ORIGINAL RESEARCH article
Front. Immunol.
Sec. Alloimmunity and Transplantation
This article is part of the Research TopicLiver Transplantation in the Era of Immunotherapy: exploring infection, immune response and management strategiesView all 5 articles
A Pre-emptive Risk Model for Acute Rejection in Liver Transplantation: An Immunopharmacologic Biomarker Panel Combining CD4+ T-Cell Profiling and Tacrolimus Exposure
Provisionally accepted
- 1Department of Hepatobiliary and Pancreaticosplenic Surgery, Beijing Chaoyang Hospital, Beijing, China
- 2Cancer Hospital Chinese Academy of Medical Sciences, Beijing, China
- 3China-Japan Friendship Hospital, Beijing, China
- 4Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
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Introduction: Acute cellular rejection (ACR) is a T cell-driven event in liver transplantation. Current monitoring relies on detecting graft injury, lacking tools for pre-emptive risk assessment based on the patient's real-time immune status. Methods: We developed an immunopharmacologic risk model in a retrospective cohort of 98 liver transplant recipients (18 with biopsy-proven ACR). The model integrated peripheral CD4+ T-cell percentage (flow cytometry) and tacrolimus trough level. Firth-penalized logistic regression was used for model development, with internal validation via bootstrapping. Results: The parsimonious model, comprising only CD4+ T-cell percentage and tacrolimus level, demonstrated good discrimination (AUC 0.774, 95% CI 0.674-0.874) and calibration. Critically, lead-time analysis revealed the model provided a median warning window of 8 days (IQR: 3.5 days) prior to biochemical injury onset. It offered significant incremental value over monitoring tacrolimus alone (AUC 0.774 vs. 0.694, ΔAUC=0.080, p=0.007) or CD4+ T cells alone (AUC 0.774 vs. 0.733, ΔAUC=0.041, p=0.014). Conclusion: We identify and validate a novel, clinically actionable immunopharmacologic biomarker panel for ACR. This model enables pre-emptive risk stratification by capturing the high-risk confluence of immune activation and subtherapeutic immunosuppression, paving the way for personalized immunotherapy in transplant recipients.
Keywords: acute rejection, Liver Transplantation, personalized medicine, predictivemodel, Tacrolimus, Therapeutic drug monitoring
Received: 04 Dec 2025; Accepted: 09 Feb 2026.
Copyright: © 2026 Li, Zhang, Li, 李, He, Han and Zhu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Ji-Qiao Zhu
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