Isoform specific regulation of osteopontin by AKT2 in hepatocytes and livers.

Elevated levels of osteopontin (OPN), an inflammatory cytokine, are correlated with chronic inflammatory conditions and liver cancer. In this study, we explored the regulation of OPN in liver and hepatocytes by AKT1 vs. AKT2, the two AKT isoforms expressed in hepatocytes and livers.

Retraction Notice to: LIN28 and histone H3K4 methylase induce TLR4 to generate tumor-initiating stem-like cells.

[This retracts the article DOI: 10.1016/j.isci.

PAs and NPs in liver transplantation: Perceptions, implementation, and effect.

Objectives: This study assessed the use and perceptions of physician associates/assistants (PAs) and NPs at liver transplant centers and sought to determine their financial effect.

Methods: Leaders of liver transplant programs performing 25 or more transplants in 2020 were contacted to complete an 11-question survey about the role and effect of PAs and NPs in liver transplant. A single-center retrospective analysis compared length of stay (LOS) and readmission rates for primary liver transplants and simultaneous liver-kidney transplants before and after a dedicated PA team was established.

Kidney Transplantation in ≤15 kg Children: Outcomes and Prognostic Indicators-A Review of the Organ Procurement and Transplantation Database.

Background: Approximately 2500 pediatric patients are awaiting kidney transplantation in the United States, with <5% comprising those ≤15 kg. Transplant in this cohort is often delayed by center-based growth parameters, often necessitating transplantation after the initiation of dialysis. Furthermore, prognostication remains somewhat ambiguous.

Spatially resolved immune exhaustion within the alloreactive microenvironment predicts liver transplant rejection.

Allograft rejection is common following clinical organ transplantation, but defining specific immune subsets mediating alloimmunity has been elusive. Calcineurin inhibitor dose escalation, corticosteroids, and/or lymphocyte depleting antibodies have remained the primary options for treatment of clinical rejection episodes. Here, we developed a highly multiplexed imaging mass cytometry panel to study the immune response in archival biopsies from 79 liver transplant (LT) recipients with either no rejection (NR), acute T cell-mediated rejection (TCMR), or chronic rejection (CR).

Technical optimization of spatially resolved single-cell transcriptomic datasets to study clinical liver disease.

Single cell and spatially resolved 'omic' techniques have enabled deep characterization of clinical pathologies that remain poorly understood, providing unprecedented insights into molecular mechanisms of disease. However, transcriptomic platforms are costly, limiting sample size, which increases the possibility of pre-analytical variables such as tissue processing and storage procedures impacting RNA quality and downstream analyses. Furthermore, spatial transcriptomics have not yet reached single cell resolution, leading to the development of multiple deconvolution methods to predict individual cell types within each transcriptome 'spot' on tissue sections.

β-CATENIN stabilizes HIF2 through lncRNA and inhibits intravenous immunoglobulin immunotherapy.

Introduction: Tumor-initiating cells (TICs) are rare, stem-like, and highly malignant. Although intravenous hepatitis B and C immunoglobulins have been used for HBV and HCV neutralization in patients, their tumor-inhibitory effects have not yet been examined. Hepatitis B immunoglobulin (HBIG) therapy is employed to reduce hepatocellular carcinoma (HCC) recurrence in patients after living donor liver transplantations (LDLT).

Technical optimization of spatially resolved single-cell transcriptomic datasets to study clinical liver disease.

Single cell and spatially resolved 'omic' techniques have enabled deep characterization of clinical pathologies that remain poorly understood, providing unprecedented insights into molecular mechanisms of disease. However, transcriptomic platforms are costly, limiting sample size, which increases the possibility of pre-analytical variables such as tissue processing and storage procedures impacting RNA quality and downstream analyses. Furthermore, spatial transcriptomics have not yet reached single cell resolution, leading to the development of multiple deconvolution methods to predict individual cell types within each transcriptome 'spot' on tissue sections.

Spatially resolved immune exhaustion within the alloreactive microenvironment predicts liver transplant rejection.

Allograft rejection is a frequent complication following solid organ transplantation, but defining specific immune subsets mediating alloimmunity has been elusive due to the scarcity of tissue in clinical biopsy specimens. Single cell techniques have emerged as valuable tools for studying mechanisms of disease in complex tissue microenvironments. Here, we developed a highly multiplexed imaging mass cytometry panel, single cell analysis pipeline, and semi-supervised immune cell clustering algorithm to study archival biopsy specimens from 79 liver transplant (LT) recipients with histopathological diagnoses of either no rejection (NR), acute T-cell mediated rejection (TCMR), or chronic rejection (CR).

Hepatic stellate cell stearoyl co-A desaturase activates leukotriene B4 receptor 2 - β-catenin cascade to promote liver tumorigenesis.

Hepatocellular carcinoma (HCC) is the 3 most deadly malignancy. Activated hepatic stellate cells (aHSC) give rise to cancer-associated fibroblasts in HCC and are considered a potential therapeutic target. Here we report that selective ablation of stearoyl CoA desaturase-2 (Scd2) in aHSC globally suppresses nuclear CTNNB1 and YAP1 in tumors and tumor microenvironment and prevents liver tumorigenesis in male mice.

