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Advances and challenges in the application of donor-derived cell-free DNA for diagnosis and treatment in liver transplantation: a narrative review

BMC Surgery volume 25, Article number: 203 (2025) Cite this article

Abstract

In the field of liver disease treatment, liver transplantation (LT) has become an effective option for end-stage liver disease. However, issues such as immune rejection and graft damage remain important factors influencing the success rate of liver transplantation and patients' quality of life. In recent years, with the advancement of genetic testing technologies, the study and application of donor-derived cell-free DNA (dd-cfDNA) in LT diagnosis and treatment have gradually gained attention. This review explores the research advancements in dd-cfDNA within liver transplant management, evaluating its potential applications throughout the liver transplantation process, while exploring the challenges faced by current studies and outlining future research directions. As a strategic tool for postoperative monitoring in LT, dd-cfDNA shows promising potential in areas such as immune rejection, graft damage, immunosuppressant adjustment, complication monitoring, and personalized treatment, and is poised to become a reliable biomarker in LT management.

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Introduction

With continuous advancements in medical technology, liver transplantation has become the ultimate treatment for end-stage liver disease [1]. However, ischemia–reperfusion injury (IRI), immune rejection, infections, and postoperative complications remain important factors that influence patient outcomes after liver transplantation. In recent years, an increasing number of studies have focused on the use of donor-derived cell-free DNA (dd-cfDNA) as a non-invasive biomarker for monitoring post-transplant immune status and predicting rejection [2,3,4,5]. This paper reviews the research progress and clinical applications of dd-cfDNA in liver transplantation and discusses future research directions and challenges.

In the field of organ transplantation, especially liver transplantation, the progress of research on dd-cfDNA has attracted widespread attention. This DNA fragment, derived from necrotic or apoptotic donor tissue, can be accurately detected and quantified through next-generation sequencing (NGS) and other technologies, providing a non-invasive and sensitive method for clinical monitoring of allograft injury. Firstly, the application of dd-cfDNA detection, especially in kidney transplantation, has been fully demonstrated [6]. By detecting the concentration and absolute quantification of dd-cfDNA in circulating body fluids, signs of graft injury can be detected weeks to months in advance, providing a valuable"time window"for clinical treatment and delaying the loss of graft function. In pancreas-kidney combined transplantation [7], dd-cfDNA also shows its ability to predict acute rejection reactions early, providing a simple and non-invasive method for precise postoperative rejection monitoring. Therefore, dd-cfDNA is expected to become a non-invasive dynamic indicator for detecting graft injury or acute rejection (AR) after organ transplantation. Although the application prospect of dd-cfDNA in organ transplantation is broad, its research in liver transplantation is still in its infancy and faces many difficulties that need to be overcome. This article aims to discuss the research progress of dd-cfDNA in the diagnosis and treatment of liver transplantation and its clinical application.

Biological basis of cell-free DNA

Cell-free DNA (cfDNA) is a marker of cell death [8], and therefore it may be released from necrotic or apoptotic cells in the transplanted organ or from donor-derived hematopoietic cells in the recipient's blood or other organs. Other causes of transplant organ tissue injury can also result in the release of cfDNA into the plasma. For example, infections affecting the graft, such as cytomegalovirus, biliary and vascular complications, and tumor involvement of the transplanted organ [9]. Dd-cfDNA only accounts for a small part of the total cfDNA (recipient + donor origin), and studies on sex-mismatched bone marrow and solid organ transplants have shown that cfDNA in the plasma mainly comes from hematopoietic cells, with non-hematopoietic cell sources accounting for only a small proportion [10]. During LT, the sources of dd-cfDNA mainly include the death of donor liver cells, immune reactions after transplantation, and physiological or pathological changes in the recipient's liver [11]. Especially during AR, ischemia–reperfusion injury (IRI), and early graft dysfunction after liver transplantation, the concentration of dd-cfDNA will significantly increase, providing a theoretical basis for its potential application in liver transplantation.

