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

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

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

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

Overcoming the hurdles of steatotic grafts in liver transplantation: Insights into survival and prognostic factors.

With increasing metabolic dysfunction-associated steatotic liver disease, 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 nonsteatotic donor livers, donors after circulatory death, 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. The initial 30-day postoperative period revealed significant challenges with fatty livers, demonstrating inferior GS. However, the GS discrepancy between fatty and nonfatty 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 nonsteatotic 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, the high body surface area (BSA) ratio (≥1.1) (HR 1.42, p = 0.02), calculated as donor BSA divided by recipient BSA, long cold ischemic time (≥6.5 h) (HR 1.72, p < 0.01), and recipient medical condition (intensive care unit 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 intensive care unit hospitalization as significant indicators of a 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, for example, avoiding the use of steatotic donors with long cold ischemic time and high BSA ratios for recipients in the intensive care unit, it is possible to enhance immediate GS, and in a longer time, outcomes comparable to those using nonfatty livers, donors after circulatory death 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.

Effect of transjugular intrahepatic portosystemic shunt insertion on waitlist mortality and access to liver transplantation in budd-chiari syndrome.

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(350vs113 d,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(97vs26 d,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.

Does the introduction of acuity circle policy change split liver transplantation practice?

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.

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

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

Survival benefit of liver transplantation utilizing marginal donor organ according to ABO blood type.

BACKGROUND: 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. METHOD: 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. RESULTS: 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). CONCLUSION: 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.

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

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

The short and long-term prognostic influences of liver grafts with high bilirubin levels at the time of organ recovery.

BACKGROUND: 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. METHODS: 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). RESULTS: 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). DISCUSSION: 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.

Interleukin-33 and liver natural killer cells: A novel perspective on antitumor activity in liver fibrosis.

AIM: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

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

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

The IPTA Nashville Consensus Conference on Post-Transplant lymphoproliferative disorders after solid organ transplantation in children: III - Consensus guidelines for Epstein-Barr virus load and other biomarker monitoring.

The International Pediatric Transplant Association convened an expert consensus conference to assess current evidence and develop recommendations for various aspects of care relating to post-transplant lymphoproliferative disorders after solid organ transplantation in children. In this report from the Viral Load and Biomarker Monitoring Working Group, we reviewed the existing literature regarding the role of Epstein-Barr viral load and other biomarkers in peripheral blood for predicting the development of PTLD, for PTLD diagnosis, and for monitoring of response to treatment. Key recommendations from the group highlighted the strong recommendation for use of the term EBV DNAemia instead of "viremia" to describe EBV DNA levels in peripheral blood as well as concerns with comparison of EBV DNAemia measurement results performed at different institutions even when tests are calibrated using the WHO international standard. The working group concluded that either whole blood or plasma could be used as matrices for EBV DNA measurement; optimal specimen type may be clinical context dependent. Whole blood testing has some advantages for surveillance to inform pre-emptive interventions while plasma testing may be preferred in the setting of clinical symptoms and treatment monitoring. However, EBV DNAemia testing alone was not recommended for PTLD diagnosis. Quantitative EBV DNAemia surveillance to identify patients at risk for PTLD and to inform pre-emptive interventions in patients who are EBV seronegative pre-transplant was recommended. In contrast, with the exception of intestinal transplant recipients or those with recent primary EBV infection prior to SOT, surveillance was not recommended in pediatric SOT recipients EBV seropositive pre-transplant. Implications of viral load kinetic parameters including peak load and viral set point on pre-emptive PTLD prevention monitoring algorithms were discussed. Use of additional markers, including measurements of EBV specific cell mediated immunity was discussed but not recommended though the importance of obtaining additional data from prospective multicenter studies was highlighted as a key research priority.

The IPTA Nashville consensus conference on post-transplant lymphoproliferative disorders after solid organ transplantation in children: IV-consensus guidelines for the management of post-transplant lymphoproliferative disorders in children and adolescents.

The International Pediatric Transplant Association convened an expert consensus conference to assess current evidence and develop recommendations for various aspects of care relating to post-transplant lymphoproliferative disorders (PTLD) after pediatric solid organ transplantation. This report addresses the outcomes of deliberations by the PTLD Management Working Group. A strong recommendation was made for reduction in immunosuppression as the first step in management. Similarly, strong recommendations were made for the use of the anti-CD20 monoclonal antibody (rituximab) as was the case for chemotherapy in selected scenarios. In some scenarios, there is uncoupling of the strength of the recommendations from the available evidence in situations where such evidence is lacking but collective clinical experiences drive decision-making. Of note, there are no large, randomized phase III trials of any treatment for PTLD in the pediatric age group. Current gaps and future research priorities are highlighted.

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

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

Mutations in latent membrane protein 1 of Epstein-Barr virus are associated with increased risk of posttransplant lymphoproliferative disorder in children.

Epstein-Barr virus (EBV)-positive posttransplant lymphoproliferative disorder (PTLD) results in significant morbidity and mortality in pediatric transplant recipients. Identifying individuals at an increased risk of EBV-positive PTLD could influence clinical management of immunosuppression and other therapies, improving posttransplant outcomes. A 7-center prospective, observational clinical trial of 872 pediatric transplant recipients evaluated the presence of mutations at positions 212 and 366 of EBV latent membrane protein 1 (LMP1) as an indicator of risk of EBV-positive PTLD (clinical trials: NCT02182986). DNA was isolated from peripheral blood of EBV-positive PTLD case patients and matched controls (1:2 nested case:control), and the cytoplasmic tail of LMP1 was sequenced. Thirty-four participants reached the primary endpoint of biopsy-proven EBV-positive PTLD. DNA was sequenced from 32 PTLD case patients and 62 matched controls. Both LMP1 mutations were present in 31 of 32 PTLD cases (96.9%) and in 45 of 62 matched controls (72.6%) (P = .005; OR = 11.7; 95% confidence interval, 1.5, 92.6). The presence of both G212S and S366T carries a nearly 12-fold increased risk of development of EBV-positive PTLD. Conversely, transplant recipients without both LMP1 mutations carry a very low risk of PTLD. Analysis of mutations at positions 212 and 366 of LMP1 can be informative in stratifying patients for risk of EBV-positive PTLD.

