Preoperative and postoperative predictive models of early recurrence for colorectal liver metastases following chemotherapy and curative-intent one-stage hepatectomy.

INTRODUCTION: Accurate prediction of patients at risk for early recurrence (ER) among patients with colorectal liver metastases (CRLM) following preoperative chemotherapy and hepatectomy remains limited. METHODS: Patients with CRLM who received chemotherapy prior to undergoing curative-intent resection between 2000 and 2020 were identified from an international multi-institutional database. Multivariable Cox regression analysis was used to assess clinicopathological factors associated with ER, and an online calculator was developed and validated. RESULTS: Among 768 patients undergoing preoperative chemotherapy and curative-intent resection, 128 (16.7 %) patients had ER. Multivariable Cox analysis demonstrated that Eastern Cooperative Oncology Group Performance status ≥1 (HR 2.09, 95%CI 1.46-2.98), rectal cancer (HR 1.95, 95%CI 1.35-2.83), lymph node metastases (HR 2.39, 95%CI 1.60-3.56), mutated Kirsten rat sarcoma oncogene status (HR 1.95, 95%CI 1.25-3.02), increase in tumor burden score during chemotherapy (HR 1.51, 95%CI 1.03-2.24), and bilateral metastases (HR 1.94, 95%CI 1.35-2.79) were independent predictors of ER in the preoperative setting. In the postoperative model, in addition to the aforementioned factors, tumor regression grade was associated with higher hazards of ER (HR 1.91, 95%CI 1.32-2.75), while receipt of adjuvant chemotherapy was associated with lower likelihood of ER (HR 0.44, 95%CI 0.30-0.63). The discriminative accuracy of the preoperative (training: c-index: 0.77, 95%CI 0.72-0.81; internal validation: c-index: 0.79, 95%CI 0.75-0.82) and postoperative (training: c-index: 0.79, 95%CI 0.75-0.83; internal validation: c-index: 0.81, 95%CI 0.77-0.84) models was favorable (https://junkawashima.shinyapps.io/CRLMfollwingchemotherapy/). CONCLUSIONS: Patient-, tumor- and treatment-related characteristics in the preoperative and postoperative setting were utilized to develop an online, easy-to-use risk calculator for ER following resection of CRLM.

The Spread Pattern of New Practice in Liver Transplantation in the United States.

BACKGROUND: Introducing new liver transplantation (LT) practices, like unconventional donor use, incurs higher costs, making evaluation of their prognostic justification crucial. This study reexamines the spread pattern of new LT practices and its prognosis across the United States. METHODS: The study investigated the spread pattern of new practices using the UNOS database (2014-2023). Practices included LT for hepatitis B/C (HBV/HCV) nonviremic recipients with viremic donors, LT for COVID-19-positive recipients, and LT using onsite machine perfusion (OMP). One year post-LT patient and graft survival were also evaluated. RESULTS: LTs using HBV/HCV donors were common in the East, while LTs for COVID-19 recipients and those using OMP started predominantly in California, Arizona, Texas, and the Northeast. K-means cluster analysis identified three adoption groups: facilities with rapid, slow, and minimal adoption rates. Rapid adoption occurred mainly in high-volume centers, followed by a gradual increase in middle-volume centers, with little increase in low-volume centers. The current spread patterns did not significantly affect patient survival. Specifically, for LTs with HCV donors or COVID-19 recipients, patient and graft survivals in the rapid-increasing group was comparable to others. In LTs involving OMP, the rapid- or slow-increasing groups tended to have better patient survival (p = 0.05) and significantly improved graft survival rates (p = 0.02). Facilities adopting new practices often overlap across different practices. DISCUSSION: Our analysis revealed three distinct adoption groups across all practices, correlating the adoption aggressiveness with LT volume in centers. Aggressive adoption of new practices did not compromise patient and graft survivals, supporting the current strategy. Understanding historical trends could predict the rise in future LT cases with new practices, aiding in resource distribution.

Chronological and Geographical Variations in the Incidence and Acceptance of COVID-19-Positive Donors and Outcomes Among Abdominal Transplant Patients.

