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  • An updated analysis of retransplantation following living donor liver transplantation in the US: insights from the latest UNOS database. Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society Akabane, M., Imaoka, Y., Esquivel, C. O., Sasaki, K. 2024

    Abstract

    BACKGROUND: 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.METHOD: 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 >1mo).RESULTS: Of 132,323 DDLT and 5,955 LDLT initial transplants, 3,848 DDLT and 302 LDLT recipients underwent re-LT. Of the 302 re-LT following LDLT, 156 were acute and 146 chronic. Primary non-function (PNF) was more common in DDLT, although the difference was not statistically significant (17.4%vs14.8% for LDLT; p=0.52). Vascular complications were significantly higher in LDLT (12.5%vs8.3% for DDLT; p<0.01). Acute re-LT showed a larger difference in PNF between DDLT and LDLT (49.7%vs32.0%; p<0.01). Status 1 patients were more common in DDLT (51.3%vs34.0% in LDLT; p<0.01). In the acute cohort, Kaplan-Meier curves indicated superior GS post-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.CONCLUSION: 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.

    View details for DOI 10.1097/LVT.0000000000000393

    View details for PubMedID 38727618

  • Enhancing the Usability of older DCD donors through strategic approaches in liver transplantation in the US. Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society Akabane, M., Melcher, M. L., Esquivel, C. O., Imaoka, Y., Kim, W. R., Sasaki, K. 2024

    Abstract

    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.7,602 DCD LT cases from the UNOS database(2003-2022) were reviewed. The impact of older DCD donors on graft survival(GS) was assessed using Kaplan-Meier and hazard ratio(HR) analyses.1,447 LT cases(19.0%) involved older DCD donors. Although there was a decrease in their use from 2003-2014, a resurgence was noted post-2015 and reached 21.9% of all LT in the last four years(2019-2022). Initially, 90-day and one-year GS 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 CIT(>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 CIT(≤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.

    View details for DOI 10.1097/LVT.0000000000000376

    View details for PubMedID 38625836

  • Impact of a Liver Immune Status Index among Living Liver Transplant Recipients with Hepatocellular Carcinoma. JMA journal Imaoka, Y., Ohira, M., Sato, S., Chogahara, I., Bekki, T., Imaoka, K., Nakano, R., Yano, T., Sakai, H., Kuroda, S., Tahara, H., Ide, K., Kobayashi, T., Tanaka, Y., Akabane, M., Sasaki, K., Ohdan, H. 2024; 7 (2): 232-239

    Abstract

    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.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.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).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.

    View details for DOI 10.31662/jmaj.2023-0195

    View details for PubMedID 38721076

    View details for PubMedCentralID PMC11074505

  • Impact of donor characteristics on hepatocellular carcinoma recurrence after liver transplantation. The British journal of surgery Akabane, M., Bekki, Y., Imaoka, Y., Inaba, Y., Esquivel, C. O., Melcher, M. L., Kwong, A., Sasaki, K. 2024; 111 (4)

    View details for DOI 10.1093/bjs/znae080

    View details for PubMedID 38630794

  • LightGBM outperforms other machine learning techniques in predicting graft failure after liver transplantation: Creation of a predictive model through large-scale analysis. Clinical transplantation Yanagawa, R., Iwadoh, K., Akabane, M., Imaoka, Y., Bozhilov, K. K., Melcher, M. L., Sasaki, K. 2024; 38 (4): e15316

    Abstract

    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.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.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.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.

