The principles of urgency, utility, and benefit are fundamental concepts guiding the ethical and practical decision-making process for organ allocation; however, LT allocation still follows an urgency model.

To identify and analyze data elements used in Machine Learning (ML) and Artificial Intelligence (AI) methods, data sources, and their focus on urgency, utility, or benefit in LT.

A comprehensive search across Ovid Medline and Scopus was conducted for studies published from 2002 to June 2023. Inclusion criteria targeted quantitative studies using ML/AI for candidates, donors, or recipients. Two reviewers assessed eligibility and extracted data, following PRISMA guidelines.

A total of 20 papers were included, synthesizing results into five major categories. Eight studies were led by a Spanish team, focusing on donor-recipient matching and proposing machine learning models to predict post- LT survival. Other international studies addressed organ supply-demand issues and developed predictive models to optimize LT outcomes. The studies highlight the potential of ML/AI to enhance LT allocation and outcomes. Despite advancements, limitations included the lack of robust transplant-related benefit models and improvements in urgency models compared to MELD.

This review highlighted the potential of AI and ML to enhance liver transplant allocation and outcomes. Significant advancements were noted, but limitations such as the need for better urgency models and the absence of a transplant-related benefit model remain. Most studies emphasized utility, focusing on survival outcomes. Future research should address the interpretability and generalizability of these models to improve organ allocation and post-LT survival predictions.

Liver transplantation is a critical and evolving field in modern medicine, offering life-saving treatment for patients with end-stage liver disease and other hepatic conditions. Despite its transformative potential, transplantation faces persistent challenges, including a global organ shortage, increasing liver disease prevalence, and significant waitlist mortality rates. Current donor evaluation practices often discard potentially viable livers, underscoring the need for refined graft assessment tools. This review explores advancements in graft evaluation and utilization aimed at expanding the donor pool and optimizing outcomes. Emerging technologies, such as imaging techniques, dynamic functional tests, and biomarkers, are increasingly critical for donor assessment, especially for marginal grafts. Machine learning and artificial intelligence, exemplified by tools like LiverColor, promise to revolutionize donor-recipient matching and liver viability predictions, while bioengineered liver grafts offer a future solution to the organ shortage. Advances in perfusion techniques are improving graft preservation and function, particularly for donation after circulatory death (DCD) grafts. While challenges remain-such as graft rejection, ischemia-reperfusion injury, and recurrence of liver disease-technological and procedural advancements are driving significant improvements in graft allocation, preservation, and post-transplant outcomes. This review highlights the transformative potential of integrating modern technologies and multidisciplinary approaches to expand the donor pool and improve equity and survival rates in liver transplantation.

Predicting long-term outcomes in liver transplantation remain a challenging endeavor. This research aims to harness the power of deep learning to develop an advanced prognostic model for assessing long-term outcomes, with a specific focus on distinguishing between deceased and living donor transplantation.

A comprehensive dataset from UNOS encompassing clinical, demographic, and transplant-related variables of liver transplant recipients from deceased and living donors was utilized. The main dataset has been transformed into Deceased Donor-Recipient and Living Donor-Recipient dataset. After manual extraction, the dimensionality reduction was performed with Principal component analysis in both datasets and top ranked 23 attributes were collected. A Deeplearning4j Multilayer Perceptron classifier has been employed and long-term survival analysis has been conducted with the help of liver follow-up data. The performance evaluation is done separately in datasets and evaluated the survival probabilities of 23 years.

UNOS database comprises 410 attributes and 353,589 records from 1998 to 2023. The outcome from the deep learning model was compared with actual graft survival to ensure the accuracy. The model trained 23 attributes and obtained Sensitivity, Specificity and accuracy values were 99.9, 99.9 and 99.91% using R-Living donor dataset. The Sensitivity, Specificity and Accuracy value obtained using R-Deceased donor dataset were 99.7, 99.7 and 99.86%. The short term and long-term survival prediction after liver transplantation has been done successfully with Dl4jMLP classifier with appropriate selection of attributes irrespective of donor type. This study's finding suggesting that the distinction between deceased and living donor transplantation does not significantly affect survival prediction after liver transplantation is noteworthy.

The utility of the Deeplearning4j model in survival prediction after liver transplantation has been validated in this study. Based on the findings, deceased donor transplantation could be promoted over living donor transplantation.

Several scores have been developed to stratify the risk of graft loss in controlled donation after circulatory death (cDCD). However, their performance is unsatisfactory in the Spanish population, where most cDCD livers are recovered using normothermic regional perfusion (NRP). Consequently, we explored the role of different machine learning-based classifiers as predictive models for graft survival. A risk stratification score integrated with the model of end-stage liver disease score in a donor-recipient (D-R) matching system was developed.

