Randomized trial investigating the utility of a liver tissue transcriptional biomarker in identifying adult liver transplant recipients not requiring maintenance immunosuppression.

The maintenance of stable allograft status in the absence of immunosuppression (IS), known as operational tolerance, can be achieved in a small proportion of liver transplant recipients, but we lack reliable tools to predict its spontaneous development. We conducted a prospective, multicenter, biomarker-strategy design, IS withdrawal clinical trial to determine the utility of a predictive biomarker of operational tolerance. The biomarker test, originally identified in a patient cohort with high operational tolerance prevalence, consisted of a 5-gene transcriptional signature measured in liver tissue collected before initiating IS weaning.

Long-Term Survival of Canadian Liver Transplant Recipients Remains Stagnant- A Cohort Study on the Evolution of Cause-Specific Mortality.

Objective: Recent U.S. registry publications showed no improvement in long-term survival post-liver transplant in the last three decades.

Overweight Impacts Histological Disease Activity of De Novo Metabolic Dysfunction-Associated Steatotic Liver Disease After Liver Transplantation.

Background And Aims: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a leading indication for liver transplantation (LT), but also occurs after LT. The prevalence of de novo MASLD (dnMASLD) after LT, based on both surveillance (svLbx) and indication biopsies (indLbx), is unknown. Furthermore, the impact of the distinct cardiometabolic risk factors on histological disease activity has not been assessed.

Comparative Outcome Analysis of Lenvatinib Versus Sorafenib for Recurrence of Hepatocellular Carcinoma After Liver Transplantation.

Background: Hepatocellular carcinoma (HCC) recurs after liver transplantation (LT) in ~17% of patients. We aimed to retrospectively compare the outcomes of patients treated with different tyrosine kinase inhibitors (TKIs) for recurrent HCC post-LT.

Methods: Patients with recurrent HCC post-LT between 2006 and 2019 were included.

Graft-Specific Regulatory T Cells for Long-Lasting, Local Tolerance Induction.

Background: Solid organ transplantation is hindered by immune-mediated chronic graft dysfunction and the side effects of immunosuppressive therapy. Regulatory T cells (Tregs) are crucial for modulating immune responses post-transplantation; however, the transfer of polyspecific Tregs alone is insufficient to induce allotolerance in rodent models.

Methods: To enhance the efficacy of adoptive Treg therapy, we investigated different immune interventions in the recipients.

Glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors for the treatment of diabetes mellitus in liver transplant recipients.

Aim: To investigate the efficacy and safety of glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 (SGLT2) inhibitors in liver transplant (LT) recipients with diabetes.

Methods: A single-centre, retrospective analysis of prospectively collected data from an LT recipient database (1990-2023) was conducted. We included adults with pre-existing diabetes and post-transplant diabetes, newly started on GLP-1RAs and/or SGLT2 inhibitors after LT.

Living Donor Availability Improves Patient Survival in a North American Center: An Intention-to-treat Analysis.

Objective: Assess the impact of having a living donor on waitlist outcomes and overall survival through an intention-to-treat analysis.

Background: Living-donor liver transplantation (LDLT) offers an alternative to deceased donation in the face of organ shortage. An as-treated analysis revealed that undergoing LDLT, compared to staying on the waiting list, is associated with improved survival, even at Model for End-stage Liver Disease-sodium (MELD-Na) score of 11.

Prospective comparison of liver stiffness measurement methods in surveillance biopsies after liver transplantation.

Background: Liver stiffness measurements (LSMs) have proven useful for non-invasive detection of fibrosis. Previous studies of LSMs after transplantation were performed in cohorts dominated by hepatitis C reinfections and indication biopsies for the evaluation of graft dysfunction. However, the diagnostic fidelity of LSMs for fibrosis is biased by inflammation e.

Pursuing living donor liver transplantation improves outcomes of patients with autoimmune liver diseases: An intention-to-treat analysis.

Living donor liver transplantation (LDLT) offers the opportunity to decrease waitlist time and mortality for patients with autoimmune liver disease (AILD), autoimmune hepatitis, primary biliary cholangitis, and primary sclerosing cholangitis. We compared the survival of patients with a potential living donor (pLDLT) on the waitlist versus no potential living donor (pDDLT) on an intention-to-treat basis. Our retrospective cohort study investigated adults with AILD listed for a liver transplant in our program between 2000 and 2021.

Perioperative Cardiovascular Risk Assessment and Management in Liver Transplant Recipients: A Review of the Literature Merging Guidelines and Interventions.

Liver transplantation (LT) is the second most performed solid organ transplant. Coronary artery disease (CAD) is a critical consideration for LT candidacy, particularly in patients with known CAD or risk factors, including metabolic dysfunction associated with steatotic liver disease. The presence of severe CAD may exclude patients from LT; therefore, precise preoperative evaluation and interventions are necessary to achieve transplant candidacy.

Should advanced donor age be a deterrent in the utilization of grafts from donation after cardiac death in deceased donor liver transplantation? The Toronto experience.