In 1948, Mandel and Metais first discovered the existence of cfDNA and its release during cell apoptosis or necrosis due to damage [12, 13]. The length of cfDNA segments in the plasma of healthy volunteers is 185 ~ 200 base pairs, while the length of cfDNA segments released by tumor cells exists in the form of nucleoprotein complexes and has higher variability [14]. A study on cfDNA fragment size in monitoring graft injury during living-related LT for inborn errors of metabolism found that the ratio of short to long fragments can reflect the early trend of graft injury [15]. When a large amount of short single-stranded cfDNA (160 ~ 200 base pairs) was injected into mice, it was found that despite its low concentration in the blood, it could still be detected in the glomeruli after 24 h. In contrast, when larger cfDNA fragments (2000 ~ 6000 base pairs) were injected, no cfDNA was observed in the glomeruli. This result indicates that cfDNA in the plasma may be captured in the glomeruli through an unknown mechanism based on its fragment size [16]. The clearance mechanism of cfDNA in the plasma is still unclear. Studies have shown that the liver plays an important role in the clearance of cfDNA, and the reticuloendothelial system may be involved in this process. In addition, the presence of plasma-derived cfDNA in urine suggests that the kidney may also be involved in the clearance of cfDNA. A study on the clearance of fetal cfDNA in the maternal circulation showed that only 0.2% to 19% of fetal cfDNA was cleared through the maternal kidney [17]. This finding indicates that kidney excretion plays a secondary role in the clearance of cfDNA.

Research progress of dd-cfDNA in liver transplantation

Detection techniques of dd-cfDNA

Although the extraction of cfDNA has been standardized in research, the methods used to determine its donor origin remain diverse. Studies have identified that the most straightforward approach involves detecting the sex-determining region Y (SRY) gene or the testis-specific protein Y (TSPY) gene, both of which are located in the repetitive regions of the Y chromosome [18,19,20,21,22,23]. This method is particularly effective in female recipients, as these genes are absent in their genome. The detection process is relatively simple and does not require donor genetic material for comparison, making it a convenient option. However, this approach is limited in its ability to quantify dd-cfDNA and is applicable only to a small subset of transplant recipients, thus restricting its broader application. Additionally, similar techniques can be utilized for analyzing Rh gene mismatches in cases where the donor and recipient have differing Rh genotypes [24].

Currently, in the field of organ transplantation, the most commonly employed methods for detecting dd-cfDNA include real-time quantitative polymerase chain reaction (qPCR), droplet digital PCR (dd-PCR), and NGS [25, 26]. Each of these techniques has unique features, offering effective tools for the quantification and analysis of dd-cfDNA (Table 1). The quantification of dd-cfDNA is typically based on genetic markers, such as single nucleotide polymorphisms (SNPs), which enable differentiation between donor and recipient alleles [27]. As a result, the assessment of dd-cfDNA levels can be performed without the need for prior genetic typing of both the donor and recipient. Clinical detection methods are primarily categorized into random[23, 28]and targeted approaches [29,30,31]. The random approach typically utilizes adapter ligation technology in combination with NGS, while the targeted method employs dd-PCR[29]or focuses on pre-selected SNPs within targeted NGS panels [30, 31]. It is important to note that amplification efficiency can be influenced by factors such as the size of the amplicon and the length of cfDNA fragments [26, 32, 33]. Despite these advances, there is currently no standardized protocol for detecting organ transplantation-specific targeted SNPs, and most studies rely on commercially available detection systems, including AlloSure, Prospera, and TRAC, among others [34]. In recent years, a novel approach for human leukocyte antigen (HLA)-based dd-cfDNA detection has emerged, which capitalizes on the incompatibility of the HLA-DRB1 locus between donors and recipients. This method has been optimized using dd-PCR [35]. While these techniques are capable of providing fractional measurements (e.g., % dd-cfDNA), it is worth emphasizing that absolute quantification remains unaffected by variations in recipient cfDNA, such as those induced by infections, and has been validated exclusively for dd-PCR-based methods [6, 36].

