Trending Topics in Gastroenterology | GastroAGI

Redefining Early Allograft Dysfunction in LDLT : Liver Transpl | Jun 2026

Introduction: Early allograft dysfunction (EAD) remains one of the most important early indicators of graft performance after liver transplantation. Traditionally, EAD has been defined using biochemical parameters developed largely from deceased donor liver transplantation populations. However, living donor liver transplantation (LDLT) presents unique physiological and surgical characteristics, including smaller graft volumes, regenerative dynamics, and distinct perioperative factors, which may limit the applicability of conventional EAD definitions. Problem Statement: Current EAD models may not accurately reflect graft function or predict outcomes in LDLT recipients. Reliance on static biochemical thresholds can oversimplify the complex and evolving process of graft recovery, potentially leading to inaccurate risk stratification and delayed recognition of clinically significant dysfunction. There is an increasing need for more precise, individualized, and clinically meaningful approaches tailored specifically to LDLT. Summary: This editorial highlights the need to move beyond traditional definitions of EAD and adopt a more adaptive framework for assessing graft function following LDLT. The authors emphasize that graft recovery is a dynamic process influenced by donor characteristics, graft size, recipient factors, surgical complexity, and postoperative regenerative capacity. Rather than depending solely on fixed laboratory cut-offs, future models should incorporate longitudinal clinical and biochemical trends to better capture the evolving nature of graft performance. The article also underscores the growing potential of artificial intelligence and machine-learning technologies to integrate large volumes of perioperative and postoperative data, enabling more accurate prediction of graft dysfunction and patient outcomes. Such data-driven approaches could facilitate earlier intervention, personalized monitoring, and improved clinical decision-making. As LDLT continues to expand globally, the development of graft-specific and AI-enabled assessment tools may represent a significant step toward precision transplantation, offering a more nuanced understanding of early graft recovery and ultimately improving transplant outcomes.

Bucharest Consensus: Ethical Standards for Controlled DCDD: Transplant International | June 2026

* Controlled donation after circulatory determination of death is becoming an increasingly important pathway to expand deceased organ donation worldwide. * This ESOT Bucharest international consensus provides practical, ethical, and operational standards for adult controlled DCDD programs. * The recommendations were developed using a Delphi process involving 37 experts from 15 countries, covering intensive care, transplant surgery, donation coordination, ethics, and law. * The central principle is that decisions about withdrawal of life-sustaining measures must remain completely separate from decisions about organ donation. * A robust legal framework is essential before starting or expanding controlled DCDD programs, including clear rules for death determination, consent, donation authorization, and ante-mortem interventions. * Public and professional education is necessary because controlled DCDD differs from donation after neurological determination of death and may be poorly understood. * Potential donors should be identified early as part of routine end-of-life care, and referral triggers should be built into ICU and emergency care pathways. * Treating clinicians should not unilaterally exclude patients from donation; suitability assessment should involve donation professionals and transplant teams when needed. * Prediction of time to death after withdrawal of life support is imprecise, so suitability should not rely on a single scoring tool or individual clinician judgement alone. * Communication with families should be sensitive, staged, and preferably led by trained donation professionals who are not directly responsible for the patient’s clinical care. * Families should first understand that death is expected and that withdrawal of life-sustaining measures has been decided before donation is discussed. * Patient comfort, dignity, sedation, analgesia, and family presence during withdrawal of life support must remain central and should never be compromised for donation success. * The withdrawal process and comfort care should be managed by the treating clinical team, not by donation or transplant personnel. * Ante-mortem interventions may be considered when legally permitted, clinically justified, and aligned with the patient’s values or donation goals. * The benefits of ante-mortem interventions should be balanced against their invasiveness, discomfort, risk, and potential impact on the end-of-life experience. * The consensus emphasizes that donation can serve the patient’s values when donation was known or likely to be important to them, but this must never override comfort and dignity. * Programs should collect data on missed opportunities, failed donation attempts, and logistical barriers to improve future controlled DCDD pathways. * The report highlights the need for research into ante-mortem interventions, prediction of time to death after withdrawal, and best models for family communication. * Controlled DCDD should be developed through national protocols adapted to local legal, cultural, clinical, and logistical realities. Bottom line: The Bucharest ESOT consensus establishes controlled DCDD as an ethically acceptable and clinically important donation pathway, provided that end-of-life care remains patient-centered, donation decisions are clearly separated from withdrawal decisions, and ante-mortem interventions are carefully justified and transparently discussed.

