Previous trials have reported significant reductions in post-transplant bacterial infections with pre-, peri-, or postoperative treatment with probiotics, with or without additional prebiotics. However, uncertainty remai...Previous trials have reported significant reductions in post-transplant bacterial infections with pre-, peri-, or postoperative treatment with probiotics, with or without additional prebiotics. However, uncertainty remains regarding the veracity of these results and we are not aware of the adoption of such treatment by transplant centers. We sought to confirm the efficacy of postoperative synbiotic treatment in reducing post-transplant infections in a randomized, double-blind, placebo-controlled trial. Eighty-two patients wait-listed for liver transplantation were randomized to receive a daily dose of either a synbiotic (400 billion lactic acid bacteria plus 4 bio-active fibers) or placebo (non-fermentable fiber) administered as soon as possible after surgery and continued for 14 days. Infectious complications (primary outcome), antibiotic use, and adverse events were recorded during the first 30 postoperative days. Patients were followed up for 90 days for rejection and survival. The primary analysis was by intention-to-treat. In addition, a per-protocol analysis was carried out excluding patients who failed to reach 80% of the prescribed dose of synbiotics or placebo. One patient withdrew consent after randomisation and the remaining 81 patients (39 synbiotic and 42 placebo) constituted the intention-to-treat population. Bacterial infectious complications occurred in 15 (38.5%) synbiotic and 14 (33.3%) placebo patients (adjusted p=0.68). There was one death in the synbiotic group and two deaths in the placebo group. Rejection occurred in 12 (30.8%) synbiotic and 17 (40.5%) placebo patients (p=0.49). The median (range) postoperative hospital stay was 9 (4-33) days for synbiotic and 9 (6-125) days for placebo patients (p=0.90). Per-protocol analyses did not markedly change these results. In conclusion, postoperative synbiotic supplementation did not provide significant clinical outcome benefits in patients undergoing liver transplantation.
Long-term success after liver transplantation (LT) is often hindered by side effects from lifelong immunosuppression (IS). Standard liver enzyme tests are poor indicators of graft inflammation or fibrosis. To address thi...Long-term success after liver transplantation (LT) is often hindered by side effects from lifelong immunosuppression (IS). Standard liver enzyme tests are poor indicators of graft inflammation or fibrosis. To address this, a program of surveillance liver biopsy (svLbx)-guided personalized IS has been implemented to inform decisions on IS minimization. This study, spanning from 2018 to 2024, extends previous short-term observations to assess the long-term impact of biopsy-guided Calcineurin Inhibitor (CNI) reduction in LT recipients, including follow-up biopsies. Patients' IS was adjusted based on svLbx findings, donor-specific antibodies, liver function, and comorbidities. Analyzing 242 LT recipients, the study compared outcomes in those whose CNI dosage was reduced (n=89) versus those whose dosage was maintained or increased (n=83). CNI reduction proved safe, with no increase in rejection, graft loss or death. Crucially, it significantly preserved kidney function (ΔeGFR: +0.5 vs. -6.5 mL/min) over a median follow-up of 47 months, even when controlling for baseline kidney function, CNI score, graft injury and time post-LT. Sequential biopsies revealed no worsening of fibrosis or inflammation, and non-invasive measures corroborated these findings. In conclusion, svLbx-guided CNI reduction safely maintains kidney function and prevents graft injury late after LT, making it a viable strategy for long-term IS minimization.
BACKGROUND: Elevated lipase is common in critically ill patients, including those awaiting liver transplantation (LT), but its clinical significance remains unclear. We assessed the relationship between pre-LT lipase ele...BACKGROUND: Elevated lipase is common in critically ill patients, including those awaiting liver transplantation (LT), but its clinical significance remains unclear. We assessed the relationship between pre-LT lipase elevation, radiographic (RP) or intraoperative pancreatitis (IOP), and post-LT outcomes. METHODS: We included adults undergoing LT evaluation between 1/2015-3/2025 with lipase ≥78 U/L within 14 days of the relevant index event (transplant, listing, committee deferral/decline). RP was defined by imaging evidence of peripancreatic inflammation or necrosis and IOP by intraoperative findings. Kaplan-Meier and Cox regression evaluated associations with post-LT death or graft failure. RESULTS: Among 90 transplanted patients (median age 57, 60% male), 22% died or experienced graft failure within 36 months. RP or IOP occurred in 9% of patients; all IOP cases died within two months, while 60% of RP patients died within 19 months. At 60 days post-LT, isolated lipase elevation ≥3xULN was not associated with death or graft failure (HR 1.68, p=0.61), whereas RP was strongly associated with death or graft failure (HR 5.13, p=0.04). Lipase ≥5xULN predicted RP/IOP (OR 6.92, p=0.002) across the transplanted, waitlisted, and declined/deferred cohorts. CONCLUSION: In LT candidates, RP or IOP, but not isolated biochemical lipase elevation, is a significant predictor of post-LT death or graft failure. Lipase ≥5xULN warrants further imaging to identify clinically significant pancreatitis and optimize perioperative management.