    View details for DOI 10.1111/ctr.15316

    View details for PubMedID 38607291

  • Breaking distance barriers in liver transplantation: Risk factors and outcomes of long-distance liver grafts. Surgery Imaoka, Y., Bozhilov, K. K., Bekki, Y., Akabane, M., Kwong, A. J., Ohira, M., Ohdan, H., Esquivel, C. O., Melcher, M. L., Sasaki, K. 2023

    Abstract

    Long-distance-traveling liver grafts in liver transplantation present challenges due to prolonged cold ischemic time and increased risk of ischemia-reperfusion injury. We identified long-distance-traveling liver graft donor and recipient characteristics and risk factors associated with long-distance-traveling liver graft use.We conducted a retrospective analysis of data from donor liver transplantation patients registered from 2014 to 2020 in the United Network for Organ Sharing registry database. Donor, recipient, and transplant factors of graft survival were compared between short-travel grafts and long-distance-traveling liver grafts (traveled >500 miles).During the study period, 28,265 patients received a donation after brainstem death liver transplantation and 3,250 a donation after circulatory death liver transplantation. The long-distance-traveling liver graft rate was 6.2% in donation after brainstem death liver transplantation and 7.1% in donation after circulatory death liver transplantation. The 90-day graft survival rates were significantly worse for long-distance-traveling liver grafts (donation after brainstem death: 95.7% vs 94.5%, donation after circulatory death: 94.5% vs 93.9%). The 3-year graft survival rates were similar for long-distance-traveling liver grafts (donation after brainstem death: 85.5% vs 85.1%, donation after circulatory death: 81.0% vs 80.4%). Cubic spline regression analyses revealed that travel distance did not linearly worsen the prognosis of 3-year graft survival. On the other hand, younger donor age, lower donor body mass index, and shorter cold ischemic time mitigated the negative impact of 90-day graft survival in long-distance-traveling liver grafts.The use of long-distance-traveling liver grafts negatively impacts 90-day graft survival but not 3-year graft survival. Moreover, long-distance-traveling liver grafts are more feasible with appropriate donor and recipient factors offsetting the extended cold ischemic time. Mechanical perfusion can improve long-distance-traveling liver graft use. Enhanced collaboration between organ procurement organizations and transplant centers and optimized transportation systems are essential for increasing long-distance-traveling liver graft use, ultimately expanding the donor pool.

    View details for DOI 10.1016/j.surg.2023.09.052

    View details for PubMedID 37980203

  • The short and long-term prognostic influences of liver grafts with high bilirubin levels at the time of organ recovery. Clinical transplantation Akabane, M., Bekki, Y., Imaoka, Y., Inaba, Y., Kwong, A. J., Esquivel, C. O., Melcher, M. L., Sasaki, K. 2023: e15155

    Abstract

    Donors with hyperbilirubinemia are often not utilized for liver transplantation (LT) due to concerns about potential liver dysfunction and graft survival. The potential to mitigate organ shortages using such donors remains unclear.This study analyzed adult deceased donor data from the United Network for Organ Sharing database (2002-2022). Hyperbilirubinemia was categorized as high total bilirubin (3.0-5.0 mg/dL) and very high bilirubin (≥5.0 mg/dL) in brain-dead donors. We assessed the impact of donor hyperbilirubinemia on 3-month and 3-year graft survival, comparing these outcomes to donors after circulatory death (DCD).Of 138 622 donors, 3452 (2.5%) had high bilirubin and 1999 (1.4%) had very high bilirubin levels. Utilization rates for normal, high, and very high bilirubin groups were 73.5%, 56.4%, and 29.2%, respectively. No significant differences were found in 3-month and 3-year graft survival between groups. Donors with high bilirubin had superior 3-year graft survival compared to DCD (hazard ratio .83, p = .02). Factors associated with inferior short-term graft survival included recipient medical condition in intensive care unit (ICU) and longer cold ischemic time; factors associated with inferior long-term graft survival included older donor age, recipient medical condition in ICU, older recipient age, and longer cold ischemic time. Donors with ≥10% macrosteatosis in the very high bilirubin group were also associated with worse 3-year graft survival (p = .04).The study suggests that despite many grafts with hyperbilirubinemia being non-utilized, acceptable post-LT outcomes can be achieved using donors with hyperbilirubinemia. Careful selection may increase utilization and expand the donor pool without negatively affecting graft outcome.

