Withdrawal of immunosuppression in liver allograft recipients

Padbury, Robert; Toogood, Giles J.; McMaster, P

doi:10.1002/lt.500040309

Cited by 27 publications

(21 citation statements)

References 44 publications

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“…Currently, classical induction therapy with long‐term steroid therapy is inadvisable for low‐risk liver transplantation recipients, given the efficacy of immunosuppressive regimens based on tacrolimus, mycophenolate or sirolimus, and the risk of infections and malignancies 1. With reduction of the incidence of early acute rejection and without any relevant associated toxicity, monoclonal antibodies against IL‐2Rab receptor offer the possibility of a more selective immunosuppression 10–12.…”

Section: Discussionmentioning

confidence: 99%

“…However, there are well‐known side effects that result in significant morbidities, including hypertension, obesity, diabetes, hyperlipidemia, and infectious complications. Previous reports have shown that early reduction or elimination of corticosteroids could significantly reduce the incidence of many of these complications in liver transplant recipients 1–3. However, there is a significant risk of increased incidence of acute rejection associated with early steroid withdrawal that may require treatment with high doses of pulse steroids.…”

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confidence: 99%

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Interleukin-2 receptor antibody (basiliximab) for immunosuppressive induction therapy after liver transplantation: A protocol with early elimination of steroids and reduction of tacrolimus dosage

Liu

Fan

et al. 2004

Liver Transpl

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A prospective evaluation was performed to study the potential benefits of the use of interleukin-2 receptor antibody (IL-2Rab) in the induction therapy with early elimination of steroid and reduction of tacrolimus dosage in liver transplant recipients among whom 94% had chronic hepatitis B infection. Thirty-one liver transplant recipients who underwent right-lobe live donor (n ‫؍‬ 19) or cadaveric (n ‫؍‬ 12) liver transplantation received IL-2Rab, basiliximab 20 mg intravenously within 6 hours of graft reperfusion and on postoperative day 4 (IL-2ab group). Two doses of steroid injection were given intraoperatively and on postoperative day 1. Postoperative immunosuppression was maintained with oral tacrolimus and mycophenolate mofetil without the use of steroids. The operative outcomes were compared with those of 49 patients who received standard immunosuppressive regimen consisting of tacrolimus and corticosteroid (steroid group). The overall postoperative morbidity and hospital stay were comparable between the 2 groups. There were significantly lower incidences of postoperative new-onset diabetes (0% vs 28%, P ‫؍‬ .011), acute cellular rejection (6% vs 27%, P ‫؍‬ .038), and cytomegalovirus (CMV) antigenemia (0% vs 18%, P ‫؍‬ .011) in the IL-2Rab group compared with the steroid group. The blood cholesterol level at 6 months after transplantation was significantly lower in the IL-2Rab group (

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Interleukin-2 receptor antibody (basiliximab) for immunosuppressive induction therapy after liver transplantation: A protocol with early elimination of steroids and reduction of tacrolimus dosage

Liu

Fan

et al. 2004

Liver Transpl

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“…Steroid-free immunosuppression may reduce opportunistic infections and malignancies in already immunocompromised children with hepatoblastoma due to reiterated preoperative chemotherapy (20,21). There is no difference among the type of immunosuppression received in post-transplant tumor recurrence, and the potential benefits of steroid-free immunosuppression on hepatoblastoma recurrence require further evaluation.…”

Section: Discussionmentioning

confidence: 99%

Living‐Donor Liver Transplantation for Hepatoblastoma

Kasahara

Ueda

Haga

et al. 2005

American Journal of Transplantation

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Hepatoblastoma is the most common malignant liver tumor in children. Recently, liver transplantation has been indicated for unresectable hepatoblastoma. We retrospectively reviewed 14 children with a diagnosis of hepatoblastoma who had undergone living-donor liver transplantation (LDLT) at Kyoto University Hospital. During the period from June 1990 to December 2004, 607 children underwent LDLT. Of these interventions, 2.3% were performed for hepatoblastoma. Based on radiological findings, the pre-treatment extent of disease (PRETEXT) grouping was used for pretreatment staging of the tumor. There were grade III in seven patients and grade IV in seven patients. Thirteen patients received chemotherapy, and seven underwent hepatectomy 11 times. Immunosuppressive treatment consisted of tacrolimus monotherapy in 11 patients. Actuarial 1-and 5-year graft and patient survival rates were 78.6% and 65.5%. The poor prognostic factors were macroscopic venous invasion and extrahepatic involvement with 1-year and 5-year survival rates of 33.0% and 0%. Pediatric patients without these factors showed an acceptable 5-year survival rate of 90.9%. LDLT provides a valuable alternative with excellent results in children with hepatoblastoma because it allows optimal timing of the liver transplantation, given the absence of delay between the completion of chemotherapy and planned liver transplantation.

