Kusztos VE, Wu T, Kassmeyer B
… +18 more, Hernaez R, Karvellas C, Khemichian S, Stein L, Shetty K, Lindenmeyer CC, Boike J, Rahimi R, Prasun J, Izzy M, Kriss M, Im GY, Lin MV, Jou JH, Fortune BE, Cholankeril GT, Kuo A, Simonetto DA
Postoperative delirium is a prevalent neuropsychiatric complication after liver transplantation, affecting 13%-26% of recipients. It is associated with prolonged intensive care unit and hospital stays, increased medical...Postoperative delirium is a prevalent neuropsychiatric complication after liver transplantation, affecting 13%-26% of recipients. It is associated with prolonged intensive care unit and hospital stays, increased medical costs, and significantly worse long-term prognosis. This article comprehensively reviews its pathogenesis, risk factors, assessment tools, management strategies, and future directions, aiming to provide a theoretical basis for clinical prevention, intervention, and subsequent research.
Perioperative bleeding during orthotopic liver transplantation (OLT) is primarily driven by hyperfibrinolysis and impaired coagulation, resulting in elevated morbidity, mortality, and transfusion requirements. Although t...Perioperative bleeding during orthotopic liver transplantation (OLT) is primarily driven by hyperfibrinolysis and impaired coagulation, resulting in elevated morbidity, mortality, and transfusion requirements. Although tranexamic acid (TXA) has been shown to reduce bleeding in various surgical settings, its prophylactic efficacy and safety in OLT remain unclear. We conducted a double-blinded, randomized controlled trial involving 138 adult patients undergoing OLT, who were assigned to receive either TXA (10 mg/kg bolus followed by a 1 mg/kg/h infusion) or placebo (0.9% saline). The primary outcome was the incidence of major bleeding within 24 hours of the surgical incision. Secondary outcomes included red blood cell transfusion volume, hospital length of stay, and postoperative complications. The overall incidence of major bleeding did not differ significantly between groups [TXA: 48.5% vs. placebo: 62.9%; relative risk (RR) 0.77 [95% CI 0.56-1.04]; p =0.09]. However, significant reductions were observed in subgroups with MELD 3.0 scores ≤9 ( p =0.01) and Child-Pugh A classification ( p =0.01). The TXA group had lower median intraoperative red blood cell transfusions (0 unit [IQR 0-3] vs. 2 units [IQR 0-5]; p =0.01) and shorter hospital length of stay (20 days [IQR 14-31] vs. 25 days [IQR 18-37]; p =0.04). No significant differences were found in thromboembolic complications or mortality. In conclusion, prophylactic TXA does not significantly reduce the incidence of major perioperative bleeding in OLT but may benefit lower-risk subgroups by reducing transfusion requirements and shortening hospital stays, without increasing thromboembolic or mortality risks. These findings suggest a selective role for TXA in OLT, warranting larger confirmatory trials to guide targeted use.
Koyya HR, Meredith E, Gharehmohammadi F
… +2 more, Elmahdy M, Sebro R
J Liver Transpl
· 2025 Nov · PMID 42266871
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BACKGROUND: The American Association for the Study of Liver Diseases (AASLD) and the American Society of Transplantation (AST) 2012 practice guidelines based on expert opinion provide surveillance frequency guidelines fo...BACKGROUND: The American Association for the Study of Liver Diseases (AASLD) and the American Society of Transplantation (AST) 2012 practice guidelines based on expert opinion provide surveillance frequency guidelines for dual-energy X-ray absorptiometry (DXA) bone mineral density (BMD) scans after liver transplant (LT). Since then, post-transplant immunosuppression has changed. This study aims to use statistical models to identify the optimal DXA surveillance frequency after LT. MATERIALS AND METHODS: This study retrospectively evaluated 402 LT recipients followed for up to 8 years post-LT, each with at least one pre-LT and two post-LT DXA scans. Linear mixed-effects (LME) models using random slopes and intercepts were used to identify whether BMD decline was linear or non-linear (quadratic) in time. Multivariate LME models were used to model the decline in femoral neck (FN), total hip (TH), and L1-L4 BMD decline after LT adjusting for demographic and clinical variables. RESULTS: Males had higher pre-LT BMD than females (P<0.001 at all sites). The rate of BMD loss was fastest at the FN, and faster in patients with normal pre-LT BMD than in patients with low pre-LT BMD (osteopenia/osteoporosis). The model predicted that there would be a significant FN BMD decrease in patients with normal pre-LT BMD after approximately 481 days post-LT (1 year, 3 months). CONCLUSION: LT recipients with normal pre-LT BMD should have DXA scans ~481 days post-LT. LT recipients with low BMD pre-LT who were more likely to be treated with bisphosphonates did not need annual DXA screening.