Table 1 The dd-cfDNA assay and its application in liver transplantation
Full size table

Changes in dd-cfDNA concentration during the perioperative period of LT

In liver transplant recipients, levels of dd-cfDNA in plasma increase dramatically immediately following transplantation [9, 44], accounting for up to 90% of the total free DNA present. This proportion decreases rapidly over time, with a half-life ranging from 24 to 48 h, and typically falls below 15% by the 10 th day post-surgery. However, in cases of immune rejection, the proportion of dd-cfDNA on day 10 remains elevated, around 20%, and gradually increases to 55% to 60%. Following reperfusion of the transplanted liver, elevated levels of dd-cfDNA were detected in the recipient's serum. In the absence of postoperative complications, these levels return to baseline within a few days [30, 45]. Similar trends have been observed in kidney transplant recipients, where dd-cfDNA concentrations increase immediately after transplantation but decline rapidly within the first week post-surgery [36, 46]. Studies by Zhang et al. [22, 23] have demonstrated that, in recipients with stable graft function, the plasma concentrations of dd-cfDNA are 0.9% in heart transplant recipients, 1.2% in kidney transplant recipients, and 3.5% in liver transplant recipients. These differences may be attributed to factors such as the size of the transplanted organ and the rate of cellular regeneration. Further investigations into dd-cfDNA kinetics have revealed that [39, 47], in recipients with stable graft function, the average plasma dd-cfDNA concentration ratio decreases to 0.5% ± 0.2% approximately 10 ± 6 days following transplantation. Notably, continuous monitoring of cfDNA levels during the perioperative period of living donor liver transplantation has indicated that the elevated cfDNA levels observed during surgery and the immediate postoperative phase reflect cellular trauma and inflammation associated with the transplant procedure [48].

Application of dd-cfDNA in liver transplantation

Orthotopic liver transplantation (OLT) is a critical therapeutic approach for end-stage liver diseases. However, postoperative challenges such as immune rejection, organ injury, and functional recovery continue to pose significant difficulties in clinical practice [49]. In recent years, dd-cfDNA has gained increasing attention as a non-invasive biomarker in the field of liver transplantation (Table 2). The dynamic fluctuations in dd-cfDNA levels offer valuable insights into immune responses, organ injury, and the effects of treatment, thereby providing essential support for the clinical management of liver transplant recipients [50].

Table 2 Clinical applications and significance of dd-cfDNA in liver transplantation
Full size table

Monitoring of immune rejection after transplantation

Numerous studies have explored dd-cfDNA in liver transplantation, with variations in the scale, design, detection methods, and outcomes of interest (Table 3). Nevertheless, most findings indicate that dd-cfDNA shows promise in monitoring graft health and detecting injury, especially in AR. Immune rejection is a common complication following liver transplantation, and studies have demonstrated a close association between changes in dd-cfDNA and acute rejection episodes [38, 53, 54]. Schütz et al. [5] observed that cfDNA levels in liver transplant recipients were significantly higher than those in healthy controls, with an increase in dd-cfDNA being positively correlated with the occurrence of AR. Furthermore, elevated dd-cfDNA levels can serve as an early indicator of AR [55, 56], often preceding detectable abnormalities in routine liver function tests. Subsequent research has further validated the potential of dd-cfDNA as a non-invasive tool for immune monitoring [57]. Goh et al. [58] found that persistent increases in dd-cfDNA levels were closely linked to the onset of acute immune rejection. Their study emphasized that regular dd-cfDNA monitoring allows for the timely detection of rejection, helping to prevent adverse outcomes associated with delayed diagnosis. Several studies have also tracked dd-cfDNA levels following successful treatment of acute rejection, showing that dd-cfDNA concentrations typically return to baseline levels in most cases [19, 55, 59,60,61]. However, the time required for recovery can vary. Bloom et al. highlighted that dd-cfDNA levels may remain elevated for up to one-month post-treatment and only return to baseline after two to three months, which could indicate lingering graft injury. Some studies suggest that by establishing a threshold for dd-cfDNA levels, it is possible to early differentiate between stable patients and those experiencing AR. For instance, a cutoff value of 10% dd-cfDNA threshold has been proposed to assess the stability of liver transplant recipients regarding rejection, showing good specificity and sensitivity (> 90% and > 86%, respectively) [4, 5, 45, 62]. Compared to stable patients, the dd-cfDNA percentage in liver transplant recipients with AR is approximately four times higher. The median dd-cfDNA in AR patients typically ranges from 30 to 40%, while in non-rejection cases, the median is around 11%. In addition, based on the fragment characteristics of cfDNA, the size of dd-cfDNA fragments can also aid in differentiating rejection reactions from other types of damage.

