Association of Community Socioeconomic Distress With Waitlist and Survival Outcomes in Liver Transplantation.

Background: Despite efforts to ensure equitable access to liver transplantation (LT), significant disparities remain. Although prior literature has considered the effects of patient sex, race, and income, the contemporary impact of community socioeconomic disadvantage on outcomes after waitlisting for LT remains to be elucidated. We sought to evaluate the association of community-level socioeconomic deprivation with survival after waitlisting for LT.

Group 1 innate lymphoid cells protect liver transplants from ischemia-reperfusion injury via an interferon-γ-mediated pathway.

As important immune regulatory cells, whether innate lymphoid cells (ILCs) are involved in liver transplantation (LT) remains unclear. In a murine orthotopic LT model, we dissected roles of ILCs in liver ischemia-reperfusion injury (IRI). Wild type (WT) grafts suffered significantly higher IRI in Rag2-γc double knockout (DKO) than Rag2 KO recipients, in association with downregulation of group 1 ILCs genes, including IFN-γ.

Cold stress-induced ferroptosis in liver sinusoidal endothelial cells determines liver transplant injury and outcomes.

Although cold preservation remains the gold standard in organ transplantation, cold stress-induced cellular injury is a significant problem in clinical orthotopic liver transplantation (OLT). Because a recent study showed that cold stress activates ferroptosis, a form of regulated cell death, we investigated whether and how ferroptosis determines OLT outcomes in mice and humans. Treatment with ferroptosis inhibitor (ferrostatin-1) during cold preservation reduced lipid peroxidation (malondialdehyde; MDA), primarily in liver sinusoidal endothelial cells (LSECs), and alleviated ischemia/reperfusion injury in mouse OLT.

Myeloid spatial and transcriptional molecular signature of ischemia-reperfusion injury in human liver transplantation.

Background: Ischemia-reperfusion injury (IRI) is a significant clinical concern in liver transplantation, with a key influence on short-term and long-term allograft and patient survival. Myeloid cells trigger and sustain tissue inflammation and damage associated with IRI, but the mechanisms regulating these activities are unknown. To address this, we investigated the molecular characteristics of intragraft myeloid cells present in biopsy-proven IRI- and IRI+ liver transplants.

Summary of a consensus conference on heart-liver transplantation.

Patients with severe heart disease may have coexisting liver disease from various causes. The incidence of combined heart-liver transplant (CHLT) is increasing as more patients with congenital heart disease survive to adulthood and develop advanced heart failure with associated liver disease from chronic right-sided heart or Fontan failure. However, the criteria for CHLT have not been established.

SIRT1 regulates hepatocyte programmed cell death via GSDME - IL18 axis in human and mouse liver transplantation.

Sirtuin 1 (SIRT1) is a histone/protein deacetylase in the cellular response to inflammatory, metabolic, and oxidative stressors. We previously reported that myeloid SIRT1 regulates the inflamed liver's canonical pyroptosis cell death pathway. However, whether/how hepatocyte SIRT1 is engaged in programmed cell death in the cold-stressed liver remains uncertain.

Utility of preoperative troponin I to predict mortality in adult liver transplant recipients: Revisiting pretransplant cardiac risk in the current MELD-allocation era.

Background: Preoperative risk assessment in liver transplant (LT) candidates, particularly related to cardiac risk, is an area of intense interest for transplant clinicians. Various cardiac testing methods are employed by transplant centers to characterize cardiac risk. Serum troponin is an established method for the detection of myocardial injury in a wide variety of clinical settings.

Immune Features of Disparate Liver Transplant Outcomes in Female Hispanics With Nonalcoholic Steatohepatitis.

Background: Nonalcoholic steatohepatitis (NASH) is a severe immune-mediated stage of nonalcoholic fatty liver disease that is rapidly becoming the most common etiology requiring liver transplantation (LT), with Hispanics bearing a disproportionate burden. This study aimed to uncover the underlying immune mechanisms of the disparities experienced by Hispanic patients undergoing LT for NASH.

Methods: We enrolled 164 LT recipients in our institutional review board-approved study, 33 of whom presented with NASH as the primary etiology of LT (20%), with 16 self-reported as Hispanic (48%).

Alternative splicing of CEACAM1 by hypoxia-inducible factor-1α enhances tolerance to hepatic ischemia in mice and humans.

Although alternative splicing (AS) drives transcriptional responses and cellular adaptation to environmental stresses, its contributions in organ transplantation have not been appreciated. We have shown that carcinoembryonic antigen-related cell adhesion molecule (Ceacam1; ), a transmembrane biliary glycoprotein expressed in epithelial, endothelial, and immune cells, determines donor liver transplant quality. Here, we studied how AS of affects ischemia-reperfusion injury (IRI) in mouse and human livers.

T Cell CEACAM1-TIM-3 Crosstalk Alleviates Liver Transplant Injury in Mice and Humans.