HOPE Reduces Early Liver Graft Dysfunction : JAMA Surg | May 2026

Introduction: Introduction: Liver transplantation increasingly relies on extended-criteria donor (ECD) and donation-after-circulatory-death (DCD) grafts to address organ shortages. However, these grafts are more susceptible to ischemia-reperfusion injury, which contributes to early allograft dysfunction (EAD), prolonged hospitalization, biliary complications, and inferior post-transplant outcomes. Hypothermic oxygenated perfusion (HOPE) has emerged as a promising preservation strategy that restores mitochondrial function and reduces reperfusion injury before implantation. Problem Statement: Problem Statement: Although European studies have demonstrated benefits of HOPE, evidence supporting its effectiveness in a multicenter US transplant population using higher-risk donor livers has remained limited. Whether portal-venous HOPE can meaningfully improve graft function and clinical outcomes compared with conventional static cold storage (SCS) required prospective randomized evaluation. Summary: Summary: The Bridge to HOPE Trial was a multicenter randomized clinical trial conducted across 15 US liver transplant centers, enrolling 219 recipients of extended-criteria donor livers, including both donation-after-brain-death (DBD) and DCD grafts. Patients were randomized to receive either conventional static cold storage alone or portal-venous hypothermic oxygenated perfusion following transport and before implantation. The primary endpoint was early allograft dysfunction. HOPE significantly reduced EAD compared with static cold storage alone, occurring in 20.2% of recipients versus 37.3% in the control group. This represents a clinically meaningful reduction in early graft injury and demonstrates the capacity of oxygenated machine perfusion to improve immediate graft performance. Recipients receiving HOPE also achieved significantly better Model for Early Allograft Function (MEAF) scores, indicating superior early hepatic recovery after transplantation. Furthermore, HOPE was associated with a shorter hospital stay, suggesting faster postoperative recovery and reduced healthcare utilization. Importantly, the intervention was safe and easily integrated into routine transplant workflows. One-year patient survival and graft survival were excellent in both groups and did not significantly differ, reflecting the overall high success rates of contemporary liver transplantation. Although rates of non-anastomotic biliary strictures were not significantly different, post hoc analyses suggested fewer cases of graft loss related to biliary complications in the HOPE group. Major postoperative complications were also numerically lower among HOPE recipients. The biological rationale for HOPE lies in its ability to oxygenate the graft under hypothermic conditions before reperfusion. This process replenishes mitochondrial energy stores, reduces oxidative stress, limits inflammatory activation, and minimizes ischemia-reperfusion injury. These mechanisms are particularly important for marginal donor grafts, where preservation injury contributes substantially to early dysfunction. The study is notable because it evaluated a pragmatic “back-to-base” preservation strategy that can be implemented without requiring continuous machine perfusion during transport. This makes adoption more feasible for transplant programs compared with more complex normothermic perfusion systems. Overall, this landmark randomized trial demonstrates that portal-venous HOPE significantly reduces early allograft dysfunction, improves early graft function, and shortens hospital stay in recipients of extended-risk liver grafts. These findings support HOPE as an effective and practical preservation strategy that may improve outcomes as transplant programs increasingly utilize higher-risk donor organs.

Preemptive Anti-Craving Therapy May Reduce Post-Transplant Alcohol Relapse : Liver Transpl | May 2026