INTRODUCTION: Given the importance of understanding COVID-19-positive donor incidence and acceptance, we characterize chronological and geographic variations in COVID-19 incidence relative to COVID-19-positive donor acceptance. METHODS: Data on deceased donors and recipients of liver and kidney transplants were obtained from the UNOS database between 2020 and 2023. Hierarchical cluster analysis was used to assess trends in COVID-19-positive donor incidence. Posttransplant graft and patient survival were assessed using Kaplan-Meier curves. RESULTS: From among 38 429 deceased donors, 1517 were COVID-19 positive. Fewer kidneys (72.4% vs. 76.5%, p < 0.001) and livers (56.4% vs. 62.0%, p < 0.001) were used from COVID-19-positive donors versus COVID-19-negative donors. Areas characterized by steadily increased COVID-19 donor incidence exhibit the highest transplantation acceptance rates (92.33%), followed by intermediate (84.62%) and rapidly increased (80.00%) COVID-19 incidence areas (p = 0.016). Posttransplant graft and patient survival was comparable among recipients, irrespective of donor COVID-19 status. CONCLUSIONS: Regions experiencing heightened rates of COVID-19-positive donors are associated with decreased acceptance of liver and kidney transplantation. Similar graft and patient survival is noted among recipients, irrespective of donor COVID-19 status. These findings emphasize the need for adaptive practices and unified medical consensus in navigating a dynamic pandemic.

Landscape of donor cause of death and its impact on liver transplant outcomes: a ten-year analysis from the UNOS database.

BACKGROUND: Cause of death (COD) is a predictor of liver transplant (LT) outcomes independent of donor age, yet has not been recently reappraised. METHODS: Analyzing UNOS database (2013-2022), the study explored COD trends and impacts on one-year post-LT graft survival (GS) and hazard ratios (HR) for graft failure. RESULTS: Of 80,282 brain-death donors, 55,413(69.0%) underwent initial LT. Anoxia became the predominant COD in 2015, increasing from 29.0% in 2013 to 45.1% in 2021, with notable increases in drug intoxication. Survival differences between anoxia and cerebrovascular accidents (CVA) recently became insignificant (P=0.95). Further analysis showed improved GS from intracranial hemorrhage/stroke (previously worse; P<0.01) (P=0.70). HRs for post-1-year graft failure showed reduced significance of CVA (vs.Anoxia) and intracranial hemorrhage/stroke (vs.any other COD) recently. Donors with intracranial hemorrhage/stroke, showing improved survival and HR, were allocated to recipients with lower MELD-Na, contrasting the trend for drug intoxication CODs. DISCUSSION: CVA, traditionally linked with poorer outcomes, shows improved GS and HRs (vs.Anoxia). This could be due to rising drug intoxication cases and the allocation of donors with drug intoxication to recipients with higher MELD-Na, and those with CVA to recipients with lower scores. While COD remains crucial in donor selection, proper matching can mitigate differences among CODs.

The suggestion of mitigating disparity in the liver transplantation field among ABO blood type.

Medical literature highlights differences in liver transplantation (LT) waitlist experiences among ABO blood types. Type AB candidates reportedly have higher LT rates and reduced mortality. Despite liver offering guidelines, ABO disparities persist. This study examines LT access discrepancies among blood types, focusing on type AB, and seeks equitable strategies. Using the United Network for Organ Sharing database (2003-2022), 170 276 waitlist candidates were retrospectively analyzed. Dual predictive analyses (LT opportunity and survival studies) evaluated 1-year recipient pool survival, considering waitlist and post-LT survival, alongside anticipated allocation value per recipient, under 6 scenarios. Of the cohort, 97 670 patients (57.2%) underwent LT. Type AB recipients had the highest LT rate (73.7% vs 55.2% for O), shortest median waiting time (90 vs 198 days for A), and lowest waitlist mortality (12.9% vs 23.9% for O), with the lowest median model for end-stage liver disease-sodium (MELD-Na) score (20 vs 25 for A/O). The LT opportunity study revealed that reallocating type A (or A and O) donors originally for AB recipients to A recipients yielded the greatest reduction in disparities in anticipated value per recipient, from 0.19 (before modification) to 0.08. Meanwhile, the survival study showed that ABO-identical LTs reduced disparity the most (3.5% to 2.8%). Sensitivity analysis confirmed these findings were specific to the MELD-Na score < 30 population, indicating current LT allocation may favor certain blood types. Prioritizing ABO-identical LTs for MELD-Na score < 30 recipients could ensure uniform survival outcomes and mitigate disparities.

Expanding Selection Criteria in Deceased Donor Liver Transplantation for Hepatocellular Carcinoma: Long-term Follow-up of a National Registry and 2 Transplant Centers.

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.

The Future Frontier of Liver Transplantation Exploring Young Donor Allocation Strategies for HCC Recipients.

