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Systematic Evaluation of the Safety Threshold for Allograft Macrovesicular Steatosis in Cadaveric Liver Transplantation.

ABSTRACT: Background: Currently, 30% macrovesicular steatosis (MaS) content is usually assigned empirically as the boundary between "use" and "refuse" a donor liver for liver transplantation (LT); however, this cut-off is questionable due to the lack of systemic evidence of the efficiency relative to prognosis prediction. Clinicians have tried to identify the threshold for optimized utilization of marginal steatotic allografts, but controversy exists among different studies. Aim: Our study aimed to systematically determine an acceptable donor MaS content cut-off without incurring extra risk in liver transplantation, using meta-analysis. Methods: The relevant literature reporting the relationship between MaS content and post-transplant mortality/morbidity was searched and retrieved in Pubmed, Embase, and ISI Web of Science. Results: Nine studies were enrolled into the final analysis. A categorical comparison revealed that patients who received allografts with moderate steatosis (MaS content >30%) had significantly higher risks of graft failure/dysfunction, but not of mortality. Dose-response analysis showed that donor MaS content affected the graft failure/dysfunction in a non-linear relationship. Risks associated with MaS content in terms of poorer outcomes were independent of other risk covariates for liver transplantation. A non-significant increase in risk of inferior post-transplant outcomes was observed in patients who received allografts with a MaS content <35%. The risks of post-transplant graft failure and dysfunction increased with severe donor MaS content infiltration, without a consistent relationship. Conclusions: The threshold of allograft MaS content can be safely extended to 35% without additional risk burden on post-transplant inferior outcomes. Clarification on "the effects of stratification" for MaS content can provide theoretical evidence for further optimal utilization of marginal steatotic allografts in liver transplantation.

SUBMITTER: Liu Z

PROVIDER: S-EPMC6494939 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background: Donor age affects allograft quality and the prognosis of recipients after liver transplantation (LT). Clinicians have assessed the quality of grafts from older donors based on their appearance and texture, with no reliable quantitative evidence. Our study aimed to assess the quantitative impact of donor age on post-transplant outcomes and its safety threshold for LT, based on the published literature. Methods: Relevant studies were retrieved from the Embase, PubMed, and ISI Web of Science databases. Pooled dichotomous relative risks (RRs) were calculated using metan. Continuous RRs were calculated using a two-stage random-effects model. Results: Eleven studies including 30,691 LT cases were included for further analysis. For categorical comparison, the RR of death within the first post-transplant year was significantly higher among patients who received grafts from older donors. Similarly, the RR of graft failure (GF) was increased within the 3 years after transplantation. For continuous comparison, advanced donor age affected transplant outcomes in a linear manner (P > 0.05). A 10-year increment in donor age was associated with RRs 1.10, 1.12, 1.15, 1.10, and 1.08 for 90-day, 180-day, 1-year, 3-year, and 5-year patient mortality and 1.08, 1.06, 1.10, 1.11, and 1.12, for 90-day, 180-day, 1-year, 2-year, and 3-year GF, respectively (all P < 0.05). A spline model showed that transplants using grafts from donors <43 years old were not associated with age-related risks (P > 0.05). The risk of GF was increased in subgroups with fewer LT cases, longer cold ischemic time, fewer male donors, and recipients with viral hepatitis (P < 0.05). Conclusion: Donor age might affect post-LT outcomes in a dose-dependent manner. The safety threshold for donor age in terms of GF should be lowered to 43 years as an early warning for the guarantee of satisfactory outcomes. Clinicians should weigh the benefits against the risks carefully for patients receiving grafts from older donors. Further studies are warranted to investigate the mechanisms responsible for the relationship between donor age and graft quality.

Project description:This study is aimed at determining the ability of computed tomography- (CT-) based radiomic analysis to distinguish between grade 0/1 and grade 2/3 macrovesicular steatosis (MaS) in cadaveric donor liver transplantation cases. Preoperative noncontrast-enhanced CT images of 150 patients with biopsy-confirmed MaS were analyzed retrospectively; these patients were classified into the low-grade MaS (n = 100, grade 0 or 1) and high-grade MaS (n = 50, grade 2 or 3) groups. Three-dimensional spherical regions of interest of 40 pixel (2.5 cm) in diameter were placed in the right anterior and left lateral segments of the liver. Thereafter, 300 regions of interest (ROIs) were segmented and randomly assigned to the training and testing groups at a ratio of 7 : 3. A total of 402 radiomic features were extracted from each ROI. For MaS classification, a radiomic model was established using multivariate logistic regression analysis. Clinical data, including age, sex, and liver function, were collected to establish the clinical model at the patient level. The performances of the radiomic and clinical models, i.e., the diagnostic discrimination, calibration, and clinical utilities, were evaluated. The radiomic model, with seven selected features, depicted a good discrimination with an area under the receiver operating characteristic curve (AUC) of 0.907 (95% confidence interval (CI): 0.869-0.940) in the training cohort and 0.906 (95% CI: 0.843-0.959) in the testing cohort. The calibration curve revealed good agreement between the predicted and observed probabilities in the training and testing cohorts (both P > 0.05 in the H-L test). Decision curve analysis revealed that the radiomic model was more beneficial than the treat-all or treat-none schemes for predicting the MaS grade. Alanine transaminase and gamma-glutamyl transferase were used for building the clinical model, and the AUC was 0.784 in the total cohort. The CT-based radiomic model outperforming the conventional clinical model could provide an important reference for MaS grading in cadaveric liver donors.

Project description: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.

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Systematic Evaluation of the Safety Threshold for Allograft Macrovesicular Steatosis in Cadaveric Liver Transplantation.

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