A study indicated that a high incidence of rejection and a low incidence of intolerance is related to an early steroid withdrawal following liver transplantation. The study, which is hailed as the first-of-its-kind double-blind placebo-controlled study, was undertaken to examine effects of early steroid elimination.

The study results were published in an 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).

From Eurekalert.org:

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.

The involved authors were of the view that early steroid withdrawal at day 14 cannot be termed as safe when it comes to rejection but told that it is efficient in terms of tolerability to glucose.

Tags:  diabetes, doses of steroids, early steroid withdrawal, liver transplantation, steroid, Steroid use, steroid withdrawal

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A research at Washington University School of Medicine in St. Louis has found out that steroids called glucocorticoids can cause hypertension and diabetes. The team found that a protein called peroxisome proliferator-activated receptor-alpha (PPAR-alpha) is critical in this process because it is activated by fatty acids that stimulate the diseases. The findings help explain the high incidence of diabetes and hypertension in obese individuals.

PPAR-alpha is found in the liver, kidney, muscles, blood vessels and other organs. It is activated by fatty acids, while glucocorticoids alter fatty acid processing. This correlation led the research team to assume that the two may act together to produce the disease-causing effects.

From Bio-Medicine:

The team found that when given the glucocorticoid dexamethasone, mice lacking only LDLR had increased levels of insulin, fasting glucose and leptin, all signs of diabetes. The animals also became less hypoglycemic when given insulin, suggesting that they were developing insulin resistance, the precursor to diabetes. Mice lacking both LDLR and PPAR-alpha showed no signs of diabetes.

The team also examined human liver cells in a petri dish. When PPAR-alpha was activated and steroids were added, expression of genes related to glucose production tripled.

“The scientific community hasn’t fully appreciated the potentially important role of the liver in these conditions,” Semenkovich says. “These results strongly suggest that the liver is the key to controlling blood pressure and glucose, and our preliminary evidence with human liver cells strongly suggests that the results in mice are relevant to human disease.”

The researchers claim that the results in the mice trials are relevant to human, hence they claimed that people who are overweight or obese experience diabetes and hypertension because they have higher glucocorticoids. Similarly, patients who are treated with glucocorticoids medication have higher risk of developing these diseases since their bodies receive more glucocorticoids.

Tags:  diabetes, glucocorticoids, hypertension, Steroids

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