Impact of Intrapatient Immunosuppression Variability in Liver Transplantation Outcomes: A Systematic Review and Meta-analysis

To investigate the impact of intrapatient variability (IPV) in the levels of immunosuppressant drugs on health outcomes after liver transplantation. A comprehensive systematic review and meta-analysis were conducted, examining literature from MEDLINE/PubMed, Embase, Web of Science, Cochrane Reviews, and Cochrane CENTRAL. The analysis focused on acute rejection, graft survival, acute kidney injury, and cancer risk as health outcomes. Of 2901 articles screened, 10 met the inclusion criteria. The results indicate a 19% reduction in the risk of acute rejection in patients with lower IPV (RR = 0.81; 95% confidence interval, 0.66-0.99), although 6 studies found no significant association between high IPV and acute rejection. Contrasting results were observed for graft survival, with 1 study indicating worse outcomes for high IPV, whereas another reported no significant difference. High IPV was consistently associated with acute kidney injury across 3 studies. One study suggested a link between high IPV and hepatocellular carcinoma, although a meta-analysis for these outcomes was not feasible. These findings point to a marginal but statistically significant association between high IPV and an increased risk of acute rejection, highlighting the importance of precise management of immunosuppressive drugs in liver transplant recipients to enhance patient outcomes.