Hyaluronic Acid Is a Biomarker for Allograft Dysfunction and Predicts 1-Year Graft Loss After Liver Transplantation

Transplant Proc. 2018 Dec;50(10):3635-3643. doi: 10.1016/j.transproceed.2018.09.018. Epub 2018 Sep 11.

Abstract

Background: Allograft dysfunction after liver transplantation has a profound impact on the risks of death and retransplantation within the first year. We tested whether elevated hyaluronic acid (HA; a glycosaminoglycan cleared by hepatic sinusoidal endothelium) levels may predict excess risk of graft loss.

Methods: This was a retrospective single-center prognostic cohort study. Patients with either a plasma sample before transplantation, an early post-transplantation sample nearest day 30 (range 10-89 d, 80% within days 15-60), or both were included. Plasma HA was measured with the use of enzyme-linked immunosorbent assays. The primary end point was 1-year graft loss (all-cause mortality and retransplantation). A secondary end point was biliary stricture.

Results: In this study, 169 of 196 patients who received a liver transplant in the study period were included. Pre-transplantation HA (n = 152) did not predict graft loss. Post-transplantation HA (n = 124) was higher among patients with graft loss (median, 177 μg/L [interquartile range (IQR), 89-465] vs 54 μg/L [IQR 37-93]) and was a strong predictor of this outcome (hazard ratio per 50 μg/L, 1.24 [95% confidence interval [CI], 1.14-1.34]). The discriminatory ability of HA was high (area under the receiver operating characteristic curve, 0.86 [95% CI, 0.77-0.94]) and noninferior to other liver function tests. When adjusted for known risk factors of graft loss, HA remained an independent predictor of graft loss.

Conclusions: High post-transplantation plasma HA level was a strong predictor of 1-year all-cause mortality and retransplantation, whereas pre-transplantation levels were not, despite variety in the time span of blood sampling. Prospective studies are warranted to assess the utility of HA in liver transplantation.

MeSH terms

  • Adult
  • Allografts
  • Biomarkers / blood
  • Cohort Studies
  • Female
  • Graft Survival*
  • Humans
  • Hyaluronic Acid / blood*
  • Liver Function Tests
  • Liver Transplantation* / adverse effects
  • Male
  • Middle Aged
  • Prognosis
  • Proportional Hazards Models
  • ROC Curve
  • Retrospective Studies
  • Risk Factors
  • Transplantation, Homologous

Substances

  • Biomarkers
  • Hyaluronic Acid