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“…Cerebrocardiovascular events are a major cause of longterm morbidity and mortality in these patients, and the contribution of immunosuppression to posttransplantation diabetes mellitus, obesity, hypertension, and dyslipidemia is well established. [1][2][3][4][5] Munoz et al 6 noted an increased cardiovascular risk index in long-term survivors after OLT that was attributed to obesity and hypercholesterolemia. We previously reported improvement in glucose control, hypertension, and hypercholesterolemia in patients undergoing corticosteroid withdrawal greater than 1 year after OLT.…”

confidence: 99%

Successful withdrawal of prednisone after adult liver transplantation for autoimmune hepatitis

et al. 1999

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Corticosteroid withdrawal after orthotopic liver transplantation (OLT) represents an attractive therapeutic option for ameliorating post-OLT metabolic complications, although several reports suggest patients who undergo transplantation for autoimmune hepatitis (AIH) may have a greater incidence of acute and chronic rejection when withdrawn from corticosteroid therapy. The aim of this study is to evaluate the success of corticosteroid withdrawal in patients with AIH after OLT. Twenty-six patients underwent successful OLT for AIH. In 21 of these patients, stable maintenance immunosuppression consisted of cyclosporine (CSA) and prednisone (n ‫؍‬ 20) or tacrolimus (TAC) and prednisone (n ‫؍‬ 1). In this group, a trial of prednisone withdrawal was initiated when patients were 6 months or more post-OLT, with normal liver function, and receiving an average prednisone dosage of 10 mg/d. Five additional patients treated with either TAC (n ‫؍‬ 4) or CSA (n ‫؍‬ 1) plus mycophenolate mofetil underwent a 14-day taper of prednisone. Overall, 17 of 25 patients (68%) were successfully withdrawn from corticosteroids, with a mean follow-up of 22 months (range, 1 to 34 months). Of the remaining 8 patients, 5 patients received a lower dosage of prednisone or required prednisone to control inflammatory bowel disease. Only 3 patients remained dependent on prednisone to maintain stable liver allograft function. Withdrawal from 10 to 5 mg of prednisone (n ‫؍‬ 21) resulted in four episodes of steroid-responsive and two episodes of steroid-resistant rejection in 3 patients, and 18 of 21 patients (86%) were rejection free. Withdrawal from 5 to 0 mg prednisone (n ‫؍‬ 17) resulted in eight episodes of steroid-responsive and no episodes of steroid-resistant rejection in 4 patients; 13 of 17 patients (76%) were rejection free. Of the 5 patients in the 14-day prednisonetaper group, 3 patients had steroid-responsive rejection and 1 patient required OKT3. Seventeen of 21 patients (81%) with AIH were successfully withdrawn from corticosteroids. It is notable that corticosteroid withdrawal was associated with a reduction in serum cholesterol levels, decreased use of antihypertensive agents, and reduced need for insulin or oral hypoglycemic agents. We propose corticosteroid withdrawal should be attempted in patients with underlying AIH who undergo OLT because most will benefit without significantly jeopardizing the liver allograft. Copyright 1999 by the American Association for the Study of Liver DiseasesT he benefit-risk ratio of corticosteroids as immunosuppressive therapy after orthotopic liver transplantation (OLT) has created recent debate because their deleterious side effects have become more apparent with long-term follow-up. Cerebrocardiovascular events are a major cause of longterm morbidity and mortality in these patients, and the contribution of immunosuppression to posttransplantation diabetes mellitus, obesity, hypertension, and dyslipidemia is well established. 1-5 Munoz et al 6 noted an increased cardiovascular risk index in long-te...

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Withdrawal of immunosuppression in liver allograft recipients

Cited by 27 publications

References 44 publications

Interleukin-2 receptor antibody (basiliximab) for immunosuppressive induction therapy after liver transplantation: A protocol with early elimination of steroids and reduction of tacrolimus dosage

Interleukin-2 receptor antibody (basiliximab) for immunosuppressive induction therapy after liver transplantation: A protocol with early elimination of steroids and reduction of tacrolimus dosage

Living‐Donor Liver Transplantation for Hepatoblastoma

Successful withdrawal of prednisone after adult liver transplantation for autoimmune hepatitis

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