liver-cold-storage-transplantation-cold-adaptive-daurian-ground

Liver Cold Storage and Transplantation in the Cold-Adaptive Daurian Ground Squirrels

In liver transplantation, the functional recovery of donor grafts following extended cold storage is a major challenge. The same obstacle applies to ...

post-liver-transplantation-management-specimen-collection-daurian

Post-Liver Transplantation Management and Specimen Collection in Daurian Ground Squirrels for Single-Cell RNA Sequencing

Graft functional recovery and graft-host immunocompatibility represent major prognostic concerns following liver transplantation. Critically, conventional ...

Huazhong University of Science and Technology

Ministry of Education

NHC Key Laboratory of Organ Transplantation

Chinese Academy of Medical Sciences

Organ Transplantation Clinical Medical Research Center of Hubei Province

Renal transplantation is one of the primary approaches for curing end-stage kidney disease. With advancements in immunosuppressive agents, the short-term and long-term survival rates of transplanted kidneys have significantly improved. However, infections associated with potent immunosuppression have remained a persistent challenge. Among them, BK virus (BKV) reactivation following renal transplantation leading to BK virus-associated nephropathy (BKVAN) is a major cause of graft dysfunction. However, we still face significant challenges in understanding the pathogenesis, prevention, diagnosis, and treatment of BKVAN. These challenges include: 1. The mechanism of BKV reactivation under immunosuppressive conditions has not been well elucidated, leading to difficulties in breakthroughs in clinical research on prevention, diagnosis, and treatment. 2. Lack of proper identification of high-risk individuals, and effective personalized clinical management strategies. 3.Lack of early and sensitive diagnostic markers. 4. Lack of direct and effective treatment options due to the absence of specific antiviral drugs. The purpose of this review is to summarize the current status and cutting-edge advancements in BKV-related research, providing new methods and perspectives to address future research challenges.

Challenges and opportunities in research on BK virus infection after renal transplantation.

Ischemic-type biliary lesions (ITBL) are a major cause of graft loss and even mortality after liver transplantation (LT). The underlying cellular mechanisms for ITBL remain unclear. Gut microbiota has been found to be closely related to complications after LT. Here, using gut microbiome compositions, we found patients with ITBL had a higher abundance of bacteria associated with bile salt metabolism. These bacteria are reported to convert cholic acid (CA) into deoxycholic acid (DCA), consistent with our data that there were higher DCA concentrations and DCA/CA ratio in patients with ITBL than patients without ITBL. Using an in vitro model, human intrahepatic biliary epithelial cells (HIBEC) subjected to DCA showed a higher apoptosis rate, lower viability, and higher levels of cleaved-caspase3 than CA at the same concentration. DCA also changed the morphology of mitochondria and farnesoid X receptor (FXR) expression. Interestingly, DCA-induced apoptosis rate was significantly reduced in HIBEC when the FXR or BAX gene was knocked down, suggesting that DCA-induced apoptosis was dependent on FXR-mitochondrial pathway. Furthermore, increasing DCA/CA ratio in a bile acid-feeding mouse model resulted in cholangiocyte apoptosis and impaired liver function. The patients with ITBL also showed an increased proportion of TUNEL-positive biliary epithelial cells than those without ITBL. These suggest that changes in the gut microbiota following LT may enhance the conversion of CA to DCA, and may contribute to biliary damage via FXR-mitochondrial apoptosis pathway, providing new ideas for the early monitoring and treatment of ITBL.

Gut microbiota-mediated bile acid metabolism aggravates biliary injury after liver transplantation through mitochondrial apoptosis.

Whole-liver intensity-modulated radiation therapy as a rescue therapy for acute graft-versus-host disease after liver transplantation.

Due to the easier availability of transgenic mice and reagents, the mouse orthotopic liver transplantation model offers significant advantages in liver transplantation research. However, technical challenges have limited its broader application. The most challenging steps of the procedure include manual anastomosis of the suprahepatic vena cava, cuff anastomosis of the portal vein, and maintaining the anhepatic phase within 20 minutes. This study aims to provide detailed solutions to overcome these bottlenecks and introduces a modified magnetic device to facilitate safer and more efficient cuff anastomosis. We also describe the learning curve for beginners to achieve a 30-day survival rate exceeding 90% in mouse orthotopic liver transplantation. We demonstrate that mouse orthotopic liver transplantation can be mastered within 8 months of continuous practice, with 7-day and 30-day survival rates improving from 0% to 96.7% and 0% to 93.3%, respectively. The entire procedure can be completed within 80 minutes. We believe these technical improvements will provide more practical guidance for mouse liver transplantation.

Optimizing the mouse orthotopic liver transplantation model: Learning curve, technical enhancements, and keys to success.

The BK virus has become a substantial threat to transplanted kidneys. Yet, the present understanding of the clinical course and postoperative management of BK virus infections remains inadequate. Here, we report a case of a male transplant recipient with rapid graft loss due to BK virus-associated nephropathy after the second renal transplant, who had previously experienced failure of his first kidney allograft for the same reason. The posttransplant period was uneventful until serum creatinine rose to 2.30 mg/dL on postoperative day 59. Puncture biopsy was postponed because of swelling in the transplanted kidney, and acute rejection was considered as a source of the swelling because the repetitive results of blood BK virus DNA tests were negative. Methylprednisolone 500 mg was administered empirically for 3 days, followed by a 5-day course of anti-thymocyte globulin 100 mg. On postoperative day 83, SV40 T-antigen antibody immunostaining confirmed the diagnosis of BK virus nephropathy. However, it took only 28 days for this patient to progress from abnormal kidney function to the loss of the secondary transplanted kidney, and dialysis was initiated on postoperative day 87. To our knowledge, this is the first report of BK virus resulting in acute failure of a transplanted kidney. An early biopsy is crucial, and a negative test for viremia is not sufficient to exclude the recurrence of BK virus.

ArticleTotal : 2	Year
Publication title	2025
Publication title	2025

Article	Year
Challenges and opportunities in research on BK virus infection after renal transplantation. International immunopharmacology\| PubMed ID: 39146777	2024
Gut microbiota-mediated bile acid metabolism aggravates biliary injury after liver transplantation through mitochondrial apoptosis. International immunopharmacology\| PubMed ID: 39486182	2024
Whole-liver intensity-modulated radiation therapy as a rescue therapy for acute graft-versus-host disease after liver transplantation. Chinese medical journal\| PubMed ID: 39497366	2025
Optimizing the mouse orthotopic liver transplantation model: Learning curve, technical enhancements, and keys to success. Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society\| PubMed ID: 40130965	2025
Acute Injury From BK Virus After Second Transplant Resulted in Rapid Graft Loss: A Case Report. Experimental and clinical transplantation : official journal of the Middle East Society for Organ Transplantation\| PubMed ID: 40396711	2025

Zipei Wang

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