Steroid-Free Immunosuppression Without Induction Is Safe and Effective After Liver Transplant

Bryan DeBusk, PhD

July 14, 2008

July 14, 2008 (Paris, France) — The evaluation of a protocol for steroid-free tacrolimus immunosuppression without antibody- or drug-based induction therapy has shown that about 25% of liver transplant recipients can safely avoid the use of steroids after liver transplant, eliminating the risk for infection-related complications and hypertension typically associated with steroid use.

Michael DeVera, MD, a clinician and member of the faculty of physicians at the University of Pittsburgh Medical Center, in Pennsylvania, presented the results of the study here at the 2008 Joint International Congress of ILTS, ELITA & LICAGE.

"Most centers are generally using a lot of immunosuppression after liver transplant," Dr. DeVera told Medscape Transplantation. "A the University of Pittsburgh Medical Center, we have taken a 'minimalist' approach to immunosuppression after liver transplant. We are placing patients on 1 immunosuppressive agent immediately posttransplant, without any other agents, and then adding other agents when medically required."

Dr. DeVera and his colleagues compared the outcomes of patients receiving standard immunosuppressive therapy plus induction with the outcomes of patients receiving steroid-free immunosuppressive therapy. Beginning in 2003, liver transplant recipients in the study received intraoperative steroids followed by either postoperative treatment with oral tacrolimus plus steroids and mycophenolate mofetil or sirolimus (TAC/St, n = 376) or oral tacrolimus alone (TAC, n = 360). Survival was comparable between the 2 groups at 1 year (TAC, 85%; TAC/St, 86%) and at 3 years (TAC, 76%; TAC/St, 79%), and no difference was noted in the rate of biopsy-proven acute cellular rejection (TAC, 34%; TAC/St, 31%). Steroids were eventually administered to 48% of the patients in the TAC group, primarily because of adrenal insufficiency, and 63% of patients in the TAC group eventually required treatment with mycophenolate mofetil or sirolimus, primarily for renal-sparing.

Less than 3% of patients in the TAC group experienced chronic rejection, and rejection episodes among patients in this group generally responded to steroid therapy. No difference in the incidence of steroid-resistant rejection was noted between the 2 groups, and no grafts failed because of rejection. Patients in the TAC group who remained steroid-free achieved higher tacrolimus levels on average in the 4 weeks following transplant than those who eventually received steroid treatment (10.97 ± 2.5 ng/mL vs 10.31 ± 1.8 ng/mL; P = .009). At 12 months, despite higher tacrolimus levels, serum creatinine as an indicator of renal function was comparable between patients in the TAC group who remained steroid-free and those who eventually received steroid treatment (1.4 ± 1.6 mg/dL vs 1.7 ± 1.3 mg/dL; = .09).

Dr. DeVera also reported that the frequency of cytomegalovirus infection and deaths due to infection and sepsis was lower among patients in the TAC group who remained steroid-free, but no effect of steroid use was noted on the incidence or severity of recurrent hepatitis C. The incidence of hypertension among patients in the TAC group who remained steroid-free was also lower 1 month after transplant.

Michael Ramsay, MD, secretary and treasurer of the International Liver Transplantation Society (ILTS), president of the Baylor Research Institute, and chief of service for the department of anesthesiology and pain management at Baylor University Medical Center, in Dallas, Texas, told Medscape Transplantation that Dr. DeVera's findings should help physicians reduce or eliminate some of the complications associated with immunosuppression. "This is another step forward in trying to reach the 'holy grail' of inducing immunotolerance," Dr. Ramsay remarked. "Eliminating steroids without increasing graft rejection is a significant step forward."

Dr. DeVera characterized the treatment protocol as a safe alternative to traditional immunosuppression, but noted that a physician's decision to use the approach involves a trade-off. "Our rejection rate is 33%, but this is similar to a historic control group of patients who received tacrolimus plus steroids," Dr. DeVera explained. "However, it is well known that rejections do not affect graft function or the long-term graft survival of livers. The bottom line is the trade-off between using more agents with higher cost, more side effects, and poorer patient compliance to decrease rates of rejection [and using] less immunosuppression [with] a higher rate of rejection, which does not affect graft function or survival."

The study did not receive commercial support. Neither Dr. DeVera and nor Dr. Ramsay disclosed any relevant financial relationships.

2008 Joint International Congress of ILTS, ELITA & LICAGE: Abstract 558. Presented July 11, 2008.

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