The analysis of all included trials showed that therapy with IL-2Ra was not associated with an increased incidence of malignancies, bacterial or viral infection, or adverse events in general, indicating that IL2-Ra are safe and without significant side effects for at least 12 months after liver transplantation. Longer follow-up has been reported for registry data and corroborates this analysis.46 The main limitation 3-MA manufacturer of this review is the low number of randomized controlled trials, even compared to kidney transplantation,7 which makes it difficult to acquire enough data for meaningful results. After a first unsystematic review we decided to include not only randomized
trials but also nonrandomized controlled trials in this review. Very few studies only compared IL-2Ra to placebo or no treatment and many more studies explored the effects of reduced or delayed concomitant immunosuppression. Therefore, we decided to include those studies in the analysis by Bafilomycin A1 datasheet allocating them
to predefined comparisons. Furthermore, we included and pooled studies that used a different type of IL2-Ra, had different concomitant medication (CNI and MMF), or had different follow-up times. Because all these differences may be sources of heterogeneity, it was planned to perform joint analyses and also to explore differences of effect by performing subgroup analyses and meta-regression. Due to the paucity of data on secondary outcomes we were only able to extensively analyze the primary endpoints. Another problem was the insufficient detailed reporting of outcomes; this was most evident regarding the side effects of immunosuppression. Not only did few studies give data on complications and side effects, but also these were reported in insufficient detail or were measured or grouped differently in the various trials. We endeavored to overcome this limitation by grouping data on side effects into broader categories, but this may further limit the interpretation
of the results. External and internal validity 上海皓元医药股份有限公司 of the trials and the results of this meta-analysis are difficult to assess because important methodological details were omitted in the trial reports. Although we attempted to minimize publication bias by searching for and including data from different databases, conference abstracts, and non-English language sources, the inclusion of such data further hindered assessment of validity. Nonetheless, this review and meta-analysis was conducted at an appropriate time because enough data has accumulated for a first inspection by meta-analytical methods. We do not expect more data to accumulate over the next years unless further trials are demanded of the proprietors of commercially available IL-2Ra preparations by the regulatory authorities. Fifteen patients would need to be treated to prevent one acute rejection (NNT [number needed to treat] = 15) and 29 patients would need to be treated to prevent one steroid-resistant rejection (NNT = 29).