Glucocorticosteroid-free versus glucocorticosteroid-containing immunosuppression for liver transplanted patients.Cochrane Database Syst Rev. 2015 Dec 15CD
Liver transplantation is an established treatment option for end-stage liver failure. Now that newer, more potent immunosuppressants have been developed, glucocorticosteroids may no longer be needed and their removal may prevent adverse effects.
To assess the benefits and harms of glucocorticosteroid avoidance (excluding intra-operative use) or withdrawal versus glucocorticosteroid-containing immunosuppression following liver transplantation.
We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Science Citation Index Expanded and Social Sciences Citation Index, The Transplant Library, and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) until September 2014.
Randomised clinical trials assessing glucocorticosteroid avoidance or withdrawal versus glucocorticosteroid-containing immunosuppression for liver-transplanted people. Our inclusion criteria stated that participants should have received the same co-interventions. We included trials that assessed complete glucocorticosteroid avoidance (excluding the perioperative period and excluding the occurrence of acute rejection) versus short-term glucocorticosteroids, as well as trials that assessed short-term glucocorticosteroids versus long-term glucocorticosteroids.
DATA COLLECTION AND ANALYSIS
We used RevMan to conduct meta-analyses, calculating risk ratio (RR) for dichotomous variables and mean difference (MD) for continuous variables, both with 95% confidence intervals (CIs). We used a random-effects model and a fixed-effect model and reported both results where a discrepancy existed. We assessed the risk of systematic errors using risk of bias domains. We controlled for random errors by performing Trial Sequential Analysis. We presented our results in a 'Summary of findings' table.
We included 16 completed randomised clinical trials with a total of 1347 participants. We found 10 trials that assessed complete postoperative glucocorticosteroid avoidance (excluding intra-operative use and treatment of rejection) versus short-term glucocorticosteroids (782 participants) and six trials that assessed short-term glucocorticosteroids versus long-term glucocorticosteroids (565 participants). We found one ongoing trial assessing complete postoperative glucocorticosteroid avoidance versus short-term glucocorticosteroids, which is expected to enrol 300 participants. All trials were at high risk of bias. Overall, we found no statistically significant difference for mortality (RR 1.15, 95% CI 0.93 to 1.44; low-quality evidence), graft loss including death (RR 1.16, 95% CI 0.91 to 1.48; low-quality evidence), or infection (RR 0.88, 95% CI 0.73 to 1.05; low-quality evidence) when glucocorticosteroid avoidance or withdrawal was compared with glucocorticosteroid-containing immunosuppression. Acute rejection and glucocorticosteroid-resistant rejection were statistically significantly more frequent when glucocorticosteroid avoidance or withdrawal was compared with glucocorticosteroid-containing immunosuppression (RR 1.33, 95% CI 1.08 to 1.64; moderate-quality evidence; and RR 2.14, 95% CI 1.13 to 4.02; very low-quality evidence). Diabetes mellitus and hypertension were statistically significantly less frequent when glucocorticosteroid avoidance or withdrawal was compared with glucocorticosteroid-containing immunosuppression (RR 0.81, 95% CI 0.66 to 0.99; low-quality evidence; and RR 0.76, 95% CI 0.65 to 0.90; low-quality evidence). We performed Trial Sequential Analysis for all outcomes. None of the outcomes crossed the monitoring boundaries or reached the required information size. Hence, we cannot exclude random errors from the results of the conventional meta-analyses.