MicroRNA based Prediction of Posthepatectomy Liver Failure and Mortality Outperforms Established Markers of Preoperative Risk Assessment.

Background: Posthepatectomy liver failure (PHLF) continues to be the most significant factor-determining outcome after hepatic resection, accounting for nearly half of postoperative mortality. In this study, we evaluated whether a newly developed commercially available test measuring circulating microRNAs (miRs) could predict PHLF and compared it with other established liver function tests.

Patients And Methods: A total of 329 patients undergoing liver resection were included and postoperative outcome was assessed.

Soluble TREM2 reflects liver fibrosis status and predicts postoperative liver dysfunction after liver surgery.

Background & Aims: Triggering receptor expressed on myeloid cells 2 (TREM2)-expressing macrophages and systemic levels of soluble TREM2 (sTREM2) appear critical in the development of chronic liver disease (CLD) and seem relevant in its detection. The aim of this study was to examine sTREM2 as a marker for early CLD and its potential to predict posthepatectomy liver failure (PHLF) in patients undergoing partial hepatectomy.

Methods: sTREM2 was assessed in the plasma of 108 patients undergoing liver resection.

Tumor-Extrinsic Axl Expression Shapes an Inflammatory Microenvironment Independent of Tumor Cell Promoting Axl Signaling in Hepatocellular Carcinoma.

The activation of the receptor tyrosine kinase Axl by Gas6 is a major driver of tumorigenesis. Despite recent insights, tumor cell-intrinsic and -extrinsic Axl functions are poorly understood in hepatocellular carcinoma (HCC). Thus, we analyzed the cell-specific aspects of Axl in liver cancer cells and in the tumor microenvironment.

An APRI+ALBI-Based Multivariable Model as a Preoperative Predictor for Posthepatectomy Liver Failure.

Objective And Background: Clinically significant posthepatectomy liver failure (PHLF B+C) remains the main cause of mortality after major hepatic resection. This study aimed to establish an aspartate aminotransferase to platelet ratio combined with an albumin-bilirubin grade (APRI+ALBI), based multivariable model (MVM) to predict PHLF and compare its performance to indocyanine green clearance (ICG-R15 or ICG-PDR) and albumin-ICG evaluation (ALICE).

Methods: A total of 12,056 patients from the National Surgical Quality Improvement Program database were used to generate a MVM to predict PHLF B+C.

The role of microRNAs in the different phases of liver regeneration.

Introduction: Since the first discovery of microRNAs (miRs) extensive evidence reveals their indispensable role in different patho-physiological processes. They are recognized as critical regulators of hepatic regeneration, as they modulate multiple complex signaling pathways affecting liver regeneration. MiR-related translational suppression and degradation of target mRNAs and proteins are not limited to one specific gene, but act on multiple targets.

Synergism of the receptor tyrosine kinase Axl with ErbB receptors mediates resistance to regorafenib in hepatocellular carcinoma.

Introduction: Hepatocellular carcinoma (HCC) patients at advanced stages receive immunotherapy or treatment with tyrosine kinase inhibitors (TKIs) such as Sorafenib (Sora) or Lenvatinib in frontline as well as Regorafenib (Rego) or Cabozantinib in second-line. A major hindrance of TKI therapies is the development of resistance, which renders drug treatment futile and results in HCC progression.

Methods: In this study, we addressed the impact of the receptor tyrosine kinase Axl binding to its ligand Gas6 in acquiring refractoriness to TKIs.

Hepatectomy-induced apoptotic extracellular vesicles stimulate neutrophils to secrete regenerative growth factors.

Background & Aims: Surgical resection of the cancerous tissue represents one of the few curative treatment options for neoplastic liver disease. Such partial hepatectomy (PHx) induces hepatocyte hyperplasia, which restores liver function. PHx is associated with bacterial translocation, leading to an immediate immune response involving neutrophils and macrophages, which are indispensable for the priming phase of liver regeneration.

Immunological Aspects of AXL/GAS-6 in the Context of Human Liver Regeneration.

AXL and its corresponding ligand growth arrest-specific 6 (GAS-6) are critically involved in hepatic immunomodulation and regenerative processes. Pleiotropic inhibitory effects on innate inflammatory responses might essentially involve the shift of macrophage phenotype from a pro-inflammatory M1 to an anti-inflammatory M2. We aimed to assess the relevance of the AXL/GAS-6-pathway in human liver regeneration and, consequently, its association with clinical outcome after hepatic resection.

Intrinsic and Extrinsic Control of Hepatocellular Carcinoma by TAM Receptors.

Hepatocellular carcinoma (HCC) is the major subtype of liver cancer, showing high mortality of patients due to limited therapeutic options at advanced stages of disease. The receptor tyrosine kinases Tyro3, Axl and MerTK-belonging to the TAM family-exert a large impact on various aspects of cancer biology. Binding of the ligands Gas6 or Protein S activates TAM receptors causing homophilic dimerization and heterophilic interactions with other receptors to modulate effector functions.

Humoral Immune Response in Hematooncological Patients and Health Care Workers Who Received SARS-CoV-2 Vaccinations.

Importance: To our knowledge, little is known about antibody development after SARS-CoV-2 vaccination in immunocompromised individuals, such as patients with cancer.

Objective: To determine whether hematooncological patients develop anti-SARS-CoV-2 antibodies after vaccination.

Design, Setting, And Participants: This retrospective cohort study included 2 independent cohorts of patients who were treated for hematological and solid malignant tumors between October 2020 and May 2021, comprising 901 samples from 595 patients and 58 health care workers (HCWs).

Circulating metabolites as a concept beyond tumor biology determining disease recurrence after resection of colorectal liver metastasis.

Background: Micro-metastatic growth is considered the main source of early cancer recurrence. Nutritional and microenvironmental components are increasingly recognized to play a significant role in the liver. We explored the predictive potential of preoperative plasma metabolites for postoperative disease recurrence in colorectal cancer liver metastasis (CRCLM) patients.

Consequences of Perioperative Serotonin Reuptake Inhibitor Treatment During Hepatic Surgery.

Background And Aims: Platelet-stored serotonin critically affects liver regeneration in mice and humans. Selective serotonin reuptake inhibitors (SSRIs) and serotonin noradrenalin reuptake inhibitors (SNRIs) reduce intraplatelet serotonin. As SSRIs/SNRIs are now one of the most commonly prescribed drugs in the United States and Europe and given serotonin's impact on liver regeneration, we evaluated whether perioperative use of SSRIs/SNRIs affects outcome after hepatic resection.

The von Willebrand Factor Facilitates Model for End-Stage Liver Disease-Independent Risk Stratification on the Waiting List for Liver Transplantation.

Background And Aims: The Model for End-Stage Liver Disease (MELD) is used for clinical decision-making and organ allocation for orthotopic liver transplantation (OLT) and was previously upgraded through inclusion of serum sodium (Na) concentrations (MELD-Na). However, MELD-Na may underestimate complications arising from portal hypertension or infection. The von Willebrand factor (vWF) antigen (vWF-Ag) correlates with portal pressure and seems capable of predicting complications in patients with cirrhosis.