Yuki Imaoka

All Publications

• Has Sex-Based Disparity in Liver Transplantation Opportunities and Waitlist Mortality Improved in the MELD3.0 Era?: A Preliminary Study. Clinical transplantation Akabane, M., Imaoka, Y., Esquivel, C. O., Sasaki, K. 2025; 39 (1): e70064

  Abstract

  In July 2023, the OPTN adopted MELD3.0 to address sex-based disparities in liver transplantation (LT) opportunity and waitlist mortality. No studies have proven that MELD3.0 alleviated them.We evaluated sex-based disparities in LT opportunities and waitlist mortality, utilizing the UNOS data (August 2022-March 2024), comparing pre- and post-MELD3.0 eras.Among 11 795 LT candidates (pre-MELD3.0: 7263; post-MELD3.0: 4532), the proportion of females increased from 38.8% to 42.6% post-MELD3.0. In the transplanted population, females increased from 37.7% to 41.6% post-MELD3.0. The median MELD score difference ("MELD3.0-MELD-Na") at listing was -0.26 [-2.13, 0.80] for females and -0.86 [-2.92, 0.00] for males (p < 0.01). Compared to females, males consistently showed a larger drop in points from MELD-Na to MELD3.0. In the pre-MELD3.0 era, females had lower LT opportunity (sub-hazard ratio [sHR]: 0.88 [0.83-0.93], p < 0.01) and higher waitlist mortality (sHR: 1.39 [1.20-1.62], p < 0.01). In the post-MELD3.0 era, there were no significant differences in LT opportunity (sHR: 0.93 [0.87-1.00], p = 0.07) and waitlist mortality (sHR: 1.25 [0.98-1.57], p = 0.26). Subgroup analyses based on MELD-Na groups showed that significant differences in LT opportunity and waitlist mortality in the pre-MELD3.0 era became insignificant in the post-MELD3.0 era. Multivariable competing-risk analysis showed that, in the pre-MELD3.0 era, female sex was a significant risk factor for LT opportunity (sHR: 0.90 [0.84-0.96], p < 0.01) and waitlist mortality (sHR: 1.19 [1.01-1.38], p = 0.03), but in the post-MELD3.0 era, it was not significant (sHR: 0.94 [0.86-1.02], p = 0.11 for LT opportunity/sHR: 1.08 [0.83-1.40], p = 0.57 for waitlist mortality).Our preliminary findings suggest that MELD3.0 has the potential to reduce sex-based disparities in LT opportunities and waitlist mortality.

  View details for DOI 10.1111/ctr.70064

  View details for PubMedID 39737609

• The impact of sex and body mass index in liver transplantation for acute-on-chronic liver failure. Journal of hepato-biliary-pancreatic sciences Akabane, M., Imaoka, Y., Nakayama, T., Esquivel, C. O., Sasaki, K. 2024

  Abstract

  There have been no studies evaluating how body mass index (BMI) impacts on waitlist and post-liver transplant (LT) mortality in acute-on-chronic liver failure (ACLF) by sex. We aimed to determine these impacts using the United Network for Organ Sharing (UNOS) database.Adults listed for LT with estimated ACLF (Est-ACLF) (2005-2023) were identified and subdivided by sex and BMI (high/middle/low). Competing-risk analyses evaluated impacts on waitlist mortality. Kaplan-Meier analyses assessed post-LT survival. Multivariable Cox regression identified risk factors.Of 37 251 Est-ACLF patients, 14 534 (39.0%) were female. Females had higher 90-day waitlist mortality than males (subhazard ratio [sHR]: 1.20, p < .01). High/low BMI patients had higher mortality than middle (sHR: 1.08/1.11, p < .01). In females, high BMI was associated with higher mortality than low (sHR: 1.10, p = .02); in males, low BMI was associated with higher mortality than high/middle (sHR: 1.16/1.16 vs. high/middle, p < .01). Multivariable analyses showed in females, high BMI was a significant risk factor for waitlist mortality (sHR:1.21, p < .01), while low was not; in males, high/low BMI was significant, with low having higher sHR (1.17) than high (1.09). Post-LT survival showed no significant difference in females; in males, low BMI showed worse post-3-/5-year-LT survival (p < .01). Multivariable Cox regression showed for females, neither low nor high BMI was significant for post-LT survival; for males, low BMI was significant for 1-/3-/5-year-LT survival (HR: 1.30/1.30/1.22, p < .01).Our analysis of BMI's impact on LT outcomes in ACLF by sex enables risk stratification and provides a basis for adjusting BMI.