This retrospective multicenter cohort study used 539 D-R pairs of cDCD livers recovered with NRP, including 20 donor, recipient, and NRP variables. The following machine learning-based classifiers were evaluated: logistic regression, ridge classifier, support vector classifier, multilayer perceptron, and random forest. The endpoints were the 3- and 12-mo graft survival rates. A 3- and 12-mo risk score was developed using the best model obtained.

Logistic regression yielded the best performance at 3 mo (area under the receiver operating characteristic curve = 0.82) and 12 mo (area under the receiver operating characteristic curve = 0.83). A D-R matching system was proposed on the basis of the current model of end-stage liver disease score and cDCD-NRP risk score.

The satisfactory performance of the proposed score within the study population suggests a significant potential to support liver allocation in cDCD-NRP grafts. External validation is challenging, but this methodology may be explored in other regions.

The long-term survival of liver transplant (LT) recipients is essential for optimizing organ allocation and estimating mortality outcomes. While models like the Model-for-End-Stage-Liver-Disease (MELD) predict 90-day mortality on the waiting list, they do not predict post-LT survival accurately. There is a need for predictive models that can forecast post-LT survival beyond the immediate period after transplantation.

This study introduces new temporal variation features for predicting post-LT survival during the waiting list period. Cox Proportional-Hazards regression (CoxPH), Random Survival Forest (RSF), and Extreme Gradient Boosting (XGB) models are utilized, along with patient demographics and waiting list duration. Data from 716 LT patients from the University of Minnesota CTSI (2011-2021) are used to develop, evaluate, and compare post-LT survival prediction models.

The temporal variation features, particularly when combined with the RSF model, proved most effective in predicting post-LT survival, with a C-index of 0.71 and an IBS of 0.151. This outperformed the predictive capability of the most recent MELD score, which had a C-index of <0.51 in the same cohort.

Incorporating temporal variation features with the RSF model enhances long-term post-LT survival predictions. These insights can assist clinicians and patients in making more informed decisions about organ allocation and understanding the utility of LT, ultimately leading to improved patient outcomes.

Posttransplantation complications pose a major challenge to the long-term survival and quality of life of organ transplant recipients. These complications encompass immune-mediated complications, infectious complications, metabolic complications, and malignancies, with each type influenced by various risk factors and pathological mechanisms. The molecular mechanisms underlying posttransplantation complications involve a complex interplay of immunological, metabolic, and oncogenic processes, including innate and adaptive immune activation, immunosuppressant side effects, and viral reactivation. Here, we provide a comprehensive overview of the clinical features, risk factors, and molecular mechanisms of major posttransplantation complications. We systematically summarize the current understanding of the immunological basis of allograft rejection and graft-versus-host disease, the metabolic dysregulation associated with immunosuppressive agents, and the role of oncogenic viruses in posttransplantation malignancies. Furthermore, we discuss potential prevention and intervention strategies based on these mechanistic insights, highlighting the importance of optimizing immunosuppressive regimens, enhancing infection prophylaxis, and implementing targeted therapies. We also emphasize the need for future research to develop individualized complication control strategies under the guidance of precision medicine, ultimately improving the prognosis and quality of life of transplant recipients.

The application of machine learning (ML) algorithms in various fields of hepatology is an issue of interest. However, we must be cautious with the results. In this letter, based on a published ML prediction model for acute kidney injury after liver surgery, we discuss some limitations of ML models and how they may be addressed in the future. Although the future faces significant challenges, it also holds a great potential.

Primary graft dysfunction (PGD) is the leading cause of morbidity and mortality in the first 30 days after lung transplantation. Risk factors for the development of PGD include donor and recipient characteristics, but how multiple variables interact to impact the development of PGD and how clinicians should consider these in making decisions about donor acceptance remain unclear. This was a single-center retrospective cohort study to develop and evaluate machine learning pipelines to predict the development of PGD grade 3 within the first 72 hours of transplantation using donor and recipient variables that are known at the time of donor offer acceptance. Among 576 bilateral lung recipients, 173 (30%) developed PGD grade 3. The cohort underwent a 75% to 25% train-test split, and lasso regression was used to identify 11 variables for model development. A K-nearest neighbor's model showing the best calibration and performance with relatively small confidence intervals was selected as the final predictive model with an area under the receiver operating characteristics curve of 0.65. Machine learning models can predict the risk for development of PGD grade 3 based on data available at the time of donor offer acceptance. This may improve donor-recipient matching and donor utilization in the future.

