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Objective: To evaluate long-term oncologic outcomes of patients post-living donor liver transplantation (LDLT) within and outside standard transplantation selection criteria and the added value of the incorporation of the New York-California (NYCA) score., Background: LDLT offers an opportunity to decrease the liver transplantation waitlist, reduce waitlist mortality, and expand selection criteria for patients with hepatocellular carcinoma (HCC)., Methods: Primary adult LDLT recipients between October 1999 and August 2019 were identified from a multicenter cohort of 12 North American centers. Posttransplantation and recurrence-free survival were evaluated using the Kaplan-Meier method., Results: Three hundred sixty LDLTs were identified. Patients within Milan criteria (MC) at transplantation had a 1, 5, and 10-year posttransplantation survival of 90.9%, 78.5%, and 64.1% versus outside MC 90.4%, 68.6%, and 57.7% ( P = 0.20), respectively. For patients within the University of California San Francisco (UCSF) criteria, respective posttransplantation survival was 90.6%, 77.8%, and 65.0%, versus outside UCSF 92.1%, 63.8%, and 45.8% ( P = 0.08). Fifty-three (83%) patients classified as outside MC at transplantation would have been classified as either low or acceptable risk with the NYCA score. These patients had a 5-year overall survival of 72.2%. Similarly, 28(80%) patients classified as outside UCSF at transplantation would have been classified as a low or acceptable risk with a 5-year overall survival of 65.3%., Conclusions: Long-term survival is excellent for patients with HCC undergoing LDLT within and outside selection criteria, exceeding the minimum recommended 5-year rate of 60% proposed by consensus guidelines. The NYCA categorization offers insight into identifying a substantial proportion of patients with HCC outside the MC and the UCSF criteria who still achieve similar post-LDLT outcomes as patients within the criteria., Competing Interests: G.S. discloses consultancy for Astra-Zeneca, Roche, Evidera, Novartis, and Integra. He has received financial compensation for talks for Roche, Astra-Zeneca, Chiesi, and Integra. Also, he has received a grant from Roche. The remaining authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: Patients with unresectable hilar cholangiocarcinoma (hCCA) may be eligible for curative treatment through liver transplantation (LT). Neoadjuvant protocols often include radiotherapy (RT), however, there is no standard RT approach. The purpose of this study is to characterize practice patterns of RT use before transplantation for hCCA., Methods: A survey was administered to radiation oncologists practicing at LT centers identified through the U.S. Organ Procurement and Transplant Network and the International Cholangiocarcinoma Research Network. The survey consisted of 13 questions regarding RT details as well as approaches to systemic therapy. For cross-regimen comparison, the cumulative RT tumor dose was standardized using the EQD2 method., Results: Twenty-three centers utilizing neoadjuvant therapy for hCCA were identified. Most respondents (96%) use both chemotherapy and RT as part of their protocol. Elective nodal volumes commonly included the portal vein lymph nodes (91%) and celiac artery lymph nodes (70%). After an initial 45 Gy plan, a wide range of sequential boost regimens was used. The median cumulative dose including boosts to the gross disease was 58 Gy (EQD2) with a wide range of 40 to 110 Gy. Five (22%) include brachytherapy as part of their treatment plan. The majority (96%) used concurrent chemotherapy with fluoropyrimidines., Conclusions: These results suggest significant variability of neoadjuvant RT use for hCCA before LT. A wide range of doses and fractionation schemes are utilized with cumulative doses ranging from 40 to 110 Gy (EQD2). A further study evaluating the efficacy and toxicity of these various approaches is warranted to better inform best practices., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