  View details for DOI 10.1002/jhbp.12100

  View details for PubMedID 39727045

• Hepatitis C-positive grafts for hepatitis C-negative recipients in liver transplantation: Buried treasure or depleting resource? Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society Nakayama, T., Krist, D. T., Akabane, M., Imaoka, Y., Esquivel, C. O., Kwong, A. J., Kwo, P. Y., Melcher, M. L., Sasaki, K. 2024

  Abstract

  Long-term outcomes of using hepatitis C virus (HCV) positive donors in HCV-negative recipients in liver transplantation (LT) are not well established. Data from the United Network for Organ Sharing (UNOS) database between July 1, 2015, and December 31, 2023, were analyzed. The cohort included 44,447 HCV antibody-negative (Ab-) candidates who underwent deceased donor LT. Changes in case numbers and utilization rates of HCV-positive donors, divided into HCV-viremic (NAT+) or Ab+ nonviremic (Ab+/NAT-), were assessed. Kaplan-Meier analysis and propensity score matching were used to evaluate 5-year graft survival (GS). The number of HCV-viremic donation after brain death (DBD) donors and their use in LT for HCV Ab- recipients peaked at 640 donors in 2019 and 289 LTs in 2022. In contrast, Ab+ nonviremic DBD donations are rising, with 536 donors and 284 LTs in 2023. The utilization rate of viremic DBD grafts has continuously decreased despite increased willingness by waitlist candidates to accept them. HCV-positive donation after circulatory death (DCD) donors were seldom utilized in the study period. The 5-year GS rates for HCV-viremic, Ab+ nonviremic, and naïve donors were not significantly different in either DBD (p=0.56) or DCD (p=0.52). Furthermore, Ishak stage 2 or 3 fibrotic DBD grafts had similar 5-year GS to non-fibrotic grafts. The findings suggest that the long-term outcome of using HCV-viremic DBD or DCD grafts for HCV-negative recipients is comparable to that of other graft types, and that fibrotic grafts have the potential to expand the DBD donor pool.

  View details for DOI 10.1097/LVT.0000000000000557

  View details for PubMedID 39679922

• ASO Visual Abstract: Improving Recurrence Prediction in Intrahepatic Cholangiocarcinoma-The Synergistic Impact of FIB-4 Index and Tumor Burden Score in Post-Hepatectomy Outcomes. Annals of surgical oncology Akabane, M., Kawashima, J., Woldesenbet, S., Macedo, A. B., Cauchy, F., Shen, F., Maithel, S. K., Koerkamp, B. G., Alexandrescu, S., Kitago, M., Weiss, M., Martel, G., Pulitano, C., Aldrighetti, L., Poultsides, G. A., Imaoka, Y., Guglielmi, A., Bauer, T. W., Endo, I., Gleisner, A., Marques, H. P., Pawlik, T. M. 2024

  View details for DOI 10.1245/s10434-024-16633-7

  View details for PubMedID 39638992

• Analyzing the Interaction between Time to Surgery and Tumor Burden Score in Hepatocellular Carcinoma. Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract Akabane, M., Kawashima, J., Woldesenbet, S., Altaf, A., Cauchy, F., Aucejo, F., Popescu, I., Kitago, M., Martel, G., Ratti, F., Aldrighetti, L., Poultsides, G. A., Imaoka, Y., Ruzzenente, A., Endo, I., Gleisner, A., Marques, H. P., Lam, V., Hugh, T., Bhimani, N., Shen, F., Pawlik, T. M. 2024: 101903