The core idea behind precision medicine is to pinpoint the subpopulations that differ from one another in terms of disease risk, drug responsiveness, and treatment outcomes due to differences in biology and other traits. Biomarkers are found through genomic sequencing. Multi-dimensional clinical and biological data are created using these biomarkers. Better analytic methods are needed for these multidimensional data, which can be accomplished by using artificial intelligence (AI). An updated review of 80 latest original publications is presented on four main fronts-preventive medicine, medication development, treatment outcomes, and diagnostic medicine-All these studies effectively illustrated the significance of AI in precision medicine. Artificial intelligence (AI) has revolutionized precision medicine by swiftly analyzing vast amounts of data to provide tailored treatments and predictive diagnostics. Through machine learning algorithms and high-resolution imaging, AI assists in precise diagnoses and early disease detection. AI's ability to decode complex biological factors aids in identifying novel therapeutic targets, allowing personalized interventions and optimizing treatment outcomes. Furthermore, AI accelerates drug discovery by navigating chemical structures and predicting drug-target interactions, expediting the development of life-saving medications. With its unrivaled capacity to comprehend and interpret data, AI stands as an invaluable tool in the pursuit of enhanced patient care and improved health outcomes. It's evident that AI can open a new horizon for precision medicine by translating complex data into actionable information. To get better results in this regard and to fully exploit the great potential of AI, further research is required on this pressing subject.

There is an unmet need for optimizing hepatic allograft allocation from nondirected living liver donors (ND-LLD).

Using OPTN living donor liver transplant (LDLT) data (1/1/2000-12/31/2019), we identified 6328 LDLTs (4621 right, 644 left, 1063 left-lateral grafts). Random forest survival models were constructed to predict 10-year graft survival for each of the 3 graft types.

Donor-to-recipient body surface area ratio was an important predictor in all 3 models. Other predictors in all 3 models were: malignant diagnosis, medical location at LDLT (inpatient/ICU), and moderate ascites. Biliary atresia was important in left and left-lateral graft models. Re-transplant was important in right graft models. C-index for 10-year graft survival predictions for the 3 models were: 0.70 (left-lateral); 0.63 (left); 0.61 (right). Similar C-indices were found for 1-, 3-, and 5-year graft survivals. Comparison of model predictions to actual 10-year graft survivals demonstrated that the predicted upper quartile survival group in each model had significantly better actual 10-year graft survival compared to the lower quartiles (p<0.005).

When applied in clinical context, our models assist with the identification and stratification of potential recipients for hepatic grafts from ND-LLD based on predicted graft survivals, while accounting for complex donor-recipient interactions. These analyses highlight the unmet need for granular data collection and machine learning modeling to identify potential recipients who have the best predicted transplant outcomes with ND-LLD grafts.

Many countries curate national registries of liver transplant (LT) data. These registries are often used to generate predictive models; however, potential performance and transferability of these models remain unclear. We used data from 3 national registries and developed machine learning algorithm (MLA)-based models to predict 90-day post-LT mortality within and across countries. Predictive performance and external validity of each model were assessed. Prospectively collected data of adult patients (aged ≥18 years) who underwent primary LTs between January 2008 and December 2018 from the Canadian Organ Replacement Registry (Canada), National Health Service Blood and Transplantation (United Kingdom), and United Network for Organ Sharing (United States) were used to develop MLA models to predict 90-day post-LT mortality. Models were developed using each registry individually (based on variables inherent to the individual databases) and using all 3 registries combined (variables in common between the registries [harmonized]). The model performance was evaluated using area under the receiver operating characteristic (AUROC) curve. The number of patients included was as follows: Canada, n = 1214; the United Kingdom, n = 5287; and the United States, n = 59,558. The best performing MLA-based model was ridge regression across both individual registries and harmonized data sets. Model performance diminished from individualized to the harmonized registries, especially in Canada (individualized ridge: AUROC, 0.74; range, 0.73-0.74; harmonized: AUROC, 0.68; range, 0.50-0.73) and US (individualized ridge: AUROC, 0.71; range, 0.70-0.71; harmonized: AUROC, 0.66; range, 0.66-0.66) data sets. External model performance across countries was poor overall. MLA-based models yield a fair discriminatory potential when used within individual databases. However, the external validity of these models is poor when applied across countries. Standardization of registry-based variables could facilitate the added value of MLA-based models in informing decision making in future LTs.

Accurate prediction of the mortality of post-liver transplantation is an important but challenging task. It relates to optimizing organ allocation and estimating the risk of possible dysfunction. Existing risk scoring models, such as the Balance of Risk (BAR) score and the Survival Outcomes Following Liver Transplantation (SOFT) score, do not predict the mortality of post-liver transplantation with sufficient accuracy. In this study, we evaluate the performance of machine learning models and establish an explainable machine learning model for predicting mortality in liver transplant recipients.

The optimal feature set for the prediction of the mortality was selected by a wrapper method based on binary particle swarm optimization (BPSO). With the selected optimal feature set, seven machine learning models were applied to predict mortality over different time windows. The best-performing model was used to predict mortality through a comprehensive comparison and evaluation. An interpretable approach based on machine learning and SHapley Additive exPlanations (SHAP) is used to explicitly explain the model's decision and make new discoveries.

