Liver transplantation is the most effective treatment of advanced liver disease, and the use of extended criteria donor organs has broadened the source of available livers. Although normothermic machine perfusion (NMP) has become a useful tool in liver transplantation, there are no consistent criteria that can be used to evaluate the viability of livers during NMP. This review summarizes the criteria, indicators, and methods used to evaluate liver viability during NMP. The shape, appearance, and hemodynamics of the liver can be analyzed at a macroscopic level, while markers of liver injury, indicators of liver and bile duct function, and other relevant indicators can be evaluated by biochemical analysis. The liver can also be assessed by tissue biopsy at the microscopic level. Novel methods for assessment of liver viability are introduced. The limitations of evaluating liver viability during NMP are discussed and suggestions for future clinical practice are provided.

Purpose: This study aimed to preliminarily evaluate the safety, tolerability, and antitumor efficacy of hepatitis B virus (HBV)-specific T-cell receptor (TCR)–T cell therapy combining mRNA electroporation and lentiviral transduction in patients with recurrent HBV–hepatocellular carcinoma after liver transplantation. Patients and Methods: In this pilot study (NCT04677088), two types of autologous HBV-specific TCR-redirected T cells were assessed without prior lymphodepletion: (i) multiple infusions of mRNA-electroporated HBV–TCR–T cells (mRNA–HBV–TCR–T cells) and (ii) one to three infusions of lentiviral-transduced HBV–TCR–T cells (lenti-HBV–TCR–T cells). Treatment-related adverse events were assessed using the Common Terminology Criteria for Adverse Events, and antitumor efficacy was evaluated using CT imaging according to RECIST v1.1 criteria. Progression-free survival (PFS) was defined as the time from the start of study treatment until objective tumor progression or death. Results: Both mRNA-electroporated and lentiviral-transduced HBV-specific TCR–T cells demonstrated a favorable safety profile, with only grade 1 to 2 treatment-related adverse events observed. In the mRNA–HBV–TCR–T cells cohort, the median PFS was 2.32 months (range, 1.87–2.77 months). The combination therapy cohort (mRNA–HBV–TCR–T cells + lenti-HBV–TCR–T cells) showed a median PFS of 7.34 months (range, 4.47–7.60 months). CT imaging indicated effective tumor control in the combination therapy group. Conclusions: This study preliminarily suggests that the combination of mRNA–HBV–TCR–T cells and lenti-HBV–TCR–T cells could be a safe and potentially effective approach for treating patients following liver transplantation in the context of lifelong immunosuppression drug administration. Further studies are needed to refine treatment strategies and assess long-term safety and efficacy in this special patient population.

Objective: Evaluating the safety and efficacy of implanting a liver with islet grafts into patients with end-stage liver disease and diabetes mellitus (DM). Background: DM and end-stage liver diseases are significant health concerns worldwide, often coexisting and mutually influencing each other. Addressing both diseases simultaneously is paramount. Methods: We utilized the islet transplantation combined ischemia-free liver transplantation technique to treat a patient with hepatocellular carcinoma and type 2 diabetes mellitus. The liver was procured and preserved using the ischemia-free liver transplantation technique, and during normothermic machine perfusion, isolated and purified islet grafts were transplanted into the liver through the portal vein. Finally, the liver, incorporating with the transplant islet grafts, was implanted into the recipient without interruption of blood supply. Results: The patient received both liver and islet grafts from the same donor. The patient achieved insulin-independence by post-transplant day 9, and both liver and islet function remained robust. The patient was discharged on post-transplant day 16 and experienced no surgical or transplantation-related complications during the follow-up period. Furthermore, islet grafts presence was observed in liver biopsies after islet transplantation. Conclusions: This landmark case marks the inaugural application of ischemia-free liver transplantation in humans, signifying its potential as a promising treatment modality for end-stage liver disease with DM.