  Abstract

  The impact of "Time to Surgery (TTS)" on outcomes for curative-intent hepatectomy in hepatocellular carcinoma (HCC) is debated. The interaction between Tumor Burden Score (TBS) and TTS remains unclear. This study evaluates how TBS and TTS affect long-term HCC outcomes.HCC patients undergoing curative-intent hepatectomy (2000-2022) were analyzed from a multi-institutional database and categorized by TTS (≤ or >60 days). Overall survival (OS) and cancer-specific survival were assessed.Among 910 patients, median TTS was 22 days in the short TTS group (n=485) and 120 days in the long TTS group (n=425). The long TTS group was older with higher rates of ASA class>2, diabetes, and cirrhosis. Median TBS showed no significant difference between groups (4.61vs5.00). No significant 5-year OS difference was found (70.0%vs63.1%, P=0.05). Multivariable analysis identified TBS (HR:1.07[1.03-1.11], P<0.001), log AFP (HR:1.08[1.01-1.14], P=0.02), and ALBI score (HR:2.52[1.66-3.82], P<0.001) as significant; TTS was not (HR:1.18[0.78-1.77], P=0.43). Interaction analysis showed TBS as a significant risk factor in the short TTS group (HR:1.12[1.07-1.17], P<0.001), but not in the long TTS group (HR:0.98[0.91-1.05], P=0.56). In the low TBS group (≤5), higher mortality was observed in the long TTS group (5-year OS: 82.4%vs63.0%, P=0.001), a trend not seen in the high TBS group (57.9%vs63.3%, P=0.92). Multivariable analysis stratified by TBS found long TTS as a risk factor in the low TBS group (HR:3.12[1.60-6.01], P<0.001), but not in the high TBS group (HR:0.57[0.30-1.07], P=0.08). Similar trends were observed in cancer-specific survival.While preoperative optimization is essential, minimizing TTS may improve outcomes in low TBS cohorts.

  View details for DOI 10.1016/j.gassur.2024.101903

  View details for PubMedID 39613250

• Improving Recurrence Prediction in Intrahepatic Cholangiocarcinoma: The Synergistic Impact of the FIB-4 Index and Tumor Burden Score on Post-hepatectomy Outcomes. Annals of surgical oncology Akabane, M., Kawashima, J., Woldesenbet, S., Macedo, A. B., Cauchy, F., Shen, F., Maithel, S. K., Groot Koerkamp, B., Alexandrescu, S., Kitago, M., Weiss, M., Martel, G., Pulitano, C., Aldrighetti, L., Poultsides, G. A., Imaoka, Y., Guglielmi, A., Bauer, T. W., Endo, I., Gleisner, A., Marques, H. P., Pawlik, T. M. 2024

  Abstract

  The prognostic role of the fibrosis-4 (FIB-4) index relative to intrahepatic cholangiocarcinoma (ICC) after hepatectomy remains unclear. This study sought to characterize the impact of the FIB-4 index and tumor burden score (TBS) on recurrence and overall survival (OS).ICC patients undergoing hepatectomy (2000-2020) were identified using a multi-institutional database. Patients were categorized as low (low TBS/low FIB-4 index), intermediate (low TBS/high FIB-4 index or high TBS/low FIB-4 index), and high (high TBS/high FIB-4 index).Among 1168 patients in different TBS and FIB-4 index cohorts, 3-year recurrence varied considerably. For instance, among the patients with low TBS, individuals with a high FIB-4 index had a greater risk of recurrence than patients with a low FIB-4 index (59.9 vs. 47.7%; P = 0.01). Among patients with a high TBS, individuals with a high versus a low FIB-4 index had a higher incidence of recurrence (76.8 vs. 69.0%; P = 0.04). A similar pattern was observed among patients with both a low FIB-4 index (low [47.7%] vs. high [69.0%] TBS) and a high FIB-4 index (low [59.9%] vs. high [76.8%] TBS; both P < 0.001). Patients with a high [27.5%] versus a low [48.8%] TBS; P < 0.001) and patients with a high [34.2%] versus a low [43.5%] FIB-4 index; P = 0.01) had a worse OS. The multivariable analysis demonstrated an increasing risk of recurrence in the intermediate-index (hazard ratio [HR], 1.61; 95% confidence interval [CI], 1.20-2.16; P = 0.001) and high-index (HR, 2.13; 95% CI 1.45-3.13; P < 0.001) groups versus the low-index group.Both tumor-related and non-tumorous characteristics should be used to predict risk of recurrence and survival more accurately among patients with ICC following hepatic resection.

