hepatitis (n ⫽ 1), and acute hepatic failure (n ⫽ 1). The analyzed variables were actuarial survival (grafts and children), retransplantation, primary nonfunction, initial graft malfunction (liver enzymes ⬎2000 U/L), surgical complications, rejection, and resource consumption.
RESULTS
The median hospital stay for donors was 6 days (range 5 to 21). Morbidity among the donors included: abdominal wall anesthesia (92%), biliary fistula (3%) that closed spontaneously, right pleural effusion in a right lobe donor (3%), prothrombin activity less than 40% in a right lobe donor (3%), laparotomy for wound effusion (3%), and safenectomy wound infection (3%). Patient survivals at 6 months, 1 year, and 5 years were 100%, 96%, and 96% in LRLT and 100%, 100%, and 100% for CDLT (NS). The global survivals of the series from 1998 among 142 children were 98%, 97%, and 96%. There were
no biases in the selection procedure for CDLT group. The patient who died in the LRLT group was a child with extensive intestinal aganglionism listed for hepatointestinal transplantation. LRLT was performed as a sequential transplantation; the boy died during the procedure of multivisceral transplantation 8 months later. Graft survivals were 93%, 89%, and 89% versus 96%, 96%, and 96%, respectively (NS). For the global series since 1998, including 151 grafts, the values were 93%, 91%, and 88%, respectively. Complications were biliary (LRLT, 25% versus CDLT, 3%; P ⫽ .021) portal vein thrombosis (LRLT, 7% versus CDLT, 3%; NS); hepatic artery thrombosis (LRLT, 0% versus CDLT, 3%; NS). The overall incidence of acute rejection episodes was slightly but not significantly higher among LRLT (LRLT, 18% versus CDLT, 11%, NS). We did not demonstrate significant differences in initial graft malfunction, but the liver enzymes levels were higher among the CDLT group (GOT, LRLT, 1849 versus CDLT, 3176; NS; GPT, LRLT, 1370 versus CDLT, 2770; NS). Blood product needs in both groups were red cell concentrates (LRLT, 1523 versus CDLT, 897 cc; P ⬍ .05), plasma (LRLT, 1802 cc versus CDLT, 1185 cc; P ⬍ .05), platelets (LRLT, 95 cc versus CDLT, 28; NS). Mean hospital stay was 78.6 days for LRLT and 56.6 days for CDLT (NS). ICU stay was 16.1 and 10.9 days (NS), respectively. DISCUSSION
The scarcity of donors and deaths of candidates while on the waiting list remains a big problem for transplant programs. The use of alternative techniques (split) and the high donation rate in our country (the highest in the world) are of great help in alleviating this problem. However, the availability of cadaveric organs is still insufficient to meet the demand. The probability of access to liver transplantation remains low (near 50%) and the mortality rate significant (9%).2,4 – 6 We agree with several authors that a pediatric transplantation group should be able to offer every alternative of liver transplantation, including LRLT.6 In our mind, living donation will be necessary until pretransplant mortality is zero; even in that case LRLT will be an essential tool for some indications: such as tumours and acute liver failure. Unfortunately, liver transplantation is not available in many countries. LRLT programs give developed countries a chance to help these children without interfering with their own waiting list. In our series, children coming from abroad accounted for 48% of LRLT group. In our series, we observed a lower rate of primary malfunction among the LRLT group. Elective surgery and shorter ischemia time are features of LRLT that contribute to this finding. Like other authors we did not find a lower rejection rate among LRLT.7 With respect to resource consumption, blood product needs were significantly higher among the LRLT group, a finding that can be attributed to the differences in primary diseases: biliary atresia accounted for 70% of children in the LRLT group; while children in
3938
CDLT were mostly nonoperated and suffered from less decompensated hepatopathy. Longer hospital and ICU stays may be understood in the same way. Finally, biliary complications have been reported to be frequent in LRLT.7–9 Our series included 7 of 27 cases (25%), including bile leaks (n ⫽ 4) and strictures (n ⫽ 3). Regarding the ethical justification of living donors, the issue in children is clearly different from adults, as LRLT in children is curative with only a few exceptions. Another advantage in children is the use of the left lateral segment that provides a lower complication rate than the right lobe, which is used for adults. Additionally, psychological effects of donation are important; for young parents it offers the only direct action to affect the course of their children’s disease.10 In conclusion, our results in LRLT in children were similar to those obtained in cadaveric liver transplantation. In our series we observed a trend toward less initial graft malfunction among LRLT. However, blood product needs were higher and hospitalization tended to be longer in LRLT. The benefits of LRLT are avoiding pretransplant mortality on the waiting list without significant morbidity for the donor.
HERNÁNDEZ OLIVEROS, LÓPEZ SANTAMARÍA, GÁMEZ ET AL
REFERENCES 1. ONT, Transplante Hepático en España 2002. 2002. 2. Otte JB, et al: Pediatric liver transplantation: from the full-size liver graft to reduced, split, and living related liver transplantation. Pediatr Surg Int 13:308, 1998 3. Roberts JP, et al: Influence of graft type on outcomes after pediatric liver transplantation. Am J Transplant 4:373, 2004 4. Lopez-Santamaria M, et al: Pediatric living donor liver transplantation. Transplant Proc 35:1808, 2003 5. Lopez-Santamaria M, et al: Do the results justify living donor and split liver transplant for children in Spain? Transplant Proc 34:239, 2002 6. Testa G, Malago M, Broelsch CE: From living related to in-situ split liver transplantation: how to reduce waiting-list mortality. Pediatr Transplant 5:16, 2001 7. Reding R, et al: Pediatric liver transplantation with cadaveric or living related donors: comparative results in 90 elective recipients of primary grafts. J Pediatr 134:280, 1999 8. de Ville, de Goyet J, et al: Related living donor for liver transplantation in children: results and impact. Chirurgie 122:83, 1997 9. Egawa H, et al: Biliary complications in pediatric living related liver transplantation. Surgery 124:901, 1998 10. Otte JB, et al: Parental experience with living-related donor liver transplantation. Pediatr Transplant 8:317, 2004