Tricuspid regurgitation and pulmonary artery systolic pressure may contribute to post-operative morbidity and mortality in liver transplantation. Previous studies suggest that a high Model for End-stage Liver Disease sco...Tricuspid regurgitation and pulmonary artery systolic pressure may contribute to post-operative morbidity and mortality in liver transplantation. Previous studies suggest that a high Model for End-stage Liver Disease score may influence the relationship between tricuspid regurgitation and post-operative mortality. Adult patients undergoing liver transplantation workup between 2010 and 2023 were included in this retrospective observational cohort study. Patients with significant portopulmonary hypertension were excluded. Transthoracic echocardiograms were completed pre-transplant, and patients were followed up for 1 year post-operatively. In all, 1031 patients (median MELD score 17, IQR 12-23) underwent transthoracic echocardiography for liver transplantation workup, of whom 708 underwent successful transplantation. Mild or greater tricuspid regurgitation did not predict 1-year mortality in the overall population [HR 1.79 (95% CI 0.78-4.11), p =0.19]. Among patients with MELD scores ≥20, mild or greater tricuspid regurgitation was a significant predictor of 1-year mortality [7 (12.7%) vs. 9 (3.8%), p =0.01] [HR 3.46 (1.30-10.32), p =0.02]. Tricuspid regurgitation in patients with high MELD scores was associated with a trend toward an increased risk of 30-day major adverse cardiovascular events [9 (16.4%) vs. 46 (8.1%), p =0.06], driven predominantly by rates of post-operative heart failure [12.7% vs. 3.8%, HR 3.66 (95% CI 1.30-10.32), p =0.01]. Elevated pulmonary artery systolic pressure was associated with prolonged hospital stay [30 d (14-46) vs. 15 d (11-29), p =0.01]. Our study confirms that mild or greater tricuspid regurgitation is a significant predictor of 1-year mortality in patients with high MELD scores undergoing liver transplantation. Tricuspid regurgitation severity should be considered during pre-liver transplantation risk stratification.
Gutierrez SA, Gupta N, Hsu E
… +14 more, Squires J, Ebel N, Campbell K, Desai DM, Zielsdorf S, Vittorio J, Shui AM, Lee C, Bucuvalas JC, Gottlieb LM, Lyles CR, Lai JC, Wadhwani SI, Society of Pediatric Liver Transplantation
Material economic hardship, defined as difficulty meeting essential needs (e.g., food, housing, utilities), is linked to increased morbidity in the first year after pediatric liver transplant. Its longer-term impact is l...Material economic hardship, defined as difficulty meeting essential needs (e.g., food, housing, utilities), is linked to increased morbidity in the first year after pediatric liver transplant. Its longer-term impact is less understood. We examined whether hardship at transplant was associated with hospitalizations and clinical outcomes in the second post-transplant year, and how hardship changed in the first post-transplant year. This prospective cohort study included pediatric liver transplant recipients (<18 y) and caregivers from 9 U.S. transplant centers. Caregivers completed social risk questionnaires shortly after transplant and again 1 year later. Responses were linked with the Society of Pediatric Liver Transplantation registry. McNemar's tests assessed changes in hardship over time, and log-binomial regression evaluated associations with second-year hospitalizations and ideal outcomes. Among 63 participants, 23 (37%) caregivers reported economic hardship at transplant, and 18 (29%) reported it 1 year later (χ 2 =1.32, p =0.36). Hardship status changed for some families over time. Children whose caregivers reported hardship at transplant were more likely to be hospitalized in the second year [relative risk (RR) 1.99; 95% CI 1.03, 3.84; p =0.04], a finding that remained significant after adjusting for social isolation (RR 2.35; 95% CI 1.23, 4.49; p =0.01). Our findings highlight the lasting impact of material economic hardship at transplant on longer-term health outcomes. Although the overall prevalence of hardship remained stable, a subset of families experienced changes in hardship status over time. These findings support routine screening for material economic hardship both before and after transplant to identify families in need and enhanced social care intervention strategies to reduce avoidable healthcare use.
