Liver Regeneration-Related Cytokine Profiles in Donors and Recipients Before and After Living-Donor Liver Transplant

Exp Clin Transplant. 2018 Oct;16(5):554-561. doi: 10.6002/ect.2017.0039. Epub 2018 Apr 9.

Abstract

Objectives: The liver's capability to completely regenerate after injury is a unique phenomenon in which cytokines are of particular interest. Here, we aimed to assess the release patterns and prognostic relevance of liver regeneration-related cytokines in the setting of living-donor liver transplant.

Materials and methods: Eleven cytokines related to liver regeneration (hepatocyte growth factor, interleukin 6, insulin-like growth factor-1, tumor necrosis factor alpha, transforming growth factor beta, granulocyte colony-stimulating factor, stem cell factor, chemokine (C-X-C motif) ligand 12, angiogenin, fibroblast growth factor-2, and vascular endothelial growth factor) were compared in 13 living-donor liver transplant recipients and their corresponding donors before and daily (10 days) after transplant. Patients and donors were stratified by clinical outcomes (early graft loss within 4 weeks after transplant vs beneficial outcome).

Results: Most cytokines tested (especially tumor necrosis factor alpha and stem cell factor) were elevated in recipients versus donors. Many cytokines were also increased in recipients with graft loss (especially CXCL12) and in donors of recipients with beneficial outcomes (especially fibroblast growth factor 2). Fibroblast growth factor 2 levels were also correlated positively with serum gamma-glutamyltransferase, and higher preoperative concentrations in donors were associated with recipients having beneficial outcomes, indicating an improved regenerative capacity. In contrast, elevated CXCL12 levels in recipients before and after LDLT predicted graft loss and were linked to ongoing liver damage.

Conclusions: In living-donor liver transplant, there are distinct differences between donors and recipients regarding the release of liver regeneration-related cytokines. Moreover, fibroblast growth factor 2 and CXCL12 may be of diagnostic value in a complementary way to describe or even predict the possible outcomes after transplant. These results may be of clinical interest not only for living-donor liver transplant but also for acute liver failure.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Aged
  • Biomarkers / blood
  • Cell Proliferation
  • Chemokine CXCL12 / blood
  • Cytokines / blood*
  • Female
  • Fibroblast Growth Factor 2 / blood
  • Hepatectomy
  • Humans
  • Liver Regeneration*
  • Liver Transplantation / adverse effects
  • Liver Transplantation / methods*
  • Living Donors*
  • Male
  • Middle Aged
  • Pilot Projects
  • Predictive Value of Tests
  • Risk Factors
  • Time Factors
  • Transplant Recipients*
  • Treatment Outcome
  • Young Adult

Substances

  • Biomarkers
  • CXCL12 protein, human
  • Chemokine CXCL12
  • Cytokines
  • Fibroblast Growth Factor 2