BackgroundLiver transplantation has adverse effects from life-long immunosuppression that limit the improvement of long-term outcomes. Achieving clinical operational tolerance is a major goal in organ transplantation.MethodsThis study analyzed liver transplantation patients at a single institution from 1998 to 2020, excluding those who died within 1-year posttransplant. Operational tolerance was defined as normal liver function even after immunosuppressive drugs were discontinued. Propensity score matching was implemented at a 12 ratio for the tolerant group (TG) and the nontolerant group (NTG).ResultsOut of 2,300 recipients, 99 achieved operational tolerance without rejection. No significant differences in sex or body mass index (BMI) were found between the TG and NTG. There was a significantly higher percentage of children in the TG (24.0%) than in the NTG (10.1%). The NTG had more living donor liver transplants. Among 2,054 adult recipients, no significant differences in age, sex, or BMI were found between the TG and the NTG. However, the rate of living donor liver transplantation was 40.3% (29/75) in the TG and 84.8% in the NTG (P<0.001). The propensity score-matched analysis showed higher chronic renal failure rates and a higher graft recipient weight ratio in the TG, along with shorter warm ischemic times during surgery. After immunosuppressant withdrawal, a significant increase in the ratio of CD4+CD25+ T cells to total CD4+ T cells was observed in the TG.ConclusionsThese findings suggest that larger, healthier grafts are more conducive to inducing tolerance, and regulatory T cells are crucial in achieving tolerance.

Liver transplantation is a critical procedure for patients with end-stage liver disease, but it is often hindered by ABO-incompatibility between the donor and recipient, which can lead to immediate humoral rejection. We present a unique case involving a 10-month-old patient who, by accident, received an ABO-incompatible partial liver transplant from a type A mother without undergoing desensitization. Remarkably, during a 21-year follow-up period, the patient exhibited no signs of humoral or graft rejection, despite nonadherence to medication. This case highlights the possibility of dual tolerance in pediatric ABO-incompatible liver transplantation and provides insights into immune tolerance mechanisms, with implications for enhancing patient care and reducing healthcare costs. Further research is necessary to clarify these mechanisms and to evaluate the long-term durability of tolerance in pediatric transplant recipients.

BackgroundUrinary tissue inhibitor of metalloproteinase-2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7) are G1 cell arrest biomarkers that have demonstrated accuracy and validity in predicting and diagnosing acute kidney injury (AKI). This study aimed to evaluate the validity of [TIMP-2]×[IGFBP7] in diagnosing acute allograft dysfunction and its utility in distinguishing acute rejection (AR) from nonrejection causes in kidney transplantation.MethodsThis study included 48 adult living donor kidney transplant recipients (KTRs; 18 with AR, 15 with nonrejection causes of AKI, and 15 with stable grafts). Urinary TIMP-2 and IGFBP7 were measured, and [TIMP-2]×[IGFBP7] was calculated in all subjects.ResultsIGFBP7, TIMP-2, and [TIMP-2]×[IGFBP7] were statistically significantly higher in KTRs with acute allograft dysfunction than in those with stable grafts. [TIMP-2]×[IGFBP7] was statistically significantly higher in KTRs with AR than in those with nonrejection AKI. [TIMP-2]×[IGFBP7] at a cutoff level of 0.278 (ng/mL)2/1,000 had an area under the curve (AUC) of 0.99 with a sensitivity of 100% and a specificity of 93.3% in diagnosing acute allograft dysfunction, while at a cutoff level of 0.803 (ng/mL)2/1,000 had an AUC of 0.939 with a sensitivity of 94.4% and a specificity of 83.3% in diagnosing AR.ConclusionsBesides its role in the early detection of acute allograft dysfunction, [TIMP-2]×[IGFBP7] may help to differentiate between AR and nonrejection causes in KTRs. However, whether and how urinary [TIMP-2]×[IGFBP7] can be used in clinical diagnosis still requires further research.

