Evaluation of Early Allograft Function Using the Liver Graft Assessment Following Transplantation Risk Score Model

Abstract

Importance: Early allograft dysfunction (EAD) following a liver transplant (LT) unequivocally portends adverse graft and patient outcomes, but a widely accepted classification or grading system is lacking.

Objective: To develop a model for individualized risk estimation of graft failure after LT and then compare the model's prognostic performance with the existing binary EAD definition (bilirubin level of ≥10 mg/dL on postoperative day 7, international normalized ratio of ≥1.6 on postoperative day 7, or aspartate aminotransferase or alanine aminotransferase level of >2000 U/L within the first 7 days) and the Model for Early Allograft Function (MEAF) score.

Design, setting, and participants: This retrospective single-center analysis used a transplant database to identify all adult patients who underwent a primary LT and had data on 10 days of post-LT laboratory variables at the Dumont-UCLA Transplant Center of the David Geffen School of Medicine at UCLA between February 1, 2002, and June 30, 2015. Data collection took place from January 4, 2016, to June 30, 2016. Data analysis was conducted from July 1, 2016, to August 30, 2017.

Main outcomes and measures: Three-month graft failure-free survival.

Results: Of 2021 patients who underwent primary LT over the study period, 2008 (99.4%) had available perioperative data and were included in the analysis. The median (interquartile range [IQR]) age of recipients was 56 (49-62) years, and 1294 recipients (64.4%) were men. Overall survival and graft-failure-free survival rates were 83% and 81% at year 1, 74% and 71% at year 3, and 69% and 65% at year 5, with an 11.1% (222 recipients) incidence of 3-month graft failure or death. Multivariate factors associated with 3-month graft failure-free survival included post-LT aspartate aminotransferase level, international normalized ratio, bilirubin level, and platelet count, measures of which were used to calculate the Liver Graft Assessment Following Transplantation (L-GrAFT) risk score. The L-GrAFT model had an excellent C statistic of 0.85, with a significantly superior discrimination of 3-month graft failure-free survival compared with the existing EAD definition (C statistic, 0.68; P < .001) and the MEAF score (C statistic, 0.70; P < .001). Compared with patients with lower L-GrAFT risk, LT recipients in the highest 10th percentile of L-GrAFT scores had higher Model for End-Stage Liver Disease scores (median [IQR], 34 [26-40] vs 31 [25-38]; P = .005); greater need for pretransplant hospitalization (56.8% vs 44.8%; P = .003), renal replacement therapy (42.9% vs 30.5%; P < .001), mechanical ventilation (35.8% vs 18.1%; P < .001), and vasopressors (22.9% vs 11.0%; P < .001); longer cold ischemia times (median [IQR], 436 [311-539] vs 401 [302-506] minutes; P = .04); greater intraoperative blood transfusions (median [IQR], 17 [10-26] vs 10 [6-17] units of packed red blood cells; P < .001); and older donors (median [IQR] age, 47 [28-56] vs 41 [25-52] years; P < .001).

Conclusions and relevance: The L-GrAFT risk score allows a highly accurate, individualized risk estimation of 3-month graft failure following LT that is more accurate than existing EAD and MEAF scores. Multicenter validation may allow for the adoption of the L-GrAFT as a tool for evaluating the need for a retransplant, for establishing standardized grading of early allograft function across transplant centers, and as a highly accurate clinical end point in translational studies aiming to mitigate ischemia or reperfusion injury by modulating donor quality and recipient factors.

Conflict of interest statement

Conflict of Interest Disclosures: None reported.

Figures

Figure 1.. Association of Each Laboratory Variable With the Hazard Ratios (HRs) for Graft Failure Stratified by Time Interval

Reported HRs correspond with changes from the fourth (highest) quartile to the first (lowest) quartile for all measures except rate of normalization (slope) of AST (D) and bilirubin (E) levels, where HRs correspond with changes from the lowest quartile (more negative slope indicates faster rate of normalization) to the highest quartile (less negative slope indicates slower rate of normalization). For all measures, HRs were significant and most pronounced for graft failures occurring within 3 months and universally declined and approached nonsignificant levels for graft failures occurring after 12 months. AST indicates aspartate aminotransferase; AUC, area under the curve; INR, international normalized ratio.

Figure 2.. Comparison of Model Accuracies as Measured by the Area Under the Receiver Operating Characteristic (AUROC) Curve Among 3 Models of Early Allograft Dysfunction

The Liver Graft Assessment Following Transplantation (L-GrAFT) score (A; C statistic, 0.85) had the highest AUROC statistically significantly superior to both the Model for Early Allograft Function (MEAF) score (B; C statistic, 0.70; P < .001) and the early allograft dysfunction (EAD) score (C; C statistic, 0.68; P < .001). The L-GrAFT model allowed for greater discrimination of 3-month graft-failure risk (D) compared with the MEAF score (E) and the binary EAD definition (F). Five risk groups (RGs) for 3-month graft failure for both L-GrAFT and MEAF were defined on the basis of risk score distribution, including (1) very low risk (≤50th percentile), (2) low risk (>50th to ≤90th percentile), (3) moderate risk (>90th to ≤93.3 percentile), (4) moderate-to-high risk (>93.3 to ≤96.6 percentile), and (5) high risk (>96.6 percentile). GFFS indicates graft failure–free survival.

Figure 3.. Association of Estimated Risk for 3-Month Graft Failure With Liver Graft Assessment Following Transplantation (L-GrAFT) Risk Score

The mathematical formula for calculating L-GrAFT risk score can be found in the Results section. The L-GrAFT scores corresponding to the 5 risk groups are as follows: (1) very low risk (1.3).