Liver transplantation (LT) remains the ultimate curative treatment for decompensated cirrhosis and specific hepatobiliary cancers. Adverse cardiac events significantly contribute to post-LT morbidity and mortality, and t...Liver transplantation (LT) remains the ultimate curative treatment for decompensated cirrhosis and specific hepatobiliary cancers. Adverse cardiac events significantly contribute to post-LT morbidity and mortality, and the prevalence of cardiovascular comorbidities is rising in this new era of steatotic-predominant liver disease. Therefore, successful LT recipient selection requires accurate and timely assessment of pre-LT cardiac risk. This review provides updated data on the prevalence of certain cardiac pathologies in the LT candidate population, examines how these conditions affect waitlist survival and post-LT outcomes, explores advances in screening diagnostics for better cardiac risk stratification, and discusses initial clinical management strategies to mitigate cardiac risk.
BACKGROUND & AIMS: Post-liver transplant (LT) weight gain and metabolic dysfunction predispose to cardiovascular (CV) morbidity, allograft steatosis, and reduced long-term survival. Glucagon-like peptide-1 receptor agoni...BACKGROUND & AIMS: Post-liver transplant (LT) weight gain and metabolic dysfunction predispose to cardiovascular (CV) morbidity, allograft steatosis, and reduced long-term survival. Glucagon-like peptide-1 receptor agonists (GLP-1 RA) promote weight loss and improve cardiometabolic health, yet evidence in liver transplant recipients (LTR) is limited. We aimed to evaluate the safety, tolerability, and efficacy of GLP-1 RAs in post-LT weight management. METHODS: We performed a multicenter retrospective cohort study of adult LTRs treated with GLP-1 RAs across four international centers (January 1, 2010-June 30, 2025). Regular GLP-1 RA users were compared with matched non-users by age, sex, obesity and diabetes status, transplant year, and center. Primary outcome was change in body weight 1-year post-exposure. Secondary outcomes included glycemic and lipid profiles, kidney and allograft function, immunosuppression effects, major adverse cardiovascular events (MACE), and adverse effects. Longitudinal analyses used linear mixed models with multiple imputation. RESULTS: Among 104 GLP-1 RA users, 68.3% initiated therapy for diabetes; subcutaneous semaglutide was most used at a median dose of 0.82±0.46 mg weekly. Treatment led to significant reductions in body weight (-3.8 kg; -3.9%, p<0.001), body mass index (BMI) (-1.6 kg/m2; -5.0%, p<0.001), and glycated hemoglobin (HbA1c) (-0.48%, p=0.002), with modest lipid improvement. Liver function tests and immunosuppression trough levels remained stable, and no treatment-limiting adverse events occurred. In matched analyses (80 GLP-1 RA users vs. 116 non-users), GLP-1 RAs facilitated greater weight loss (-3.4 kg difference, p=0.009) and HbA1c reduction (-0.43% difference in HbA1c, p=0.042) without increased risk of allograft dysfunction, T-cell-mediated rejection (TCMR) or MACE. CONCLUSIONS: This multicenter, international study demonstrates GLP-1 RAs are safe and moderately effective in reducing weight and improving metabolic parameters post-LT, without adverse effects on allograft function or immunosuppression, despite limitations of low dosing. Prospective, randomized trials of GLP-1 RAs in LTRs are thus warranted.