Due to a critical organ shortage, pig organs are being explored for use in transplantation. Differences between species, particularly in cell surface glycans, can trigger elevated immune responses in xenotransplantation. To mitigate the risk of hyperacute rejection, genetically modified pigs have been developed that lack certain glycans and express human complement inhibitors. Nevertheless, organs from these pigs may still provoke stronger inflammatory and innate immune reactions than allotransplants. Dysregulation of coagulation and persistent inflammation remain obstacles in the transplantation of pig organs into primates. Regulatory macrophages (Mregs), known for their anti-inflammatory properties, could offer a potential solution. Mregs secrete interleukin 10 and transforming growth factor beta, thereby suppressing immune responses and promoting the development of regulatory T cells. These Mregs are typically induced via the stimulation of monocytes or macrophages with macrophage colony-stimulating factor and interferon gamma, and they conspicuously express the stable marker dehydrogenase/reductase 9. Consequently, understanding the precise mechanisms governing Mreg generation, stability, and immunomodulation could pave the way for the therapeutic use of Mregs generated in vitro. This approach has the potential to reduce the required dosages and durations of anti-inflammatory and immunosuppressive medications in preclinical and clinical settings.

Over the past decade, the field of solid organ transplantation has undergone significant changes, with some of the most notable advancements occurring in liver transplantation. Recent years have seen substantial progress in preoperative patient optimization protocols, anesthesia monitoring, coagulation management, and fluid management, among other areas. These improvements have led to excellent perioperative outcomes for all surgical patients, including those undergoing liver transplantation. In the last few decades, there have been numerous publications in the field of liver transplantation, but controversies related to perioperative management of liver transplant recipients persist. In this review article, we address the unresolved issues surrounding the anesthetic management of patients scheduled for liver transplantation.

Posttransplant lymphoproliferative disorder (PTLD) is a rare and serious complication of kidney transplantation (KT), with 85% of cases being of B cell lineage. We present a case of T cell PTLD (T-PTLD) that rapidly progressed to liver failure, septic shock, and death despite various therapeutic interventions. A 50-year-old woman underwent ABO- and human leukocyte antigen-compatible preemptive living donor KT for diabetic end-stage kidney disease under basiliximab induction therapy. During routine monitoring, 2 months after KT, her Epstein-Barr (EB) viral load was found to be elevated to 318,443 copies/mL. Despite a reduction in maintenance immunosuppressants and preemptive rituximab treatment, the EB viremia continued to increase. Eight months after KT, abdominopelvic computed tomography revealed multifocal splenic lesions and nonspecific lymph node enlargement. Concurrently, the patient’s liver function tests began to deteriorate without evidence of viral hepatitis infection. A liver biopsy confirmed the diagnosis of EB virus-associated T-PTLD with CD3 and CD56 expression. Only 2 months after the PTLD diagnosis, the patient developed acute and severe liver failure. She died 12 days after being hospitalized, despite the administration of rescue cytotoxic chemotherapy. This case exemplifies the challenges of managing refractory EB virus-associated T-PTLD after KT, for which no specific treatment options are currently available. Further research into preventative and therapeutic methods for T-PTLD is warranted.

BackgroundObtaining consent from potential donor families is a challenging step in the donation process and is influenced by various factors.MethodsIn this cross-sectional study, we utilized a questionnaire containing 14 questions about facilitators and barriers in the family interview process. The questionnaire was distributed in March 2023 to intensive care unit (ICU) nurses who had experience with donor family interviews. We collected the opinions of these respondents on hospital performance and drew comparisons between the studied hospitals.ResultsA total of 60 participating ICU nurses provided mean scores for hospital performance in family interviews of 2.60±0.84 for type I hospitals (those providing neurosurgery and trauma care) and 2.035±0.890 for type II hospitals (those without neurosurgery and trauma services; P=0.04). The mean scores for public and private hospitals were 1.86±0.86 and 2.59±0.85, respectively (P=0.008). Based on the findings, the most important facilitators were the availability of organ donation staff and access to a professional team for family discussions. Conversely, poor physician communication skills and limited communication capabilities among medical staff were identified as significant barriers. Implementation of a professional team for family interviews was found to be more critical for type II hospitals. Poor physician communication skills were a significant concern in public hospitals, while families’ lack of awareness of patient prognosis emerged as a key barrier in private hospitals.ConclusionsThis study highlights numerous facilitators and barriers that vary across hospitals. Addressing these issues individually and developing tailored plans to enhance hospital performance in interviewing donor families is essential.

