"Steroid-Free Immunosuppression After Liver Transplant Reduces Acute Cellular Rejection: Presented at AASLD"
By Crystal Phend
SAN FRANCISCO, CA -- November 15, 2005 -- Steroid-free immunosuppression including mycophenolate mofetil (CellCept) might reduce the risk of acute cellular rejection without increasing hepatitis C recurrence in liver transplant recipients, according to researchers here at the annual meeting of the American Association for the Study of Liver Disease (AASLD).
"The fear initially was would there be more rejections in the non-steroid arm," said study presenter Hugo E. Vargas, MD, Associate Professor of Medicine, Mayo Clinic, Phoenix, Arizona, United States, in his presentation on November 13[th.
An estimated 40% to 50% of liver transplant patients are infected with the hepatitis C virus.
In their open-label study, Dr. Vargas and colleagues compared the relatively new non-steroidal immunosuppressive drug CellCept in two combinations to a combination including a steroidal drug.
Dr. Vargas presented the results on 262 patients with 1-year of follow-up, who were randomized before transplantation to one of three arms: the immunosuppressant tacrolimus and the corticosteroid prednisone (arm 1); tacrolimus, prednisone and CellCept (arm 2); tacrolimus, CellCept and 3-dose daclizumab, an immunosuppressive, humanized immunoglobulin G1 monocolonal antibody (arm 3).
The preliminary analysis found a slightly lower rejection rate for the steroid-free arm 3, but differences between groups were not significant -- 16% arm 1, 17% arm 2, and 8% arm 3.
Acute cellular rejection (ACR) tended to be moderate rather than severe in the CellCept arms. Moderate ACR was not significantly different between groups and occurred in six patients in arm 1, four patients in arm 2, and eight patients in arm 3.
There was a significantly lower rate of severe acute cellular rejection in the steroid-free arm. Of all ACR cases in each group, severe ACR accounted for 25% in arm 1, 43% in arm 2, and 0% in arm 3.
Although immunosuppression reduces the risk of transplant rejection, it raises concerns of hepatitis C virus recurrence. Therefore, the researches measured recurrence in study subjects by liver biopsy at days 90 and 365.
They found virus recurrence-free rates of 57%, 54% and 56%, in arms 1, 2 and 3, respectively. Moderate recurrence was also similar between groups. Severe recurrence (high viral loads) occurred in 9%, 14% and 12%, respectively.
There was a non-significant trend for less aggressive progression of recurrence, an increase of more than one stage between biopsies, in the CellCept groups.
Virus RNA levels, graft survival and patient survival rates were similar between groups, although liver function tests were significantly better in the non-steroidal group.
Incidence of diabetes, malignancies, infections, hypertension and hyperlipidemia were similar in the three groups.
Dr. Vargas cautioned that the data are interim results, particularly with regard to hepatitis C recurrence, which often takes longer than a year to develop.
However, he speculated, "I think the behavior of the virus doesn't change depending on regimen used."
Dr. Vargas presented the study on behalf of the Hepatitis C-Three Group of Decatur, Georgia, United States, but was not an author. He disclosed support by Roche, which makes CellCept.
[Presentation title: Multicenter Randomized Hepatitis C (HCV) Three Trial Post Liver Transplantation (OLT): a One-Year Follow up Report. Session 8]
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