Introduction Alcohol-Associated Liver Disease has become one of the leading indications for Liver Transplantation worldwide. Although transplantation provides excellent survival benefit, post-transplant alcohol relapse remains a major concern because it can contribute to graft injury, recurrent liver disease, cardiovascular complications and reduced long-term survival. Strategies to prevent relapse after transplantation remain incompletely standardized, particularly among patients identified as high risk for recurrent alcohol use. Problem Statement Evidence supporting proactive pharmacologic anti-craving interventions after liver transplantation is limited, and optimal relapse-prevention strategies in high-risk transplant recipients remain poorly defined. Summary This rapid communication evaluated the impact of preemptive anti-craving therapy on post-transplant alcohol relapse among high-risk liver transplant recipients. The study addresses a highly relevant and evolving area within transplant hepatology, where the focus is increasingly shifting from rigid pretransplant abstinence rules toward structured longitudinal addiction management. The central finding was that early implementation of anti-craving pharmacotherapy appeared to reduce rates of alcohol relapse after transplantation in individuals considered at elevated relapse risk. Although details regarding specific agents and long-term relapse severity were limited in the brief report format, the findings support the growing concept that alcohol use disorder should be managed as a chronic relapsing neurobehavioral disease requiring ongoing therapeutic intervention rather than solely psychosocial monitoring. The study is clinically important because relapse risk after transplantation is multifactorial and cannot be reliably predicted by abstinence duration alone. Psychiatric comorbidity, prior relapse history, social instability and untreated craving pathways all contribute to recurrent alcohol use risk. Pharmacologic craving suppression may therefore provide an additional biologic layer of protection during the vulnerable post-transplant recovery period. These findings align with broader shifts in addiction medicine emphasizing integrated multidisciplinary care models that combine transplant hepatology, psychiatry, behavioral therapy and medication-assisted treatment. Increasing evidence suggests that structured post-transplant addiction management may improve not only abstinence outcomes but also graft survival and overall quality of life. Potential anti-craving agents in this context may include medications such as Acamprosate, Naltrexone or baclofen-based approaches, although individual agent selection in transplant recipients requires careful consideration of hepatic metabolism, neuropsychiatric effects and drug interactions with immunosuppressive therapy. Importantly, the study also contributes to ongoing efforts to destigmatize alcohol-associated liver disease within transplantation. Demonstrating benefit from proactive relapse-prevention therapy reinforces the principle that relapse risk can be medically managed rather than viewed solely as a behavioral failure. The work further supports the movement toward precision psychosocial risk stratification in transplant hepatology. Rather than universally applying identical monitoring strategies, high-risk individuals may benefit from intensified multidisciplinary follow-up and early pharmacologic intervention. However, larger prospective studies remain necessary to define optimal timing, duration and choice of anti-craving therapies after transplantation. Long-term effects on sustained abstinence, graft outcomes, survival and quality of life also require further validation. Overall, this study suggests that preemptive anti-craving pharmacotherapy may reduce post-transplant alcohol relapse among high-risk liver transplant recipients. The findings support a proactive addiction medicine framework within transplant hepatology and highlight the importance of integrating pharmacologic relapse prevention into comprehensive post-transplant care pathways.

ACLF Definitions: JCTH | May 2026

- Acute-on-chronic liver failure (ACLF) is a severe syndrome characterized by acute decompensation, organ failure, and high short-term mortality in patients with cirrhosis. However, ACLF lacks a universally accepted definition. Multiple frameworks exist globally, leading to inconsistencies in diagnosis, risk stratification, clinical trials, and regulatory pathways. - This multinational study compared the newly proposed 2025 consensus ACLF definition with the outcome-based A-TANGO classification, which was designed using mortality-calibrated organ failure thresholds. - The major challenge in ACLF is balancing harmonization with clinical accuracy. Broader consensus definitions may improve standardization but risk missing clinically important patients if sensitivity declines. The critical question addressed in this study was: Does the newer consensus framework accurately identify high-risk ACLF patients, or does it underdiagnose clinically meaningful disease compared with outcome-based models? - This large multinational study involving nearly 5,000 patients from India and China demonstrated major differences between the two ACLF frameworks. The A-TANGO model identified substantially more patients as ACLF compared with the consensus definition. Importantly, many patients labeled “non-ACLF” by the consensus criteria but classified as ACLF by A-TANGO had significant short-term mortality, with 28-day mortality ranging from 18%–27%. A-TANGO consistently showed higher sensitivity for predicting mortality, whereas the consensus definition was more specific but captured a smaller and more advanced liver-centered phenotype. The study also demonstrated that the consensus “non-ACLF” group was not truly low risk. A-TANGO further stratified these patients into progressively higher mortality groups, revealing hidden clinical heterogeneity. Overall, the findings suggest that A-TANGO may identify patients earlier in the disease trajectory, potentially at a stage where intervention remains possible. In contrast, the consensus framework appears to diagnose ACLF later, potentially missing high-risk patients with evolving multi-organ dysfunction. This work has major implications for clinical care, ICU triage, transplant decisions, and future ACLF trial design.