Use and outcomes of hepatitis B virus-positive grafts in orthotopic liver transplantation in the United States from 1999 to 2021.

The demand for orthotopic liver transplantation (OLT) is projected to increase, which indicates a need to expand the liver donor pool. We aimed to investigate the use of hepatitis B virus (HBV)-positive grafts and the outcomes of recipients undergoing OLT with HBV-positive grafts. We conducted a retrospective cohort study analyzing all deceased donors and OLT recipients in the Organ Procurement and Transplantation Network database from January 1999 through March 2021. Donor HBV status was positive if hepatitis B surface antigen was positive or HBV nucleic acid testing was detectable. Recipients of HBV-positive allografts were matched 1:5 to recipients of HBV-negative allografts based on recipient and donor age, transplant year, recipient sex, donation after circulatory death, recipient location, and Model for End-Stage Liver Disease score at transplant. Among the 185,212 potential donors, 422 (0.2%) were HBV positive, and 265 (63%) of the HBV-positive grafts were transplanted (14 of 265 [5.3%] in HBV-positive recipients). The overall discard rate for HBV-positive donors of 37.2% (157/422) remained significantly higher than the discard rate for HBV-negative donors of 26.5% (49,026/185,212) during the study period ( p < 0.001). Recipients of HBV-positive ( n = 209) grafts had similar mortality (log-rank, p = 0.47) and graft loss (log-rank, p = 0.72) rates to the matched recipients of HBV-negative allografts ( n = 1045). The 3-year graft survival rate was 77.9% for the HBV-positive group and 79.7% in the matched HBV-negative group. Based on this analysis, transplant recipients of HBV-positive liver allografts do not experience increased rates of mortality or graft loss. One strategy that may help expand the donor pool and lower the waitlist mortality rate is using HBV-positive allografts.

Has the risk of liver re-transplantation improved over the two decades?

BACKGROUND: 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. METHODS: 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. RESULTS: 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. DISCUSSION: 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.

Highlights from the 12th congress of the international pediatric transplant association, Austin, Texas 2023.

The 12th Congress of the (IPTA) event in Austin, Texas, had over 400 attendees from 40 countries. The attendees included a diverse mix of pediatric transplant professionals from several specialties including physicians, surgeons, scientists, nurses, organ procurement personnel, advance transplant providers, pharmacists, administrators, fellows, residents, and students. The 4-day event featured nearly 200 abstracts, 90 oral presentations, 24 mini oral presentations, and more than 80 poster presentations. All of these presentations encouraged vibrant discussions and supported the exchange of new clinical and basic science information regarding clinical care management, basic science research, socioeconomic, and ethical and organ donation issues relevant to pediatric transplantation. We briefly describe here the highest scored presented abstracts at IPTA 2023 that are divided into two categories: clinical and basic sciences.

Characterization of reproductive proteins in the Mexican fruit fly points towards the evolution of novel functions.

Seminal fluid proteins (Sfps) modify female phenotypes and have wide-ranging evolutionary implications on fitness in many insects. However, in the Mexican fruit fly, Anastrepha ludens, a highly destructive agricultural pest, the functions of Sfps are still largely unknown. To gain insights into female phenotypes regulated by Sfps, we used nano-liquid chromatography mass spectrometry to conduct a proteomic analysis of the soluble proteins from reproductive organs of A. ludens. The proteins predicted to be transferred from males to females during copulation were 100 proteins from the accessory glands, 69 from the testes and 20 from the ejaculatory bulb, resulting in 141 unique proteins after accounting for redundancies from multiple tissues. These 141 included orthologues to Drosophila melanogaster proteins involved mainly in oogenesis, spermatogenesis, immune response, lifespan and fecundity. In particular, we found one protein associated with female olfactory response to repellent stimuli (Scribble), and two related to memory formation (aPKC and Shibire). Together, these results raise the possibility that A. ludens Sfps could play a role in regulating female olfactory responses and memory formation and could be indicative of novel evolutionary functions in this important agricultural pest.

Outcomes after liver transplantation in MPV17 deficiency (Navajo neurohepatopathy): A single-center case series.

BACKGROUND: MPV17-related mitochondrial DNA maintenance defect (MPV17 deficiency) is a rare, autosomal recessive mitochondrial DNA depletion syndrome with a high mortality rate in infancy and early childhood due to progression to liver failure. Liver transplantation for children with MPV17 deficiency has been considered controversial due to uncertainty about the potential progression of extrahepatic manifestations following liver transplantation. METHODS: We describe our institution's experience for two infants diagnosed with infantile MPV17 deficiency who presented in acute on chronic liver failure, but with normal development and normal neurological status who successfully underwent liver transplantation. RESULTS: Both patients underwent successful liver transplantation with normal development and neurological status at 3 years and 16 months post-transplant, respectively. CONCLUSIONS: In this rare disease population, we describe two infants with MPV17 deficiency who underwent liver transplantation for acute on chronic liver failure who continue to have normal development, without progression of neurological disease. MPV17 deficiency should not be considered a contraindication to liver transplantation.