BACKGROUND: Pre-transplant exposure to immune checkpoint inhibitors (ICIs) significantly increases the risk of allograft rejection after liver transplantation (LT); however, whether ICI-related rejection leads to increased graft loss remains controversial. Therefore, this study aimed to investigate the association between ICI-related allograft rejection and perioperative graft loss. METHODS: This was a retrospective analysis of adult liver transplant recipients with early biopsy-proven T-cell-mediated rejection (TCMR) at Liver Transplantation Center of Sun Yat-sen Memorial Hospital from June 2019 to September 2024. The pathological features, clinical characteristics, and perioperative graft survival were analyzed. RESULTS: Twenty-eight patients who underwent early TCMR between June 2019 and September 2024 were included. Based on pre-LT ICI exposure, recipients were categorized into ICI-related TCMR (irTCMR, n = 12) and conventional TCMR (cTCMR, n = 16) groups. Recipients with irTCMR had a higher median Banff rejection activity index (RAI) (6 vs . 5, P = 0.012) and more aggressive tissue damage and inflammation. Recipients with irTCMR showed higher proportion of treatment resistance, achieving a complete resolution rate of only 8/12 compared to 16/16 for cTCMR. Graft loss occurred in 5/12 of irTCMR recipients within 90 days after LT, with no graft loss in cTCMRs recipients. Cox analysis demonstrated that irTCMR with an ICI washout period of <30 days was an independent risk factor for perioperative graft loss (hazard ratio [HR], 6.540; 95% confidence interval [CI], 1.067-40.067, P = 0.042). CONCLUSION IrTCMR is associated with severe pathological features, increased resistance to treatment, and higher graft loss in adult liver transplant recipients.
Humans ; Liver Transplantation/adverse effects* ; Male ; Female ; Middle Aged ; Retrospective Studies ; Graft Rejection/immunology* ; Immune Checkpoint Inhibitors/therapeutic use* ; Adult ; T-Lymphocytes/drug effects* ; Graft Survival/immunology* ; Aged

Objective To evaluate the clinical efficacy of heterozygous living donor liver transplantation for pediatric maple syrup urine disease. Methods A 3-year-old boy was admitted to the hospital on July 5, 2017 due to maple syrup urine disease for half a year. The child presented with paroxysmal dysarthria and motor dysfunction of the lower limbs under fasting status for half a year, accompanied with obvious maple syrup urine odor and slow language development. No other growth abnormality or mental defects were observed. Serum branched chain amino acid (BCAA) assay detected that the level of leucine was 684 μmol/L and 559 μmol/L for the valine. The child was diagnosed with maple syrup urine disease type b based on gene detection combined with BCAA assay. Living donor liver transplantation from his biological father was performed. Postoperatively, routine immunosuppression, anti-virus, anti-infection therapies, maintenance of fluid, electrolyte, and acid-base balance and other necessary nutritional support were given. The dose of tacrolimus was adjusted according to biochemical parameters and cytochrome P450(CYP)3A5 genotype of the recipient. Glucocorticoid administration was terminated at approximately 6 months after operation. Results The liver function of the recipient was recovered to normal range at postoperative 1 month, and basically stabilized at 3 years after surgery. The amino acid level was decreased to normal level immediately after operation, and BCAA was continually declined after normal diet for postoperative 1 month. As of the submission date, the recipient grew well in a stable condition and achieved high quality of life. Conclusions Heterozygous living donor liver transplantation is a safe and effective treatment of maple syrup urine disease, which reduces the possibility of sudden acute metabolic events, significantly improves the quality of life of the recipient and provides a novel idea for surgical treatment of maple syrup urine disease.

Objective To summarize the therapeutic effects of living related donor liver transplantation for Crigler-Najjar syndrome type Ⅰ (CNS type Ⅰ). Methods A 3-month-old male infant had appeared a progressive xanthochromia of the skin and sclera 4 d after birth without obvious cause. Other causative factors were eliminated after relevant tests were completed, and identified as CNS type Ⅰ by genetic testing. Living related donor liver transplantation was performed with his mother as the donor. An immunosuppression regimen was routinely applied postoperatively and tacrolimus doses were adjusted according to biochemical indicators and cytochrome P450 (CYP) 3A5 genotype of the recipient. Results The liver enzymes of the recipient returned to normal at 7 d postoperatively, and bilirubin decreased daily and fell to the normal range at 22 d postoperatively. Followed up to the submission date, the recipient's xanthochromia of skin and scleral faded with normal bilirubin and stable liver enzymes. The condition of the recipient was generally good with high quality of life. Conclusions Living donor liver transplantation can treat unconjugated hyperbilirubinemia and other diseases caused by CNS type Ⅰ, which greatly improve the quality of life of patients.

Liver fibrosis is a common pathological response in chronic liver injury. In the pathological process of hepatic injury, signaling pathways associated with hepatic fibrosis, which mediates the repair, proliferation and fibrosis of the liver secrete different cytokines. In these pathways, transforming growth factor beta (TGFβ) and signal transducer and activator of transcription 3 (STAT3) play key roles in the proliferation and activation of hepatic stellate cells (HSCs) and promote epithelial mesenchymal transition. In addition, it is also involved in the process of proliferation and transformation of collagen and extracellular matrix molecules into myofibroblasts. TGFβ and STAT3 molecular-related signaling pathways mediate the loss of epithelial phenotype and gene expression in mature epithelial cells, transforming them into mesenchymal cells, and producing anti-apoptosis to hepatocytes and promoting the proliferation of HSCs. However, the mechanisms by which STAT3 and TGFβ molecules are involved in the development and progression of liver fibrosis are not sound distinct. In this review, we attempt to know the mechanisms and interactions of TGFβ and STAT3 molecules that mediate potential liver fibrosis, and promote their role in promoting HSCs production and epithelial mesenchymal transition.

Acute-on-chronic liver failure is a common form of liver failure characterized by complicated clinical manifestations and high mortality.The pathophysiology of ACLF is still unclear.More efficacious treatments are based mainly on a better understanding of the pathophysiology of ACLF.The advances in the pathophysiology of ACLF have been extremely encouraging in the last few years.In this article,we reviewed the progress of ACLF,its definition,etiology and,pathophysiology.