Cited by 37Organ Transplantation Techniques and OutcomesTransplantation: Methods and OutcomesHepatocellular Carcinoma Treatment and Prognosis

Identifying Modifiable Predictors of Long‐Term Survival in Liver Transplant Recipients with Diabetes Mellitus Using Machine Learning

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Yasodhara, Angeline, Dong, Victor, Azhie, Amirhossein, Goldenberg, Anna, Bhat, Mamatha·2021·Liver Transplantation

Abstract

Diabetes mellitus (DM) significantly impacts long-term survival after liver transplantation (LT). We identified survival factors for LT recipients who had DM to inform preventive care using machine-learning analysis. We analyzed risk factors for mortality in patients from across the United States using the Scientific Registry of Transplant Recipients (SRTR). Patients had undergone LT from 1987 to 2019, with a follow-up of 6.47 years (standard deviation [SD] 5.95). Findings were validated on a cohort from the University Health Network (UHN) from 1989 to 2014 (follow-up 8.15 years [SD 5.67]). Analysis was conducted with Cox proportional hazards and gradient boosting survival. The training set included 84.67% SRTR data (n = 15,289 patients), and the test set included 15.33% SRTR patients (n = 2769) and data from UHN patients (n = 1290). We included 18,058 adults (12,108 [67.05%] men, average age 54.21 years [SD 9.98]) from the SRTR who had undergone LT and had complete data for investigated features. A total of 4634 patients had preexisting DM, and 3158 had post-LT DM. The UHN data consisted of 1290 LT recipients (910 [70.5%] men, average age 54.0 years [SD 10.4]). Increased serum creatinine and hypertension significantly impacted mortality with preexisting DM 1.36 (95% confidence interval [CI], 1.21-1.54) and 1.20 (95% CI, 1.06-1.35) times, respectively. Sirolimus use increased mortality 1.36 times (95% CI, 1.18-1.58) in nondiabetics and 1.33 times (95% CI, 1.09-1.63) in patients with preexisting DM. A similar effect was found in post-LT DM, although it was not statistically significant (1.38 times; 95% CI, 1.07-1.77; P = 0.07). Survival predictors generally achieved a 0.60 to 0.70 area under the receiver operating characteristic for 5-year mortality. LT recipients who have DM have a higher mortality risk than those without DM. Hypertension, decreased renal function, and sirolimus for maintenance immunosuppression compound this mortality risk. These predisposing factors must be intensively treated and modified to optimize long-term survival after transplant.

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  1. [15]Wiesner R. The safety and efficacy of sirolimus and low‐dose tacrolimus versus tacrolimus in de novo orthotopic liver transplant recipients: results from a pilot study. Hepatology 2002; 36: 208A.
  2. [31]Chen T, Guestrin C. XGBoost: a scalable tree boosting system. Proceedings of the 22nd ACM SIGKDD International Conference on Knowledge Discovery and Data Mining, Association for Computing Machinery, San Francisco, CA; 2016: 785‐ 794.
  3. [32]Bergstra J, Yamins D, Cox DD. Making a science of model search: Hyperparameter optimization in hundreds of dimensions for vision architectures. ICML '13: Proceedings of the 30th International Conference on International Conference on Machine Learning 28. Atlanta, GA, USA: JMLR; 2013: I‐115– I‐123. https://dl.acm.org/doi/10.5555/3042817.3042832. · DOI

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Authors
Yasodhara, A., Dong, V., Azhie, A., Goldenberg, A., & Bhat, M.
Affiliations
  • University of Toronto (CA)
  • Interdepartmental Division of Critical Care Medicine,Toronto,Ontario,Canada
  • University Health Network (CA)
Corresponding author
  • Goldenberg, Anna
  • Bhat, Mamatha
Venue
Liver Transplantation
Published
2021-02-02
Volume
27
Issue
4
Pages
536-547
ISSN
  • 1527-6465 (ISSN-L)
  • 1527-6473
OpenAlex
W3096756677
Cited by
37
References
29
Citations by year
2026: 3 · 2025: 11 · 2024: 8 · 2023: 8 · 2022: 2 · 2021: 5
FWCI
3.43
Type
journal article
Language
en
Open access
Locations
  • Liver Transplantation (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
Funders
Canadian Institute for Advanced Research
Topics
  • Health Sciences › Medicine › Surgery › Organ Transplantation Techniques and Outcomes
  • Health Sciences › Medicine › Surgery › Transplantation: Methods and Outcomes
  • Health Sciences › Medicine › Hepatology › Hepatocellular Carcinoma Treatment and Prognosis
Keywords
diabetes mellitus, post-transplant diabetes mellitus, long-term survival, mortality risk factors, rapamycin, serum creatinine, hypertension, pregestational diabetes, machine learning prediction, Scientific Registry of Transplant Recipients, Cox proportional hazards model, transplant recipients, preventive medicine, immunosuppression, post-transplant complications
MeSH terms
Machine Learning, Adult, Diabetes Mellitus, Humans, Male, Middle Aged, Retrospective Studies, Risk Factors, United States, Liver Transplantation, Transplant Recipients

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