Table 3 Comparison of diagnostic performance of different dd-cfDNA thresholds for detecting liver graft injury
Full size table

Monitoring graft injury

It is important to note that increases in dd-cfDNA levels are not always indicative of AR but can also occur in response to other causes of acute graft injury [3]. Studies have shown that [51], during ischemia–reperfusion injury (IRI), a common occurrence in liver transplants, extensive cell death results in the release of large amounts of cfDNA, leading to a marked elevation in dd-cfDNA levels in the bloodstream. Thus, dd-cfDNA may serve as a potential biomarker for assessing the extent of graft injury. Furthermore, a prospective observational cohort study found that dd-cfDNA levels serve as a reliable marker of graft injury after liver transplantation, with its increase being inversely correlated with liver function recovery [63]. In other words, patients with slower liver function recovery tend to exhibit higher levels of dd-cfDNA, indicating that dd-cfDNA can function as an early biomarker of liver injury. One of the major advantages of dd-cfDNA monitoring is its ability to assess graft integrity in a non-organ- or disease-specific manner, making it applicable for detecting tissue injury in various allografts, including heart, lung, liver, and kidney [64,65,66,67]. Endothelial cells play a significant role in the early immune response, inflammatory response, and microvascular injury following transplantation [68]. A significant portion of dd-cfDNA is derived from the endothelial cells of the allogeneic graft. IRI may be the cause of high dd-cfDNA levels immediately after transplantation, likely associated with endothelial cell damage and dysfunction Long-term monitoring of dd-cfDNA concentrations can provide valuable prognostic information regarding the survival and function of liver grafts [69]. In particular, within the first 2 to 3 months post-transplantation, dynamic changes in dd-cfDNA levels can offer insights into the immune status and liver function recovery of the recipient.

Guiding individualized immunosuppressive therapy protocols

Immunosuppression (IS) plays a crucial role in preventing rejection after liver transplantation. However, the dosage and effectiveness of immunosuppressants must be precisely monitored to avoid both under- and over-suppression. Studies have shown that dynamic changes in dd-cfDNA levels are closely associated with the effectiveness of immunosuppressive treatment [70, 71]. A sustained increase in dd-cfDNA levels during immunosuppressive therapy may indicate insufficient IS [72], suggesting the need for timely adjustments in the dosage of immunosuppressive agents. Maintaining a high level of IS, particularly with calcineurin inhibitors (CNI), reduces the risk of AR but can increase the incidence of adverse effects such as infections, chronic kidney disease (CKD), malignancies, and cardiovascular diseases [73,74,75,76,77,78,79]. Therefore, continuous monitoring of dd-cfDNA levels offers a valuable tool for guiding individualized adjustments in immunosuppressive therapy post-transplant. This approach may help reduce the risk of early graft loss by ensuring optimal immunosuppression. One of the key advantages of dd-cfDNA monitoring is its ability to detect injury before clinical symptoms manifest, allowing for timely intervention in AR and other causes of graft injury, ultimately improving transplant outcomes.