Laique S, Bansal PK, Nadeem MA
… +20 more, Wehrle CJ, Verma S, Giuseppucci A, Berber B, Sanha V, Hellickson K, George M, Allkhushi E, Dewey E, Allende D, Zhou K, Khalil M, Kwon DCH, Aucejo F, Kim J, Fujiki M, Pita A, Schlegel A, Hashimoto K, Modaresi Esfeh J
Obesity and metabolic dysfunction-associated steatotic liver disease (MASLD) are major barriers to access to living donor liver transplantation (LDLT) and are increasingly prevalent among potential LDLT donors. The exten...Obesity and metabolic dysfunction-associated steatotic liver disease (MASLD) are major barriers to access to living donor liver transplantation (LDLT) and are increasingly prevalent among potential LDLT donors. The extent to which obesity drives donor attrition during referral/evaluation and whether carefully selected donors with obesity are associated with inferior outcomes is poorly defined. We aimed to characterize donor attrition from obesity and MASLD and evaluate donor/recipient outcomes among donors with obesity. All adult LDLT-donor referrals (n=1963) at a high-volume US center (2018-2024) were included. Donor progression through screening, evaluation, and donation was assessed by BMI category. Institutional data were complemented by national SRTR-Registry analysis of the association between donor BMI and recipient survival in adult LDLT recipients (2010-2024). From 1963 referrals, 843 completed preliminary screening, including 295 donors with obesity. Only 14% of donors with obesity proceeded to donation versus 22% without obesity. Most donors with obesity were excluded before in-person evaluation, and >50% were declined after evaluation, most commonly due to MASLD. Donors with obesity proceeding to donation experienced longer evaluation-to-donation intervals but similar surgical complication profiles. Recipient outcomes did not differ by donor obesity status, including biliary or vascular complications or 1-year recipient survival. In national analyses, donor BMI was not independently associated with recipient survival. Obesity and MASLD are dominant drivers of early donor attrition in LDLT, frequently limiting access before definitive evaluation. However, carefully selected donors with class I obesity demonstrate preserved donor safety and comparable recipient outcomes at both institutional and national levels. These findings support a more individualized donor assessment strategy that prioritizes metabolic evaluation rather than BMI alone while maintaining donor safety and access to living donation.
Liver failure is associated with severe lipid alterations, including pronounced reductions of high-density lipoprotein cholesterol (HDL-C) levels that are also of prognostic value. In the present study, we developed an o...Liver failure is associated with severe lipid alterations, including pronounced reductions of high-density lipoprotein cholesterol (HDL-C) levels that are also of prognostic value. In the present study, we developed an optimized prognostic model based on HDL-C and other readily available blood parameters for survival prediction in patients with acutely decompensated (AD) cirrhosis. We measured HDL-C in biobanked plasma samples of patients recruited from the large prospective CANONIC and PREDICT cohorts. Multivariable competing risk analysis was performed with death as the event of interest and liver transplantation (LT) as the competing risk. Cox proportional hazards regression was used to construct a new prognostic model, and its performance was evaluated using the C-index and compared with other prognostic scores using the Integrated Discrimination Index statistics test. We analyzed 1035 patients with AD/ACLF (median age 59 y; 70% male; ACLF at inclusion 20%; etiology alcohol 59%). Multivariable analysis yielded 6 independent prognostic variables associated with 90-day survival: age, HDL-C, creatinine, sodium, WBC, and INR, which were incorporated in a new prognostic model termed CLIF-C HDL score. The new model showed superior discrimination ability for the prediction of 90-day mortality by C-index of 0.768 for CLIF-C HDL score versus 0.735 for MELD-Na ( p <0.001) versus 0.738 for MELD 3.0 ( p <0.001). This superior performance of the CLIF-C HDL score was confirmed in 2 external validation cohorts (Turin, n=338; Vienna, n=185). The new prognostic CLIF-C HDL score yields superior accuracy for the prediction of short-term mortality in AD cirrhosis as compared with other prognostic scores.