Liver transplantation (LT) has for decades been a well-established treatment for end-stage liver disease and malignancy, becoming the standard of care for select patients with these life-limiting conditions. Due to a lim...Liver transplantation (LT) has for decades been a well-established treatment for end-stage liver disease and malignancy, becoming the standard of care for select patients with these life-limiting conditions. Due to a limited pool of high-quality deceased donor organs, there is an existing and growing disparity between those in need of and those able to access LT. Living donor liver transplantation (LDLT) has emerged as one way to mitigate this disparity. Despite Australia's place in history as the first reported LDLT from mother-to-child in 1987, living donation for adults is rare, in part due to perceived lack of need due to the historically low waitlist mortality data. This Perspective reviews the history of LDLT and utilises Australia as a case-study for exploring the necessity for LDLT in existing deceased donor liver transplant programs, the ethical considerations, risks and benefits of the procedure, and the means to implement LDLT.
BACKGROUND AND AIM: Optimizing health and quality of life for pediatric liver transplant (LT) recipients requires balancing protection of the liver graft with overall burden of treatments on the child. Since the AASLD's...BACKGROUND AND AIM: Optimizing health and quality of life for pediatric liver transplant (LT) recipients requires balancing protection of the liver graft with overall burden of treatments on the child. Since the AASLD's 2013 guidelines, strategies for achieving this balance have evolved, with a particular focus on mitigating long-term complications. Advances include operative and intensive care strategies for reducing complications, minimizing exposure to immunosuppression and its long-term adverse effects for other organs, infection prevention with prophylaxis and vaccination, optimizing support of early nutrition and development, and improving support around transition from pediatric to adult care. This document aims to provide an evidence-based guideline to comprehensive care of pediatric LT recipients, starting at transplant and continuing as they advance to adulthood. METHODS: A multidisciplinary writing group of pediatric liver transplant experts and a medical librarian was convened by AASLD, with guidance by its Practice Guidelines Development Policy, and in collaboration with the North American Society of Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) and the American Society of Transplantation (AST). We conducted a systematic global literature review, formulated key clinical questions, and developed recommendations. Each recommendation was graded using the Oxford Centre for Evidence-Based Medicine framework and categorized by strength through a consensus voting process. CONCLUSION: All recommendations are based on best-available evidence and reflect expert consensus. Most of the evidence basis remains retrospective or observational data, or extrapolation from related populations. To continue improving long-term outcomes after pediatric liver transplant, multi-disciplinary, multi-center collaboration to strengthen the evidence will be essential.
Post-transplant immunosuppression (IS) significantly impacts patient and graft outcomes. The Starzl Network for Excellence in Pediatric Transplantation (SNEPT), a multicenter learning health network dedicated to pediatri...Post-transplant immunosuppression (IS) significantly impacts patient and graft outcomes. The Starzl Network for Excellence in Pediatric Transplantation (SNEPT), a multicenter learning health network dedicated to pediatric liver transplant, identified IS optimization as a priority project. Here we describe SNEPT's development of consensus care plans (CCPs) for induction IS after pediatric liver transplantation, using an adapted nominal group technique to achieve consensus. First, 16 SNEPT transplant centers across the U.S. and Canada shared individual center IS protocols. Collation of center-specific protocols identified five key medications (basiliximab, thymoglobulin, corticosteroids, mycophenolate mofetil, and tacrolimus). Dosing consensus and variability across all 16 center protocols were summarized by SNEPT's Optimizing IS working group. Through iterative cycles of feedback conducted in-person and virtually, 2022-2025, CCPs for each medication were developed, reviewed with stakeholders and revised. CCPs were finalized with consensus from all 16 centers. CCPs were presented at SNEPT's network-wide meeting as well as at individual center multidisciplinary meetings to assess accuracy of captured current practice and agreement with implementation. CCPs were finalized with universal network consensus and will be implemented across the network, laying foundational work for prospective quality improvement and comparative effectiveness studies.