Citations

Abstract Background Lymphocytic choriomeningitis virus (LCMV) infection in immunocompromised hosts can result in disseminated disease, meningoencephalitis, and death. Published cases in transplant recipients have been traced to transmission from infected donors. We report 2 cases of serious, non–donor-derived LCMV infection in solid organ transplant recipients. Methods Initial identification of LCMV infection was done by using metagenomic next-generation sequencing (mNGS). Subsequent evaluations and confirmatory testing involved molecular diagnostics, serology, and phylogenetic analysis. A detailed epidemiologic investigation was conducted. Results LCMV was detected by mNGS in 2 solid organ transplant recipients from distinct donors. A heart transplant recipient (from donor 1) died of progressive, disseminated LCMV infection, while a kidney transplant recipient (from donor 2) with LCMV meningoencephalitis survived. A multistate laboratory and epidemiologic investigation of both donors and all their organ recipients was initiated. Postmortem samples were obtained from both donors, and pretransplant and/or posttransplant samples were obtained from 5 of the 6 organ recipients. mNGS, serologic, and real-time reverse-transcription polymerase chain reaction testing confirmed LCMV infection in both solid organ transplant recipients. Epidemiologic investigation revealed significant pretransplant rodent exposures for both LCMV-infected recipients. Laboratory studies for the other organ recipients from both donors were negative for LCMV infection. Conclusions Our investigations suggest that LCMV infection in 2 solid organ transplant recipients originated from rodent exposure preceding transplantation and were not donor derived. Although uncommon, healthcare providers should be aware of LCMV-associated serious and life-threatening illness in immunocompromised hosts. Diagnostic modalities are limited to reference laboratories.

Background. The availability of in situ normothermic regional perfusion (NRP) or ex situ normothermic machine perfusion (NMP) has revolutionized donation after circulatory death (DCD) liver transplant (LT). While some have suggested that NRP and NMP may represent competing technologies for DCD LT, there are many scenarios where these technologies can function in a complementary manner. Methods. Between January 2022 and March 2024, 83 DCD LTs were performed using NRP (62 NRP alone and 21 NRP + NMP) and were compared with 297 static cold storage (SCS) DCD LTs. NRP + NMP was used in scenarios with (1) long travel distances, (2) complicated transplant recipients, or (c) the need for additional liver graft recovery in “marginal” cases. Results. Ischemic cholangiopathy was lower in the NRP alone group (0%) and the NRP + NMP group (0%) compared with the SCS group (16.8; P < 0.001 and P = 0.04, respectively). In addition, early allograft dysfunction, number of packed red blood cells transfused, and acute kidney injury were lower in the NRP alone and NRP + NMP groups compared with the SCS group. Graft survival was higher in cases where NRP was used than in cases where SCS was used ( P = 0.016). In all the cases where lactate remained elevated at the end of NRP (mean 8.2 ± 2.0), it ultimately normalized at the end of NMP (0.92 ± 0.56). Conclusions. The present study demonstrates lower rates of ischemic cholangiopathy and improved graft survival with NRP alone or NRP + NMP compared with SCS when using liver grafts from DCD donors. It also demonstrates that excellent outcomes can be achieved with sequential NRP + NMP in cases with prolonged travel distances, complicated recipients, or when there is a need for additional liver recovery in “marginal” cases.

There is a paucity of data on the impact of cold ischemia time before the initiation of normothermic machine perfusion (NMP), particularly in more susceptible organs such as livers from donation after circulatory death (DCD) donors. The present analysis aimed to investigate the impact of prolonged time from cross-clamp until NMP start on early allograft dysfunction and other peri–liver transplant (LT) outcomes. All DCD LT performed and placed on NMP at Mayo Clinic Arizona, Florida, and Rochester from January 2022 to March 2024 were included. The decision was made a priori to divide the population into 2 groups based on terciles: typical cross-clamp to on-pump time (lower 2 terciles) versus prolonged cross-clamp to on-pump time (upper tercile; >2 h 45.6 min). Three hundred eighty-four DCD LT undergoing NMP met the inclusion criteria. The rate of early allograft dysfunction was significantly higher in the prolonged cross-clamp to on-pump group (51.2%) compared to the typical cross-clamp to on-pump group (37.6%) (p = 0.01). The prolonged cross-clamp to on-pump group also had higher rates of acute kidney injury and the number of packed red blood cells transfused during LT. No significant difference in ischemic cholangiopathy (2.4% vs. 3.1%; p = 0.68) or graft survival at 12 months was seen between the prolonged cross-clamp to on-pump and typical cross-clamp to on-pump group, respectively. Following cross-clamp, DCD liver grafts should be placed on the NMP pump as quickly as is safely and logistically possible. In cases where delays are unavoidable, such as waiting for biopsy results or liver reallocation with another center, acceptable results can still be achieved, and therefore, livers with prolonged times should still be used.

AbstractLiver transplantation (LT) with hepatitis B core antibody (anti‐HBc) positive grafts to hepatitis B surface‐antigen (HBsAg) negative recipients is safe and has likely contributed to improvements in organ access over the years. The incidence of de novo hepatitis B infection (HBV) in these instances is low with appropriate prophylaxis and is affected by recipient immunologic status. There is debate as to whether hepatitis B surface antibody (anti‐HBs) positivity may safely inform prophylaxis discontinuation post‐LT. In this retrospective study of all hepatitis B surface antigen (HBsAg) negative recipients of anti‐HBc positive organs at three large academic centers between January 2014 and December 2019, nine LT recipients discontinued prophylaxis after developing anti‐HBs antibodies 1 year or later post‐LT. Three of the nine patients (33%) developed de novo HBV, defined by positive HBsAg or hepatitis B virus (HBV) DNA, during the study period. The remaining six patients had no evidence of HBV infection after a mean follow‐up of 37 months. The patients without de novo HBV had higher anti‐HBs titers at the time of prophylaxis discontinuation and were less likely to have negative anti‐HBs at the time of transplant or negative anti‐HBc at any time point. These results suggest that quantitative anti‐HBs titer thresholds rather than qualitative anti‐HBs positivity at 1 year or later after LT should be used to identify patients at decreased risk of de novo infection and help guide prophylaxis duration.