Ferroptosis Blockade Improves Liver and Lung Graft Function : Cell | May 2026

Introduction Ischemia–reperfusion injury (IRI) remains a major barrier in organ transplantation and contributes significantly to graft dysfunction, early allograft injury and organ discard. Ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation, has recently emerged as a key mechanism underlying tissue injury during ischemia and reperfusion. Problem Statement Despite increasing recognition of ferroptosis in transplant-associated injury, no clinically applicable therapies currently target this pathway. Existing ferroptosis inhibitors have been limited by poor pharmacokinetics and inadequate translational potential, while the precise temporal dynamics of lipid peroxidation during human transplantation remain incompletely characterized. Summary This landmark translational study identifies ferroptosis as a major therapeutic target in transplantation and introduces FXT-001 as a first-in-class drug-like ferroptosis inhibitor with promising clinical applicability. The investigators demonstrated that lipid peroxidation rapidly peaks within the first hour after graft reperfusion in human liver transplantation and correlates with severe ischemia–reperfusion injury. FXT-001 combines radical-trapping antioxidant activity with iron-binding capacity, enabling dual suppression of lipid peroxidation and ferroptotic cell death. Mechanistic studies showed preferential localization of FXT-001 within mitochondria and endolysosomal compartments, where it modulates subcellular iron handling and prevents membrane lipid radical propagation. In clinically relevant porcine liver donation-after-circulatory-death models, FXT-001 significantly reduced hepatocellular injury markers, improved glucose metabolism and preserved choleretic function during ex situ reperfusion. Parallel experiments in porcine and declined human donor lungs demonstrated reduced edema formation, lower extravascular lung water and improved graft compliance following ferroptosis inhibition. Importantly, the study also developed next-generation analogues, FXT-002 and FXT-003, with improved pharmacokinetic and safety profiles while retaining potent ferroptosis inhibition. The findings position ferroptosis inhibition as a potentially transformative strategy not only in transplantation but also across a broad spectrum of ischemia-associated conditions including myocardial infarction, stroke and vascular surgery. Overall, this work provides one of the strongest translational demonstrations to date that pharmacologic ferroptosis blockade can meaningfully improve organ preservation and graft function in human-relevant systems.

Living-Donor Liver Transplantation Improves Survival in Unresectable Colorectal Liver Metastases : Liver Transpl | May 2026

Introduction Colorectal liver metastases remain a major cause of cancer-related mortality, and curative treatment is traditionally limited to patients eligible for hepatic resection. However, many patients present with technically unresectable liver-only disease despite favorable tumor biology and good response to systemic chemotherapy. In recent years, liver transplantation has re-emerged as a potential treatment strategy for carefully selected patients with unresectable colorectal liver metastases. Problem Statement Although promising survival outcomes have been reported with liver transplantation in selected metastatic colorectal cancer patients, widespread adoption remains limited by donor organ scarcity, concerns regarding recurrence and uncertainty regarding long-term oncologic benefit compared with modern systemic therapy alone. Summary This study demonstrates that liver transplantation using a living-donor RAPID approach provides a substantial survival advantage over chemotherapy alone in carefully selected patients with unresectable colorectal liver metastases. Eligible patients had liver-confined disease with stable disease or tumor regression following systemic therapy, reflecting strict biologic selection criteria. Patients undergoing transplantation achieved markedly superior long-term survival compared with patients who could not proceed because of donor unavailability, supporting transplantation as a potentially curative strategy in highly selected metastatic colorectal cancer. The RAPID technique, involving staged partial liver transplantation with delayed hepatectomy, also highlights an innovative approach to expanding transplant feasibility while minimizing donor burden. Although recurrence remained common after transplantation, recurrent disease was often compatible with prolonged post-recurrence survival, suggesting that transplantation may meaningfully alter disease trajectory even when recurrence occurs. Importantly, the study reinforces the growing concept that tumor biology and treatment responsiveness may be more relevant than traditional metastatic classification alone when considering advanced surgical or transplant-based oncologic strategies. Overall, these findings strengthen the evolving role of liver transplantation in transplant oncology and support living-donor transplantation as a feasible pathway to expand access for selected patients with unresectable colorectal liver metastases.

ABO-Incompatible Liver Transplantation Shows Comparable Outcomes in Children | Liver Transplantation

Introduction Liver transplantation is the definitive treatment for children with end-stage liver disease, yet waitlist mortality remains a major challenge, particularly in infants and critically ill children with limited donor availability. ABO-incompatible (ABO-I) liver transplantation has emerged as a potential strategy to expand the donor pool, although concerns regarding antibody-mediated rejection and vascular complications have historically limited its broader use. Problem Statement Despite increasing clinical experience, uncertainty persists regarding the long-term safety and efficacy of ABO-I liver transplantation in pediatric recipients. Variability in institutional protocols, including desensitization strategies and immunosuppression approaches, has further complicated the development of standardized practice recommendations. Summary This large multicenter analysis from the SPLIT registry demonstrates that pediatric recipients of ABO-incompatible liver transplantation achieve graft and patient survival outcomes comparable to those receiving ABO-compatible grafts. Although ABO-I recipients were generally more critically ill at the time of transplantation—with greater need for intensive care, ventilatory support and parenteral nutrition—three-year graft and patient survival did not differ significantly between the two groups. These findings support the growing view that ABO-I transplantation can safely expand donor access in pediatric liver transplantation, particularly for high-risk infants facing prolonged wait times. Importantly, younger children undergoing ABO-I transplantation demonstrated a higher incidence of early portal vein thrombosis, highlighting the need for careful vascular surveillance and optimized perioperative management in this subgroup. The accompanying center-level survey also revealed marked heterogeneity in eligibility criteria, desensitization practices and immunosuppressive protocols across transplant programs, emphasizing the absence of standardized approaches. Overall, this study provides important real-world evidence supporting broader implementation of ABO-I pediatric liver transplantation while underscoring the need for prospective studies to refine protocols and improve consistency across centers.

