Immune checkpoint inhibitors (ICIs) have improved the management of patients with intermediate- and advanced-stage HCC, even making some of them potential candidates for liver transplantation. However, acute rejection has been observed after ICI therapy, challenging its safety in transplant settings. We summarize the key basic impact of immune checkpoints on HCC and liver transplantation. We analyze the available case reports and case series on the use of ICI therapy prior to and after liver transplantation. A three-month washout period is desirable between ICI therapy and liver transplantation to reduce the risk of acute rejection. Whenever possible, ICIs should be avoided after liver transplantation, and especially so early after a transplant. Globally, more robust prospective data in the field are required.

The liver is the most common site of metastasis of colorectal cancer (CRC), and colorectal liver metastasis is one of the major causes of CRC-related deaths worldwide. The tumor microenvironment, particularly the extracellular matrix (ECM), plays a critical role in CRC metastasis and chemoresistance. Based on findings from clinical and basic research, this review attempts to offer a complete understanding of the role of the ECM in colorectal liver metastasis and to suggest potential ways for therapeutic intervention. First, the ECMs’ role in regulating cancer cell fate is explored. We then discuss the hepatic ECM fingerprint and its influence on the metastatic behavior of CRC cells, highlighting key molecular interactions that promote metastasis. In addition, we examine how changes in the ECM within the metastatic niche contribute to chemoresistance, focusing on ECM remodeling by ECM stiffening and the activation of specific signaling pathways. Understanding these mechanisms is crucial for the development of novel strategies to overcome metastasis and improve outcomes for CRC patients.

Background: Pediatric liver surgery is complex, and complications are not uncommon. Centralization of highly specialized surgery has been shown to improve quality of care. In 2012, pediatric liver surgery was centralized in Switzerland in one national center. This study analyses results before and after centralization. Methods: Retrospective monocentric comparative study. Analysis of medical records of children (0–16 years) operated for any liver tumor between 1 January 2001 and 31 December 2020. Forty-one patients were included: 14 before centralization (before 1 January 2012) and 27 after centralization (after 1 January 2012). Epidemiological, pre-, intra-, and post-operative data were collected. Fischer’s exact and t-test were used to compare groups. Results: The two cohorts were homogeneous. Operating time was reduced, although not significantly, from 366 to 277 min. Length of postoperative stay and mortality were not statistically different between groups. Yet, after centralization, overall postoperative complication rate decreased significantly from 57% to 15% (p = 0.01), Clavien > III complications decreased from 50% to 7% (p < 0.01), and hepatic recurrences were also significantly reduced (40% to 5%, p = 0.03). Conclusion: Centralization of the surgical management of liver tumors in Switzerland has improved quality of care in our center by significantly reducing postoperative complications and hepatic recurrence.

In France, liver grafts that have been refused at least 5 times can be “rescued” and allocated to a centre which chooses a recipient from its own waiting list, outside the patient-based allocation framework. We explored whether these “rescued” grafts were associated with worse graft/patient survival, as well as assessing their effect on survival benefit. Among 7,895 candidates, 5,218 were transplanted between 2009 and 2014 (336 centre-allocated). We compared recipient/graft survival between patient allocation and centre allocation, considering a selection bias and the distribution of centre-allocation recipients among the transplant teams. We used a propensity score approach and a weighted Cox model using the inverse probability of treatment weighting method. We also explored the survival benefit associated with centre-allocation grafts. There was a significantly higher risk of graft loss/death in the centre allocation group compared to the patient allocation group (hazard ratio 1.13; 95% CI 1.05–1.22). However, this difference was no longer significant for teams that performed more than 7% of the centre-allocation transplantations. Moreover, receiving a centre-allocation graft, compared to remaining on the waiting list and possibly later receiving a patient-allocation graft, did not convey a poorer survival benefit (hazard ratio 0.80; 95% CI 0.60–1.08). In centres which transplanted most of the centre-allocation grafts, using grafts repeatedly refused for top-listed candidates was not detrimental. Given the organ shortage, our findings should encourage policy makers to restrict centre-allocation grafts to targeted centres. “Centre allocation” (CA) made it possible to save 6 out of 100 available liver grafts that had been refused at least 5 times for use in the top-listed candidates on the national waiting list. In this series, the largest on this topic, we showed that, in centres which transplanted most of the CA grafts, using grafts repeatedly refused for top-listed candidates did not appear to be detrimental. In the context of organ shortage, our results, which could be of interest for any country using this CA strategy, should encourage policy makers to reassess some aspects of graft allocation by restricting CA grafts to targeted centres, fostering the “best” matching between grafts and candidates on the waiting list.

Liver transplantation (LT) for hepatocellular carcinoma (HCC) is performed worldwide, with 5-year survival rates of approximately 70%. However, post-transplant HCC recurrence occurs in 15-20% of recipients. We aimed to evaluate, for the first time, long-term recurrence-free survival in a large international cohort of patients undergoing LT for HCC using grafts treated with hypothermic oxygenated machine perfusion (HOPE). This observational post hoc analysis of the multicenter European HOPE-REAL study (NCT05520320) included adult recipients with HCC (N = 599) who received a liver from either a donation after brain death (DBD) or donation after circulatory death (DCD) donor, preserved using HOPE, dual-HOPE (DHOPE), or normothermic regional perfusion followed by HOPE (NRP-HOPE) between 2012 and 2022. Propensity score matching was used to compare outcomes between HCC and non-HCC recipients within the HOPE-REAL cohort, and between HOPE-treated HCC recipients and an external control cohort receiving non-perfused livers (n = 484). The overall HCC recurrence rate in the HOPE-REAL cohort was 6.9% (41/599), with no significant difference between DBD and DCD liver transplants (7.1% [25/350] vs. 6.4% [16/249]; p = 0.346). One-, 3-, and 5-year overall survival rates were 92%, 86%, and 81%, while recurrence-free survival rates were 90%, 83%, and 78%, respectively. Five-year overall survival was similar between 347 HOPE-treated HCC recipients (82%) and 347 matched non-HCC recipients (84%) (p = 0.625). In contrast, compared to an external cohort of 312 non-perfused HCC recipients, 5-year overall survival was significantly higher in 312 matched HOPE-treated HCC recipients (74% vs. 84%; p = 0.034). HCC recurrence was rare after transplantation of livers treated with HOPE. Long-term survival in HOPE-treated HCC recipients was significantly better than in those receiving non-perfused livers, and comparable to outcomes in non-HCC recipients. These findings warrant validation in a randomized clinical trial. This post hoc analysis of the HOPE REAL study demonstrates, for the first time, low hepatocellular carcinoma (HCC) recurrence rates in a large cohort of hypothermic oxygenated machine perfusion-treated liver transplant recipients with HCC, and significantly better survival outcomes compared to matched recipients of non-perfused grafts. These findings may have important implications, particularly as tumor-related indications for liver transplantation continue to rise. Machine liver perfusion could emerge as a novel strategy to improve oncological outcomes in high-risk cancer conditions after transplantation, potentially via mitigation of inflammation and reduced tumor cell seeding. NCT05520320