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

TY - JOUR

T1 - Hyaluronic Acid Is a Biomarker for Allograft Dysfunction and Predicts 1-Year Graft Loss After Liver Transplantation

AU - Rostved, A A

AU - Ostrowski, S R

AU - Peters, L

AU - Lundgren, J D

AU - Hillingsø, J

AU - Johansson, P I

AU - Rasmussen, A

N1 - Copyright © 2018 Elsevier Inc. All rights reserved.

PY - 2018/12

Y1 - 2018/12

N2 - 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.

AB - 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.

KW - Adult

KW - Allografts

KW - Biomarkers/blood

KW - Cohort Studies

KW - Female

KW - Graft Survival

KW - Humans

KW - Hyaluronic Acid/blood

KW - Liver Function Tests

KW - Liver Transplantation/adverse effects

KW - Male

KW - Middle Aged

KW - Prognosis

KW - Proportional Hazards Models

KW - ROC Curve

KW - Retrospective Studies

KW - Risk Factors

KW - Transplantation, Homologous

U2 - 10.1016/j.transproceed.2018.09.018

DO - 10.1016/j.transproceed.2018.09.018

M3 - Journal article

C2 - 30577249

SN - 0041-1345

VL - 50

SP - 3635

EP - 3643

JO - Transplantation Proceedings

JF - Transplantation Proceedings

IS - 10

ER -