A Multidrug Donor Preconditioning Improves Steatotic Rat Liver Allograft Function and Recipient Survival After Transplantation

Transpl Int. 2024 Dec 13:37:13557. doi: 10.3389/ti.2024.13557. eCollection 2024.

Abstract

The scarcity of donors has prompted the growing utilization of steatotic livers, which are susceptible to injuries following orthotopic liver transplantation (OLT). This study aims to assess the efficacy of multidrug donor preconditioning (MDDP) in alleviating injuries of steatotic grafts following rat OLT. Lean rats were subjected to a Western-style diet with high-fat (HF) and high-fructose (HFr) for 30 days to induce steatosis. Both lean and steatotic livers were implanted into lean recipients fed with a chow diet after OLT. The HF + HFr diet effectively elevated blood triglyceride and cholesterol levels and induced fat accumulation in rat livers. Our results demonstrated a significant decrease in alanine aminotransferase levels (p = 0.003), aspartate aminotransferase levels (p = 0.021), and hepatic Suzuki scores (p = 0.045) in the steatotic rat liver allograft group following MDDP treatment on post-operation day (POD) 7. Furthermore, the survival rates of steatotic rat liver allografts with MDDP (19/21, 90.5%) were significantly higher than those in the steatotic control (12/21, 57.1%, *p = 0.019). These findings indicate that MDDP treatment improves steatotic rat liver allograft function and recipient survival following OLT.

Keywords: allograft function; donor shortage; ischemia reperfusion injury; multidrug donor preconditioning; orthotopic liver transplantation; rat steatotic liver donor.

MeSH terms

  • Alanine Transaminase / blood
  • Allografts
  • Animals
  • Aspartate Aminotransferases / blood
  • Cholesterol / blood
  • Diet, High-Fat
  • Fatty Liver*
  • Fructose
  • Graft Survival* / drug effects
  • Liver / pathology
  • Liver Transplantation*
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Tissue Donors
  • Transplantation Conditioning / methods
  • Triglycerides / blood

Substances

  • Alanine Transaminase
  • Triglycerides
  • Aspartate Aminotransferases
  • Fructose
  • Cholesterol

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This research received funding from the Research Funding Program at University Medical Center Göttingen and the Else Kröner Fresenius Foundation. We acknowledge support by the Open Access Publication Funds of the Göttingen University.