Jiro Kusakabe

Objective: To evaluate national trends and clinical outcomes of donation after circulatory death (DCD) simultaneous liver–kidney transplantation (SLKT) in the US, particularly in the modern era following adoption of machine perfusion (MP) and normothermic regional perfusion (NRP). Background: Utilization of DCD donors for liver transplantation has increased substantially in the US, and MP and NRP were reported to reduce complications, including reperfusion syndrome and early allograft dysfunction. However, national trends and outcomes of DCD-SLKT in the contemporary era of organ perfusion have not been characterized. Methods: Using UNOS STAR files, we analyzed 10.687 adult primary SLKT performed between 2000 and 2025. Outcomes of DCD and donation after brain death (DBD) SLKT during 2020–2025 were compared using propensity score matching (PSM) to adjust for donor and recipient characteristics. Kaplan–Meier methods were used to assess graft/patient survival. Results: The utilization of DCD-SLKT increased markedly after 2018, accounting for 29.3% of all SLKT cases in 2024. In 2024, liver MP, kidney MP, and NRP were used in 58.1%, 82.9%, and 40.1% of DCD-SLKT cases. Before matching, recipients in the DBD-SLKT group more frequently required dialysis at transplantation (69.1% vs 54.2%) and were hospitalized preoperatively (51.0% vs 17.2%), and had higher MELD scores (30 vs 23) during 2020–2025. Median follow-up was shorter in DCD-SLKT (706 vs 364 days), reflecting the more recent adoption of DCD transplantation. Liver graft/patient survival were comparable between DCD- and DBD-SLKT regardless of PSM. Conclusions: Utilization of DCD donors for SLKT has increased substantially in parallel with the expanding use of MP and NRP, with graft/patient outcomes comparable to those of DBD-SLKT regardless of PSM. However, DBD-SLKT recipients had higher baseline preoperative risk. These support broader adoption of DCD donors for SLKT in appropriately selected recipients.

Objective: We evaluated the impact of normothermic regional perfusion (NRP) on short and mid-term outcomes of kidney transplantation (KT) using donation after circulatory death (DCD). We further examined the influence of NRP duration and identified subgroups most likely to benefit from its use. Background: NRP has recently gained adoption in DCD-KT as a means to mitigate donor warm ischemic injury. However, its effect on graft and patient outcomes, particularly beyond 1 year, remains uncertain, and the role of NRP duration and subgroup-specific benefits has not been well defined. Patients and Methods: Using United Network for Organ Sharing Standard Transplant Analysis and Research files, we analyzed 21,010 primary adult DCD-KT cases performed between 2020 and 2025. Based on prior literature, cases were classified as non-NRP (0 to 30 minutes from circulatory death to cross-clamp) or NRP (30 to 180 minutes). Propensity score matching adjusted for donor and recipient differences. Kaplan–Meier methods assessed graft and patient survival. Results: After propensity score matching, NRP was associated with reduced delayed graft function (30.3% vs 49.7%), shorter hospital stay (median: 4 vs 5 days), and improved overall graft and patient survival ( P = 0.007 and 0.047). No difference was observed in overall graft survival between short and long NRP durations ( P = 0.62). Subgroup analyses for 1-year graft survival revealed that the benefit of NRP was more evident in cases of elderly recipients or donors, high donor body mass index, higher Kidney Donor Profile Index, and prolonged pretransplant dialysis. Conclusions: NRP improved both short- and mid-term outcomes, including 3-year/overall graft/patient survival. NRP duration did not significantly affect overall graft survival. The benefits of NRP were pronounced in high-risk subgroups.