As a tool for early detection of other complications

With the continuous advancement of research, dd-cfDNA has demonstrated significant potential not only as a biomarker for early detection of rejection and graft injury but also as an effective early warning system for a variety of transplant-related complications [52, 80,81,82]. Studies have increasingly shown that fluctuations in dd-cfDNA levels can serve as reliable predictors of adverse events following transplantation, including infections, hemorrhage, and other postoperative complications. Notably, during the first week after transplantation, dd-cfDNA levels may show a potential correlation with the onset of these complications [48], making it a valuable tool for early intervention before clinical symptoms become apparent. This ability to detect complications early may help clinicians in managing transplant recipients, particularly in the early postoperative period when prompt clinical responses are important. Most studies have focused on the long-term prognostic value of dd-cfDNA in kidney, lung, and heart transplantations [83]. While similar results may be expected in liver transplantation [84], further research is needed to confirm the relationship between dd-cfDNA and long-term results in LT. Changes in dd-cfDNA concentrations over time can offer insights into the survival prospects of liver transplant recipients, particularly within the first 2 to 3 months post-transplant. During this period, the dynamic fluctuations in dd-cfDNA levels are reflective of the recipient's immune status, as well as liver function recovery. Monitoring these changes can guide clinicians in assessing graft health, detecting subclinical rejection, and evaluating the effectiveness of immunosuppressive therapies. In this context, dd-cfDNA becomes an invaluable tool for assessing the progress of graft function and optimizing post-transplant management strategies. Continuous monitoring of dd-cfDNA levels has predictive value for assessing graft survival. Traditional monitoring methods, such as liver biopsy, remain the gold standard for diagnosing graft rejection and injury; however, they are invasive, carry inherent risks, and are not suitable for frequent or routine use [85, 86]. By contrast, dd-cfDNA testing only requires a routine blood sample, making it a far more accessible, non-invasive, and cost-effective alternative. Furthermore, dd-cfDNA monitoring significantly reduces patient discomfort and minimizes the risk of infection associated with more invasive methods. It also helps reduce healthcare costs, making it a more sustainable option for long-term surveillance. The ability of dd-cfDNA to sensitively detect early signs of graft injury, rejection, and other transplant-related complications enables timely intervention and more personalized treatment strategies [11, 87].

Future prospects and challenges

An expanding body of evidence suggests that dd-cfDNA may hold potential in the diagnosis and management of liver transplantation [83, 88]. Firstly, by regularly monitoring dd-cfDNA levels, early signs of IRI or immune rejection can be detected, allowing for timely intervention. Secondly, the adoption of dd-cfDNA-guided personalized immunosuppressive therapy is progressively gaining traction [71]. Adjusting the dosage and regimen of immunosuppressants according to the patient's immune status and dd-cfDNA levels can improve treatment outcomes and reduce the risk of side effects. Research results indicate [63] that dd-cfDNA levels are closely related to graft function and can serve as one of the indicators for predicting graft survival rates. Lastly, with the continuous development of technology, more in-depth research using dd-cfDNA for genetic mutation detection and epigenetic analysis is being gradually conducted [89], providing more comprehensive information for the diagnosis and treatment of liver transplantation. It should be noted that the methodologies and findings of current studies are not entirely consistent. Moreover, the clinical implementation of dd-cfDNA as a diagnostic test in liver transplantation has yet to be fully validated, limiting its widespread application at this stage.

