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Successful Prednisone Withdrawal After Living-Related Liver Transplantation
STEROID WITHDRAWAL Successful Prednisone Withdrawal After Living-Related Liver Transplantation M. Abe, S. Fuchinoue, T. Koike, S. Sato, Y. Uchida, T. Murakami, J. Sageshima, K. Utumi, Y. Ishii, K. Kitajima, O. Yoshitake, I. Nakajima, and T. Agishi
L
IFETIME immunosuppression has been a necessity after clinical whole-organ transplantation. However, the use of steroids has been associated with multiple side effects and morbidity.1 We evaluated the safety of steroid withdrawal after living-related liver transplantation (OLT) and the effect on growth. PATIENTS AND METHODS Seventeen OLTs performed between April 1995 and May 1996 with at least 15 months of follow-up represented the study group. FK506 and prednisone was used for both induction and maintenance therapy. Steroid therapy was initiated with methylprednisolone, 10 mg/kg intraoperatively, and continued postoperatively with methylprednisolone 2 mg/kg for 1 to 3 days and tapered to 0.5 mg/kg of prednisone by day 7. After 21 days, the daily prednisone dose with good graft function was gradually decreased to 0.3 mg/kg. The reduction or withdrawal was completed between the 3rd and 6th months. The FK506 dose was adjusted in all patients to maintain blood troughs levels between 10 to 20 ng/mL. Baseline enzyme measurements of AST, ALT, GGTP, and serum bilirubin were performed weekly or biweekly as well as FK506 trough levels. Acute rejection was diagnosed on liver biopsy or defined clinically as an otherwise unexplained rise in bilirubin and transaminase.
Growth was expressed as height between pretransplantation and posttransplantation in the points of evaluation. Height was expressed as height standard deviation of expected height in the longitudinal growth curve.
RESULTS
Steroids were withdrawn from the immunosuppressive regimen of 12 of 17 (71%) of OLT patients (SW group). Steroid could not be withdrawn in 5 of 17 patients because of unstable liver function (NSW group). Table 1 depicts the demographic features of the 17 patients prospectively weaned. The two groups were compared as to sex, donor age and sex, cause of liver failure, ABO blood group, HLA-AB, -DR mismatches, CDC results, and number of acute rejections. The significant differences were that the SW group was younger and was higher in ratio of graft From the Departments of Surgery III, Tokyo Women’s Medical College, Tokyo, Japan. Address reprint requests to Dr M. Abe, Surgical Research Lab, Harvard Medical School, 260 Longwood Ave, #E-142, Boston, MA 02115.
Table 1. Recipient Demographics According to Living-Related Liver Graft Function Status
Male/female Age at Tx, mean 6 SD, y (range) Donor age at Tx, mean 6 SD, y (range) Donor sex, Male/female Cause of liver cailure (CBA/the others) Compatible blood type (%) HLA-AB mismatch, mean 6 SD HLA-DR mismatch, mean 6 SD CDC test at preTx (positive %) T B Acute rejection numbers (,3 months) graft weight/recipient body weight (%)
SW (N 5 12)
NSW (N 5 5)
7/5 3.1 6 4.0 (0.5–11.0)* 33.3 6 6.1 (26.2– 48.3) 6/6 9/3 58.3 1.6 6 0.5 0.7 6 0.5
3/2 9.8 6 6.7 (0.9 –19.3)* 39.7 6 9.9 (23.5– 49.1) 3/2 2/3 60.0 1.6 6 0.5 0.8 6 0.4
0 0 0.5 6 0.5 2.9 6 1.4†
0 25 2.0 6 1.0 1.1 6 0.6†
*†P , .05 for pairwise compairson. Tx 5 transplantation, CBA 5 congenital biliary atresia, HLA 5 human leukocyte antigen.
© 1998 by Elsevier Science Inc. 655 Avenue of the Americas, New York, NY 10010
0041-1345/98/$19.00 PII S0041-1345(98)00307-8
Transplantation Proceedings, 30, 1441–1442 (1998)
1441
1442
weight to recipient’s body weight. Only one patient (8.3%) in the SW group experienced a single episode of acute rejection after steroid withdrawal. It reversed with increasing FK506 dose and without requiring resumption of steroid therapy. Periods of growth posttransplantation were evaluated in the 17 patients who had a minimum follow-up of 15 months at the time of analysis. Ten of 12 patients in the SW group and two of five patients in the NSW group had a negative standard deviation at pretransplantation. All of the SW group had improved in height standard deviation of longitudinal growth curve. Two of five in the NSW group improved.
ABE, FUCHINOUE, KOIKE ET AL
were particular hopeful that an improvement in growth would be seen after steroid withdrawal. Many studies have suggested children maintained steroid-free had an improved height standard deviation score as compared with children on daily steroids.3 CONCLUSION
Withdrawal of corticosteroids after 3 to 6 months can be successfully achieved in the majority of OLT patients and is associated with a low rate of rejection and an effect of growth.