With regard to predictive power, our results demonstrated that the feature set selected by BPSO outperformed both the feature set in the existing risk score model (BAR score, SOFT score) and the feature set processed by principal component analysis (PCA). The best-performing model, extreme gradient boosting (XGBoost), was found to improve the Area Under a Curve (AUC) values for mortality prediction by 6.7%, 11.6%, and 17.4% at 3 months, 3 years, and 10 years, respectively, compared to the SOFT score. The main predictors of mortality and their impact were discussed for different age groups and different follow-up periods.

Our analysis demonstrates that XGBoost can be an ideal method to assess the mortality risk in liver transplantation. In combination with the SHAP approach, the proposed framework provides a more intuitive and comprehensive interpretation of the predictive model, thereby allowing the clinician to better understand the decision-making process of the model and the impact of factors associated with mortality risk in liver transplantation.

Liver transplantation outcomes have improved in recent years. However, with the emergence of expanded donor criteria, tools to better assist donor-recipient matching have become necessary. Most of the currently proposed scores based on conventional biostatistics are not good classifiers of a problem that is considered "unbalanced." In recent years, the implementation of artificial intelligence in medicine has experienced exponential growth. Deep learning, a branch of artificial intelligence, may be the answer to this classification problem. The ability to handle a large number of variables with speed, objectivity, and multi-objective analysis is one of its advantages. Artificial neural networks and random forests have been the most widely used deep classifiers in this field. This review aims to give a brief overview of D-R matching and its evolution in recent years and how artificial intelligence may be able to provide a solution.

Decision-making based on artificial intelligence (AI) methodology is increasingly present in all areas of modern medicine. In recent years, models based on deep-learning have begun to be used in organ transplantation. Taking into account the huge number of factors and variables involved in donor-recipient (D-R) matching, AI models may be well suited to improve organ allocation. AI-based models should provide two solutions: complement decision-making with current metrics based on logistic regression and improve their predictability. Hundreds of classifiers could be used to address this problem. However, not all of them are really useful for D-R pairing. Basically, in the decision to assign a given donor to a candidate in waiting list, a multitude of variables are handled, including donor, recipient, logistic and perioperative variables. Of these last two, some of them can be inferred indirectly from the team's previous experience. Two groups of AI models have been used in the D-R matching: artificial neural networks (ANN) and random forest (RF). The former mimics the functional architecture of neurons, with input layers and output layers. The algorithms can be uni- or multi-objective. In general, ANNs can be used with large databases, where their generalizability is improved. However, they are models that are very sensitive to the quality of the databases and, in essence, they are black-box models in which all variables are important. Unfortunately, these models do not allow to know safely the weight of each variable. On the other hand, RF builds decision trees and works well with small cohorts. In addition, they can select top variables as with logistic regression. However, they are not useful with large databases, due to the extreme number of decision trees that they would generate, making them impractical. Both ANN and RF allow a successful donor allocation in over 80% of D-R pairing, a number much higher than that obtained with the best statistical metrics such as model for end-stage liver disease, balance of risk score, and survival outcomes following liver transplantation scores. Many barriers need to be overcome before these deep-learning-based models can be included for D-R matching. The main one of them is the resistance of the clinicians to leave their own decision to autonomous computational models.

Introduction: Liver transplantation (LT) is burdened by the risk of post-operative morbidity. Identifying patients at higher risk of developing complications can help allocate resources in the perioperative phase. Controlling Nutritional Status (CONUT) score, based on lymphocyte count, serum albumin, and cholesterol levels, has been applied to various surgical specialties, proving reliable in predicting complications and prognosis. Our study aims to investigate the role of the CONUT score in predicting the development of early complications (within 90 days) after LT. Methods: This is a retrospective analysis of 209 patients with a calculable CONUT score within 2 months before LT. The ability of the CONUT score to predict severe complications, defined as a Comprehensive Complication Index (CCI) ≥42.1, was examined. Inverse Probability Treatment Weighting was used to balance the study population against potential confounders. Results: Patients with a CCI ≥42.1 had higher CONUT score values (median: 7 vs. 5, P-value < 0.0001). The CONUT score showed a good diagnostic ability regarding post-LT morbidity, with an AUC = 0.72 (95.0%CI = 0.64-0.79; P-value < 0.0001). The CONUT score was the only independent risk factor identified for a complicated post-LT course, with an odds ratio = 1.39 (P-value < 0.0001). The 90-day survival rate was 98.8% and 87.5% for patients with a CONUT score <8 and ≥8, respectively. Conclusions: Pre-operative CONUT score is a helpful tool to identify patients at increased post-LT morbidity risk. Further refinements in the score composition, specific to the LT population, could be obtained with prospective studies.