A systematic review and meta-analysis of liver xenotransplantation from genetically modified pigs to nonhuman primates

OBJECTIVE: This meta-analysis synthesizes preclinical evidence on the safety and efficacy of genetically modified pigs to nonhuman primates (NHPs) liver xenotransplantation. BACKGROUND: The outcomes of liver xenotransplantation from genetically modified pig-to-NHP remain suboptimal. METHODS: A systematic search of Embase, PubMed, and Scopus was conducted to identify and select relevant experimental studies. Data on survival rates and complications were extracted. Data on survival and complications were pooled using a random-effects model to generate summary effect sizes (ES) and 95% confidence intervals (CI). RESULTS: Eleven studies involving 59 pig-to-NHPs liver xenotransplantations were included. The pooled median survival time was 5 days [interquartile ranges (IQR): 1-9 days]. The 1-day, 3-day, 7-day, and 14-day pooled survival rates were 88.6% (95% CI: 0.682-0.999), 78.8% (95% CI: 0.526-0.976), 29.2% (95% CI: 0.133-0.473), and 4.2% (95% CI: 0.000-0.141), respectively. Coagulopathy was the leading cause of death (32.2%). The pooled incidence of acute rejection, coagulopathy, surgery-related complications, and infection-related complications was 0.034 (95% CI: 0.000-0.131), 0.522 (95% CI: 0.308-0.733), 0.134 (95% CI: 0.037-0.261), and 0.282 (95% CI: 0.111-0.482), respectively. Subgroup analysis revealed trends towards improved early survival with heterotopic transplantation over orthotopic, and immunosuppressive regimens including co-stimulation blockade were associated with significantly higher survival rates at day 7 ( P = 0.013) and day 14 ( P = 0.042) compared to blocker-free regimens. CONCLUSIONS: The results indicate that pig-to-NHP liver xenotransplantation has limited short-term survival, with coagulopathy being a major challenge. Further research is needed to optimize this procedure and facilitate its clinical translation.