    View details for DOI 10.1111/ctr.15155

    View details for PubMedID 37812571

  • Identifying high TRAIL-expressing liver NK cells from deceased and living donors for effective immunotherapy Imaoka, Y., Akabane, M., Ohira, M., Ohdan, H., Sasaki, K. LIPPINCOTT WILLIAMS & WILKINS. 2023: 48-49
  • Preserving Liver Natural Killer Cell Activity: Developing Novel Culture Techniques for "Off-the-Shelf" Cell Immunotherapy Imaoka, Y., Akabane, M., Ohira, M., Ohdan, H., Sasaki, K. LIPPINCOTT WILLIAMS & WILKINS. 2023: 169
  • Has the risk of liver re-transplantation improved over the two decades? Clinical transplantation Akabane, M., Bekki, Y., Imaoka, Y., Inaba, Y., Esquivel, C. O., Kwong, A., Melcher, M. L., Sasaki, K. 2023: e15127

    Abstract

    Despite advancements in liver transplantation (LT) over the past two decades, liver re-transplantation (re-LT) presents challenges. This study aimed to assess improvements in re-LT outcomes and contributing factors.Data from the United Network for Organ Sharing database (2002-2021) were analyzed, with recipients categorized into four-year intervals. Trends in re-LT characteristics and postoperative outcomes were evaluated.Of 128,462 LT patients, 7254 received re-LT. Graft survival (GS) for re-LT improved (91.3%, 82.1%, and 70.8% at 30 days, 1 year, and 3 years post-LT from 2018 to 2021). However, hazard ratios (HRs) for GS remained elevated compared to marginal donors including donors after circulatory death (DCD), although the difference in HRs decreased in long-term GS. Changes in re-LT causes included a reduction in hepatitis C recurrence and an increase in graft failure post-primary LT involving DCD. Trends identified included recent decreased cold ischemic time (CIT) and increased distance from donor hospital in re-LT group. Meanwhile, DCD cohort exhibited less significant increase in distance and more marked decrease in CIT. The shortest CIT was recorded in urgent re-LT group. The highest Model for End-Stage Liver Disease score was observed in urgent re-LT group, while the lowest was recorded in DCD group. Analysis revealed shorter time interval between previous LT and re-listing, leading to worse outcomes, and varying primary graft failure causes influencing overall survival post-re-LT.While short-term re-LT outcomes improved, challenges persist compared to DCD. Further enhancements are required, with ongoing research focusing on optimizing risk stratification models and allocation systems for better LT outcomes.

    View details for DOI 10.1111/ctr.15127

    View details for PubMedID 37772621

  • Overcoming the hurdles of steatotic grafts in liver transplantation: insights into survival and prognostic factors. Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society Akabane, M., Imaoka, Y., Esquivel, C. O., Melcher, M. L., Kwong, A., Sasaki, K. 2023