Background.: This study compares selection criteria for liver transplant (LT) for hepatocellular carcinoma (HCC) for inclusivity and predictive ability to identify the most permissive criteria that maintain patient outcomes. Methods.: The Scientific Registry of Transplant Recipients (SRTR) database was queried for deceased donor LT’s for HCC (2003–2020) with 3-y follow-up; these data were compared with a 2-center experience. Milan, University of California, San Francisco (UCSF), 5-5-500, Up-to-seven (U7), HALT-HCC, and Metroticket 2.0 scores were calculated. Results.: Nationally, 26 409 patients were included, and 547 at the 2 institutions. Median SRTR-follow-up was 6.8 y (interquartile range 3.9–10.1). Three criteria allowed the expansion of candidacy versus Milan: UCSF (7.7%, n = 1898), Metroticket 2.0 (4.2%, n = 1037), and U7 (3.5%, n = 828). The absolute difference in 3-y overall survival (OS) between scores was 1.5%. HALT-HCC (area under the curve [AUC] = 0.559, 0.551–0.567) best predicted 3-y OS although AUC was notably similar between criteria (0.506 < AUC < 0.527, Mila n = 0.513, UCSF = 0.506, 5-5-500 = 0.522, U7 = 0.511, HALT-HCC = 0.559, and Metroticket 2.0 = 0.520), as was Harrall’s c-statistic (0.507 < c-statistic < 0.532). All scores predicted survival to P < 0.001 on competing risk analysis. Median follow-up in our enterprise was 9.8 y (interquartile range 7.1–13.3). U7 (13.0%, n = 58), UCSF (11.1%, n = 50), HALT-HCC (6.4%, n = 29), and Metroticket 2.0 (6.3%, n = 28) allowed candidate expansion. HALT-HCC (AUC = 0.768, 0.713–0.823) and Metroticket 2.0 (AUC = 0.739, 0.677–0.801) were the most predictive of recurrence. All scores predicted recurrence and survival to P < 0.001 using competing risk analysis. Conclusions.: Less restrictive criteria such as Metroticket 2.0, UCSF, or U7 allow broader application of transplants for HCC without sacrificing outcomes. Thus, the criteria for Model for End-stage Liver Disease-exception points for HCC should be expanded to allow more patients to receive life-saving transplantation.

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Antibody-mediated rejection (AMR) is a refractory rejection after ABO blood-type incompatible (ABOi) or donor-specific antibody (DSA)-positive liver transplantation (LT). Pretransplant rituximab desensitization dramatically reduced posttransplant AMR development; however, risk factors for AMR in the rituximab era remain unclear in both ABOi living-donor LT (ABOi-LDLT) and preformed DSA-positive LT (pDSA-LT). Of our 596 adult LDLTs (≥18 y) after rituximab introduction (2004–2019), 136 were ABOi-LDLT (22.8%). After excluding retransplants (9), acute liver failure (7), and protocol deviations (16), 104 ABOi-LDLTs were finally enrolled. Of these, 19 recipients developed AMR, 18 of which occurred within 2 weeks after transplantation (95%). ABOi-AMR significantly worsened graft and recipient survival than those without (p=0.02 and 0.04, respectively). Model for End-stage Liver Disease (MELD) ≤13 (OR: 5.15 [1.63–16.3], p=0.005) and pre-rituximab anti-ABO IgM-titer ≥128 (OR: 3.25 [1.05–10.0], p=0.03) were identified as independent risk factors for ABOi-AMR development. Recipients fulfilling both factors showed significantly worse survival rates than those who did not (p=0.003). Of 352 adult LTs, after introducing the LABScreen Single Ag method (2009–2019), pDSA with mean fluorescence intensity (MFI) ≥500 was detected in 50 cases (14.2%). After excluding 10 ABOi-LDLTs, 40 pDSA-LTs were finally analyzed, of which 5 developed AMR. The combination of high-titer (sum-MFI ≥10,000) and multi-loci pDSAs was a significant risk factor for pDSA-AMR development (p p=0.56). In conclusion, preoperative MELD ≤13 and pre-rituximab anti-ABO IgM-titer ≥128 for ABOi-LDLT, and the combination of sum-MFI ≥10,000 and multi-loci pDSAs for pDSA-LT, are risk factors for AMR in the era of rituximab desensitization. Characteristically, ABOi-AMR significantly deteriorated graft and recipient survival, whereas pDSA-AMR did not.