As with any other intervention in health, liver transplantation (LT) entails a variety of risks, including donor-transmitted cancers (DTCs). At present, 2%-4% of used deceased organ donors are known to have a current or past history of malignancy. The frequency of DTCs is consistently reported at 3-6 cases per 10 000 solid organ transplants, with a similar frequency in the LT setting. A majority of DTCs are occult cancers unknown in the donor at the time of transplantation. Most DTCs are diagnosed within 2 y after LT and are associated with a 51% probability of survival at 2 y following diagnosis. The probability of death is greatest for DTCs that have already metastasized at the time of diagnosis. The International Liver Transplantation Society-Sociedad Española de Trasplante Hepático working group on DTC has provided guidance on how to minimize the occurrence of DTCs while avoiding the unnecessary loss of livers for transplantation both in deceased and living donor LT. The group endorses the Council of Europe classification of risk of transmission of cancer from donor to recipient (minimal, low to intermediate, high, and unacceptable), classifies a range of malignancies in the liver donor into these 4 categories, and recommends when to consider LT, mindful of the risk of DTCs, and the clinical condition of patients on the waiting list. We further provide recommendations to professionals who identify DTC events, stressing the need to immediately alert all stakeholders concerned, so a coordinated investigation and management can be initiated; decisions on retransplantation should be made on a case-by-case basis with a multidisciplinary approach., Competing Interests: The authors declare no funding or conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Portopulmonary hypertension (POPH) is the presence of pulmonary arterial (PA) hypertension in patients with portal hypertension and is associated with significant morbidity and mortality. In a cohort of POPH patients, we describe the clinical outcomes of POPH patients who underwent liver transplantation (LT)., Methods: Retrospectively collected data from a prospectively assembled cohort of all consecutive POPH adults evaluated in 3 transplant centers from 1996 to 2019., Results: From a cohort of 228 POPH patients, 50 patients underwent LT. Significant hemodynamic improvement after PA-targeted therapy was observed, with 58% receiving only monotherapy pretransplant. After LT, 21 (42%) patients were able to discontinue and remained off PA-targeted therapy. The 1-, 3-, and 5-y unadjusted survival rates after LT were 72%, 63%, and 60%, respectively. An elevated pulmonary vascular resistance (PVR) before LT was associated with worse survival rate (HR, 1.91; 95% CI, 1.07-3.74, P = 0.04). No survival difference was observed in those granted MELD exception or transplants performed before or after the year 2010., Conclusions: Significant number of POPH patients discontinued PA-targeted therapy after LT. Higher PVR before LT was associated with worse survival, as was monotherapy use. Despite effective PA-targeted therapies, POPH survival outcomes after LT in our cohort were modest and may reflect the need for more aggressive therapy., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Transplant oncology defines any application of transplant medicine and surgery aimed at improving cancer patients' survival and/or quality of life. In practice, liver transplantation for selected hepato-biliary cancers is the only solid organ transplant with demonstrated efficacy in curing cancer. Four are the proposed future contributions of transplant oncology in hepato-biliary cancer (4-e). (1) evolutionary approach to cancer care that includes liver transplantation; (2) elucidation of self and non-self recognition systems, by linking tumor and transplant immunology; (3) exploration of innovative endpoints both in clinical and experimental settings taking advantage from the access to the entire liver explant; (4) extension of surgical limitation in the multidisciplinary approach to hepato-biliary oncology. The aim of this review is to define the principles of transplant oncology that may be applied to hepato-biliary cancer treatment and research, attempting to balance current evidences with future opportunities., Competing Interests: The authors declare no conflict of interests., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Liver transplantation for cholangiocarcinoma has been an absolute contraindication worldwide due to poor results. However, in recent years and thanks to improvements of patient management and treatments of this cancer, this indication has been revisited. This consensus paper, approved by the International Liver Transplant Society, aims to provide a collection of expert opinions, consensus, and best practices surrounding liver transplantation for cholangiocarcinoma.