Cardiovascular Disease Remains a Major Threat After Kidney and Liver Transplantation Heart | 2026

Introduction Kidney and liver transplantation substantially improve survival and quality of life in patients with end-stage organ disease. However, cardiovascular disease (CVD) remains a leading cause of long-term morbidity and premature mortality after transplantation. Despite successful graft function, transplant recipients continue to face a substantial burden of cardiovascular complications that extends well beyond the peri-transplant period. Problem Statement Although transplantation reduces mortality compared with dialysis or untreated end-stage liver disease, it does not eliminate cardiovascular risk. Kidney and liver transplant recipients remain vulnerable to a broad spectrum of cardiac disorders, including coronary artery disease, heart failure, arrhythmias, valvular disease and pulmonary hypertension. This persistent risk reflects the combined effects of pre-existing cardiometabolic disease, transplant-related metabolic injury and chronic exposure to immunosuppressive therapy, creating a complex and often under-recognized cardiovascular burden. Summary This review highlights the persistent and multifactorial cardiovascular risk faced by kidney and liver transplant recipients, emphasizing that transplantation should be viewed as a transition to chronic cardiovascular risk management rather than risk resolution. The authors describe how pre-transplant vascular disease is compounded after transplantation by weight gain, dyslipidaemia, diabetes, hypertension and immunosuppression-related metabolic toxicity, resulting in sustained cardiovascular vulnerability. Importantly, this risk spans multiple cardiac phenotypes, including ischemic heart disease, heart failure, arrhythmias, valvular dysfunction and pulmonary vascular disease, each requiring organ-specific clinical consideration. The review underscores that cardiovascular surveillance in transplant recipients must extend beyond traditional risk assessment and incorporate longitudinal, multidisciplinary care tailored to graft type and metabolic profile. A central message is that long-term transplant success depends not only on graft survival, but also on proactive cardiovascular prevention, early recognition of evolving cardiac disease and coordinated management across transplant, cardiology and metabolic care teams.

Deceased Donor Liver Transplantation Increases Risk of Biliary Cast Syndrome Liver Transplantation | April 2026

Introduction Biliary cast syndrome (BCS) is an uncommon but clinically significant biliary complication after liver transplantation, characterized by the formation of obstructive biliary debris within the graft biliary tree. It has traditionally been associated with ischemic biliary injury, biliary strictures, and hepatic artery compromise, and may contribute to recurrent cholangitis, graft dysfunction, and, in severe cases, graft loss. However, contemporary data defining its risk profile—particularly across living donor and deceased donor liver transplantation—remain limited. Problem Statement The determinants of BCS after liver transplantation are incompletely understood, especially whether the risk differs meaningfully between living donor liver transplantation (LDLT) and deceased donor liver transplantation (DDLT). This distinction is clinically important because donor type influences ischemic exposure, biliary vulnerability, and postoperative management. Clarifying the major predictors of BCS and its long-term clinical impact may improve surveillance strategies and guide early intervention. Summary In this single-center retrospective study of 469 adult liver transplant recipients, BCS developed in 6.6% of patients. The risk was markedly higher after DDLT than LDLT, identifying deceased donor grafts as the strongest independent predictor of BCS. Additional major risk factors included biliary stricture, hepatic arterial complications, and older donor age, reinforcing the central role of ischemic and biliary injury in BCS pathogenesis. Despite its clinical relevance, BCS did not adversely affect long-term graft or overall survival when managed appropriately. Endoscopic intervention appeared effective in controlling disease progression and preserving outcomes, even in patients with established BCS. These findings highlight DDLT recipients as a higher-risk population requiring closer biliary surveillance and support early endoscopic management as a key strategy to maintain favorable long-term transplant outcomes.