  View details for DOI 10.1245/s10434-024-16455-7

  View details for PubMedID 39511008

  View details for PubMedCentralID 4324507

• Revisiting the Prognostic Influences of Donor-Recipient Size Mismatch in Deceased Donor Liver Transplantation. Transplantation direct Nakayama, T., Akabane, M., Imaoka, Y., Esquivel, C. O., Melcher, M. L., Sasaki, K. 2024; 10 (11): e1722

  Abstract

  Background: Liver transplantation (LT) outcomes are influenced by donor-recipient size mismatch. This study re-evaluated the impact on graft size discrepancies on survival outcomes.Methods: Data from 53389 adult LT recipients from the United Network for Organ Sharing database (2013-2022) were reviewed. The study population was divided by the body surface area index (BSAi), defined as the ratio of donor body surface area (BSA) to recipient BSA, into small-for-size (BSAi<0.78), normal-for-size (BSAi 0.78-1.24), and large-for-size (BSAi>1.24) grafts in deceased donor LT (SFSD, NFSD, and LFSD). Multivariate Cox regression and Kaplan-Meier survival analyses were conducted.Results: The frequency of size mismatch in deceased donor LT increased over the past 10 y. SFSD had significantly worse 90-d graft survival (P<0.01), and LFSD had inferior 1-y graft survival among 90-d survivors (P=0.01). SFSD was hazardous within 90 d post-LT because of vascular complications. Beyond 1 y, graft size did not affect graft survival. LFSD risk within the first year was mitigated with lower model for end-stage liver disease (MELD) 3.0 scores (<35) or shorter cold ischemia time (<8h).Conclusions: The negative impacts on donor-recipient size mismatch on survival outcomes are confined to the first year post-LT. SFSD is associated with a slight decrease in 90-d survival rates. LFSD should be utilized more frequently by minimizing cold ischemia time to <8h, particularly in patients with MELD 3.0 scores below 35. These findings could improve donor-recipient matching and enhance LT outcomes.

  View details for DOI 10.1097/TXD.0000000000001722

  View details for PubMedID 39440201

• Abdominal aortic calcification among gastroenterological and transplant surgery. Annals of gastroenterological surgery Imaoka, Y., Ohira, M., Akabane, M., Sasaki, K., Ohdan, H. 2024; 8 (6): 987-998

  Abstract

  This review discusses the increasing global trend towards an aging population, which has resulted in a growing number of surgeries being performed on elderly patients, particularly those living with cancer. The focus was on the implications of abdominal aortic calcification (AAC), an indicator of systemic atherosclerosis, in these patients. This comprehensive review provided evidence detailing the complex processes of atherosclerosis and vascular calcification and various approaches to assess this condition. The prevalence of AAC is related to multiple factors, including cardiovascular disease, inflammation, frailty in various types of gastroenterological surgery. Additionally, notable links were found between AAC, postoperative complications, and patient survival following gastroenterological surgery. This study highlights how AAC could negatively impact the health status of elderly patients and undermine treatment efficacy, stressing the need for more research in this domain to improve patient outcomes.

  View details for DOI 10.1002/ags3.12816

  View details for PubMedID 39502733

  View details for PubMedCentralID PMC11533033

• Does the introduction of acuity circle policy change split liver transplantation practice? Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society Nakayama, T., Akabane, M., Imaoka, Y., Esquivel, C. O., Melcher, M. L., Sasaki, K. 2024

  Abstract

  With the Acuity Circles (AC) policy aiming to reduce disparities in liver transplantation (LT) access, the allocation of high-quality grafts has shifted, potentially affecting the use and outcomes of split LT. Data from the United Network for Organ Sharing (UNOS) database (February 4, 2016, to February 3, 2024) were analyzed, including 1,470 candidates who underwent deceased donor split LT, with 681 adult and 789 pediatric cases. The study periods were divided into pre-AC (February 4, 2016, to February 3, 2020) and post-AC (February 4, 2020, to February 3, 2024). The study assessed changes in split LT volumes and examined the impact of center practices. Both adult and pediatric split LTs decreased in the initial three years post-policy change, followed by an increase in the final year, with an overall 11.9% and 13.9% decrease between the eras. Adult female split LT cases remained consistent, ensuring access for smaller recipients. High-quality "splittable" livers were increasingly allocated to high MELD patients (MELD-Na ≥30). Despite the overall decrease in case volume, adult split LT volume increased in newly active LDLT centers, with six centers increasing LDLT volume by over 50.0%. Pediatric split LT volumes decreased despite additional priorities for pediatric candidates. The number of split LTs decreased in the initial period after the AC policy introduction, but there was a consistent need for small female candidates. In the adult population, LDLT and split LT demonstrated a synergistic effect in boosting center transplant volumes, potentially improving access for female candidates who need small grafts.