Background: The role of donor age in liver transplantation (LT) outcomes for hepatocellular carcinoma (HCC) is controversial. Given the significant risk of HCC recurrence post-LT, optimizing donor/recipient matching is crucial. This study reassesses the impact of young donors on LT outcomes in patients with HCC. Methods: A retrospective review of 11 704 LT cases from the United Network for Organ Sharing database (2012-2021) was conducted. The study focused on the effect of donor age on recurrence-free survival, using hazard associated with LT for HCC (HALT-HCC) and Metroticket 2.0 scores to evaluate post-LT survival in patients with HCC. Results: Of 4706 cases with young donors, 11.0% had HCC recurrence or death within 2 y, and 18.3% within 5 y. These outcomes were comparable with those of non-young donors. A significant correlation between donor age and post-LT recurrence or mortality (P = 0.04) was observed, which became statistically insignificant after tumor-related adjustments (P = 0.32). The Kaplan-Meier curve showed that recipients with lower HALT-HCC scores (<9) and Metroticket 2.0 scores (<2.2) significantly benefited from young donors, unlike those exceeding these score thresholds. Cox regression analysis showed that donor age significantly influenced outcomes in recipients below certain score thresholds but was less impactful for higher scores. Conclusions: Young donors are particularly beneficial for LT recipients with less aggressive HCC, as indicated by their HALT-HCC and Metroticket 2.0 scores. These findings suggest strategically allocating young donors to recipients with less aggressive tumor profiles, which could foster more efficient use of the scarce donor supply and potentially enhance post-LT outcomes.

Continuous Risk Score Predicts Waitlist and Post-transplant Outcomes in Hepatocellular Carcinoma Despite Exception Changes.

BACKGROUND & AIMS: Continuous risk-stratification of candidates and urgency-based prioritization have been utilized for liver transplantation (LT) in patients with non-hepatocellular carcinoma (HCC) in the United States. Instead, for patients with HCC, a dichotomous criterion with exception points is still used. This study evaluated the utility of the hazard associated with LT for HCC (HALT-HCC), an oncological continuous risk score, to stratify waitlist dropout and post-LT outcomes. METHODS: A competing risk model was developed and validated using the UNOS database (2012-2021) through multiple policy changes. The primary outcome was to assess the discrimination ability of waitlist dropouts and LT outcomes. The study focused on the HALT-HCC score, compared with other HCC risk scores. RESULTS: Among 23,858 candidates, 14,646 (59.9%) underwent LT and 5196 (21.8%) dropped out of the waitlist. Higher HALT-HCC scores correlated with increased dropout incidence and lower predicted 5-year overall survival after LT. HALT-HCC demonstrated the highest area under the curve (AUC) values for predicting dropout at various intervals post-listing (0.68 at 6 months, 0.66 at 1 year), with excellent calibration (R2 = 0.95 at 6 months, 0.88 at 1 year). Its accuracy remained stable across policy periods and locoregional therapy applications. CONCLUSIONS: This study highlights the predictive capability of the continuous oncological risk score to forecast waitlist dropout and post-LT outcomes in patients with HCC, independent of policy changes. The study advocates integrating continuous scoring systems like HALT-HCC in liver allocation decisions, balancing urgency, organ utility, and survival benefit.

An updated analysis of retransplantation following living donor liver transplantation in the United States: Insights from the latest UNOS database.

There is no recent update on the clinical course of retransplantation (re-LT) after living donor liver transplantation (LDLT) in the US using recent national data. The UNOS database (2002-2023) was used to explore patient characteristics in initial LT, comparing deceased donor liver transplantation (DDLT) and LDLT for graft survival (GS), reasons for graft failure, and GS after re-LT. It assesses waitlist dropout and re-LT likelihood, categorizing re-LT cohort based on time to re-listing as acute or chronic (≤ or > 1 mo). Of 132,323 DDLT and 5955 LDLT initial transplants, 3848 DDLT and 302 LDLT recipients underwent re-LT. Of the 302 re-LT following LDLT, 156 were acute and 146 chronic. Primary nonfunction (PNF) was more common in DDLT, although the difference was not statistically significant (17.4% vs. 14.8% for LDLT; p = 0.52). Vascular complications were significantly higher in LDLT (12.5% vs. 8.3% for DDLT; p < 0.01). Acute re-LT showed a larger difference in primary nonfunction between DDLT and LDLT (49.7% vs. 32.0%; p < 0.01). Status 1 patients were more common in DDLT (51.3% vs. 34.0% in LDLT; p < 0.01). In the acute cohort, Kaplan-Meier curves indicated superior GS after re-LT for initial LDLT recipients in both short-term and long-term ( p = 0.02 and < 0.01, respectively), with no significant difference in the chronic cohort. No significant differences in waitlist dropout were observed, but the initial LDLT group had a higher re-LT likelihood in the acute cohort (sHR 1.40, p < 0.01). A sensitivity analysis focusing on the most recent 10-year cohort revealed trends consistent with the overall study findings. LDLT recipients had better GS in re-LT than DDLT. Despite a higher severity of illness, the DDLT cohort was less likely to undergo re-LT.

