Late Conversion to Sirolimus in Liver Transplant Recipients is a Safe Clinical Strategy: Presented at ICTS

By Claire Sowerbutt

VANCOUVER -- August 18, 2010 -- Converting patients who have undergone liver transplantation to calcineurin inhibitor (CNI)-free immunosuppression with sirolimus at 5 years or more post transplant is a safe clinical strategy, as it does not increase the risk for acute rejection (ACR) or steroid resistant rejection, researchers said here at the 23rd International Congress of the Transplant Society (ICTS).

While sirolimus-based CNI-free immunosuppression is useful in managing long-term complications in liver transplant recipients, information regarding this strategy is limited.

"Concerns of potential complications and risk for late ACR in a patient with otherwise stable immunosuppression cause many clinicians to avoid late conversion, since late ACR can negatively impact survival in liver transplant," reported Greg McKenna, MD, Transplant Services Department, Baylor Regional Transplant Institute, Dallas, Texas, and colleagues. "By avoiding later conversions, these co-morbidities and complications can progress, even to the patient's detriment."

Dr. McKenna and colleagues presented findings from what is the largest experience of conversion to sirolimus-based CNI-free immunosuppression.

The single centre, retrospective analysis utilised a prospectively identified database of 2,218 orthotopic liver transplant (OLT) recipients of Baylor Transplant Institute seen from January 1985 to December 2005.

The sirolimus cohort included all patients converted to sirolimus at >=5 years (late conversion. The control group (n = 1636) consisted of all surviving patients at >=5 years post transplant who had never received sirolimus either as de novo immunosuppression or as conversion therapy. The rates of ACR and patient survival were compared between the 2 groups.

The total number of patients converted to sirolimus was 476/2218 (21.5%), with 140 (29.4%) of 476 undergoing late conversion. The leading cause of conversion was nephrotoxicity (91.6%), followed by malignancy (2.1%), neurotoxicity (1.4%), and hepatitis C virus progression (1.4%).

The median time to late conversion was 8.8 years, the median duration 4.2 years, and the number of patients currently on sirolimus is 53.3%.

Patient death occurred in 13.6% of the 140 patients who underwent late sirolimus conversion, and was the leading reason for treatment cessation. The second leading reason was pending surgical procedures (8.6%).

Compared with the control group, fewer patients who underwent late sirolimus conversion experienced ACR (2.1% vs 3.5 %, respectively) -- the difference was not significant. The 3 episodes of ACR in the late conversion cohort occurred on days 115, 175, and 986 post conversion. Steroid resistant rejection did not occur at all in the sirolimus cohort, whereas there was a 0.5% incidence in the control group.

With respect to complications, there were no incidences of hepatic artery thrombosis, cytomegalovirus, and Epstein Barr virus or bilary complications in the late conversion group. However, a 2.9% incidence of hernia (4/140), and a 0.7% (1/140) incidence of Herpes simplex virus was reported.

"There was no significant difference in patient survival between the sirolimus cohort and the control group," the authors reported. "This is in itself significant, since 90% of the patients in the sirolimus cohort were converted for renal dysfunction and would be expected to have worse patient survival."

"Late conversion to sirolimus should not be deterred by concerns of complications or risks of rejection, even in patients on long-term stable immunosuppression, and should be done if the clinical situation warrants it," they concluded.

[Presentation title: The Safety of Late Conversion to Sirolimus in Liver Transplantation. Abstract MO12.05]

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