  View details for DOI 10.1097/LVT.0000000000000513

  View details for PubMedID 39412327

• Beyond 75: Graft Allocation and Organ Utility Implications in Liver Transplantation. Transplantation direct Akabane, M., Kwong, A., Imaoka, Y., Esquivel, C. O., Kim, W. R., Melcher, M. L., Sasaki, K. 2024; 10 (10): e1661

  Abstract

  The global surge in aging has intensified debates on liver transplantation (LT) for candidates aged 75 y and older, given the prevalent donor scarcity. This study examined both the survival benefits and organ utility of LT for this age group.A total of 178 469 adult LT candidates from the United Network for Organ Sharing database (2003-2022) were analyzed, with 112 266 undergoing LT. Post-LT survival outcomes and waitlist dropout rates were monitored across varying age brackets. Multivariable Cox regression analysis determined prognostic indicators. The 5-y survival benefit was assessed by comparing LT recipients to waitlist candidates using hazard ratios. Organ utility was evaluated through a simulation model across various donor classifications.Among candidates aged 75 y and older, 343 received LT. The 90-d graft and patient survival rates for these patients were comparable with those in other age categories; however, differences emerged at 1 and 3 y. Age of 75 y or older was identified as a significant negative prognostic indicator for 3-y graft survival (hazard ratio: 1.72 [1.20-2.42], P < 0.01). Dropout rates for the 75 y and older age category were 12.0%, 24.1%, and 35.1% at 90 d, 1 y, and 3 y, respectively. The survival benefit of LT for the 75 y and older cohort was clear when comparing outcomes between LT recipients and those on waitlists. However, organ utility considerations did not favor allocating livers to this age group, regardless of donor type. Comparing 3-y patient survival between LT using donors aged 60 y and younger and older than 60 y showed no significant difference (P = 0.50) in the 75 y or older cohort.Although LT offers survival benefits to individuals aged 75 y and older, the system may need rethinking to optimize the use of scarce donor livers, perhaps by matching older donors with older recipients.

  View details for DOI 10.1097/TXD.0000000000001661

  View details for PubMedID 39359941

  View details for PubMedCentralID PMC11446594

• Innovative Strategies for Liver Transplantation: The Role of Mesenchymal Stem Cells and Their Cell-Free Derivatives. Cells Akabane, M., Imaoka, Y., Kawashima, J., Endo, Y., Schenk, A., Sasaki, K., Pawlik, T. M. 2024; 13 (19)

  Abstract

  Despite being the standard treatment for end-stage liver disease, liver transplantation has limitations like donor scarcity, high surgical costs, and immune rejection risks. Mesenchymal stem cells (MSCs) and their derivatives offer potential for liver regeneration and transplantation. MSCs, known for their multipotency, low immunogenicity, and ease of obtainability, can differentiate into hepatocyte-like cells and secrete bioactive factors that promote liver repair and reduce immune rejection. However, the clinical application of MSCs is limited by risks such as aberrant differentiation and low engraftment rates. As a safer alternative, MSC-derived secretomes and extracellular vesicles (EVs) offer promising therapeutic benefits, including enhanced graft survival, immunomodulation, and reduced ischemia-reperfusion injury. Current research highlights the efficacy of MSC-derived therapies in improving liver transplant outcomes, but further studies are necessary to standardize clinical applications. This review highlights the potential of MSCs and EVs to address key challenges in liver transplantation, paving the way for innovative therapeutic strategies.

  View details for DOI 10.3390/cells13191604

  View details for PubMedID 39404368

  View details for PubMedCentralID PMC11475694

• Evaluation of prognostic efficacy of liver immune status index in predicting postoperative outcomes in hepatocellular carcinoma patients: A multi-institutional retrospective study. Journal of hepato-biliary-pancreatic sciences Imaoka, Y., Ohira, M., Kobayashi, T., Honmyo, N., Hamaoka, M., Onoe, T., Takei, D., Oishi, K., Abe, T., Nakayama, T., Akabane, M., Sasaki, K., Ohdan, H. 2024