Impact of a Liver Immune Status Index among Living Liver Transplant Recipients with Hepatocellular Carcinoma.

Introduction: Hepatocellular carcinoma (HCC) is a major global health challenge, being the fifth most prevalent neoplasm and the third leading cause of cancer-related deaths worldwide. Liver transplantation offers a potentially curative approach for HCC, yet the risk of recurrence posttransplantation remains a significant concern. This study investigates the influence of a liver immune status index (LISI) on the prognosis of patients undergoing living-donor liver transplantation for HCC. Methods: In a single-center study spanning from 2001 to 2020, 113 patients undergoing living-donor liver transplantation for HCC were analyzed. LISI was calculated for each donor liver using body mass index, serum albumin levels, and the fibrosis-4 index. This study assessed the impact of donor LISI on short-term recurrence rates and survival, with special attention to its correlation with the antitumor activity of natural killer (NK) cells in the liver. Results: The patients were divided into two grades (high donor LISI, >-1.23 [n = 43]; and low donor LISI, ≤-1.23 [n = 70]). After propensity matching to adjust the background of recipient factors, the survival rates at 1 and 3 years were 92.6% and 88.9% and 81.5% and 70.4% in the low and high donor LISI groups, respectively (p = 0.11). The 1- and 3-year recurrence-free survival were 88.9% and 85.2% and 74.1% and 55.1% in the low and high donor LISI groups, respectively (p = 0.02). Conclusions: This study underscores the potential of an LISI as a noninvasive biomarker for assessing liver NK cell antitumor capacity, with implications for living-donor liver transplantation for HCC. Donor LISI emerges as a significant predictor of early recurrence risk following living-donor liver transplantation for HCC, highlighting the role of the liver antitumor activity of liver NK cells in managing liver malignancies.

Epstein-Barr virus-associated post-transplant lymphoproliferative disorders in pediatric transplantation: A prospective multicenter study in the United States.

BACKGROUND: Epstein-Barr virus (EBV)-associated post-transplant lymphoproliferative disorders (PTLD) is the most common malignancy in children after transplant; however, difficulties for early detection may worsen the prognosis. METHODS: The prospective, multicenter, study enrolled 944 children (≤21 years of age). Of these, 872 received liver, heart, kidney, intestinal, or multivisceral transplants in seven US centers between 2014 and 2019 (NCT02182986). In total, 34 pediatric EBV+ PTLD (3.9%) were identified by biopsy. Variables included sex, age, race, ethnicity, transplanted organ, EBV viral load, pre-transplant EBV serology, immunosuppression, response to chemotherapy and rituximab, and histopathological diagnosis. RESULTS: The uni-/multivariable competing risk analyses revealed the combination of EBV-seropositive donor and EBV-naïve recipient (D+R-) was a significant risk factor for PTLD development (sub-hazard ratio: 2.79 [1.34-5.78], p = .006) and EBV DNAemia (2.65 [1.72-4.09], p < .001). Patients with D+R- were significantly more associated with monomorphic/polymorphic PTLD than those with the other combinations (p = .02). Patients with monomorphic/polymorphic PTLD (n = 21) had significantly more EBV DNAemia than non-PTLD patients (p < .001) and an earlier clinical presentation of PTLD than patients with hyperplasias (p < .001), within 6-month post-transplant. Among non-liver transplant recipients, monomorphic/polymorphic PTLD were significantly more frequent than hyperplasias in patients ≥5 years of age at transplant (p = .01). CONCLUSIONS: D+R- is a risk factor for PTLD and EBV DNAemia and associated with the incidence of monomorphic/polymorphic PTLD. Intensive follow-up of EBV viral load within 6-month post-transplant, especially for patients with D+R- and/or non-liver transplant recipients ≥5 years of age at transplant, may help detect monomorphic/polymorphic PTLD early in pediatric transplant.

