Background and Aims: Acute cellular rejection (ACR) is a frequent complication after liver transplantation. By reducing ischemia and graft damage, dynamic preservation techniques may diminish ACR. We performed a systematic review to assess the effect of currently tested organ perfusion (OP) approaches versus static cold storage (SCS) on post-transplant ACR-rates. Approach and Results: A systematic search of Medline, Embase, Cochrane Library, and Web of Science was conducted. Studies reporting ACR-rates between OP and SCS and comprising at least 10 liver transplants performed with either hypothermic oxygenated perfusion (HOPE), normothermic machine perfusion, or normothermic regional perfusion were included. Studies with mixed perfusion approaches were excluded. Eight studies were identified (226 patients in OP and 330 in SCS). Six studies were on HOPE, one on normothermic machine perfusion, and one on normothermic regional perfusion. At meta-analysis, OP was associated with a reduction in ACR compared with SCS [OR: 0.55 (95% CI, 0.33–0.91), p=0.02]. This effect remained significant when considering HOPE alone [OR: 0.54 (95% CI, 0.29–1), p=0.05], in a subgroup analysis of studies including only grafts from donation after cardiac death [OR: 0.43 (0.20–0.91) p=0.03], and in HOPE studies with only donation after cardiac death grafts [OR: 0.37 (0.14–1), p=0.05]. Conclusions: Dynamic OP techniques are associated with a reduction in ACR after liver transplantation compared with SCS. PROSPERO registration: CRD42022348356.

The risk of cancer recurrence after liver surgery mainly depends on tumour biology, but preclinical and clinical evidence suggests that the degree of perioperative liver injury plays a role in creating a favourable microenvironment for tumour cell engraftment or proliferation of dormant micro-metastases. Understanding the contribution of perioperative liver injury to tumour recurrence is imperative, as these pathways are potentially actionable. In this review, we examine the key mechanisms of perioperative liver injury, which comprise mechanical handling and surgical stress, ischaemia-reperfusion injury, and parenchymal loss leading to liver regeneration. We explore how these processes can trigger downstream cascades leading to the activation of the immune system and the pro-inflammatory response, cellular proliferation, angiogenesis, anti-apoptotic signals, and release of circulating tumour cells. Finally, we discuss the novel therapies under investigation to decrease ischaemia-reperfusion injury and increase regeneration after liver surgery, including pharmaceutical agents, inflow modulation, and machine perfusion.

More than 40% of patients with colorectal cancer present liver metastases (CRLM) during the course of their disease and up to 50% present with unresectable disease. Without surgical interventions, survival for patients treated with systemic therapies alone is dismal. In the past, liver transplantation (LT) for patients with unresectable CRLM failed to show any survival benefit due to poor selection, ineffective chemotherapeutic regimens, unbalanced immunosuppression and high perioperative mortality. Since then and for many years LT for CRLM was abandoned. The turning point occurred in 2013, when the results from the Secondary Cancer (SECA I) pilot study performed at Oslo University were published reporting a 60% 5-year overall survival after LT in patients with unresectable CRLM. These results effectively reignited the interest in LT as a potential therapy for CRLM, and several trials are undergoing. The aims of this article are to give a comprehensive overview of the available evidence on LT for CRLM, discuss the open issues in this rapidly evolving field, and highlight possible ways to address the future of this fascinating therapeutic alternative for selected patients with CRLM.

Liver resection (LR) is considered the treatment of choice for resectable neuroendocrine liver metastases (NELM), while liver transplantation (LT) is currently reserved for highly selected unresectable patients. We retrospectively analyzed data from consecutive patients undergoing either curative resection or transplantation for liver‐only NELM meeting Milan criteria at a single center between 1984 and 2019. Patients who fit Milan criteria were 48 in the transplantation group and 56 in the resection group. After a median follow‐up of 158 months for the transplantation group and 126 for the resection group, the 10‐year survival rate was 93% for transplantation and 75% for resection (p = .007). The 10‐year disease‐free survival rate was 52% for transplantation and 18% for resection (p < .001). Transplantation was associated with improved survival at univariate analysis. The median disease‐free interval between surgery and recurrence was 78 months for transplantation vs. 24 months for resection (p < .001). The transplantation group had more multisite recurrences (12/25, 48% vs. 5/42, 12% in the resection group, p = .001), while most recurrences in the resection group were intra‐hepatic (37/42, 88%, versus 2/25, 8% in the transplantation group). In conclusion, LT was associated with improved survival outcomes in NELM meeting the Milan criteria compared with LR.

