A Randomized Prospective Trial of Steroid Withdrawal After Liver Transplantation1,2

McDiarmid, Sue V.; Farmer, Dana A.; Goldstein, Leonard I.; Martin, Paul L.; Vargas, Jorge; Tipton, James R.; Simmons, Fred A.; Busuttil, Ronald W.

doi:10.1097/00007890-199560120-00013

Cited by 93 publications

(65 citation statements)

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“…In addition to inhibiting the release and function of cytokines, such as interleukin-2, steroids can also regulate T-and B-lymphocyte apoptosis [4] . However, there are wellknown adverse effects that result in significant morbidity, including hypertension, diabetes, hyperlipidemia, obesity, and infectious complications.…”

Section: Discussionmentioning

confidence: 99%

Early steroid withdrawal after liver transplantation for hepatocellular carcinoma

Chen

He²,

Zeng³

et al. 2007

WJG

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AIM:To evaluate the impact of early steroid withdrawal on the incidence of rejection, tumor recurrence and complications after liver transplantation for advancedstage hepatocellular carcinoma. METHODS:F i f ty-fo u r p a t i e n t s u n d e r w e n t l i ve r transplantation for advanced-stage hepatocellular carcinoma from April 2003 to June 2005. These cases were divided into a steroid-withdrawal group (group A, n = 28) and a steroid-maintenance group (group B, n = 26). In group A, steroid was withdrawn 3 mo after transplantation. In group B, steroid was continuously used postoperatively. The incidence of rejection, 6-mo and 1-year recurrence rate of carcinoma, 1-year survival rate, mean serum tacrolimus trough level, and liver and kidney function were compared between the two groups. RESULTS:In the two groups, no statistical difference was observed in the incidence of rejection (14.3 vs 11.5%, P > 0.05), mean serum tacrolimus trough levels (6.9 ± 1.4 vs 7.1 ± 1.1 µg/L, P > 0.05), liver and kidney function after 6 mo [alanine aminotransferase (ALT): 533 ± 183 vs 617 ± 217 nka/L, P > 0.05; creatinine: 66 ± 18 vs 71 ± 19 µmol/L, P > 0.05], 6-mo recurrence rate of carcinoma (25.0 vs 42.3%, P > 0.05), and 1-year survival rate (64.2 vs 46.1%, P > 0.05). The 1-year tumor recurrence rate (39.2 vs 69.2%, P < 0.05), serum cholesterol level (3.9 ± 1.8 vs 5.9 ± 2.6 mmol/L, P < 0.01) and fasting blood sugar (5.1 ± 2.1 vs 8.9 ± 3.6 mmol/L, P < 0.01) were significantly different. These were lower in the steroid-withdrawal group than in the steroidmaintenance group. CONCLUSION:Early steroid withdrawal was safe after liver transplantation in patients with advanced-stage hepatocellular carcinoma. When steroids were withdrawn 3 mo post-operation, the incidence of rejection did not increase, and there was no demand to maintain tacrolimus at a high level. In contrast, the tumor recurrence rate and the potential of adverse effects decreased significantly. This may have led to an increase in long-term survival rate.

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Section: Discussionmentioning

confidence: 99%

Early steroid withdrawal after liver transplantation for hepatocellular carcinoma

Chen

He²,

Zeng³

et al. 2007

WJG

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“…5 Since then, nine centers have reported successful steroid withdrawal rates of between 88% and 100% in over 500 patients. 3 Two of these studies 6,7 were randomized controlled trials in which patients withdrawn from steroids had the same survival and incidence of acute rejection as those maintained longterm. The benefits of steroid withdrawal in these randomized controlled trials included a lower incidence of hypertension, diabetes, bone complications, and hypercholesterolemia.…”

mentioning

confidence: 99%

Early steroid withdrawal after liver transplantation: The canadian tacrolimus versus microemulsion cyclosporin a trial: 1-year follow-up

