Immunosuppression in Liver Transplantation

Cattral, Mark S.; Lilly, Leslie; Levy, Gary

doi:10.1055/s-2000-13160

Cited by 21 publications

(12 citation statements)

References 65 publications

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“…Standardization of surgical techniques, advances in anesthetic management, and the introduction of safer and more potent immunosuppressive drugs have further contributed to this development (3)(4)(5). Today, orthotopic liver transplantation (OLT) has become an accepted therapy for endstage liver disease and fulminant hepatic failure (6)(7)(8).…”

Section: Introductionmentioning

confidence: 99%

Clinical Implications of Hepatic Preservation Injury After Adult Liver Transplantation

Glanemann

Langrehr

Stange

et al. 2003

American Journal of Transplantation

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Several advances in organ preservation have allowed for improved results after liver transplantation; however, little information is available regarding the clinical impact of preservation injury on the postoperative course. The medical records of 889 liver transplants were retrospectively reviewed. Preservation injury was classified according to postoperative aspartate aminotransferase values as minor (<1000 U/L), moderate (1000–5000 U/L), or severe (>5000 U/L). The following criteria were analyzed and compared according to the extent of preservation injury: patient and graft survival, retransplantation rate, duration of hospitalization and postoperative ventilation, as well as incidence of rejection, infection, and hemodialysis. The majority of patients received a liver with minor preservation injury (75.9%), whereas 22.7% and 1.3% of grafts showed moderate or severe injury. Graft survival was significantly lower in patients with severe preservation injury, when compared to minor or moderate injury. The relative risk for initial nonfunction was 39.36‐fold increased (95% confidence interval (ci): 10.3–150.2), as it was increased for duration of postoperative ventilation (6.92‐fold; 95%ci: 2.1–22.3) and hemodialysis (6.13‐fold; 95%ci: 1.9–19.3). Since the incidence of retransplantation was significantly increased (50%), patient survival remained comparable between all groups. Severe preservation injury had a tremendous impact on the postoperative clinical course, requiring the maximum medical effort to achieve adequate patient survival.

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Section: Introductionmentioning

confidence: 99%

Clinical Implications of Hepatic Preservation Injury After Adult Liver Transplantation

Glanemann

Langrehr

Stange

et al. 2003

American Journal of Transplantation

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“…By inhibiting the release of eicosanoids and other mediators of inflammation, they restore vascular integrity and reduce migration of inflammatory cells into tissue. 3,9,10 Finally, high-dose corticosteroids also have a direct cytotoxic effect on proliferating cells. This complex mode of action explains why high-dose corticosteroids are effective in the treatment of acute cellular rejection where a wide range of immunologic and inflammatory effector mechanisms of graft damage is involved.…”

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confidence: 99%

“…14 Nevertheless, high-dose corticosteroids still remain the first-line treatment for grade II and III acute hepatic cellular rejection. 10 The side effects of corticosteroids are well known. When given in high doses for short courses, the main complications are the following: increased susceptibility to infections; impaired wound healing; hyperglycemia; salt retention, hypertension, or both; and psychiatric disorders.…”

mentioning

confidence: 99%

“…Corticosteroids have been shown to be a major risk factor also for the development of life-threatening bacterial infections. 3,10 In addition, it should be taken into account also that the hospital stay related to the steroid treatment of acute hepatic cellular rejection affects the first-year cost of liver transplantation. 15 Although there is little objective evidence in favor of any particular steroid agent, intravenous methylprednisolone is used in most liver transplant centers because it is more potent as an anti-inflammatory agent and it has slightly weaker mineralcorticoid properties as compared with prednisolone and prednisone.…”

mentioning

confidence: 99%

“…Most of the schedules are based on those developed empirically for the treatment of acute renal graft rejection. 3,10,16 To date, no controlled study has been performed in liver transplantation to determine the optimal steroid regimen.…”

mentioning

confidence: 99%

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Comparison between two high-dose methylprednisolone schedules in the treatment of acute hepatic cellular rejection in liver transplant recipients: A controlled clinical trial

Volpin

2002

Liver Transplantation

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Intravenous methylprednisolone is used in most liver transplant centers as first-line therapy of acute hepatic cellular rejection in patients who undergo liver transplant. However, no controlled study has been performed to date to define the optimal dose and duration of the steroid regimen. The schedules that actually are used in most transplant centers are drawn from those that were developed empirically for the treatment of acute renal graft rejection. Thus, the aim of the study was to compare two schedules of steroid treatment of acute hepatic cellular rejection among those most widely used. Thirty-eight eligible patients with grade II or III acute hepatic cellular rejection were randomized to receive two different highdose methylprednisolone schedules. Eighteen patients were randomized in group A (intravenous dose of 1,000 mg of methylprednisolone followed by a 6-day taper from 200 to 20 mg/d). Twenty patients were randomized in group B (intravenous dose of 1,000 mg of methylprednisolone for three consecutive days). The response to treatment was evaluated by means of a second liver biopsy. The treatment of group A proved to be more effective than treatment of group B. The resolution of acute hepatic cellular rejection was observed in 83.3% of cases in group A and 50.0% of cases in group B (P < .05). The treatment of group A proved to be safer also than treatment of group B. Patients randomized in group B showed a higher prevalence of infections (90.0% of cases versus 55.5% of cases; P < .01) mainly because of bacterial (80.0% versus 50.0%; P < .05) and viral (50.0% versus 16.6%; P < .05) agents. In conclusion, the study shows that intravenous administration of 1,000 mg of D espite the use of new and potent immunosuppressive regimens, rejection still remains one of the most important causes of graft failure and morbidity after liver transplantation. 1,2 The efficacy of the new and potent immunosuppressive agents in controlling rejection always has to be balanced against the increased risk of adverse effects. 3 Thus, maintenance immunosuppressive regimens are always a compromise between their efficacy and safety in clinical practice. As a consequence, episodes of acute cellular rejection can occur requiring additional immunosuppressive therapy for their treatment. The prevalence of clinically significant acute cellular rejection ranges from 24% to 80%. 4,5 Moreover, the prevalence of graft failure as a consequence of acute cellular rejection ranges from 5% to 15%. 4,5 In most transplant centers, high-dose corticosteroids are the mainstay for the treatment of acute hepatic cellular rejection in transplant recipients. In particular, they are used in the treatment of grade II and III acute hepatic cellular rejection because their spontaneous resolution seems to be unlikely. [6][7][8] Corticosteroids are preferred to other immunosuppressive agents in the treatment of acute cellular rejection after liver transplantation for their broad range of actions. They inhibit graft antigen-induced lymphocyte activation induc...

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Idiopathic posttransplantation hepatitis?

Shaikh

Demetris

2007

Liver Transpl

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Immunosuppression in Liver Transplantation

Cited by 21 publications

References 65 publications

Clinical Implications of Hepatic Preservation Injury After Adult Liver Transplantation

Clinical Implications of Hepatic Preservation Injury After Adult Liver Transplantation

Comparison between two high-dose methylprednisolone schedules in the treatment of acute hepatic cellular rejection in liver transplant recipients: A controlled clinical trial

Idiopathic posttransplantation hepatitis?

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