LIN28 and histone H3K4 methylase induce TLR4 to generate tumor-initiating stem-like cells.

Chemoresistance and plasticity of tumor-initiating stem-like cells (TICs) promote tumor recurrence and metastasis. The gut-originating endotoxin-TLR4-NANOG oncogenic axis is responsible for the genesis of TICs. This study investigated mechanisms as to how TICs arise through transcriptional, epigenetic, and post-transcriptional activation of oncogenic TLR4 pathways.

Transfusion-free Strategies in Liver and Pancreatic Surgery: A Predictive Model of Blood Conservation for Transfusion Avoidance in Mainstream Populations.

Objective: The objective of this study is to (1) describe the techniques and prove the feasibility of performing complex hepatobiliary and pancreatic surgery on a Jehovah Witness (JW) population.  (2) Describe a strategy that offsets surgical blood loss by the manipulation of circulating blood volume to create reserve whole blood upon anesthesia induction.

Background: Major liver and pancreatic resections often require operative transfusions.

Controversy Over Liver Transplantation or Resection for Neuroendocrine Liver Metastasis: Tumor Biology Cuts the Deal.

Background: In patients with neuroendocrine liver metastasis (NELM), liver transplantation (LT) is an alternative to liver resection (LR), although the choice of therapy remains controversial. In this multicenter study, we aim to provide novel insight in this dispute.

Methods: Following a systematic literature search, 15 large international centers were contacted to provide comprehensive data on their patients after LR or LT for NELM.

Arterial Anastomosis Using Microsurgical Techniques in Adult Live Donor Liver Transplant: A Focus on Technique and Outcomes at a Single Institution.

Background:  Microvascular hepatic artery reconstruction (MHAR) is associated with decreased rates of hepatic artery thrombosis (HAT) in living donor liver transplantation (LDLT). There is a paucity of literature describing the learning points and initiation of this technique at the institutional level. The objective of this study is to report our institutional experience using MHAR in adult LDLT with a focus on technique and outcomes.

Adaptation of Imaging Mass Cytometry to Explore the Single Cell Alloimmune Landscape of Liver Transplant Rejection.

Rejection continues to be an important cause of graft loss in solid organ transplantation, but deep exploration of intragraft alloimmunity has been limited by the scarcity of clinical biopsy specimens. Emerging single cell immunoprofiling technologies have shown promise in discerning mechanisms of autoimmunity and cancer immunobiology. Within these applications, Imaging Mass Cytometry (IMC) has been shown to enable highly multiplexed, single cell analysis of immune phenotypes within fixed tissue specimens.

Activated and nonactivated MSCs increase survival in humanized mice after acute liver injury through alcohol binging.

The ability of the liver to regenerate after injury makes it an ideal organ to study for potential therapeutic interventions. Mesenchymal stem cells (MSCs) possess self-renewal and differentiation properties, as well as anti-inflammatory properties that make them an ideal candidate for therapy of acute liver injury. The primary aim of this study is to evaluate the potential for reversal of hepatic injury using human umbilical cord-derived MSCs.

A Programmatic Response, Including Bamlanivimab or Casirivimab-imdevimab Administration, Reduces Hospitalization and Death in COVID-19 Positive Abdominal Transplant Recipients.

Background: (COVID-19) has resulted in significant morbidity and mortality in solid organ transplant recipients. In December 2020, at the peak of the Los Angeles outbreak, our center rapidly implemented a protocol to improve outpatient management and provide bamlanivimab or casirivimab-imdevimab [COVID monoclonal antibody (mAb) therapies] to all eligible COVID-19 positive liver and kidney transplant recipients.

Methods: A retrospective review of all abdominal organ transplant recipients who were COVID-19 polymerase chain reaction positive between February 2020 and February 2021 from our center was performed.

Microscope-Assisted Arterial Anastomosis in Adult Living Donor Liver Transplantation: A Systematic Review and Meta-analysis of Outcomes.

Background:  Living donor liver transplantation (LDLT) has expanded the availability of liver transplant but has been associated with early technical complications including the devastating complication of hepatic artery thrombosis (HAT), which has been reported to occur in 14% to 25% of LDLT using standard anastomotic techniques. Microvascular hepatic artery reconstruction (MHAR) has been implemented in an attempt to decrease rates of HAT. The purpose of this study was to review the available literature in LDLT, specifically related to MHAR to determine its impact on rates of posttransplant complications including HAT.

Potential association between public medical insurance, waitlist mortality, and utilization of living donor liver transplantation: An analysis of the Scientific Registry of Transplant Recipients.

Background: The Affordable Care Act (ACA) and subsequent Medicaid expansion has increased utilization of public health insurance. Living donor liver transplantation (LDLT) increases access to transplant and is associated with improved survival but consistently represents < 5% of LT in the United States.

Study Design: National registry data were analyzed to evaluate the impact of insurance payor on waitlist mortality and LDLT rates at LDLT centers since implementation of the ACA.

Assessment of the global practice of living donor liver transplantation.

Criteria that drive the selection and utilization of living liver donors are limited. Herein, the global availability of living donor liver transplantation (LDLT) and components of donor selection and utilization were assessed via an international survey. There were 124 respondents representing 41 countries, including 47 from Asia/Middle East (A/ME), 20 from Europe, and 57 from the Americas.