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Hyaluronic Acid is a Biomarker for Allograft Dysfunction and Predicts 1-year Outcome after Liver Transplantation

ABSTRACT: Introduction: Allograft dysfunction after liver transplantation has a profound impact on risk of death and retransplantation within the first year. We tested whether elevated hyaluronic acid (HA) (a glycosaminoglycan cleared by hepatic sinusoidal endothelium) and bacterial translocation (reflected by elevated soluble CD14 (sCD14)) levels may predict excess risk of graft loss. Methods: This is a retrospective single center prognostic cohort study. Patients with either a plasma sample pretransplant, an early post-transplant sample nearest day 30 (range 10-89 days, 80% within day 15 to 60) or both were included. Plasma HA and sCD14 were measured using enzyme-linked immunosorbent assays. The primary endpoint was 1-year graft loss (all-cause mortality and re-plantation). Secondary endpoint was biliary strictures. Findings: In this study 169 of 196 patients who received a liver transplant in the study period was included. Neither pretransplant sCD14 nor HA (n=152) predicted graft loss. Post-transplant HA (n=124) was higher among patients with graft loss (median 177 µg/l, IQR 89-465 versus median 54 µg/l, IQR 37-93) and was a strong predictor of this outcome (hazard ratio per 50 µg/l: 1.24, 95% CI: 1.14-1.34). The discriminatory ability of HA was high (AUROC 0.86, 95% CI: 0.77-0.94) and non-inferior to other liver function tests. When adjusted for known risk factors of graft loss, HA remained an independent predictor of graft loss whereas sCD14 did not. Non-anastomotic strictures could be predicted by sCD14. The main limitation of the study was the variety in the timespan of blood sampling. Conclusion: High post-transplant plasma HA levels was a strong predictor of one-year all-cause mortality and retransplantation whereas pretransplant levels were not. Prospective studies are warranted to further establish the reliability and kinetics of HA in predicting clinical outcomes in liver transplant patients.

SUBMITTER: Andreas Arendtsen Rostved

PROVIDER: S-BSST102 | biostudies-other |

REPOSITORIES: biostudies-other

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Project description:BackgroundIschemia-reperfusion injury (IRI) is the pathophysiological hallmark of hepatic dysfunction after orthotopic liver transplantation (OLT). Related to IRI, early allograft dysfunction (EAD) after OLT affects short- and long-term outcome. During inflammatory states, the liver seems to be the main source of procalcitonin (PCT), which has been shown to increase independently of bacterial infection. This study investigates the association of PCT, IRI and EAD as well as the predictive value of PCT during the first postoperative week in terms of short- and long-term outcome after OLT.MethodsPatients ≥ 18 years undergoing OLT between January 2016 and April 2020 at the University Hospital of Zurich were eligible for this retrospective study. Patients with incomplete PCT data on postoperative days (POD) 1 + 2 or combined liver-kidney transplantation were excluded. The PCT course during the first postoperative week, its association with EAD, defined by the criteria of Olthoff, and IRI, defined as aminotransferase level > 2000 IU/L within 2 PODs, were analysed. Finally, 90-day as well as 12-month graft and patient survival were assessed.ResultsOf 234 patients undergoing OLT, 110 patients were included. Overall, EAD and IRI patients had significantly higher median PCT values on POD 2 [31.3 (9.7-53.8) mcg/l vs. 11.1 (5.3-25.0) mcg/l; p < 0.001 and 27.7 (9.7-51.9) mcg/l vs. 11.5 (5.5-25.2) mcg/l; p < 0.001] and impaired 90-day graft survival (79.2% vs. 95.2%; p = 0.01 and 80.4% vs. 93.8%; p = 0.033). IRI patients with PCT < 15 mcg/l on POD 2 had reduced 90-day graft and patient survival (57.9% vs. 93.8%; p = 0.001 and 68.4% vs. 93.8%; p = 0.008) as well as impaired 12-month graft and patient survival (57.9% vs. 96.3%; p = 0.001 and 68.4% vs. 96.3%; p = 0.008), while the outcome of IRI patients with PCT > 15 mcg/l on POD 2 was comparable to that of patients without IRI/EAD.ConclusionGenerally, PCT is increased in the early postoperative phase after OLT. Patients with EAD and IRI have a significantly increased PCT maximum on POD 2, and impaired 90-day graft survival. PCT measurement may have potential as an additional outcome predictor in the early phase after OLT, as in our subanalysis of IRI patients, PCT values < 15 mcg/l were associated with impaired outcome.

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Hyaluronic Acid is a Biomarker for Allograft Dysfunction and Predicts 1-year Outcome after Liver Transplantation

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