DISCUSSION
The potential benefits of steroid weaning are too obvious to enumerate. However, weaning carries a risk of rejection. In the present study steroid withdrawal was a safe undertaking in liver graft recipients with stable graft function. The incidence of acute rejection compares favorably with that occurring in other studies.2 In the pediatric population we
REFERENCES 1. Starzl TE, Koep LJ, Schroter GPE, et al: Transplant Proc II:252, 1979 2. Klintmalm GBG, Nery JR, Husberg BS, et al: Hepatology 10:978, 1993 3. Dunn SP, Falkenstein K, Lawrence JP, et al: Transplantation 57:789, 1994
L
IFETIME immunosuppression has been a necessity after clinical whole-organ transplantation. However, the use of steroids has been associated with multiple side effects and morbidity.1 We evaluated the safety of steroid withdrawal after living-related liver transplantation (OLT) and the effect on growth. PATIENTS AND METHODS Seventeen OLTs performed between April 1995 and May 1996 with at least 15 months of follow-up represented the study group. FK506 and prednisone was used for both induction and maintenance therapy. Steroid therapy was initiated with methylprednisolone, 10 mg/kg intraoperatively, and continued postoperatively with methylprednisolone 2 mg/kg for 1 to 3 days and tapered to 0.5 mg/kg of prednisone by day 7. After 21 days, the daily prednisone dose with good graft function was gradually decreased to 0.3 mg/kg. The reduction or withdrawal was completed between the 3rd and 6th months. The FK506 dose was adjusted in all patients to maintain blood troughs levels between 10 to 20 ng/mL. Baseline enzyme measurements of AST, ALT, GGTP, and serum bilirubin were performed weekly or biweekly as well as FK506 trough levels. Acute rejection was diagnosed on liver biopsy or defined clinically as an otherwise unexplained rise in bilirubin and transaminase.
Growth was expressed as height between pretransplantation and posttransplantation in the points of evaluation. Height was expressed as height standard deviation of expected height in the longitudinal growth curve.
RESULTS
Steroids were withdrawn from the immunosuppressive regimen of 12 of 17 (71%) of OLT patients (SW group). Steroid could not be withdrawn in 5 of 17 patients because of unstable liver function (NSW group). Table 1 depicts the demographic features of the 17 patients prospectively weaned. The two groups were compared as to sex, donor age and sex, cause of liver failure, ABO blood group, HLA-AB, -DR mismatches, CDC results, and number of acute rejections. The significant differences were that the SW group was younger and was higher in ratio of graft From the Departments of Surgery III, Tokyo Women’s Medical College, Tokyo, Japan. Address reprint requests to Dr M. Abe, Surgical Research Lab, Harvard Medical School, 260 Longwood Ave, #E-142, Boston, MA 02115.
Table 1. Recipient Demographics According to Living-Related Liver Graft Function Status
Male/female Age at Tx, mean 6 SD, y (range) Donor age at Tx, mean 6 SD, y (range) Donor sex, Male/female Cause of liver cailure (CBA/the others) Compatible blood type (%) HLA-AB mismatch, mean 6 SD HLA-DR mismatch, mean 6 SD CDC test at preTx (positive %) T B Acute rejection numbers (,3 months) graft weight/recipient body weight (%)
SW (N 5 12)
NSW (N 5 5)
7/5 3.1 6 4.0 (0.5–11.0)* 33.3 6 6.1 (26.2– 48.3) 6/6 9/3 58.3 1.6 6 0.5 0.7 6 0.5
3/2 9.8 6 6.7 (0.9 –19.3)* 39.7 6 9.9 (23.5– 49.1) 3/2 2/3 60.0 1.6 6 0.5 0.8 6 0.4
0 0 0.5 6 0.5 2.9 6 1.4†
0 25 2.0 6 1.0 1.1 6 0.6†
*†P , .05 for pairwise compairson. Tx 5 transplantation, CBA 5 congenital biliary atresia, HLA 5 human leukocyte antigen.
© 1998 by Elsevier Science Inc. 655 Avenue of the Americas, New York, NY 10010
0041-1345/98/$19.00 PII S0041-1345(98)00307-8
Transplantation Proceedings, 30, 1441–1442 (1998)
1441
1442
weight to recipient’s body weight. Only one patient (8.3%) in the SW group experienced a single episode of acute rejection after steroid withdrawal. It reversed with increasing FK506 dose and without requiring resumption of steroid therapy. Periods of growth posttransplantation were evaluated in the 17 patients who had a minimum follow-up of 15 months at the time of analysis. Ten of 12 patients in the SW group and two of five patients in the NSW group had a negative standard deviation at pretransplantation. All of the SW group had improved in height standard deviation of longitudinal growth curve. Two of five in the NSW group improved.
ABE, FUCHINOUE, KOIKE ET AL
were particular hopeful that an improvement in growth would be seen after steroid withdrawal. Many studies have suggested children maintained steroid-free had an improved height standard deviation score as compared with children on daily steroids.3 CONCLUSION
Withdrawal of corticosteroids after 3 to 6 months can be successfully achieved in the majority of OLT patients and is associated with a low rate of rejection and an effect of growth.
DISCUSSION
The potential benefits of steroid weaning are too obvious to enumerate. However, weaning carries a risk of rejection. In the present study steroid withdrawal was a safe undertaking in liver graft recipients with stable graft function. The incidence of acute rejection compares favorably with that occurring in other studies.2 In the pediatric population we
REFERENCES 1. Starzl TE, Koep LJ, Schroter GPE, et al: Transplant Proc II:252, 1979 2. Klintmalm GBG, Nery JR, Husberg BS, et al: Hepatology 10:978, 1993 3. Dunn SP, Falkenstein K, Lawrence JP, et al: Transplantation 57:789, 1994