Background. In organ transplantation, ischemia, and reperfusion injury (IRI) is considered as an inevitable event and the major contributor to graft failure. Ischemia-free liver transplantation (IFLT) is a novel transplant procedure that can prevent IRI and provide better transplant outcomes. However, a large animal model of IFLT has not been reported. Therefore, we develop a new, reproducible, and stable model of IFLT in pigs for investigating mechanisms of IFLT in IRI. Methods. Ten pigs were subjected to IFLT or conventional liver transplantation (CLT). Donor livers in IFLT underwent 6-h continuous normothermic machine perfusion (NMP) throughout graft procurement, preservation, and implantation, whereas livers in CLT were subjected to 6-h cold storage before implantation. The early reperfusion injury was compared between the 2 groups. Results. Continuous bile production, low lactate, and liver enzyme levels were observed during NMP in IFLT. All animals survived after liver transplantation. The posttransplant graft function was improved with IFLT when compared with CLT. Minimal histologic changes, fewer apoptotic hepatocytes, less sinusoidal endothelial cell injury, and proinflammatory cytokine (interleukin [IL]-1β, IL-6, and tumor necrosis factor-α) release after graft revascularization were documented in the IFLT group versus the CLT group. Conclusions. We report that the concept of IFLT is achievable in pigs. This innovation provides a potential strategy to investigate the mechanisms of IRI and provide better transplant outcomes for clinical practice.

Conventional ischemia-free liver transplantation (CIFLT) represents a pioneering procedure that circumvents ischemia-reperfusion injury to livers throughout the transplant procedure. However, its complexity has limited its widespread adoption. This study introduced a simplified ischemia-free liver transplantation (SIFLT) technique by providing an alternating flow of the portal vein and hepatic artery, demonstrating its efficacy and safety. In this retrospective study, 32 patients who received SIFLT and 32 who received CIFLT were included between January 2021 and January 2024. The intraoperative and postoperative outcomes were collected and elevated. Patients who underwent SIFLT had a shorter anhepatic phase (44.0±2.4 vs. 51.6±2.4 min, p=0.03), along with a comparatively reduced intraoperative blood loss compared to those who underwent CIFLT. Furthermore, the SIFLT group exhibited significantly lower peak AST levels within postoperative 7 days (413.1±62.6 vs. 707.5±110.7 U/L, p=0.02). The incidence of early allograft dysfunction, primary nonfunction, and transplant-related complications were similar across both groups. There were no significant differences in the number of Clavien-Dindo classification of surgical complications and comprehensive complication index at 3 months after transplantation. Kaplan-Meier analysis confirmed similar patient and graft survival rates. The subgroup analysis of extended criteria donor demonstrated that SIFLT can effectively reduce anhepatic phase and intraoperative blood loss and can achieve a clinical prognosis similar to CIFLT. Additionally, histological analysis revealed that both groups demonstrated well-preserved livers and bile ducts. The SIFLT simplifies the intricate surgical procedure while ensuring the protection of livers from ischemia-reperfusion injury. This technique holds promise for enabling patients to achieve clinical outcomes comparable to those of CIFLT.

The incidence of liver diseases is on the leading rise worldwide, but there is a lack of exact research models mimic liver diseases. Using the normothermic machine perfusion (NMP) platform to study diseased livers recovered from the liver transplantation (LT) recipients seems promising. Therefore, the aim of this study was to establish the first machine perfusion system called Life-XDL to cultivate diseased liver. Four diseased livers recovered from LT recipients within different diagnoses were collected. The diseased livers were connected to the Life-XDL machine perfusion system that circulated Life-XDL perfusate providing oxygen and nutrients. The pressure and flow of the device was recorded and blood gas analysis and laboratory test of perfusate and bile was examined to analyze the function of the diseased livers. Liver tissues after perfusion were collected for histological analysis. Experiments showed that Life-XDL kept the diseased livers at the physiological state with providing stable hemodynamics and suitable partial pressure of oxygen and carbon dioxide. The results of blood gas analysis and laboratory test results demonstrated restoration and maintenance of metabolism and less damage. Moreover, the bile production of case 1, 3 and 4 diseased livers represented its vivid functionality. The pathological characteristics were kept stable before and after NMP. Overall, we successfully establish the Life-XDL machine perfusion system which specially for diseased human whole liver and develop a new diseased human whole organ model in vitro through normothermic machine perfusion that recapitulate the main features of the human liver disease, which showing great promise as disease modeling platforms.