Despite the promising potential of dd-cfDNA as a biomarker for immune rejection in liver transplantation, several challenges persist: 1) Complexity of dd-cfDNA origin [90, 91]. The cfDNA not only originates from the donor liver but may also be derived from other organs or cells in the recipient, particularly under pathological conditions. Accurately distinguishing between dd-cfDNA and recipient-derived cfDNA remains a technical challenge. In clinical practice, distinguishing whether an increase in dd-cfDNA is due to IRI or AR is of significant clinical value. For example, a study by Agbor-Enoh et al. [92] demonstrated that dd-cfDNA fragments (< 120 bp) in antibody-mediated rejection (AMR) are smaller in size compared to those in acute cellular rejection (ACR). Epigenetics may also provide valuable insights. Epigenetic marks regulate chromatin compaction, thereby influencing gene expression. The most extensively studied of these marks are DNA methylation and post-translational modifications of histones. Some studies have utilized tissue-specific methylation patterns to identify the origin of cfDNA and construct methylation profiles specific to different tissues [93, 94]. In the context of transplantation, this approach can be employed to assess the proportion of dd-cfDNA. Epigenetic regulation plays a key role in inflammation-related pathways [95]. Inflammation is associated with global DNA hypomethylation, which can be instrumental in distinguishing IRI. 2) Standardization concerns [96, 97]. The standardization and harmonization of dd-cfDNA detection techniques remain unresolved issues. Variations in methods and protocols across different laboratories may impact the consistency and reliability of results. The donor's health status can impact dd-cfDNA levels and bias the diagnosis. Research has demonstrated that maintaining consistency with a single platform is crucial when conducting dd-cfDNA testing and creating comparative data in clinical practice [98]. We believe that the broad adoption of dd-cfDNA monitoring in LT necessitates further validation through comprehensive clinical randomized controlled trials to support its implementation. It is expected that the accuracy and precision of dd-cfDNA will continue to improve as research progresses. Another important issue in the field of liver transplantation is the potential difference in dd-cfDNA levels between split liver transplantation and whole liver transplantation, as well as between first-time and multiple transplantations. This requires further study for confirmation. 3) Barriers to clinical translation. Dd-cfDNA, as a biomarker for graft injury in solid organ transplantation, requires more prospective studies to establish its clinical utility [69]. Widespread clinical adoption is also hindered by practical challenges, including cost and specialized equipment requirements. Nevertheless, with ongoing advancements in technology, the clustered regularly interspaced short palindromic repeats-associated proteins (CRISPR–Cas) system-based assay [99, 100], known for their high sensitivity, specificity, low cost, and ease of use, are emerging as promising alternatives for dd-cfDNA detection. A cohort study utilizing the CRISPR-Cas system-based to detect Mycobacterium tuberculosis cfDNA has demonstrated the feasibility of this CRISPR-Cas system -based diagnostic technology in clinical practice [101].

In recent years, the value of dd-cfDNA in early diagnosis and prediction of rejection reactions after liver transplantation, as well as its role in assessing graft injury and monitoring treatment outcomes, still requires further research and discussion, and it has not yet been widely applied in clinical practice. Additionally, how to combine dd-cfDNA with other immunological monitoring techniques and indicators to develop more reliable and precise biomarkers for optimal diagnostic and treatment strategies is also an important direction for future research. With the continuous development of liver transplantation technology, machine perfusion (MP) has gradually become an indispensable part of the liver transplantation process [102, 103]. Notably, a study by Kanou et al. [104] found that detecting cfDNA in ex vivo lung perfusion fluid can help assess the injury to the donor lung before transplantation and has a predictive role in the risk of primary graft dysfunction in lung transplantation. By leveraging the mechanical perfusion platform to move the detection of liver graft injury to the pre-transplant mechanical perfusion period, focusing on the role of dd-cfDNA in the perfusion fluid in indicating graft injury has significant clinical value. However, research on the application of dd-cfDNA in liver transplantation machine perfusion is still in the exploratory phase, and there is a lack of large-scale clinical data to support its use. Therefore, future studies should focus on further investigating the combined detection of dd-cfDNA with other biomarkers in the perfusion fluid, such as enzymes and cytokines associated with graft damage. This research direction has the potential to enhance the diagnostic value of dd-cfDNA in the liver transplantation machine perfusion process, thereby providing more precise monitoring tools for clinical practice. The dynamic monitoring of dd-cfDNA in conjunction with MP technology can provide important information for assessing cold ischemic injury to liver grafts, optimizing perfusion schemes, and improving transplant success rates. It is expected to become a standardized monitoring tool in the mechanical perfusion process of liver transplantation, further advancing liver transplantation technology and improving patient prognosis and quality of life.

