Steroid withdrawal is safe and beneficial in stable cyclosporine-treated liver transplant patients

Gómez, R; Moreno, Enrique; Colina, Francisco; Loinaz, Carmelo; González-Pinto, I; Lumbreras, Carlos; Pérez-Cerdá, F; Castellón, C; García, Ignacio

doi:10.1016/s0168-8278(98)80214-6

Cited by 51 publications

(33 citation statements)

References 27 publications

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“…Steroid withdrawal can be safely performed following liver transplantation with little increased risk of acute rejection and with reduced hypertension, lower serum cholesterol, less obesity and a reduced incidence of post-transplantation diabetes [55][56][57]. As with kidney transplantation, very early steroid withdrawal after liver transplantation results in an increase in the incidence of rejection though without increased graft loss [55].…”

Section: Steroid Withdrawal After Liver Transplantationmentioning

confidence: 99%

Immunosuppressive agents in solid organ transplantation: Mechanisms of action and therapeutic efficacy

Taylor

Watson

Bradley

2005

Critical Reviews in Oncology/Hematology

380

250

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Section: Steroid Withdrawal After Liver Transplantationmentioning

confidence: 99%

Immunosuppressive agents in solid organ transplantation: Mechanisms of action and therapeutic efficacy

Taylor

Watson

Bradley

2005

Critical Reviews in Oncology/Hematology

380

250

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“…However, several trials have shown success in withdrawing steroid therapy at short time intervals after OLT. [14][15][16] Previous attempts at complete steroid abstinence in OLT have had mixed results, with a significant number of patients subsequently requiring steroid treatment for rejection. [5][6][7][8] Tisone et al 6 randomized 45 patients to the administration of cyclosporine and azathioprine with or without steroids.…”

Section: Discussionmentioning

confidence: 99%

Steroid-free liver transplantation using rabbit antithymocyte globulin induction: Results of a prospective randomized trial

Eason

Loss

Blazek

et al. 2001

Liver Transplantation

121

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Steroids have been 1 of the primary modes of immunosuppression since the inception of transplantation and have been credited with both the prevention and treatment of rejection. Steroids also have been held responsible for increased infections, posttransplantation diabetes, and recurrent hepatitis after orthotopic liver transplantation (OLT). The purpose of this ongoing prospective randomized trial is to eliminate steroid use in OLT through induction with rabbit antithymocyte globulin (RATG). This is the first report of a prospective randomized trial in OLT achieving complete absence of steroids. Seventy-one adult patients were prospectively randomized to administration of RATG or steroids. Thirty-six patients were randomized to the administration of RATG induction at a dose of 1.5 mg/kg intravenously (IV) beginning during the anhepatic phase. No steroids were administered. Patients were administered a second 1.5-mg/kg dose of RATG post-OLT day 1. Thirty-five patients were randomized to the administration of methylprednisolone, which had been our standard immunosuppressive protocol. These patients were administered methylprednisolone, 1,000 mg IV, initiated during the anhepatic phase and followed by steroid taper. Maintenance immunosuppression consisted of tacrolimus and mycophenolate, with or without prednisone. Three patients died in each group, for an overall survival rate of 91% in each group. One patient in each group required re-OLT, for a graft survival rate of 89% in each group. Seven patients administered RATG had biopsy-proven rejection (20.5%), all of whom were successfully treated by increasing tacrolimus doses. Eleven patients administered steroid had biopsy-proven rejection (32%), 7 (64%) of whom required additional steroids for treatment, whereas 4 patients (36%) were successfully treated by increasing tacrolimus doses. The incidence of rejection was not statistically significant; however, there was a significant difference in the incidence of steroid-requiring rejection (P ‫؍‬ .01). The incidence of recurrent hepatitis C was 50% in RATG patients and 71% in steroid patients (P ‫؍‬ not significant). The incidence and severity of infectious complications were slightly lower in RATG patients, accounted for by a greater incidence of cytomegalovirus (CMV) infection in the steroid patients. RATG induction enables complete avoidance of steroid use in OLT with a trend toward a lower rejection rate, decreased incidence of post-OLT diabetes and recurrent hepatitis C, and decreased CMV infection. This prospective randomized trial gives encouraging support that steroids can be safely eliminated in OLT. (Liver Transpl 2001;7: 693-697.) S teroids have been a cornerstone of immunosuppression since the inception of transplantation and are credited with both the prevention and treatment of rejection. However, steroids have also been shown to increase infectious complications, bone disease, and posttransplantation diabetes and possibly increase the incidence and severity of recurrent hepatitis C virus (HCV) infecti...

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“…Resumption of steroid treatment was not required since acute or chronic rejection was not detected in any case. In addition, improvements in blood pressure and serum cholesterol levels were seen [16]. A significant increase in BMD may occur after discontinuation of exogenous glucocorticoid therapy or reversal of endogenous Cushing's syndrome [17,18].…”

Section: Discussionmentioning

confidence: 99%

Long-Term Follow-up of Bone Mass after Orthotopic Liver Transplantation: Effect of Steroid Withdrawal from the Immunosuppressive Regimen

íG

Gómez

Jódar

et al. 2002

Osteoporosis International

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Glucocorticoids have been suggested to play a major role in transplantation-related osteopenia. In this study we assess the long-term changes and the effect of steroid withdrawal from the standard immunosuppressive regimen on bone mineral density (BMD) after orthotopic liver transplantation (OLT). Sixty-nine non-osteoporotic patients (20 women, 49 men), aged 48 +/- 9.5 years (mean +/- SD), and with a follow-up of 58.3 +/- 23.2 months (range 24-121 months) were studied. Immunosuppressive treatment consisted of prednisone, cyclosporin A and azathioprine. In 41 patients (group A), prednisone was tapered and withdrawn after 36.2 +/- 19.3 months (range 13-79 months), whereas in 28 patients (group B) prednisone was maintained. BMD in the spine (L1-L4) was serially measured by dual-energy X-ray absorptiometry (Hologic QDR 1,000w) at baseline, before steroid withdrawal and at the end of study. Age- and sex-matched Z-scores of BMD were calculated. No differences were found in age, body mass index, time since OLT, or baseline BMD between the two groups. BMD had significantly increased in both groups at the end of follow-up period (group A, +8.1 +/- 8.7%; group B, +3.2 +/- 8.0%, p < 0.05). However, the Z-score was significantly higher in group A than in group B at the end of study (-0.44 +/- 1.05 vs -0.99 +/- 0.77; p<0.05). BMD recovery was lower in pre-OLT biliary cirrhosis patients. Bone mass improvement was independent of the time since OLT in both groups, and of the time of steroid withdrawal in group A. Our data confirm that steroid withdrawal accelerates the recovery of bone mass in patients who have undergone a successful liver transplantation.

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Steroid withdrawal is safe and beneficial in stable cyclosporine-treated liver transplant patients

Cited by 51 publications

References 27 publications

Immunosuppressive agents in solid organ transplantation: Mechanisms of action and therapeutic efficacy

Immunosuppressive agents in solid organ transplantation: Mechanisms of action and therapeutic efficacy

Steroid-free liver transplantation using rabbit antithymocyte globulin induction: Results of a prospective randomized trial

Long-Term Follow-up of Bone Mass after Orthotopic Liver Transplantation: Effect of Steroid Withdrawal from the Immunosuppressive Regimen

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