The impact of county-level food access on the mortality and post-transplant survival among patients with steatotic liver disease.

BACKGROUND: The impact of county-level food access on mortality associated with steatotic liver disease, as well as post-liver transplant outcomes among individuals with steatotic liver disease, have not been characterized. METHODS: Data on steatotic liver disease-related mortality and outcomes of liver transplant recipients with steatotic liver disease between 2010 and 2020 were obtained from the Centers for Disease Control Prevention mortality as well as the Scientific Registry of Transplant Recipients databases. These data were linked to the food desert score, defined as the proportion of the total population in each county characterized as having both low income and limited access to grocery stores. RESULTS: Among 2,710 counties included in the analytic cohort, median steatotic liver disease-related mortality was 27.3 per 100,000 population (interquartile range 24.9-32.1). Of note, patients residing in counties with high steatotic liver disease death rates were more likely to have higher food desert scores (low: 5.0, interquartile range 3.1-7.8 vs moderate: 6.1, interquartile range, 3.8-9.3 vs high: 7.6, interquartile range 4.1-11.7). Among 28,710 patients who did undergo liver transplantation, 5,310 (18.4%) individuals lived in counties with a high food desert score. Liver transplant recipients who resided in counties with the worst food access were more likely to have a higher body mass index (>35 kg/m2: low food desert score, 17.3% vs highest food desert score, 20.1%). After transplantation, there was no difference in 2-year graft survival relative to county-level food access (food desert score: low: 88.4% vs high: 88.6%; P = .77). CONCLUSION: Poor food access was associated with a higher incidence rate of steatotic liver disease-related death, as well as lower utilization of liver transplants. On the other hand, among patients who did receive a liver transplant, there was no difference in 2-year graft survival regardless of food access strata. Policy initiatives should target the expansion of transplantation services to vulnerable communities in which there is a high mortality of steatotic liver disease.

LightGBM outperforms other machine learning techniques in predicting graft failure after liver transplantation: Creation of a predictive model through large-scale analysis.

BACKGROUND: The incidence of graft failure following liver transplantation (LTx) is consistent. While traditional risk scores for LTx have limited accuracy, the potential of machine learning (ML) in this area remains uncertain, despite its promise in other transplant domains. This study aims to determine ML's predictive limitations in LTx by replicating methods used in previous heart transplant research. METHODS: This study utilized the UNOS STAR database, selecting 64,384 adult patients who underwent LTx between 2010 and 2020. Gradient boosting models (XGBoost and LightGBM) were used to predict 14, 30, and 90-day graft failure compared to conventional logistic regression model. Models were evaluated using both shuffled and rolling cross-validation (CV) methodologies. Model performance was assessed using the AUC across validation iterations. RESULTS: In a study comparing predictive models for 14-day, 30-day and 90-day graft survival, LightGBM consistently outperformed other models, achieving the highest AUC of.740,.722, and.700 in shuffled CV methods. However, in rolling CV the accuracy of the model declined across every ML algorithm. The analysis revealed influential factors for graft survival prediction across all models, including total bilirubin, medical condition, recipient age, and donor AST, among others. Several features like donor age and recipient diabetes history were important in two out of three models. CONCLUSIONS: LightGBM enhances short-term graft survival predictions post-LTx. However, due to changing medical practices and selection criteria, continuous model evaluation is essential. Future studies should focus on temporal variations, clinical implications, and ensure model transparency for broader medical utility.

Enhancing the usability of older DCD donors through strategic approaches in liver transplantation in the United States.

The use of older donors after circulatory death (DCD) for liver transplantation (LT) has increased over the past decade. This study examined whether outcomes of LT using older DCD (≥50 y) have improved with advancements in surgical/perioperative care and normothermic machine perfusion (NMP) technology. A total of 7602 DCD LT cases from the United Network for Organ Sharing database (2003-2022) were reviewed. The impact of older DCD donors on graft survival was assessed using the Kaplan-Meier and HR analyses. In all, 1447 LT cases (19.0%) involved older DCD donors. Although there was a decrease in their use from 2003 to 2014, a resurgence was noted after 2015 and reached 21.9% of all LTs in the last 4 years (2019-2022). Initially, 90-day and 1-year graft survivals for older DCDs were worse than younger DCDs, but this difference decreased over time and there was no statistical difference after 2015. Similarly, HRs for graft loss in older DCD have recently become insignificant. In older DCD LT, NMP usage has increased recently, especially in cases with extended donor-recipient distances, while the median time from asystole to aortic cross-clamp has decreased. Multivariable Cox regression analyses revealed that in the early phase, asystole to cross-clamp time had the highest HR for graft loss in older DCD LT without NMP, while in the later phases, the cold ischemic time (>5.5 h) was a significant predictor. LT outcomes using older DCD donors have become comparable to those from young DCD donors, with recent HRs for graft loss becoming insignificant. The strategic approach in the recent period could mitigate risks, including managing cold ischemic time (≤5.5 h), reducing asystole to cross-clamp time, and adopting NMP for longer distances. Optimal use of older DCD donors may alleviate the donor shortage.

