Immune checkpoint inhibitors (ICIs) may lead to rejection and even graft loss of solid organ transplant recipients, making them not widely used in transplant patients. There is insufficient clinical experience in using ICIs as a bridging or downstaging therapy before transplantation. We performed a retrospective review of patients receiving programmed cell death 1 inhibitor (PD1) before liver transplantation for HCC in our center and analyzed the data of these patients with the purpose of investigating the safety and feasibility of preoperative PD1 inhibitor among liver transplant recipients and exploring the preoperative correlation ICIs and the postoperative risk of rejection and immune-related graft loss. A total of 16 patients enrolled in this study. Acute rejection occurred in 9 patients, with an incidence of 56.3%. The median time of rejection was 7 days after surgery. The median FK506 concentration at the time of rejection was 7.1 μg/L. All rejection reactions were reversed after adjusting the immunosuppression regimen. The interval between the last PD1 inhibitor and transplantation in the rejection group was shorter than that in the nonrejection group, and there was a statistical difference [21.0 (15.5–27.5) days vs. 60.0 (34.0–167.0) days, p=0.01]. In conclusion, PD1 inhibitor is a safe and feasible method for bridging or downstaging treatment before liver transplantation. Although preoperative PD1 inhibitor may increase the incidence of postoperative rejection, it is not associated with increased immune-related graft loss and patient death.

MicroRNAs (miRNAs) play a pivotal role in hepatocellular carcinoma (HCC) progression and have been confirmed to participate in the carcinogenesis and development of HCC. However, the relationship between miR-497-5p and HCC remains unclear. Kaplan–Meier curve analysis and the log-rank test were used to investigate the efficacy of miR-497-5p on overall survival (OS) and disease-free survival (DFS) in patients with HCC. According to in vitro experiments, programmed cell death 4 (PDCD4) was a target of miR-497-5p by the dual-luciferase activity assay. The efficacy of PDCD4 on cell proliferation and metastasis in HCC was examined by transwell assays, CCK-8 assays and reverse transcription quantitative PCR (RT-qPCR). Additionally, we conducted a luciferase activity reporter assay to confirm the interaction between lncRNA XIST and miR-49-5p. Then, to evaluate the relationship between lncRNA XIST and miR-497-5p, several mechanistic experiments, including qRT-PCR, Western blotting, transwell assays and tumor xenograft assays, were performed. miR-497-5p was upregulated in HCC tissues, and high expression of miR-497-5p resulted in increases in tumor size and tumor number and a higher tumor-node-metastasis (TNM) stage and Edmondson grade in patients with HCC. Silencing miR-497-5p inhibited the proliferation and migration of HCC cells. PDCD4, which was downregulated in HCC tissues, was shown to be a target of miR-497-5p and was negatively correlated with the expression of miR-497-5p. lncRNA XIST was found to act as a miR-497-5p sponge and to regulate the level of PDCD4, which is targeted by miR-497-5p. lncRNA XIST was observed to be downregulated in the HCC tissues and positively correlated with the expression of PDCD4. Our findings reveal that the XIST/miR-497-5p/PDCD4 axis participates in HCC development and that XIST could be used as a biomarker of HCC.

Non‐SMC condensing I complex subunit H (NCAPH) is a member of the Barr protein family and part of the condensin I complex. The upregulation of NCAPH is associated with poor prognosis in patients with colon cancer. However, the relationship between NCAPH and hepatocellular carcinoma (HCC) remains unclear. This study aimed to explore NCAPH expression in HCC tissues and to investigate NCAPH functions in HCC cells. In this study, we found that high expression of NCAPH in HCC indicated worse prognosis via bioinformatics analysis. Consistently, quantitative real‐time polymerase chain reaction assays in 20 pairs of HCC specimens and the immunohistochemical analysis of 100 HCC tissues showed the upregulation of NCAPH. We established stable NCAPH‐overexpressing and NCAPH knockdown cell lines. Cell Counting Kit‐8 assays and colony formation assay were performed to analyze cell proliferation. Migration and invasion were analyzed by Transwell assays. Subcutaneous xenograft models were used to explore the role of NCAPH in tumor formation in vivo. Our results showed that NCAPH promoted tumor proliferation, migration, and invasion in vitro and in vivo. In conclusion, our findings indicate that NCAPH could serve as a novel prognostic biomarker and a potential therapeutic target for patients with HCC.

Background Ischaemia-reperfusion injury is considered an inevitable component of organ transplantation, compromising organ quality and outcomes. Although several treatments have been proposed, none has avoided graft ischaemia and its detrimental consequences.

Background: Liver transplantation (LT) is an effective option for hepatocellular carcinoma (HCC) and end-stage liver cirrhosis. However, organ shortage and tumor recurrence are the main obstacles limiting its popularization and application in HCC patients. Testing for circulating tumor cells (CTCs) would be a valuable strategy to predict the recurrence and metastasis of HCC after LT. Various CTCs detection methods have different advantages and disadvantages. This study aims to investigate the predictive value of testing for CTCs based on immunofluorescence in situ hybridization of peripheral blood cells in patients with HCC after LT. Methods: A total of 50 patients who received testing for CTCs and then underwent LT were enrolled in this study. Negative enrichment and immunofluorescence in situ hybridization (imFISH) methods were introduced to detect CTCs. Results: Twenty-six (52%) patients were CTC-positive, and 24 (48%) patients were CTC-negative. The results showed that CTCs result was correlated with tumor size (ꭓ²=5.773, P=0.016), AFP level (ꭓ²=5.454, P=0.020), tumor grade (ꭓ²=6.478, P=0.039) and Recurrence(ꭓ²=6.211, P=0.013).Twelve patients had recurrence after LT within one year. The results showed that the CTCs result (P=0.034) was the only independent factor impacting long-term survival. The 1-year disease-free survival rates of CTC-negative and CTC-positive patients were 91.6% and 61.5%, respectively (P=0.020). The 1-year overall survival of CTC-positive patients and CTC-negative was 88.5% and 91.7%, respectively (P=0.751). Conclusions: CTCs result was closely related to the early recurrence of patients with HCC after LT. CTC-positive patients had a worse prognosis after LT than the CTC-negative group.

Background.: Traditional liver transplant strategies with cold preservation usually result in ischemia-reperfusion injury (IRI) to the donor liver. Regular normothermic machine perfusion (NMP) donor livers suffer IRI twice. Here, we aimed to introduce a novel technique called continuous NMP without recooling to avoid a second IRI and its application in livers from extended criteria donors. Methods.: Seven donor livers transplanted following continuous NMP without recooling, 7 donor livers transplanted following standard NMP, and 14 livers under static cold storage (SCS) were included in this study. Perioperative outcomes were recorded and analyzed between groups. Results.: During the NMP without a recooling procedure, all livers cleared lactate quickly to normal levels in a median time of 100 min (interquartile range, 60–180) and remained stable until the end of perfusion. In the NMP without recooling and standard NMP groups, posttransplant peak aspartate aminotransferase and alanine aminotransferase levels were both significantly lower than those in the SCS group (P = 0.0015 and 0.016, respectively). The occurrence rate of early allograft dysfunction was significantly lower in the NMP without recooling group than in the SCS group (P = 0.022), whereas there was no difference in the NMP group with or without recooling (P = 0.462). Conclusions: Our pilot study revealed a novel technique designed to avoid secondary IRI. This novel technique is shown to have at least a comparable effect on the standard NMP, although more data are needed to show its superiority in the future.