Links between donor macrosteatosis, interleukin-33 and complement after liver transplantation

Area of Science:

• Hepatology
• Transplantation Immunology
• Biomarker Discovery

Background:

• Increasing prevalence of nonalcoholic fatty liver disease leads to greater use of steatotic liver grafts.
• Extended criteria grafts, including those with steatosis, pose increased risks in transplantation.
• Lack of prognostic factors to predict dysfunction in macrosteatotic grafts necessitates further research.

Purpose of the Study:

• To investigate the association between interleukin-33 (IL-33) and complement activation in liver transplant recipients.
• To evaluate IL-33 and complement as potential markers for early liver dysfunction following reperfusion of macrosteatotic grafts.

Main Methods:

• Retrospective analysis of 99 liver transplant recipients and their donors.
• Assessment of donor graft steatosis by pathology.
• Quantification of plasma IL-33, C3a, and C5a using ELISA post-reperfusion.
• Analysis of gene expression in donor liver biopsies.

Main Results:

• Recipients of moderate macrosteatotic grafts (≥30% steatosis) showed significantly higher AST/ALT levels and increased early allograft dysfunction (60% vs. 18%).
• Elevated circulating IL-33 levels were observed in recipients of macrosteatotic grafts and correlated with higher AST/ALT.
• Activated complement components (C3a, C5a) were elevated in recipients with moderate macrosteatotic grafts.

Conclusions:

• Circulating IL-33 and activated complement levels post-reperfusion may serve as biomarkers for early allograft dysfunction in recipients of macrosteatotic liver grafts.
• These findings can aid in identifying patients at higher risk for post-transplant liver dysfunction.