    Abstract

    With increasing metabolic dysfunction associated steatotic liver disease (MASLD), the use of steatotic grafts in liver transplantation (LT) and their impact on postoperative graft survival (GS) needs further exploration.Analyzing adult LT recipient data (2002-2022) from the United Network for Organ Sharing database, outcomes of LT using steatotic (≥30% macrosteatosis) and non-steatotic donor livers, donors after circulatory death (DCD), and standard-risk older donors (age 45-50) were compared. GS predictors were evaluated using Kaplan-Meier and Cox regression analyses.Of the 35,345 LT donors, 8.9% (3,155) were fatty livers. Initial 30-day postoperative period revealed significant challenges with fatty livers, demonstrating inferior GS. However, the GS discrepancy between fatty and non-fatty livers subsided over time (p=0.10 at 5 y). Long-term GS outcomes showed comparable or even superior results in fatty livers relative to non-steatotic livers, conditional on surviving the initial 90 postoperative days (p=0.90 at 1 y) or 1 year (p=0.03 at 5 y). In the multivariable Cox regression analysis, high body surface area (BSA) ratio (≥1.1) (hazard ratio [HR] 1.42, p=0.02), calculated as donor BSA divided by recipient BSA, long cold ischemic time (≥6.5 hours) (HR 1.72, p<0.01), and recipient medical condition (ICU hospitalization) (HR 2.53, p<0.01) emerged as significant adverse prognostic factors. Young (<40 y) fatty donors showed a high BSA ratio, diabetes, and ICU hospitalization as significant indicators of worse prognosis (p<0.01).Our study emphasizes the initial postoperative 30-day survival challenge in LT using fatty livers. However, with careful donor-recipient matching, e.g. avoiding use of steatotic donors with long cold ischemic time and high BSA ratios for recipients in the ICU, it is possible to enhance immediate GS, and in a longer time, outcomes comparable to those using non-fatty livers, DCD livers, or standard-risk older donors, can be anticipated. These novel insights into decision-making criteria for steatotic liver use provide invaluable guidance for clinicians.

    View details for DOI 10.1097/LVT.0000000000000245

    View details for PubMedID 37616509

  • Decreased Utilization Rate of Grafts for Liver Transplantation After Implementation of Acuity Circle-based Allocation. Transplantation Bekki, Y., Myers, B., Tomiyama, K., Imaoka, Y., Akabane, M., Kwong, A. J., Melcher, M. L., Sasaki, K. 2023

    Abstract

    The allocation system for livers began using acuity circles (AC) in 2020. In this study, we sought to evaluate the impact of AC policy on the utilization rate for liver transplantation (LT).Using the US national registry data between 2018 and 2022, LTs were equally divided into 2 eras: pre-AC (before February 4, 2020) and post-AC (February 4, 2020, and after). Deceased potential liver donors were defined as deceased donors from whom at least 1 organ was procured.The annual number of deceased potential liver donors increased post-AC (from 10 423 to 12 259), approaching equal to that of new waitlist registrations for LT (n = 12 801). Although the discard risk index of liver grafts was comparable between the pre- and post-AC eras, liver utilization rates in donation after brain death (DBD) and donation after circulatory death (DCD) donors were lower post-AC (P < 0.01; 79.8% versus 83.4% and 23.7% versus 26.0%, respectively). Recipient factors, ie, no recipient located, recipient determined unsuitable, or time constraints, were more likely to be reasons for nonutilization after implementation of the AC allocation system compared to the pre-AC era (20.0% versus 12.3% for DBD donors and 50.1% versus 40.8% for DCD donors). Among non-high-volume centers, centers with lower utilization of marginal DBD donors or DCD donors were more likely to decrease LT volume post-AC.Although the number of deceased potential liver donors has increased, overall liver utilization among deceased donors has decreased in the post-AC era. To maximize the donor pool for LT, future efforts should target specific reasons for liver nonutilization.

    View details for DOI 10.1097/TP.0000000000004751

    View details for PubMedID 37585345

  • Evaluating the outcomes of donor-recipient age differences in young adults undergoing liver transplantation. Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society Snyder, A., Kojima, L., Imaoka, Y., Akabane, M., Kwong, A., Melcher, M. L., Sasaki, K. 2023

