Lai Wei

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. Export

Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer, usually occurring in the background of chronic liver disease. HCC lethality rate is in the third highest place in the world. Patients with HCC have concealed early symptoms and possess a high-level of heterogeneity. Once diagnosed, most of the tumors are in advanced stages and have a poor prognosis. The sensitivity and specificity of existing detection modalities and protocols are suboptimal. HCC calls for more sophisticated and individualized therapeutic regimens. Liquid biopsy is non-invasive, repeatable, unaffected by location, and can be monitored dynamically. It has emerged as a useable aid in achieving precision malignant tumor treatment. Circulating tumor cells (CTCs), circulating nucleic acids, exosomes and tumor-educated platelets are the commonest components of a liquid biopsy. It possesses the theoretical ability to conquer the high heterogeneity and the difficulty of early detection for HCC patients. In this review, we summarize the common enrichment techniques and the clinical applications in HCC for different liquid biopsy components. Tumor recurrence after HCC-related liver transplantation is more insidious and difficult to treat. The clinical use of liquid biopsy in HCC-related liver transplantation is also summarized in this review.

Liver transplantation (LT) is the primary treatment for patients with early‑stage hepatocellular carcinoma (HCC). However, the 5‑year survival rate after LT remains low for patients with advanced HCC. Recently, combining programmed cell death protein‑1 (PD‑1) inhibitors with hepatic arterial infusion chemotherapy (HAIC) has achieved promising outcomes in advanced HCC treatment. However, there is a lack of sufficient clinical data demonstrating its effectiveness as a pre‑LT down‑staging treatment. The current study presented a case of advanced HCC beyond the Milan criteria who underwent LT and achieved a favorable outcome following PD‑1 inhibitor combined with FOLFOX‑HAIC therapy. Of note, due to treatment‑induced tumor necrosis, precise post‑treatment tumor size evaluation became challenging. To address this, circulating tumor DNA (ct‑DNA) clearance was used as the LT criterion. After three cycles of Pembrolizumab and FOLFOX‑HAIC therapy, the patient's serum ctDNA became undetectable and serum α‑fetoprotein levels returned to normal. Magnetic resonance imaging results also revealed a significant reduction in liver tumor size post down‑staging treatment. Subsequent to LT, serum ctDNA was monitored every two months, consistently yielding diminished results. There were no clinical signs of recurrence 19 months post‑LT. These findings suggest that Pembrolizumab in combination with FOLFOX‑HAIC may serve as a potential down‑staging strategy prior to LT. In addition, ctDNA clearance may be considered a viable biomarker for LT eligibility.

A growing body of evidence suggested that gut microbiota is associated with liver diseases through the gut–liver axis. The imbalance of gut microbiota could be correlated with the occurrence, development, and prognosis of a series of liver diseases, including alcoholic liver disease (ALD), non-alcoholic fatty liver disease (NAFLD), viral hepatitis, cirrhosis, primary sclerosing cholangitis (PSC), and hepatocellular carcinoma (HCC). Fecal microbiota transplantation (FMT) seems to be a method to normalize the patient’s gut microbiota. This method has been traced back to the 4th century. In recent decade, FMT has been highly regarded in several clinical trials. As a novel approach to reconstruct the intestinal microecological balance, FMT has been used to treat the chronic liver diseases. Therefore, in this review, the role of FMT in the treatment of liver diseases was summarized. In addition, the relationship between gut and liver was explored through the gut–liver axis, and the definition, objectives, advantages, and procedures of FMT were described. Finally, the clinical value of FMT therapy in liver transplant (LT) recipients was briefly discussed.

Background: Acute antibody-mediated rejection (AMR) is an uncommon complication after ABO-compatible liver transplantation (LT). This case series investigated the clinicopathologic characteristics and outcomes of acute AMR in LT recipients with autoimmune liver disease (ALD). Patients and Methods: Among 809 patients who underwent LT from January 2014 to December 2020, four ALD patients developed AMR, which was confirmed based on clinical features, histopathology of liver biopsy, donor-specific antibodies (DSA) or panel reactive antibody (PRA) level. Therapies were individualized based on clinical manifestations. Results: The incidence of acute AMR was 0.49%, and the incidence of acute AMR with ALD and non-ALD recipients was 11.1% and 0%, respectively. Three patients had strongly positive HLA class II DSA, and one patient was with the PRA class I and II sensitivities, which were >80%; complement component 4d (C4d) staining was negative in all patients. The first patient underwent re-LT, and the other three patients had good prognoses with treatments. Conclusions: ALD patients are prone to acute AMR after LT, thus should be kept vigilant against the occurrence of acute AMR.