Background: Hepatic steatosis is strongly associated with cardiovascular disease in the general population. Whether recurrent or de novo, it can occur in the allograft, but the impact on survival and long-term clinical outcomes remains unclear. In this study, we aim to determine both the frequency and impact of allograft steatosis on long-term posttransplant outcomes., Methods: A retrospective review of 588 adult liver transplant (LT) recipients (1999-2006) was performed. Cox regression analysis (time-dependent) was used to evaluate differences in time to steatosis post-LT, patient survival, and cardiovascular outcomes., Results: Mean age 51.9 ± 10.6 years, 64.6% males, underlying nonalcoholic steatohepatitis (NASH) (9.4%), previous tobacco (52%), pre-LT diabetes mellitus (30.3%), pre-LT hypertension (23.2%), and known cardiovascular disease (9.7%). Overall, 254 recipients developed allograft steatosis (at 10 years: 77.6% NASH recipients, 44.7% Non-NASH recipients). Risk factors for allograft steatosis were female sex (hazard ratio [HR], 1.47; 95% confidence interval [CI], 1.09-2.00; P = 0.014), hepatitis C virus diagnosis (HR, 2.49; 95% CI, 1.77-3.94; P < 0.001), and time-dependent BMI (per unit: HR, 1.08; 95% CI, 1.05-1.10; P < 0.001). Allograft steatosis was not associated with post-LT survival (P = 0.25) nor cardiovascular events (HR, 1.08; 95% CI, 0.73-1.59; P = 0.70). Underlying NASH associated with cardiovascular events (HR, 2.04; 95% CI, 1.37-3.04; P < 0.001)., Conclusions: Allograft steatosis is common but not associated with survival or cardiovascular events in this study. Larger prospective studies are needed to better define the natural history of allograft steatosis.

Background: Weight gain early after transplant is a risk factor for posttransplant metabolic syndrome (PTMS), cardiovascular events, and renal insufficiency. The impact of mammalian target of rapamycin inhibition on posttransplant weight gain and the development of PTMS components postliver transplantation were examined in a randomized, controlled study., Methods: After a run-in period, patients (N = 719) were randomized at 30 ± 5 days posttransplant in a 1:1:1 ratio to 3 treatment groups: (i) everolimus (EVR) + reduced tacrolimus (TAC) (n = 245); (ii) TAC control (n = 243) or (iii) TAC elimination (n = 231). In this post hoc analysis, weight change at 12 and 24 months was compared between groups. Vital signs, lipids, and laboratory parameters at 12 and 24 months and rates of PTMS were assessed., Results: Mean increase in weight from baseline was higher at month 12 in the TAC control arm (8.15 ± 9.27 kg) than in the EVR + reduced TAC (5.88 ± 12.60 kg, P = 0.056) and the TAC elimination arms (4.76 ± 9.94 kg, P = 0.007). At month 24, the TAC control arm displayed a significantly greater weight increase (9.54 ± 10.21 kg) than either the EVR + reduced TAC (6.69 ± 8.37 kg, P = 0.011) or the TAC elimination groups (6.01 ± 9.98 kg, P = 0.024). Rates of PTMS were similar for the EVR + reduced TAC (71.8%), TAC elimination (70.3%) and TAC control (67.4%) arms (P = NS)., Conclusions: EVR with reduced-exposure TAC attenuated weight gain at 1 and 2 years posttransplant compared with a standard TAC immunosuppression regimen. Rates of PTMS were comparable between EVR-containing and TAC control regimens.

Background: It has been postulated that short wait time before liver transplant (LT) for hepatocellular carcinoma (HCC) results in the inclusion of tumors with aggressive biology, but prolonged wait time could result in a shift to more aggressive tumor behavior. We therefore test the hypothesis that a wait time "sweet spot" exists with a lower risk for HCC recurrence compared with the other 2 extremes., Methods: This multicenter study included 911 patients from 3 LT centers with short, medium, and long wait times (median of 4, 7, and 13 months, respectively) who received Model for End Stage Liver Disease exception listing for HCC from 2002 to 2012., Results: Wait time, defined as time from initial HCC diagnosis to LT, was less than 6 months in 32.4%, 6 to 18 months in 53.7%, and greater than 18 months in 13.9%. Waitlist dropout was observed in 18.4% at a median of 11.3 months. Probability of HCC recurrence at 1 and 5 years were 6.4% and 15.5% with wait time of less than 6 or greater than 18 months (n = 343) versus 4.5% and 9.8% with wait time of 6 to 18 months (n = 397), respectively (P = 0.049). When only pre-LT factors were considered, wait time of less than 6 or greater than 18 months (HR, 1.6; P = 0.043) and AFP greater than 400 at HCC diagnosis (HR, 3.0; P < 0.001) predicted HCC recurrence in multivariable analysis., Conclusions: This large multicenter study provides evidence of an association between very short (<6 months) or very long (>18 months) wait times and an increased risk for HCC recurrence post-LT. The so-called sweet spot of 6 to 18 months should be the target to minimize HCC recurrence.