Background: Advanced donor age paired with donation after cardiac death (DCD) increases the risk of transplantation, precluding widespread use of grafts from such donors worldwide. Our aim was to analyze outcomes of liver transplantation using grafts from older DCD donors and donation after brain death (DBD) donors.

Methods: Patients who underwent liver transplantation using grafts from deceased donors between January 2016 and December 2021 were included in the study.

Unique 40-year survival after heart transplantation with normal graft function and spontaneous operational tolerance.

Unique 40-year survival after heart transplantation with normal graft function and spontaneous operational tolerance.

Trajectories of patients relisted for liver transplantation.

Introduction And Objectives: Recurrent cirrhosis complicates 10-30% of Liver transplants (LT) and can lead to consideration for re-transplantation. We evaluated the trajectories of relisted versus primary listed patients on the waitlist using a competing risk framework.

Materials And Methods: We retrospectively examined 1,912 patients listed for LT at our centre between from 2012 to 2020.

A Comprehensive Review of Liver Allograft Fibrosis and Steatosis: From Cause to Diagnosis.

Despite advances in posttransplant care, long-term outcomes for liver transplant recipients remain unchanged. Approximately 25% of recipients will advance to graft cirrhosis and require retransplantation. Graft fibrosis progresses in the context of de novo or recurrent disease.

Outcomes of re-referrals of patients with alcohol-associated liver disease, who were previously declined for liver transplantation.

Since 2018, our program has utilized specific psychosocial criteria and a multidisciplinary approach to assess patients for liver transplant due to alcohol-associated liver disease (ALD), rather than the 6-month abstinence rule alone. If declined based on these criteria, specific recommendations are provided to patients and their providers regarding goals for re-referral to increase the potential for future transplant candidacy. Recommendations include engagement in treatment for alcohol use disorder, serial negative biomarker testing, and maintenance of abstinence from alcohol.

Development of Beta-Amyloid-Specific CAR-Tregs for the Treatment of Alzheimer's Disease.

Background: Alzheimer's disease (AD) is a neurodegenerative disease that remains uncured. Its pathogenesis is characterized by the formation of β-amyloid (Aβ) plaques. The use of antigen-specific regulatory T cells (Tregs) through adoptive transfer has shown promise for the treatment of many inflammatory diseases, although the effectiveness of polyspecific Tregs is limited.

Living donor liver transplantation can address disparities in transplant access for patients with primary sclerosing cholangitis.

Background: Liver transplantation (LT) is frequently lifesaving for people living with primary sclerosing cholangitis (PSC). However, patients are waitlisted for LT according to the model for end-stage liver disease-sodium (MELD-Na) score, which may not accurately reflect the burden of living with PSC. We sought to describe and analyze the clinical trajectory for patients with PSC referred for LT, in a mixed deceased donor/living donor transplant program.

Association of torque teno virus viremia with liver fibrosis in the first year after liver transplantation.

Introduction: Torque teno virus (TTV) replication is controlled by immune status, mirroring a degree of immunosuppression after solid organ transplantation. TTV viraemia (TTVv) was associated with acute cellular rejection and infection within the first year after liver transplantation (LT). Long-term data on TTV after LT and correlation with graft injury from protocol biopsies are limited.

Daily Low-Volume Paracentesis and Clinical Complications in Patients With Refractory Ascites.

Importance: The potential association of low-volume paracentesis of less than 5 L with complications in patients with ascites remains unclear, and individuals with cirrhosis and refractory ascites (RA) treated with devices like Alfapump or tunneled-intraperitoneal catheters perform daily low-volume drainage without albumin substitution. Studies indicate marked differences regarding the daily drainage volume between patients; however, it is currently unknown if this alters the clinical course.

Objective: To determine whether the incidence of complications, such as hyponatremia or acute kidney injury (AKI), is associated with the daily drainage volume in patients with devices.

Evaluation of immunoserological detection of anti-liver kidney microsomal, anti-soluble liver antigen and anti-mitochondrial antibodies.

Autoantibodies are the diagnostic hallmark of autoimmune liver diseases. Indirect immunofluorescence (IFT) is the reference method for the detection of anti-mitochondrial antibodies (AMA) and anti-liver kidney microsomal type-1 (anti-LKM1) antibodies, and inhibition ELISA (iELISA) for anti-soluble liver antigen (anti-SLA) antibodies. Given the complexity of these techniques, commercial ELISAs have emerged as a practical alternative, but without head-to-head validations.

Generation of Chimeric Antigen Receptors against Tetraspanin 7.

Adoptive transfer of antigen-specific regulatory T cells (Tregs) has shown promising results in the treatment of autoimmune diseases; however, the use of polyspecific Tregs has limited effects. However, obtaining a sufficient number of antigen-specific Tregs from patients with autoimmune disorders remains challenging. Chimeric antigen receptors (CARs) provide an alternative source of T cells for novel immunotherapies that redirect T cells independently of the MHC.