  Abstract

  Hepatocellular carcinoma (HCC) ranks third in cancer-related deaths globally. Despite treatment advances, high post-hepatectomy recurrence rates (RR), especially with liver fibrosis and hepatitis C virus infection, remain challenging. Key prognostic factors include vascular invasion and perioperative blood loss, impacting extrahepatic recurrence. Natural killer (NK) cells are crucial in countering circulating tumor cells through TRAIL-mediated pathways. The aim of this study was to validate the liver immune status index (LISI) as a predictive tool for liver NK cell antitumor efficiency, particularly in HCC patients with vascular invasion.A retrospective analysis of 1337 primary HCC hepatectomies was conducted by the Hiroshima Surgical Study Group of Clinical Oncology (HiSCO). Clinicodemographic data were extracted from electronic medical records. Prognostic indices (FIB-4, ALBI, ALICE, GNRI, APRI, and LISI) were evaluated using area under the receiver operating characteristic curve values. Survival analyses employed Kaplan-Meier estimations and log-rank tests.LISI significantly correlated with other prognostic markers and stratified patients into risk groups with distinct overall survival (OS) and RR. It showed superior predictive performance for 2-year OS and RR, especially in patients with vascular invasion. Over longer periods, APRI and FIB-4 index reliabilities improved. The HISCO-HCC score, combining LISI, tumor burden score, and alpha-fetoprotein levels, enhanced prognostic accuracy.LISI outperformed existing models, particularly in HCC with vascular invasion. The HISCO-HCC score offers improved prognostic precision, guiding immunotherapeutic strategies and individualized patient care in HCC.

  View details for DOI 10.1002/jhbp.12070

  View details for PubMedID 39313837

• Survival benefit of liver transplantation utilizing marginal donor organ according to ABO blood type. Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society Akabane, M., Bekki, Y., Inaba, Y., Imaoka, Y., Esquivel, C. O., Kwong, A., Kim, W. R., Sasaki, K. 2024

  Abstract

  The current liver transplantation (LT) allocation policy focuses on the Model for End-Stage Liver Disease (MELD) scores, often overlooking factors like blood type and survival benefits. Understanding blood types' impact on survival benefits is crucial for optimizing the MELD 3.0 classification.This study used the United Network for Organ Sharing national registry database (2003-2020) to identify LT characteristics per ABO blood type and to determine the optimal MELD 3.0 scores for each blood type, based on survival benefits.The study included LT candidates aged 18 years or older listed for LT (total N=150,815; A:56,546, AB:5,841, B:18,500, O:69,928). Among these, 87,409 individuals (58.0%) underwent LT (A:32,156, AB:4,362, B:11,786, O:39,105). Higher transplantation rates were observed in AB and B groups, with lower median MELD 3.0 scores at transplantation (AB:21, B:24 vs. A/O:26, p<0.01) and shorter waiting times (AB:101 days, B:172 days vs. A:211 days, O:201 days, p<0.01). A preference for Donation after Cardiac Death (DCD) was seen in A and O recipients. Survival benefit analysis indicated that B blood type required higher MELD 3.0 scores for transplantation than A and O (Donation after Brain Death transplantation: ≥15 in B vs. ≥11 in A/O; DCD transplantation: ≥21 in B vs. ≥11 in A, ≥15 in O).The study suggests revising the allocation policy to consider blood type for improved post-LT survival. This calls for personalized LT policies, recommending higher MELD 3.0 thresholds, particularly for individuals with type B blood.

  View details for DOI 10.1097/LVT.0000000000000460

  View details for PubMedID 39287561

• Comment on "Age Matters: What Affects the Cumulative Lifespan of a Transplanted Liver?". Annals of surgery open : perspectives of surgical history, education, and clinical approaches Akabane, M., Imaoka, Y., Nakayama, T., Sasaki, K. 2024; 5 (3): e475

  View details for DOI 10.1097/AS9.0000000000000475

  View details for PubMedID 39310331

  View details for PubMedCentralID PMC11415112

• Effect of transjugular intrahepatic portosystemic shunt insertion on waitlist mortality and access to liver transplantation in budd-chiari syndrome. Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society Akabane, M., Imaoka, Y., Nakayama, T., Esquivel, C. O., Sasaki, K. 2024