Effect of the opioid crisis on the liver transplantation donor pool: A national analysis.

BACKGROUND: Over the last decade there has been a surge in overdose deaths due to the opioid crisis. We sought to characterize the temporal change in overdose donor (OD) use in liver transplantation (LT), as well as associated post-LT outcomes, relative to the COVID-19 era. METHODS: LT candidates and donors listed between January 2016 and September 2022 were identified from the Scientific Registry of Transplant Recipients database. Trends in LT donors and changes related to OD were assessed pre- versus post-COVID-19 (February 2020). RESULTS: Between 2016 and 2022, most counties in the United States experienced an increase in overdose-related deaths (n = 1284, 92.3%) with many counties (n = 458, 32.9%) having more than a doubling in drug overdose deaths. Concurrently, there was an 11.2% increase in overall donors, including a 41.7% increase in the number of donors who died from drug overdose. In pre-COVID-19 overdose was the 4th top mechanism of donor death, while in the post-COVID-19 era, overdose was the 2nd most common cause of donor death. OD was younger (OD: 35 yrs, IQR 29-43 vs. non-OD: 43 yrs, IQR 31-56), had lower body mass index (≥35 kg/cm2, OD: 31.2% vs. non-OD: 33.5%), and was more likely to be HCV+ (OD: 28.9% vs. non-OD: 5.4%) with lower total bilirubin (≥1.1 mg/dL, OD: 12.9% vs. non-OD: 20.1%) (all p < .001). Receipt of an OD was not associated with worse graft survival (HR .94, 95% CI .88-1.01, p = .09). CONCLUSIONS: Opioid deaths markedly increased following the COVID-19 pandemic, substantially altering the LT donor pool in the United States.

Early Onset Intrahepatic Cholangiocarcinoma: Clinical Characteristics, Oncological Outcomes, and Genomic/Transcriptomic Features.

INTRODUCTION: Data on clinical characteristics and disease-specific prognosis among patients with early onset intrahepatic cholangiocarcinoma (ICC) are currently limited. METHODS: Patients undergoing hepatectomy for ICC between 2000 and 2020 were identified by using a multi-institutional database. The association of early (≤50 years) versus typical onset (>50 years) ICC with recurrence-free (RFS) and disease-specific survival (DSS) was assessed in the multi-institutional database and validated in an external cohort. The genomic and transcriptomic profiles of early versus late onset ICC were analyzed by using the Total Cancer Genome Atlas (TCGA) and Memorial Sloan Kettering Cancer Center databases. RESULTS: Among 971 patients undergoing resection for ICC, 22.7% (n = 220) had early-onset ICC. Patients with early-onset ICC had worse 5-year RFS (24.1% vs. 29.7%, p < 0.05) and DSS (36.5% vs. 48.9%, p = 0.03) compared with patients with typical onset ICC despite having earlier T-stage tumors and lower rates of microvascular invasion. In the validation cohort, patients with early-onset ICC had worse 5-year RFS (7.4% vs. 20.5%, p = 0.002) compared with individuals with typical onset ICC. Using the TCGA cohort, 652 and 266 genes were found to be upregulated (including ATP8A2) and downregulated (including UTY and KDM5D) in early versus typical onset ICC, respectively. Genes frequently implicated as oncogenic drivers, including CDKN2A, IDH1, BRAF, and FGFR2 were infrequently mutated in the early-onset ICC patients. CONCLUSIONS: Early-onset ICC has distinct clinical and genomic/transcriptomic features. Morphologic and clinicopathologic characteristics were unable to fully explain differences in outcomes among early versus typical onset ICC patients. The current study offers a preliminary landscape of the molecular features of early-onset ICC.