    Abstract

    BACKGROUND: The current liver allocation system may be disadvantaging younger adult recipients as it does not incorporate the donor-recipient age difference. Given the longer life expectancy of younger recipients, the influences of older donor grafts on their long-term prognosis should be elucidated. This study sought to reveal the long-term prognostic influence of the donor-recipient age difference in young adult recipients.METHODS: Adult patients who received initial liver transplants from deceased donors between 2002-2021 were identified from the UNOS database. Young recipients (patients ≤45 y.o) were categorized into 4 groups: donor age younger than the recipient, 0-9 years older, 10-19 years older, or ≥20 years older. Older recipients were defined as patients ≥65 y.o. To examine the influence of the age difference in long-term survivors, conditional graft survival (CGS) analysis was conducted on both younger and older recipients.RESULTS: Among 91,952 transplant recipients, 15,170 patients were ≤45 years old (16.5%); these were categorized into 6,114 (40.3%), 3,315 (21.9%), 2,970 (19.6%), and 2,771 (18.3%) for groups 1-4, respectively. Group 1 demonstrated the highest probability of survival followed by groups 2, 3, and 4 for the actual graft survival and CGS analyses. In younger recipients who survived at least 5 years post-transplant, inferior long-term survival was observed when there was an age difference of ≥10 years (86.9% vs. 80.6%, log-rank P<0.01) while there was no difference in older recipients (72.6% vs. 74.2%, log-rank P=0.89).CONCLUSION: In younger patients who are not in emergent need of a transplant, preferential allocation of younger aged donor offers would optimize organ utility by increasing postoperative graft survival time.

    View details for DOI 10.1097/LVT.0000000000000109

    View details for PubMedID 36847140

  • ASO Visual Abstract: The Current State of Liver Transplantation for Colorectal Liver Metastases in the United States: A Call for Standardized Reporting. Annals of surgical oncology Sasaki, K., Ruffolo, L. I., Kim, M. H., Fujiki, M., Hashimoto, K., Imaoka, Y., Melcher, M. L., Aucejo, F. N., Tomiyama, K., Hernandez-Alejandro, R. 2023

    View details for DOI 10.1245/s10434-023-13234-8

    View details for PubMedID 36807717

  • The Current State of Liver Transplantation for Colorectal Liver Metastases in the United States: A Call for Standardized Reporting. Annals of surgical oncology Sasaki, K., Ruffolo, L. I., Kim, M. H., Fujiki, M., Hashimoto, K., Imaoka, Y., Melcher, M. L., Aucejo, F. N., Tomiyama, K., Hernandez-Alejandro, R. 2023

    Abstract

    BACKGROUND: Current success in transplant oncology for select liver tumors, such as hepatocellular carcinoma, has ignited international interest in liver transplantation (LT) as a therapeutic option for nonresectable colorectal liver metastases (CRLM). In the United States, the CRLM LT experience is limited to reports from a handful of centers. This study was designed to summarize donor, recipient, and transplant center characteristics and posttransplant outcomes for the indication of CRLM.METHODS: Adult, primary LT patients listed between December 2017 and March 2022 were identified by using United Network Organ Sharing database. LT for CRLM was identified from variables: "DIAG_OSTXT"; "DGN_OSTXT_TCR"; "DGN2_OSTXT_TCR"; and "MALIG_TY_OSTXT."RESULTS: During this study period, 64 patients were listed, and 46 received LT for CRLM in 15 centers. Of 46 patients who underwent LT for CRLM, 26 patients (56.5%) received LTs using living donor LT (LDLT), and 20 patients received LT using deceased donor (DDLT) (43.5%). The median laboratory MELD-Na score at the time of listing was statistically similar between the LDLT and DDLT groups (8 vs. 9, P = 0.14). This persisted at the time of LT (8 vs. 12, P = 0.06). The 1-, 2-, and 3-year, disease-free, survival rates were 75.1, 53.7, and 53.7%. Overall survival rates were 89.0, 60.4, and 60.4%, respectively.CONCLUSIONS: This first comprehensive U.S. analysis of LT for CRLM suggests a burgeoning interest in high-volume U.S. transplant centers. Strategies to optimize patient selection are limited by the scarce oncologic history provided in UNOS data, warranting a separate registry to study LT in CRLM.

    View details for DOI 10.1245/s10434-023-13147-6

    View details for PubMedID 36719568

  • The future direction of liver transplantation for intrahepatic cholangiocarcinoma HEPATOMA RESEARCH Akabane, M., Imaoka, Y., Sasaki, K. 2023; 9