  Abstract

  BACKGROUND: The impact of transjugular intrahepatic portosystemic shunt (TIPS) on waitlist mortality and liver transplantation (LT) urgency in Budd-Chiari Syndrome (BCS) patients remains unclear.METHOD: We analyzed BCS patients listed for LT in the UNOS database(2002-2024) to assess TIPS's impact on waitlist mortality and LT access via competing-risk analysis. We compared trends across two phases:Phase1(2002-2011) and Phase2(2012-2024).RESULTS: Of 815 BCS patients, 263(32.3%) received TIPS at listing. TIPS group had lower MELD-Na scores(20vs22,p<0.01), milder ascites(p=0.01), and fewer Status1 patients(those at risk of imminent death while awaiting LT)(2.7%vs8.3%,p<0.01) at listing compared to those without TIPS. TIPS patients had lower LT rates(43.3%vs56.5%,p<0.01) and longer waitlist times(350vs113d,p<0.01). TIPS use increased in Phase2(64.3%vs35.7%,p<0.01). Of 426 transplanted patients, 134(31.5%) received TIPS, showing lower MELD-Na scores(24vs27,p<0.01) and better medical conditions(Intensive care unit:14.9%vs21.9%,p<0.01) at LT. Status1 patients were fewer (3.7%vs12.3%,p<0.01), with longer waiting days(97vs26d,p<0.01) in TIPS group. TIPS use at listing increased from Phase1(25.6%) to Phase2(37.7%). From Phase1 to Phase2, ascites severity improved, re-LT cases decreased(Phase1:9.8%vsPhase2:2.2%,p<0.01), and cold ischemic time slightly decreased(Phase1:7.0vsPhase2:6.4 hours,p=0.14). Median donor body mass index significantly increased. No significant differences were identified in patient/graft survival at 1-/5-/10-year intervals between phases or TIPS/non-TIPS patients. While 90-day waitlist mortality showed no significant difference(p=0.11), TIPS trended towards lower mortality(subHazard ratio[sHR]:0.70[0.45-1.08]). Multivariable analysis indicated that TIPS was a significant factor in decreasing mortality(sHR:0.45[0.27-0.77],p<0.01). TIPS group also showed significantly lower LT access(sHR:0.65[0.53-0.81],p<0.01). Multivariable analysis showed that TIPS was a significant factor in decreasing access to LT(sHR:0.60[0.46-0.77],p<0.01). Sub-group analysis excluding Status1 or HCC showed similar trends.CONCLUSION: TIPS in BCS patients listed for LT reduces waitlist mortality and LT access, supporting its bridging role.

  View details for DOI 10.1097/LVT.0000000000000469

  View details for PubMedID 39177578

• Interleukin-33 and liver natural killer cells: A novel perspective on antitumor activity in liver fibrosis. Hepatology research : the official journal of the Japan Society of Hepatology Imaoka, Y., Ohira, M., Imaoka, K., Bekki, T., Nakano, R., Yano, T., Tanaka, Y., Nakayama, T., Akabane, M., Tajima, T., Yokota, S., Krams, S. M., Martinez, O. M., Esquivel, C. O., Sasaki, K., Ohdan, H. 2024

  Abstract

  Liver fibrosis, heralding the potential progression to cirrhosis and hepatocellular carcinoma (HCC), compromises patient survival and augments post-hepatectomy recurrence. This study examined the detrimental effects of liver fibrosis on the antitumor functions of liver natural killer (NK) cells and the interleukin-33 (IL-33) signaling pathway.Our investigation, anchored in both human physiologies using living and deceased donor livers and the carbon tetrachloride (CCl4)-induced mouse fibrosis model, aimed to show a troubling interface between liver fibrosis and weakened hepatic immunity.The Fibrosis-4 (FIB-4) index emerged as a salient, non-invasive prognostic marker, and its elevation correlated with reduced survival and heightened recurrence after HCC surgery even after propensity matching (n = 385). We established a strong correlation between liver fibrosis and liver NK cell dysfunction by developing a method for extracting liver NK cells from the liver graft perfusate. Furthermore, liver fibrosis ostensibly disrupted chemokines and promoted IL-33 expression, impeding liver NK cell antitumor activities, as evidenced in mouse models. Intriguingly, our results implicated IL-33 in diminishing the antitumor responses of NK cells. This interrelation, consistent across both mouse and human studies, coincides with clinical data suggesting that liver fibrosis predisposes patients to an increased risk of HCC recurrence.Our study revealed a critical relationship between liver fibrosis and compromised tumor immunity, emphasizing the potential interference of IL-33 with NK cell function. These insights advocate for advanced immunostimulatory therapies targeting cytokines, such as IL-33, aiming to bolster the hepatic immune response against HCC in the context of liver fibrosis.