Conclusion

In conclusion, dd-cfDNA has emerged as a promising non-invasive biomarker with significant biological relevance in the context of allogeneic liver transplantation. Beyond its established role in monitoring immune rejection and graft injury, dd-cfDNA offers valuable potential for evaluating the efficacy of immunosuppressive therapies, detecting early signs of complications, and supporting personalized treatment strategies. The clinical application of dd-cfDNA faces several challenges, including its complex origin, standardizing detection methods, and its clinical translation. Establishing critical thresholds for dd-cfDNA, analyzing dd-cfDNA fragment sizes, and incorporating epigenetic approaches may help address these challenges. A CRISPR-Cas-based detection technology may also offer potential solutions to these challenges in the future. Moreover, MP not only improves the quality of donor livers but also provides an early"Window"for detecting graft injury by shifting the monitoring of graft damage to the perfusion phase. This approach focuses on biomarkers in the perfusion fluid, with dd-cfDNA being a promising candidate. Although dd-cfDNA has shown promising potential as a biomarker in the field of liver transplantation, further research is needed to fully realize its clinical application value.

Data availability

No datasets were generated or analysed during the current study.

Abbreviations

LT:

Liver transplantation

DNA:

Deoxyribonucleic acid

Dd-cfDNA:

Donor-derived cell-free DNA

NGS:

Next-generation sequencing

AR:

Acute rejection

IRI:

Ischemia-reperfusion injury

SRY:

Sex-determining region Y

TSPY:

Testis-specific protein Y

DNA:

Deoxyribonucleic acid

RNA:

Ribonucleic acid

PCR:

Polymerase chain reaction

qPCR:

Quantitative polymerase chain reaction

dd-PCR:

Droplet digital PCR

SNPs:

Single nucleotide polymorphisms

HLA:

Human leukocyte antigen

OLT:

Orthotopic liver transplantation

IS:

Immunosuppression

CNI:

Calcineurin inhibitors

CKD:

Chronic kidney disease

CRISPR-Cas:

Clustered regularly interspaced short palindromic repeats-associated proteins

MP:

Machine perfusion

ALT:

Alanine Aminotransferase

AST:

Aspartate Aminotransferase

ACR:

Acute cellular rejection

AMR:

Antibody-mediated rejection

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Funding

This review was supported by the Spring City Plan: the High-level Talent Promotion and Training Project of Kunming (2022SCP002), Research Unit Project of Chinese Academy of Medical Sciences (2019-I2M-5-030), National Natural Science Foundation of China (81721091), National S&T Major Project (No. 2017ZX10203205). The funder did not participate in the designing, performing or reporting in the current study.

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Authors and Affiliations

  1. Zhejiang Chinese Medical University, Hangzhou, 310053, China

    Yiwu Zhong & Xu Hu

  2. Key Laboratory of Artificial Organs and Computational Medicine in Zhejiang Province, Shulan International Medical College, Zhejiang Shuren University, Hangzhou, Zhejiang, China

    Xiaoping Li & Jianhui Li

  3. NHC Key Laboratory of Combined Multi-Organ Transplantation, Hangzhou, 310003, China

    Yinbiao Qiao, Haoyu Li, Shijie Zhou, Shusen Zheng & Jianhui Li

  4. Department of Hepatobiliary and Pancreatic Surgery, Key Laboratory of Artificial Organs and Computational Medicine of Zhejiang Province, Shulan (Hangzhou) Hospital, Shulan International Medical College, Zhejiang Shuren University, Hangzhou, 310022, China

    Shusen Zheng & Jianhui Li

  5. The Organ Repair and Regeneration Medicine Institute of Hangzhou, Hangzhou, 310003, China

    Jianhui Li

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Yiwu Zhong and Xiaoping Li: Framework construction, article writing, project administration, and literature collection. Yinbiao Qiao and Haoyu Li: Review & editing. Xu Hu and Shijie Zhou: Literature search and framework construction. Shusen Zheng and Jianhui Li: Review & editing, resource, funding.

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Zhong, Y., Hu, X., Li, X. et al. Advances and challenges in the application of donor-derived cell-free DNA for diagnosis and treatment in liver transplantation: a narrative review. BMC Surg 25, 203 (2025). https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s12893-025-02911-y

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BMC Surgery

ISSN: 1471-2482

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