Greig

Lilly

Scudamore

et al. 2003

Liver Transplantation

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Corticosteroid therapy contributes significant toxicity to liver transplantation. The safety and efficacy of early steroid withdrawal were determined in patients treated with either tacrolimus or microemulsion cyclosporin A (microCsA). The primary outcome was the proportion of patients who were steroid-free 1 year posttransplantation. From the seven Canadian adult liver transplant centers, 143 patients were randomly allocated oral treatment with either tacrolimus (n ‫؍‬ 71) or micro-CsA (n ‫؍‬ 72), together with corticosteroids and azathioprine. Eligibility criteria for steroid withdrawal included freedom from acute rejection for a minimum of 3 months, and prednisone <0.15 mg/kg/d. In eligible patients, the daily steroid dose was reduced by 2.5 mg each month until complete discontinuation was achieved. At 1 year after transplantation, 75% of the tacrolimus patients and 63% of the micro-CsA patients were steroid-free (P ‫؍‬ .20). Of all of the patients who became eligible for steroid withdrawal, steroid discontinuation was achieved in over 80%. One-year patient survival was 97% with tacrolimus and 89% with micro-CsA (P ‫؍‬ .052) . Graft survival was 97% and 86%, respectively (P ‫؍‬ .017). The overall incidence of acute rejection during the first year was 35% with tacrolimus and 43% with micro-CsA (P ‫؍‬ .26). There was no difference in survival, acute rejection, or rate of steroid withdrawal when adjusting for hepatitis C. All acute rejection episodes experienced during steroid withdrawal were steroid-responsive. Steroid-resistant rejection occurred in 5.6% of the tacrolimus and 9.7% of the micro-CsA patients. One patient, in the micro-CsA group, experienced refractory rejection. Chronic rejection was not observed in either group. The toxicity profiles were similar. Postoperative serum creatinine levels were similar, and dialysis was required in less than 10% of patients in each group. Infectious complications were similar in both groups. Neurotoxicity was a serious adverse event in 13% and 10% of patients receiving tacrolimus and micro-CsA, respectively. Early steroid withdrawal is safe and effective after liver transplantation using either tacrolimus plus azathioprine or micro-CsA plus azathioprine immunoprophylaxis. (Liver Transpl 2003;9:587-595.)T he calcineurin inhibitors tacrolimus and cyclosporin A are considered the immunologic foundation for liver transplantation; however, effective immunosuppression in the perioperative period seems to require the administration of corticosteroids, and most patients are maintained on prednisone for the long term. 1 The toxicities of corticosteroids, many of which are additive to those of tacrolimus or cyclosporin A, include increased susceptibility to infection (particularly opportunistic organisms), hypertension, hyperlipidemia, diabetes mellitus, osteoporosis and aseptic necrosis, cushingoid facies, acne, and growth retardation in children. Because the cumulative toxicities of immunosuppressive agents remain a major source of morbidity and mortality after liver transp...

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“…[27][28][29] Uncontrolled trials of steroid withdrawal suggested that these patients do have better growth. However, McDiarmid et al, 21 in a randomized controlled study with approximately 30 patients in each group, did not observe an improvement in growth in the steroid-free group at an approximately 19-month follow-up. There is also a suggestion of a higher incidence of acute rejection after steroid withdrawal in pediatric patients.…”

Section: Steroidsmentioning

confidence: 92%

“…20 The strict entry criteria used in some late steroid withdrawal protocols mean that a much smaller percentage of patients finally remained steroid free. [21][22][23][24] The rate of acute rejection after the withdrawal of steroids ranges from 4.5% to 9.0%. [19][20][21][22][23][24] In all cases, rejection episodes have been reversed successfully with either boluses of methylprednisolone or reinstitution of maintenance prednisolone.…”

Section: Steroidsmentioning

confidence: 99%

Withdrawal of immunosuppression in liver allograft recipients

1998

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A Randomized Prospective Trial of Steroid Withdrawal After Liver Transplantation1,2

Cited by 93 publications

References 0 publications

Early steroid withdrawal after liver transplantation for hepatocellular carcinoma

Early steroid withdrawal after liver transplantation for hepatocellular carcinoma

Early steroid withdrawal after liver transplantation: The canadian tacrolimus versus microemulsion cyclosporin a trial: 1-year follow-up

Withdrawal of immunosuppression in liver allograft recipients

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