Corticosteroid-free immunosuppression in liver transplantation: a meta-analysis and meta-regression of outcomes

Abstract

To examine the impact of steroid withdrawal from the immunosuppression protocols in liver transplantation. The electronic databases Medline, Embase, Pubmed and the Cochrane Library were searched. Meta-analysis pooled the effects of outcomes of a total of 2590 patients enrolled into 21 randomized controlled trials (RCTs), using classic and modern meta-analytic methods. Meta-analysis of RCTs addressing patients transplanted for any indication showed no differences between corticosteroid-free immunosuppression and steroid-based protocols in most of the analyzed outcomes. More importantly, steroid-free cohorts appeared to benefit in terms of de novo diabetes mellitus development [R.R = 1.86 (1.43, 2.41)], Cytomegalovirus (CMV) infection [R.R = 1.47 (0.99, 2.17)], cholesterol levels [WMD = 19.71 (13.7, 25.7)], the number of patients that received the allocated treatment [O.R = 1.55 (1.17, 2.05)], severe acute rejection [R.R = 1.71 (1.14, 2.54)] and overall acute rejection [R.R = 1.31 (1.09, 1.58)] (when steroids were replaced in the steroid-free arm). Taking RCTs into account independently when steroids were not replaced, overall acute rejection was favoring the steroid-based arm [R.R = 0.75 (0.58, 0.98)]. Studies addressing exclusively transplanted HCV patients demonstrated a significant advantage of steroid-free protocols considering HCV recurrence [R.R = 1.15 (1.01, 1.13)], acute graft hepatitis [O.R = 3.15 (1.18, 8.40)], and treatment failure [O.R = 1.87 (1.33, 2.63)]. No unfavorable effects were observed after steroid withdrawal during short-term follow-up. On the contrary, significant advantages were documented.