The purpose of the present systematic review was to evaluate the incidence, risk factors, and outcome of hyperbilirubinemia after cardiac surgery. Methods: The Population, Interventions, Comparators, Outcomes, and Study design (PICOS) framework was employed to develop the search strategy, and the findings are reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. PubMed, Embase, and the Cochrane Library were systematically searched

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... for studies that provided data on the incidence, risk factors, and outcomes of hyperbilirubinemia in cardiac surgery patients from January 1960 to May 2020. Publication bias was graphically explored through funnel plots, and the Newcastle-Ottawa quality assessment scale (NOS) was used to evaluate the quality of the included studies. Results: Ten studies with 6,100 patients were included in our systematic review. The pooled incidence of hyperbilirubinemia was 23% [95% confidence interval (CI), 0.13-0.32]. Preoperative factors, including right atrial pressure [mean difference (MD), 4.65; 95% CI, 4.43-4.88], total bilirubin (TB) concentration (MD, 0.72; 95% CI, 0.65-0.79), alkaline phosphatase (MD, 27.38; 95% CI, 12.94-41.82), and alanine aminotransferase (MD, 12.02; 95% CI, 10.73-13.31), and intraoperative factors, including cardiopulmonary bypass (CPB) time (MD, 1.57; 95% CI, 0.52-2.63), aortic cross-clamping (ACC) time (MD, 11.82; 95% CI" and the amount of blood transfused (MD, 3.77; 95% CI, 0.68-6.85), were the most robust risk factors for hyperbilirubinemia after cardiac surgery. Additionally, postoperative hyperbilirubinemia was associated with increased in-hospital mortality [odds ratio (OR), 9.9; 95% CI, 5.00-19.60, P<0.0001]. Discussion: Hyperbilirubinemia was common and was associated with increased in-hospital mortality. Preoperative high right atrial pressure, high TB concentration, prolonged CPB and ACC time, and a large amount of blood transfused were the commonly observed risk factors for postoperative hyperbilirubinemia in cardiac surgery patients. Addressing these risk factors may be helpful to lower the occurrence of postoperative hyperbilirubinemia.