Background.: This study compares selection criteria for liver transplant (LT) for hepatocellular carcinoma (HCC) for inclusivity and predictive ability to identify the most permissive criteria that maintain patient outcomes. Methods.: The Scientific Registry of Transplant Recipients (SRTR) database was queried for deceased donor LT’s for HCC (2003–2020) with 3-y follow-up; these data were compared with a 2-center experience. Milan, University of California, San Francisco (UCSF), 5-5-500, Up-to-seven (U7), HALT-HCC, and Metroticket 2.0 scores were calculated. Results.: Nationally, 26 409 patients were included, and 547 at the 2 institutions. Median SRTR-follow-up was 6.8 y (interquartile range 3.9–10.1). Three criteria allowed the expansion of candidacy versus Milan: UCSF (7.7%, n = 1898), Metroticket 2.0 (4.2%, n = 1037), and U7 (3.5%, n = 828). The absolute difference in 3-y overall survival (OS) between scores was 1.5%. HALT-HCC (area under the curve [AUC] = 0.559, 0.551–0.567) best predicted 3-y OS although AUC was notably similar between criteria (0.506 < AUC < 0.527, Mila n = 0.513, UCSF = 0.506, 5-5-500 = 0.522, U7 = 0.511, HALT-HCC = 0.559, and Metroticket 2.0 = 0.520), as was Harrall’s c-statistic (0.507 < c-statistic < 0.532). All scores predicted survival to P < 0.001 on competing risk analysis. Median follow-up in our enterprise was 9.8 y (interquartile range 7.1–13.3). U7 (13.0%, n = 58), UCSF (11.1%, n = 50), HALT-HCC (6.4%, n = 29), and Metroticket 2.0 (6.3%, n = 28) allowed candidate expansion. HALT-HCC (AUC = 0.768, 0.713–0.823) and Metroticket 2.0 (AUC = 0.739, 0.677–0.801) were the most predictive of recurrence. All scores predicted recurrence and survival to P < 0.001 using competing risk analysis. Conclusions.: Less restrictive criteria such as Metroticket 2.0, UCSF, or U7 allow broader application of transplants for HCC without sacrificing outcomes. Thus, the criteria for Model for End-stage Liver Disease-exception points for HCC should be expanded to allow more patients to receive life-saving transplantation.

Background: Liver transplantation (LT) is a well-established treatment for hepatocellular carcinoma (HCC), but there are ongoing debates regarding outcomes and selection. This study examines the experience of LT for HCC at a high-volume centre. Methods: A prospectively maintained database was used to identify HCC patients undergoing LT from 2000 to 2020 with more than or equal to 3-years follow-up. Data were obtained from the centre database and electronic medical records. The Metroticket 2.0 HCC-specific 5-year survival scale was calculated for each patient. Kaplan–Meier and Cox-regression analyses were employed assessing survival between groups based on Metroticket score and individual donor and recipient risk factors. Results: Five hundred sixty-nine patients met criteria. Median follow-up was 96.2 months (8.12 years; interquartile range 59.9–147.8). Three-year recurrence-free (RFS) and overall survival (OS) were 88.6% (n=504) and 86.6% (n=493). Five-year RFS and OS were 78.9% (n=449) and 79.1% (n=450). Median Metroticket 2.0 score was 0.9 (interquartile range 0.9–0.95). Tumour size greater than 3 cm (P=0.012), increasing tumour number on imaging (P=0.001) and explant pathology (P<0.001) was associated with recurrence. Transplant within Milan (P<0.001) or UCSF criteria (P<0.001) had lower recurrence rates. Increasing alpha-fetoprotein (AFP)-values were associated with more HCC recurrence (P<0.001) and reduced OS (P=0.008). Chemoembolization was predictive of recurrence in the overall population (P=0.043) and in those outside-Milan criteria (P=0.038). A receiver-operator curve using Metroticket 2.0 identified an optimal cut-off of projected survival greater than or equal to 87.5% for predicting recurrence. This cut-off was able to predict RFS (P<0.001) in the total cohort and predict both, RFS (P=0.007) and OS (P=0.016) outside Milan. Receipt of donation after brain death (DBD) grafts (55/478, 13%) or living-donor grafts (3/22, 13.6%) experienced better survival rates compared to donation after cardiac death (DCD) grafts (n=15/58, 25.6%, P=0.009). Donor age was associated with a higher HCC recurrence (P=0.006). Both total ischaemia time (TIT) greater than 6hours (P=0.016) and increasing TIT correlated with higher HCC recurrence (P=0.027). The use of DCD grafts for outside-Milan candidates was associated with increased recurrence (P=0.039) and reduced survival (P=0.033). Conclusion: This large two-centre analysis confirms favourable outcomes after LT for HCC. Tumour size and number, pre-transplant AFP, and Milan criteria remain important recipient HCC-risk factors. A higher donor risk (i.e. donor age, DCD grafts, ischaemia time) was associated with poorer outcomes.