Donor–recipient human leukocyte antigen (HLA) compatibility has not been considered to significantly affect liver transplantation (LT) outcomes; however, its significance in living‐donor LT (LDLT), which is mostly performed between blood relatives, remains unclear. This retrospective cohort study included 1954 LDLTs at our institution (1990–2020). The primary and secondary endpoints were recipient survival and the incidence of T cell–mediated rejection (TCMR) after LDLT, respectively, according to the number of HLA mismatches at all five loci: HLA‐A, HLA‐B, HLA‐C, HLA‐DR, and HLA‐DQ. Subgroup analyses were also performed in between‐siblings that characteristically have widely distributed 0–10 HLA mismatches. A total of 1304 cases of primary LDLTs were finally enrolled, including 631 adults (recipient age at LT ≥18 years) and 673 children (<18 years). In adult‐to‐adult LDLT, the more HLA mismatches at each locus, the significantly worse the recipient survival was (p = 0.03, 0.01, 0.03, 0.001, and <0.001 for HLA‐A, HLA‐B, HLA‐C, HLA‐DR, and HLA‐DQ, respectively). This trend was more pronounced when multiple loci were combined (all p < 0.001 for A + B + DR, A + B + C, DR + DQ, and A + B + C + DR + DQ). Notably, a total of three or more HLA‐B + DR mismatches was an independent risk factor for both TCMR (hazard ratio [HR] 2.66, 95% confidence interval [CI] 1.21–5.87; p = 0.02) and recipient survival (HR 2.44, 95% CI 1.11–5.35; p = 0.03) in between‐siblings. By contrast, HLA mismatch did not affect pediatric LDLT outcomes at any locus or in any combinations; however, it should be noted that all donor–recipient relationships are parent‐to‐child that characteristically possesses one or less HLA mismatch at each locus and maximally five or less mismatches in total. In conclusion, HLA mismatch significantly affects not only TCMR development but also recipient survival in adult LDLT, but not in children.

Aim: Six‐month recipient mortality after adult‐to‐adult living‐donor liver transplantation (LDLT) remains high. Early and accurate prediction of recipient outcome and continuous monitoring of recipient severity after surgery are both essential for guiding appropriate care. This study was designed to identify early post‐transplant parameters associated with 6‐month mortality, and thereby to construct a discriminatory prognostic index (PI).Methods: We retrospectively analyzed 400 consecutive primary adult‐to‐adult LDLTs in our center (2006–2017). Perioperative variables were comprehensively analyzed for their accuracy in predicting recipient mortality by comparing the area under the receiver operating characteristic (AUROC) of each factor.Results: The AUROCs of preoperative predictive factors, for example, Model for End‐stage Liver Disease (MELD) score and donor age, were 0.56 and 0.64, respectively, whereas those of post‐transplant platelet count (PLT), total bilirubin (T‐BIL), and prothrombin time – international normalized ratio (INR) on postoperative day (POD)‐7−14 were 0.71/0.84, 0.68/0.82, and 0.71/0.78, respectively. Logistic regression analysis provided a formula: PI_POD‐14 = 3.39 + 0.12 × PLT_POD‐14 − 0.09 × T‐BIL_POD‐14 − 1.23 × INR_POD‐14, indicating a high AUROC of 0.87. Recipient 6‐month survival with PI_POD‐14 < 2.38 (n = 173) was 71.7%, whereas that with PI_POD‐14 ≥ 2.38 (n = 222) was 97.7% (P < 0.001). The AUROCs of PI_POD‐7 were as high as 0.8 in the subgroups with younger donors (<50 years of age), right lobe grafts, ABO‐identical/compatible combinations, or low MELD score (<20), indicating usefulness of PI to identify unexpectedly complicated cases within the first week.Conclusions: A novel, post‐transplant survival estimator, PI, accurately predicts recipient 6‐month mortality within 1–2 weeks after adult LDLT. Daily monitoring of PI could facilitate early interventions including retransplantation in critically ill patients.