  View details for DOI 10.1111/hepr.14102

  View details for PubMedID 39134448

• The Spread Pattern of New Practice in Liver Transplantation in the United States. Clinical transplantation Akabane, M., Imaoka, Y., Esquivel, C. O., Kim, W. R., Sasaki, K. 2024; 38 (7): e15379

  Abstract

  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.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.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.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.

  View details for DOI 10.1111/ctr.15379

  View details for PubMedID 38952196

• The suggestion of mitigating disparity in the liver transplantation field among ABO blood type. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons Akabane, M., Imaoka, Y., Esquivel, C. O., Kim, W. R., Sasaki, K. 2024

  Abstract

  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 offer guidelines, ABO disparities persist. This study examines LT access discrepancies among blood types, focusing on type AB, and seeks equitable strategies. Using the UNOS database(2003-2022), 170,276 waitlist candidates were retrospectively analyzed. Dual predictive analyses(LT Opportunity&Survival Studies) evaluated 1-year recipient pool survival, considering waitlist and post-LT survival, alongside anticipated allocation value per recipient, under six scenarios. Of the cohort, 97,670 patients(57.2%) underwent LT. Type AB recipients had the highest LT rate(73.7vs55.2% for O), shortest median waiting time(90vs198days for A), and lowest waitlist mortality(12.9vs23.9% for O), with the lowest median MELD-Na score(20vs25 for A/O). The LT Opportunity Study revealed that reallocating type A(or A&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 most(3.5% to 2.8%). Sensitivity analysis confirmed these findings were specific to the MELD-Na<30 population, indicating current LT allocation may favor certain blood types. Prioritizing ABO-identical LTs for MELD-Na<30 recipients could ensure uniform survival outcomes and mitigate disparities.

  View details for DOI 10.1016/j.ajt.2024.06.004

  View details for PubMedID 38866110

• Expanding Selection Criteria in Deceased Donor Liver Transplantation for Hepatocellular Carcinoma: Long-term Follow-up of a National Registry and 2 Transplant Centers. Transplantation Wehrle, C. J., Kusakabe, J., Akabane, M., Maspero, M., Zervos, B., Modaresi Esfeh, J., Whitsett Linganna, M., Imaoka, Y., Khalil, M., Pita, A., Kim, J., Diago-Uso, T., Fujiki, M., Eghtesad, B., Quintini, C., Kwon, C. D., Pinna, A., Aucejo, F., Miller, C., Mazzaferro, V., Schlegel, A., Sasaki, K., Hashimoto, K. 2024

  Abstract

  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.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.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.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.

  View details for DOI 10.1097/TP.0000000000005097

  View details for PubMedID 38831488

• Abdominal aortic calcification among gastroenterological and transplant surgery ANNALS OF GASTROENTEROLOGICAL SURGERY Imaoka, Y., Ohira, M., Akabane, M., Sasaki, K., Ohdan, H. 2024

  View details for DOI 10.1002/ags3.12816

  View details for Web of Science ID 001239002000001

• Landscape of donor cause of death and its impact on liver transplant outcomes: a ten-year analysis from the UNOS database. HPB : the official journal of the International Hepato Pancreato Biliary Association Akabane, M., Imaoka, Y., Esquivel, C. O., Sasaki, K. 2024

  Abstract

  Cause of death (COD) is a predictor of liver transplant (LT) outcomes independent of donor age, yet has not been recently reappraised.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.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.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.

  View details for DOI 10.1016/j.hpb.2024.05.019

  View details for PubMedID 38879433

• 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

• Evaluating Predictors of Quality in Liver NK Cells Among Deceased Donors CELL TRANSPLANTATION Imaoka, Y., Ohira, M., Nakayama, T., Akabane, M., Tajima, T., Yokota, S., Krams, S. M., Martinez, O. M., Esquivel, C. O., Sasaki, K., Ohdan, H. 2024; 33

  View details for DOI 10.1177/09636897241283289

  View details for Web of Science ID 001328777900001

• 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

  View details for DOI 10.1097/01.tp.0000993992.73475.a0

  View details for Web of Science ID 001089038800068

• 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

  View details for DOI 10.1097/01.tp.0000994700.79816.86

  View details for Web of Science ID 001089038800244

• 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

  View details for DOI 10.20517/2394-5079.2023.45

  View details for Web of Science ID 001065297000029