The prognostic impact of preoperative body composition in perihilar and intrahepatic cholangiocarcinoma.

Cholangiocarcinoma (CCA) is a rare but highly aggressive malignancy of the biliary system. Although it is amenable to surgical resection in early disease, outcomes are frequently dismal. Here, we investigated the prevalence of body composition (BC) alterations and their prognostic role for surgical patients with intrahepatic (iCCA) and perihilar (pCCA) disease.

Outcome of liver cancer patients with SARS-CoV-2 infection: An International, Multicentre, Cohort Study.

Background & Aims: Information about the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in patients with liver cancer is lacking. This study characterizes the outcomes and mortality risk in this population.

Methods: Multicentre retrospective, cross-sectional, international study of liver cancer patients with SARS-CoV-2 infection registered between February and December 2020.

The therapeutic landscape of hepatocellular carcinoma.

The liver is endowed with an amazing regenerative capacity that allows it to withstand an enormous amount of damage. Nevertheless, it is precisely this highly regenerative capacity that renders it susceptible to dysplasia and liver cancer. Liver cancer is not only one of the most common cancers but also one of the deadliest.

Soluble Urokinase Plasminogen Activator Receptor Levels Are Associated with Severity of Fibrosis in Patients with Primary Sclerosing Cholangitis.

The soluble urokinase-type plasminogen activator receptor (suPAR) has evolved as a useful biomarker for different entities of chronic liver disease. However, its role in patients with primary sclerosing cholangitis (PSC) is obscure. We analyzed plasma levels of suPAR in 84 patients with PSC and compared them to 68 patients with inflammatory bowel disease (IBD) without PSC and to 40 healthy controls.

The macrophage-associated microRNA-4715-3p / Gasdermin D axis potentially indicates fibrosis progression in nonalcoholic fatty liver disease: evidence from transcriptome and biological data.

Nonalcoholic fatty liver disease (NAFLD) is highly possible to progress to cirrhosis, malignancy, and liver failure through fibrogenesis. The enormous potential of pathogenetic and therapeutic targets in NAFLD has been revealed. This study aimed to explore novel factors potentially indicating or mediating NAFLD progression.

Distribution of gastrointestinal neuroendocrine tumors in Europe: results from a retrospective cross-sectional study.

Background: Gastrointestinal (non-pancreatic) neuroendocrine tumors (GI-NETs) represent a rare but increasingly common tumor entity. Prognosis and biological behavior of these tumors is extremely heterogenous and largely dependent on the specific tumor site, stage and differentiation. However, systematic data on the epidemiology of GI-NET, especially in terms of geographic distributions are missing.

Updated epidemiology of hepatitis C virus infections and implications for hepatitis C virus elimination in Germany.

In 2014, an analysis was conducted to evaluate the hepatitis C virus (HCV) epidemiology and disease burden in Germany. Since then, there have been considerable developments in HCV management such as the implementation of direct acting antivirals. The aim of this analysis was to assess the recent data available for Germany, establish an updated 2020 HCV prevalence and cascade of care and evaluate the impact of what-if scenarios on the future burden of disease using modelling analysis.

[Management of acutely decompensated liver cirrhosis in emergency and critical care medicine].

Acute decompensation in patients with liver cirrhosis is characterized by the development of ascites, gastrointestinal bleeding, hepatic encephalopathy, or bacterial infection and is often accompanied by further extrahepatic organ dysfunction. Since critically ill patients with decompensated cirrhosis have a high mortality risk, rapid identification and treatment of the triggering event of decompensation (e.g.

Efficacy and safety of an orally administered DGAT2 inhibitor alone or coadministered with a liver-targeted ACC inhibitor in adults with non-alcoholic steatohepatitis (NASH): rationale and design of the phase II, dose-ranging, dose-finding, randomised, placebo-controlled MIRNA (Metabolic Interventions to Resolve NASH with fibrosis) study.

Introduction: Small molecule inhibitors of the terminal step in intrahepatic triglyceride synthesis (diacylglycerol acyltransferase 2 inhibitor (DGAT2i, PF-06865571, ervogastat)) and upstream blockade of lipogenesis via acetyl-coenzyme A carboxylase inhibitor (ACCi, PF-05221304, clesacostat) showed promise in reducing hepatic steatosis in early clinical trials. This study assesses efficacy and safety of these metabolic interventions to resolve non-alcoholic steatohepatitis (NASH) with fibrosis.

Methods And Analysis: This phase II, randomised, dose-ranging, dose-finding study evaluates DGAT2i 25-300 mg two times per day (BID) or 150-300 mg once a day, DGAT2i 150-300 mg BID+ACCi 5-10 mg BID coadministration or matching placebo in a planned 450 adults with biopsy-confirmed NASH and liver fibrosis stages 2-3 from approximately 220 sites in 11 countries across North America, Europe and Asia.

BMP feed-forward loop promotes terminal differentiation in gastric glands and is interrupted by H. pylori-driven inflammation.

Helicobacter pylori causes gastric inflammation, gland hyperplasia and is linked to gastric cancer. Here, we studied the interplay between gastric epithelial stem cells and their stromal niche under homeostasis and upon H. pylori infection.

Portal fibroblasts with mesenchymal stem cell features form a reservoir of proliferative myofibroblasts in liver fibrosis.

Background And Aims: In liver fibrosis, myofibroblasts derive from HSCs and as yet undefined mesenchymal cells. We aimed to identify portal mesenchymal progenitors of myofibroblasts.

