A new study on early steroid withdrawal following liver transplantation found that there was a higher incidence of rejection and a lower incidence of glucose intolerance necessitating treatment for diabetes. It was the first double-blind placebo-controlled study to examine the effects of early steroid elimination.
The results of this study appear in the December 2004 issue of Liver Transplantation, the official journal of the American Association for the Study of Liver Diseases (AASLD) and the International Liver Transplantation Society (ILTS). The journal is published on behalf of the societies by John Wiley & Sons, Inc. and is available online via Wiley InterScience.
The normal course of treatment after liver transplantation includes calcineurin inhibitors (a class of immunosuppressants) and steroids to minimize rejection and improve survival rates, but the long-term complications of these drugs can be fatal. Steroid use in particular can lead to diabetes, high cholesterol and hypertension, which increase the risk of heart disease, and can lead to death. Several previous studies have reported that early withdrawal from steroids reduced the incidence of these side effects, but that rejection increased, although it could be controlled with steroid pulse therapy (in which high doses of steroids are administered intravenously for a short period of time). The current multicenter study was the first prospective double-blind, placebo-controlled trial to compare early steroid withdrawal with continued use.
Led by Georges-Philippe Pageaux, of the Centre Hospitalier University St.-Eloi in Montpellier, France, the study examined 174 patients in 15 French liver transplantation centers over a 14-month period from December 1999 to August 2001. The patients were randomly divided into two groups seven days following transplant: 90 of them continued to receive steroids for six months, while 84 received a placebo starting at day 14 (following 7 days of tapering from steroids). At the end of six months, 22 patients in the steroid group (24.4 percent) and 32 patients in the placebo group (38.1 percent) experienced acute rejection. Although there was no statistical difference in the two groups for high cholesterol and hypertension, 22.2 percent of patients in the steroid group developed diabetes compared with 14.3 percent of placebo patients. At the end of 12 months, the incidence of acute rejection was 25.6 percent in the steroid group versus 39.3 percent in the placebo group, but there no longer a difference in diabetes between the two groups.
"Although the incidence of acute rejection in the placebo group was increased, it was easily controlled in most of the cases and did not affect long-term graft histology or survival," the authors note, adding that the increase may ultimately be acceptable if steroids could be eliminated. However, the main goal of steroid elimination is to reduce metabolic complications and this study showed no difference in cholesterol or hypertension, with a trend toward a decreased incidence of diabetes in the placebo group.
The authors conclude: "Indeed, while there are many arguments in favor of corticosteroid withdrawal beyond 3 months posttransplantation, in terms of safety and efficacy, our study demonstrates that earlier withdrawal at day 14 is not completely safe in terms of rejection, but seems efficient in terms of improvement of glucose tolerability," which could decrease long-term mortality due to cardiovascular disease.