BackgroundGraft-versus-host disease (GVHD) is a rare, but potentially fatal complication of liver transplantation. One-way human leukocyte antigens (HLA) mismatch has emerged as a risk factor for GVHD. However, the risk of mortality associated with HLA-one-way mismatch (OWMM) remains uncertain. We investigated the incidence and characteristics of GVHD.MethodsIn total, 899 patients who underwent liver transplantation at a single center were retrospectively reviewed. The incidence of GVHD and 1- and 5-year survival rates were compared according to whether HLA-OWMM developed.ResultsIn the HLA-OWMM group, GVHD developed in two patients (14.3%). Notably, GVHD was only observed in living donor liver transplant (LDLT) recipients in the HLA-OWMM group. The HLA-OWMM group exhibited a lower 1-year patient survival rate than the control (i.e., non-HLA-OWMM) group (78.6% vs. 90.7%, P=0.120). However, the 5-year survival rate in the HLA-OWMM group was similar to that in the control group (78.6% vs. 78.2%, P=0.821). When the HLA-OWMM group was further stratified by the number of mismatched loci, the 5-year survival rate was 83.3% in patients with HLA-OWMM at one to two loci and 75.0% in those with HLA-OWMM at three loci.ConclusionsDespite the higher incidence of GVHD in LDLT recipients with HLA-OWMM, the 5-year patient survival rates were comparable to those in recipients without HLA-OWMM. The decision to perform LDLT in patients with HLA-OWMM depends on the patient’s status and the organ supply of a specific region.

Background: Hepatic artery dissection (HAD) is an uncommon complication of living donor liver transplantation (LDLT) and is associated with hepatic artery thrombosis (HAT).Since the incidence of HAD is low, clinical outcomes have not been well studied so far.The aim of this study is to identify the natural course of HAD and to suggest an appropriate management strategy.Methods: Patients who underwent adult LDLT at Asan Medical Center were retrospectively reviewed between January 2010 and December 2022.We divided the subgroups based on the range of HAD, as well as the use of anticoagulants.The study outcomes were an event of HAT.Results: Among 4,065 LDLT recipients, 114 patients (2.8%) were diagnosed with HAD.HAD was diagnosed on a mean of 10 (range, 1-55) postoperative days.The isolated proper hepatic artery (PHA) involved group accounted for 47.3% (54/114) of the cases, while the diffuse type of HAD was 60 (52.6%).Ninety-two patients (80.7%) had resolution and the mean time to resolution was 104.3 days (range, 19-448).The HAT was diagnosed in seven patients (6.1%), all of which occurred in the isolated PHA group (7/54, 13%).According to the medication type, 47 patient received only antiplatelet agents while 67 patients received additional oral anticoagulant.In comparison between two groups, there were no significant differences in HAT and graft failure (P=0.444,P=1).The resolution rate of HAD was higher in the anticoagulant group (33/47 [70.2%] vs. 59/67 [88.1%],P=0.017).The time to resolution of HAD was shorter in the anticoagulant group but there was no significant difference (109.38±18.63,62.56±8.15;P=0.695).Conclusions: HAD is mostly benign and spontaneously resolved within 4 months.The diffuse type of HAD does not increase the risk of HAT or graft failure.The conservative treatment is sufficient and the addition of oral anticoagulants may be beneficial in the resolution of HAD.