Liver transplantation is a critical procedure for patients with end-stage liver disease, offering the potential for an improved quality of life and an increased lifespan [1]. However, the transplantation process is complex and challenging, with finding a suitable donor often posing a major challenge. One of the challenges in liver transplantation is ABO-incompatibility between the donor and recipient, which can lead to immediate humoral rejection [2]. Recent advances and strategies have been developed to overcome ABO-incompatible liver transplantation, making it more feasible in certain situations [3,4].

ABO-incompatibility arises when the donor's and recipient's blood types differ, leading the recipient's immune system to identify the donor's blood as foreign and initiate an immune response [4]. This can result in early and immediate humoral rejection, which can be life-threatening [4]. To reduce the risk of rejection, pretransplant desensitization procedures are often employed to diminish the recipient's immune reaction to the donor's blood type. Therefore, despite the potential for rejection, there have been successful instances of ABO-incompatible liver transplantation [4]. In certain cases, recipients have developed immune tolerance to the donor's blood type, enabling successful transplantation without the need for desensitization [4]. The underlying mechanisms of immune tolerance in these instances remain elusive, necessitating further research to improve our understanding of this phenomenon.

In this case report, we present a 10-month-old patient with blood type O who underwent an accidental ABO-incompatible partial liver transplant from a type A mother. Despite not undergoing pretransplant desensitization, the patient has not exhibited early or immediate humoral rejection to date. Furthermore, the patient has shown no signs of graft rejection, even though immunosuppressive medication was omitted due to nonadherence to the prescribed therapeutic regimen.

This study was conducted in compliance with the principles of the Declaration of Helsinki. This study was approved by the Institutional Review Board of Chonnam National University Hospital (IRB No. BTMP-2023-460). The requirement for informed consent was waived because this study was conducted through a retrospective review of medical records.

A 10-month-old patient with blood type O underwent a partial liver transplant from a type A mother. The patient had previously undergone a Kasai procedure 7 months before liver transplantation; however, biliary cirrhosis continued to progress, necessitating a living donor liver transplantation. Despite pretransplant blood typing, communication errors within the transplant team led to the mismatched transplant being performed without pretransplant desensitization. Remarkably, no early or immediate humoral rejection was observed during the postoperative period. At the time of transplantation, the patient's isoagglutinin A and B levels were below 1:8. Even without pretransplant desensitization, the patient has been regularly attending outpatient clinic visits. However, her adherence to the medication regimen, particularly with immunosuppressive agents, has waned over time. Currently, she is not taking her prescribed immunosuppressants, yet she has not experienced any acute or chronic rejection episodes to date. Fig. 1 presents recent computed tomography (CT) images taken 21 years after the ABO-incompatible pediatric liver transplantation. The images show evidence of a successful liver transplant, with good patency of the hepatic artery, portal vein, and hepatic vein, and no signs of biliary dilatation. Additionally, splenomegaly and perisplenic varices are present, findings that are consistent with those from a CT scan conducted 18 years posttransplantation. The patient's platelet count has been on a gradual decline, with the most recent test showing a count of 101,000/µL.

Figure 1. Computed tomography images at 21 years after transplantation. (A) Coronal view: patent hepatic artery and portal vein flow with splenomegaly and perisplenic varices. (B) Axial view: patent portal flow and hepatic vein flow without bile duct dilatation.

This case report highlights the achievement of two distinct types of tolerance, demonstrating both operational tolerance and blood group antigen immune tolerance. Tolerance related to blood type has garnered significant interest in the field of transplantation research. Numerous case reports and studies have documented instances of accidental ABO-incompatible solid organ transplants. However, it is important to note that such cases have not been reported in liver transplantation [5-7]. An accidental ABO-incompatible organ transplant occurs when the procedure is performed without awareness of the donor and recipient having incompatible blood types as defined by the ABO blood group system. While the majority of these patients experienced hyperacute or acute rejection, leading to poor outcomes, some have survived due to interventions such as plasmapheresis. The mechanisms underlying blood group antigen immune tolerance are not fully understood. It is speculated that the recipient's immune system may absorb and become tolerant to the donor's blood group antigens [8]. In the study by Pan et al. [9], two models of tolerance are proposed: the passive model, which is based on the immaturity of the neonatal immune system and its involvement in clonal deletion within the thymus, and the active model, which focuses on the interactions within the immune network and the critical role of regulatory T cells.

Operational tolerance refers to the stable graft function in transplant recipients without the need for ongoing immunosuppressive therapy [10,11]. This phenomenon has been observed in pediatric liver transplant recipients [12,13]. The mechanisms underlying operational tolerance are not fully understood, but evidence suggests that regulatory T cells play a crucial role in inducing and maintaining operational tolerance [12]. Researchers have also proposed that regulatory T cells might suppress effector T cell responses, leading to the acceptance of the allograft [14].

To our knowledge, this is the first case report to describe the achievement of both blood group antigen and operational tolerance following pediatric ABO-incompatible liver transplantation. This finding is significant because it highlights the possibility of successful outcomes in ABO-incompatible transplants in pediatric patients without the need for pretransplant desensitization. The development of dual tolerance in our case indicates that the mechanisms of immune tolerance in pediatric transplantation may be interrelated and could offer novel insights into the management of ABO-incompatible transplantation.

This case report has significant implications for the management of ABO-incompatible transplantation within the pediatric population. The emergence of dual tolerance has the potential to diminish the necessity for intensive pretransplant desensitization and ongoing immunosuppressive therapy, which could lead to enhanced patient outcomes and a reduction in healthcare expenditures. However, this report is limited by an incomplete understanding of the mechanisms underlying tolerance and the necessity for extended follow-up to evaluate the persistence of the observed tolerance. Additional research is needed to further clarify the mechanisms of immune tolerance in ABO-incompatible pediatric transplantation, evaluate the clinical relevance of these findings, and determine their applicability to a wider pediatric transplant recipient cohort. This should include larger cohort studies and detailed mechanistic investigations.

Conflict of Interest

No potential conflict of interest relevant to this article was reported.

Author Contributions

Conceptualization: HSK, SJNC. Data curation: HSK, HKL. Visualization: HSK, HKL, SL. Writing–original draft: HSK, SJNC, HKL. Writing–review & editing: all authors. All authors read and approved the final manuscript.