Approach And Results: Portal mesenchymal cells were isolated from mouse bilio-vascular tree and analyzed by single-cell RNA-sequencing.

Nuclear Receptors Linking Metabolism, Inflammation, and Fibrosis in Nonalcoholic Fatty Liver Disease.

Nonalcoholic fatty liver disease (NAFLD) and its progressive form nonalcoholic steatohepatitis (NASH) comprise a spectrum of chronic liver diseases in the global population that can lead to end-stage liver disease and hepatocellular carcinoma (HCC). NAFLD is closely linked to the metabolic syndrome, and comorbidities such as type 2 diabetes, obesity and insulin resistance aggravate liver disease, while NAFLD promotes cardiovascular risk in affected patients. The pathomechanisms of NAFLD are multifaceted, combining hepatic factors including lipotoxicity, mechanisms of cell death and liver inflammation with extrahepatic factors including metabolic disturbance and dysbiosis.

Studying metabolism with multi-organ chips: new tools for disease modelling, pharmacokinetics and pharmacodynamics.

Non-clinical models to study metabolism including animal models and cell assays are often limited in terms of species translatability and predictability of human biology. This field urgently requires a push towards more physiologically accurate recapitulations of drug interactions and disease progression in the body. Organ-on-chip systems, specifically multi-organ chips (MOCs), are an emerging technology that is well suited to providing a species-specific platform to study the various types of metabolism (glucose, lipid, protein and drug) by recreating organ-level function.

Immune Regulatory 1 Cells: A Novel and Potent Subset of Human T Regulatory Cells.

A subset of T regulatory cells (Tregs), identified by TIRC7 (T cell immune response cDNA 7) expression is designated as Immune Regulatory 1 Cells (IR1 cells). TIRC7 is an immune checkpoint inhibitor, co-localized with the T- cell receptor, HLA-DR and CTLA-4 during T-cell activation, which delivers regulatory signals binding to its ligand, HLA-DR 2 domain. IR1 cells express FOXP3, and multiple other markers associated with immune suppression.

Single Cell RNA Sequencing in NASH.

Single cell RNA sequencing (scRNA-seq) allows to uncover cellular heterogeneity and the identification of novel subpopulations. In non-alcoholic steatohepatitis (NASH), scRNA-seq is particularly powerful to understand non-parenchymal cell heterogeneity in the liver, e.g.

Prognostic and Predictive Molecular Markers in Cholangiocarcinoma.

Cholangiocarcinoma (CCA) is the second most common primary liver cancer and subsumes a heterogeneous group of malignant tumors arising from the intra- or extrahepatic biliary tract epithelium. A rising mortality from CCA has been reported worldwide during the last decade, despite significant improvement of surgical and palliative treatment. Over 50% of CCAs originate from proximal extrahepatic bile ducts and constitute the most common CCA entity in the Western world.

Evaluation of Inhibitory Antibodies against the Muscarinic Acetylcholine Receptor Type 3 in Patients with Primary Biliary Cholangitis and Primary Sclerosing Cholangitis.

Background: Primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) constitute rare chronic inflammatory biliary diseases which likely comprise genetic, environmental and autoimmune factors. Specific inhibitory (auto-) antibodies against the muscarinic acetylcholine receptor type 3 (mAChR3 auto-ab) may contribute to the pathogenesis of chronic biliary inflammation by modulating mAChR3- mediated signaling.

Aims: The aim of this study was to analyze the prevalence and relevance of inhibitory mAChR3 auto-ab (mAChR3inh+ auto-ab) in a large cohort of PBC patients from two independent tertiary centers in Berlin and Leipzig in comparison to a large PSC cohort.

Shear wave elastography and shear wave dispersion imaging in primary biliary cholangitis-a pilot study.

Background: Primary biliary cholangitis (PBC) is a chronic liver disease that can lead to liver fibrosis and cirrhosis. Two-dimensional shear wave elastography (2D-SWE) is a modern technique for fibrosis assessment. However, data regarding its performance in PBC is sparse.

Macrophages in cholangiopathies.

Purpose Of Review: Cholangiopathies are a heterogeneous class of liver diseases where cholangiocytes are the main targets of liver injury. Although available and emerging therapies mainly target bile acids (ursodeoxycholic acid/UDCA, 24-Norursodeoxycholic acid/norUDCA) and related signaling pathways (obeticholic acid, fibrates, FXR, and PPAR agonists), the mechanisms underlying inflammation, ductular reaction and fibrosis in cholestatic liver diseases remain poorly understood.

Recent Findings: Data from patients with cholestatic diseases, such as primary biliary cholangitis (PBC) or primary sclerosing cholangitis (PSC) as well as mouse models of biliary injury emphasize the role of immune cells in the pathogenesis of cholestatic disorders and indicate diverse functions of hepatic macrophages.

Liver Fibrosis-From Mechanisms of Injury to Modulation of Disease.

The Transregional Collaborative Research Center "Organ Fibrosis: From Mechanisms of Injury to Modulation of Disease" (referred to as SFB/TRR57) was funded for 13 years (2009-2021) by the German Research Council (DFG). This consortium was hosted by the Medical Schools of the RWTH Aachen University and Bonn University in Germany. The SFB/TRR57 implemented combined basic and clinical research to achieve detailed knowledge in three selected key questions: (i) What are the relevant mechanisms and signal pathways required for initiating organ fibrosis? (ii) Which immunological mechanisms and molecules contribute to organ fibrosis? and (iii) How can organ fibrosis be modulated, e.