Background & Aims: Carcinoembryonic antigen-related cell adhesion molecule 1 (CC1) acts through homophilic and heterophilic interactions with T cell immunoglobulin domain and mucin domain-containing protein 3 (TIM-3), which regulates innate immune activation in orthotopic liver transplantation (OLT). We investigated whether cluster of differentiation (CD) 4 T cell-dependent CC1-TIM-3 crosstalk may affect OLT outcomes in mice and humans.

Methods: Wild-type (WT) and CC1-deficient (CC1 knock-out [KO]) mouse livers were transplanted into WT, CC1KO, or T-cell TIM-3 transgenic (TIM-3Tg)/CC1KO double-mutant recipients.

SIRT1 Regulates Hepatocyte Programmed Cell Death via GSDME - IL18 Axis in Human and Mouse Liver Transplantation.

Sirtuin 1 (SIRT1) is a histone/protein deacetylase involved in cellular senescence, inflammation, and stress resistance. We previously reported that myeloid SIRT1 signaling regulates the inflamed liver's canonical pyroptosis cell death pathway. However, whether/how hepatocyte SIRT1 is engaged in programmed cell death in the cold-stressed liver remains uncertain.

Clinical Impact and Safety of Non-Target Punctures (NTP) during Portal Vein Access in TIPS Procedure.

Background: Although non-target puncture (NPT)-related complications are well known to clinicians performing TIPS, there is no NTP-focused study to assess the true clinical sequalae of NTP-related complications. In this study, the aim was to evaluate the incidence, safety, clinical outcomes and complications related to NTPs during the portal access of TIPS procedures.

Methods: A retrospective review of 369 TIPS procedures from October 2007 to September 2019 was performed.

Intrahepatic transcriptomics differentiate advanced fibrosis and clinical outcomes in adults with the Fontan circulation.

Background: The molecular mechanisms underlying Fontan associated liver disease (FALD) remain largely unknown. We aimed to assess intrahepatic transcriptomic differences among patients with FALD according to the degree of liver fibrosis and clinical outcomes.

Methods: This retrospective cohort study included adults with the Fontan circulation at the Ahmanson/UCLA Adult Congenital Heart Disease Center.

Recipient signaling regulates ischemia reperfusion-induced ER stress and metabolic responses in liver transplantation: from mouse-to-human.

T-cell immunoglobulin and mucin ()4 is expressed on APCs, including macrophages, as one of the main amplifiers in the mechanism of liver ischemia-reperfusion injury (IRI) following orthotopic liver transplantation (OLT). Though donor selectively expressed on Kupffer cells serves as a checkpoint regulator of innate immune-driven IRI cascades, its role on cells outside the OLT remains unclear. To dissect the role of donor vs.

Implications of Pleural Fluid Composition in Persistent Pleural Effusion following Orthotopic Liver Transplant.

Persistent pleural effusions (PPEf) represent a known complication of orthotopic liver transplant (OLT). However, their clinical relevance is not well described. We evaluated the clinical, biochemical, and cellular characteristics of post-OLT PPEf and assessed their relationship with longitudinal outcomes.

Neutrophil CEACAM1 determines susceptibility to NETosis by regulating the S1PR2/S1PR3 axis in liver transplantation.

Neutrophils, the largest innate immune cell population in humans, are the primary proinflammatory sentinel in the ischemia-reperfusion injury (IRI) mechanism in orthotopic liver transplantation (OLT). Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1, CC1, or CD66a) is essential in neutrophil activation and serves as a checkpoint regulator of innate immune-driven IRI cascade in OLT. Although CC1 alternative splicing generates two functionally distinct short and long cytoplasmic isoforms, their role in neutrophil activation remains unknown.

Combined hepatocellular carcinoma-cholangiocarcinoma in a patient with Fontan-associated liver disease.

We present a rare case of combined hepatocellular carcinoma-cholangiocarcinoma in a woman with a history of univentricular congenital heart disease requiring multiple corrective operations including Fontan procedure. During workup for elevated alpha fetal protein, a right hepatic lobe lesion was identified with biopsy showing poorly differentiated hepatocellular carcinoma. She underwent successful segment 5 liver resection.

Novel role of macrophage TXNIP-mediated CYLD-NRF2-OASL1 axis in stress-induced liver inflammation and cell death.

Background & Aims: The stimulator of interferon genes (STING)/TANK-binding kinase 1 (TBK1) pathway is vital in mediating innate immune and inflammatory responses during oxidative/endoplasmic reticulum (ER) stress. However, it remains unknown whether macrophage thioredoxin-interacting protein (TXNIP) may regulate TBK1 function and cell death pathways during oxidative/ER stress.

Methods: A mouse model of hepatic ischaemia/reperfusion injury (IRI), the primary hepatocytes, and bone marrow-derived macrophages were used in the myeloid-specific TXNIP knockout (TXNIP) and TXNIP-proficient (TXNIP) mice.