Background. Surgical-site infections (SSIs) are common in liver transplant recipients. The optimal SSI antimicrobial prophylaxis agent and duration are not established. We aimed to explore risk factors for SSIs after transplant, with a particular interest in the impact of perioperative antibiotic regimen on the development of SSIs. Methods. Retrospective study of adults undergoing liver transplant across 3 transplant programs between January 1, 2020, and June 01, 2021. Results. Of 557 patients included in the study, 32 (5.7%) were infected or colonized with a multidrug-resistant organism (MDRO) within 1 y before liver transplant. Narrow-spectrum SSI prophylaxis with ceftriaxone or cefazolin alone was administered in 488 of 577 patients (87.6%); the remaining 69 patients (12.4%) received broad-spectrum prophylaxis with vancomycin and aztreonam (n = 40), piperacillin–tazobactam (n = 11), carbapenems (n = 8), ceftriaxone and another antibiotic (n = 7), and others. Patients with pretransplant MDRO were more likely to receive broad-spectrum coverage than those without pretransplant MDROs (28.1% versus 11.4%, P = 0.005). SSIs were identified in 40 patients (7.2%); 25 (62.5%) were organ–space infections, 3 (7.5%) were deep incisional infections, and 12 (30.0%) were superficial incisional infections. The median time from liver transplant to SSIs was 14 d (interquartile range, 10–20.2). MDROs were identified in 12 SSIs (30%). Multivariable analysis revealed no significant association between antimicrobial spectrum and risk of SSIs (P = 0.5), whereas surgical leak (P<0.001) and reoperation (P = 0.017) were independently associated with increased risk of SSIs. SSIs were not significantly associated with composite risk of death or liver allograft failure. Conclusions. The spectrum of antimicrobial prophylaxis did not impact the development of SSIs in liver transplant recipients.

Introduction Liver acceptance patterns vary significantly between transplant centers. Data pertaining to outcomes of livers declined by local and regional centers and allocated nationally remains limited. Project aim The objective was to compare post-liver transplant outcomes between liver allografts transplanted as a result of national and local-regional allocation. Design This was a retrospective evaluation of 109 nationally allocated liver allografts used for transplant by a single center. Outcomes of nationally allocated grafts were compared to standard allocation grafts (N = 505) during the same period. Results Recipients of nationally allocated grafts had lower model for end stage liver disease scores (17 vs 22, P = .001). Nationally allocated grafts were more likely to be post-cross clamp offers (29.4% vs 13.4%, P = .001) and have longer cold ischemia times (median hours 7.8 vs 5.5, P = .001). Early allograft dysfunction was common (54.1% vs 52.5%, P = .75) and did not impact hospital length of stay (median 5 vs 6 days, P = .89). There were no differences in biliary complications ( P = .11). There were no differences in patient ( P = .88) or graft survival ( P = .35). In a multivariate model, after accounting for differences in cold ischemia time and posttransplant biliary complications, nationally allocated grafts were not associated with increased risk for graft loss (HR 0.9, 95% CI 0.4-1.8). Abnormal liver biopsy findings (33.0%) followed by donor donation after circulatory death status (22.9%) were the most common reasons for decline by local-regional centers. Conclusion Despite longer cold ischemia times, patient and graft survival outcomes remain excellent and comparable to those seen from standard allocation grafts.

Abstract Background: Starting in November 2017, 3 liver transplant centers in a single health care system tested and implemented a new protocol to begin accepting livers from hepatitis C virus–seropositive donors for seronegative liver transplant recipients. Although reports show an increase in donors after protocol implementation, there are no details regarding protocol uptake at each transplant center. Literature is limited on protocol implementation that is developed and disseminated by the same protocol producers. The purpose of this study was to evaluate the implementation of a new liver transplant protocol adopted at 3 transplant centers in the same health care system. Methods: A multimethod implementation study using interview, survey, and transplant data was conducted to develop a conceptual model of protocol implementation, identify facilitators of and barriers to implementation, and detect differences in implementation between 3 centers. Results: The conceptual model included 4 domains: rationale, development, implementation, and sustainability. Facilitators included clear, science-based rationale, input from multiple hepatologists, leadership support, and funded pilot data. Barriers included insurance coverage of posttransplant medication and donor field availability. A total of 94 physicians and staff at the 3 transplant centers completed the survey. Implementation factors were all rated moderately high to high at all 3 centers. One-way analysis of variance showed significant differences in mean implementation scores between the centers (F(2, 84)=11.65; P<.001) and between physicians at the 3 centers (F(2, 23)=4.65; P=.02); post hoc comparisons indicated that the scores for physicians differed only between the leading center and 1 participating center. Transplant numbers increased across all 3 centers from 2017 to 2021. Conclusions: Protocol implementation was successful across all 3 centers, especially at the leading transplant center where the protocol was developed. Future efforts should examine the appropriateness of the protocol for other organs (eg, heart, kidney) and additional medical outcome data (eg, mortality, morbidity, quality of life). Trial Registration: Not applicable