Serum GLYcomics to Predict Graft Loss and Mortality After Liver Transplantation

Overview

The first 12 months after liver transplantation (LT) are decisive in posttransplant outcome, as almost half of deaths and two thirds of graft loss requiring retransplant occur in the first year after LT. Since delaying retransplantation in those patients that experience an unfavorable posttransplant course directly impacts their outcome, timely decision making is of paramount importance in these individuals. However, balancing the need and right timing for retransplantation in individual patients with a complicated posttransplant course is currently a difficult challenge that relies on imperfect clinical variables and biomarkers, as well as the experienced judgment of the transplant team. Building on the findings of a pilot study in liver transplant recipients (n = 131) led by the Ghent University Hospital, we want to validate the prognostic performance of the GlycoTransplantTest on a multicentric scale. In this pilot study, a single glycomic signature at day 7 after LT allowed accurate prediction of graft loss at 3 months after LT. The serum glycome of those patients experiencing graft loss was characterized by increased undergalactosylation and an increased presence of fucosylated and triantennary glycans. After statistical modeling, use of an optimized cutoff based on the relative abundance of 13 serum glycans showed a strong association with graft loss at 3 months (odds ratio 70.211; P\<0.001; 95% CI: 10.876-453.23). Using sequential measurements of serum glycomics in liver transplant recipients, we want to prospectively study and validate the predictive value of the serum glycomic signature for graft survival and overall survival at 3-months (primary end point) and 12-months after liver transplantation (secondary end point). Determination of the serum glycomic profile is a high-throughput technique that allows to study and quantify the relative abundance of sugar chains (glycans) anchored at specific sites of serum proteins. This technique has shown a very strong prognostic value for graft loss at 3-months after liver transplantation in a pilot study at the Ghent University Hospital. In this large-scale multicentric prognostic study, we will collect serum samples of liver transplant recipients at fixed time points. Apart from the serum glycomic profile, we will collect data from the patients electronic record: demographic data (gender, age), data directly relevant to the indication of transplant (eg. imaging for primary liver cancer, lab values for diagnosis of end-stage liver disease), and outcome data (graft survival, overall survival, follow-up time). This list is non-exhaustive. Using this approach, we will demonstrate the predictive validity of serum glycomics in liver transplant recipients for graft survival and overall survival at 3- and 12-months post-LT. Building on these data, the use of a simple blood test could differentiate patients at risk of graft loss and thus represent a paradigm shift directing these patients to timely treatment adaptations.