HCC recurrence following liver transplantation (LT) is highly morbid and occurs despite strict patient selection criteria. Individualized prediction of post-LT HCC recurrence risk remains an important need. Clinico-radiologic and pathologic data of 4981 patients with HCC undergoing LT from the US Multicenter HCC Transplant Consortium (UMHTC) were analyzed to develop a REcurrent Liver cAncer Prediction ScorE (RELAPSE). Multivariable Fine and Gray competing risk analysis and machine learning algorithms (Random Survival Forest and Classification and Regression Tree models) identified variables to model HCC recurrence. RELAPSE was externally validated in 1160 HCC LT recipients from the European Hepatocellular Cancer Liver Transplant study group. Of 4981 UMHTC patients with HCC undergoing LT, 71.9% were within Milan criteria, 16.1% were initially beyond Milan criteria with 9.4% downstaged before LT, and 12.0% had incidental HCC on explant pathology. Overall and recurrence-free survival at 1, 3, and 5 years was 89.7%, 78.6%, and 69.8% and 86.8%, 74.9%, and 66.7%, respectively, with a 5-year incidence of HCC recurrence of 12.5% (median 16 months) and non-HCC mortality of 20.8%. A multivariable model identified maximum alpha-fetoprotein (HR = 1.35 per-log SD, 95% CI,1.22–1.50, p < 0.001), neutrophil-lymphocyte ratio (HR = 1.16 per-log SD, 95% CI,1.04–1.28, p < 0.006), pathologic maximum tumor diameter (HR = 1.53 per-log SD, 95% CI, 1.35–1.73, p < 0.001), microvascular (HR = 2.37, 95%–CI, 1.87–2.99, p < 0.001) and macrovascular (HR = 3.38, 95% CI, 2.41–4.75, p < 0.001) invasion, and tumor differentiation (moderate HR = 1.75, 95% CI, 1.29–2.37, p < 0.001; poor HR = 2.62, 95% CI, 1.54–3.32, p < 0.001) as independent variables predicting post-LT HCC recurrence (C-statistic = 0.78). Machine learning algorithms incorporating additional covariates improved prediction of recurrence (Random Survival Forest C-statistic = 0.81). Despite significant differences in European Hepatocellular Cancer Liver Transplant recipient radiologic, treatment, and pathologic characteristics, external validation of RELAPSE demonstrated consistent 2- and 5-year recurrence risk discrimination (AUCs 0.77 and 0.75, respectively). We developed and externally validated a RELAPSE score that accurately discriminates post-LT HCC recurrence risk and may allow for individualized post-LT surveillance, immunosuppression modification, and selection of high-risk patients for adjuvant therapies.

Immune cell–based therapies are promising strategies to facilitate immunosuppression withdrawal after organ transplantation. Regulatory dendritic cells (DCreg) are innate immune cells that down-regulate alloimmune responses in preclinical models. Here, we performed clinical monitoring and comprehensive assessment of peripheral and allograft tissue immune cell populations in DCreg-infused live-donor liver transplant (LDLT) recipients up to 12 months (M) after transplant. Thirteen patients were given a single infusion of donor-derived DCreg 1 week before transplant (STUDY) and were compared with 40 propensity-matched standard-of-care (SOC) patients. Donor-derived DCreg infusion was well tolerated in all STUDY patients. There were no differences in postoperative complications or biopsy-confirmed acute rejection compared with SOC patients up to 12M. DCreg administration was associated with lower frequencies of effector T-bet⁺Eomes⁺CD8⁺T cells and CD16^brightnatural killer (NK) cells and an increase in putative tolerogenic CD141⁺CD163⁺DCs compared with SOC at 12M. Antidonor proliferative capacity of interferon-γ⁺(IFN-γ⁺) CD4⁺and CD8⁺T cells was lower compared with antithird party responses in STUDY participants, but not in SOC patients, at 12M. In addition, lower circulating concentrations of interleukin-12p40 (IL-12p40), IFN-γ, and CXCL10 were detected in STUDY participants compared with SOC patients at 12M. Analysis of 12M allograft biopsies revealed lower frequencies of graft-infiltrating CD8⁺T cells, as well as attenuation of cytolytic T_H1 effector genes and pathways among intragraft CD8⁺T cells and NK cells, in DCreg-infused patients. These reductions may be conducive to reduced dependence on immunosuppressive drug therapy or immunosuppression withdrawal.

Our experience with living related donor (LRD) pancreas transplants shows that they can be performed with low morbidity and mortality for both donors and recipients. The recipient survival rate is 90% at both 1 and 5 years post-transplant. Our overall pancreas graft survival rate is comparable to that for cadaver transplants; if only technically successful cases are included, the graft survival rate is significantly better for LRD (versus cadaver) transplants. Advantages for LRD recipients include fewer rejection episodes, less immunosuppression, lower incidence of graft loss from rejection, and elimination of waiting time. Donor mortality in our series was 0%, and the incidence of surgical complications about 10–15%. LRD pancreas transplants are an attractive option for endocrine replacement therapy in certain diabetic patients. Optimal candidates are: (i) patients who are highly sensitized and have a low probability of receiving a cadaver graft; (ii) patients who should avoid high-dose immunosuppression; (iii) patients with nondiabetic identical twins; and (iv) uremic patients who want one operation with no waiting in order to remain or become dialysis free as well as insulin-independent. These transplants can be performed safely in all recipient categories—pancreas transplant alone, pancreas after kidney or simultaneous pancreas—kidney transplant. In all groups, LRD transplants should be done only when the donor, the recipient, and the entire family understands the advantages and disadvantages of LRD versus cadaver transplants.

In recent years, liver transplantation has emerged as a treatment for patients with stage IV colorectal liver metastases (CRLM). Given the limited number of available deceased donor grafts, the use of living donor liver transplantation (LDLT) can be an important option. We performed a retrospective analysis of 10 patients that underwent LDLT for CRLM at our institution. 90% of patients were male with median age of 58 years and median MELD of 11 (range:6-32). The rectum was the most common primary location (40%). Synchronous liver tumors were found in 50%. Pre-transplant patients underwent resection (60%), HAI pump (50%) and/or RFA (50%). Everybody underwent adjuvant chemotherapy. Median cold ischemia time was 103 min (range:93-207 min), median total OR time was 11.5 h (range:8.5-13.9 h). 30% of patients had postoperative complications requiring re-operation. Mean RFS was 2.2 years (95%CI 1.2-3.2 y), mean OS was 3.0 years (95%CI 2.5-3.6 y). 30% of patients suffered a recurrence and 90% of patients are currently alive. This study represents the largest single center analysis in North America on patients undergoing LDLT for CRLM. LDLT is a safe and effective alternative for patients with CRLM who do not have progressive disease or extrahepatic metastasis.