A5082666731- Liver Disease Diagnosis and Treatment
- Alcohol Consumption and Health Effects
- Liver Disease and Transplantation
- Diabetes and associated disorders
- Gut microbiota and health
- Clostridium difficile and Clostridium perfringens research
- Immune Cell Function and Interaction
- Hepatitis C virus research
- IL-33, ST2, and ILC Pathways
- Pancreatitis Pathology and Treatment
- Complement system in diseases
- Diet, Metabolism, and Disease
- Trauma, Hemostasis, Coagulopathy, Resuscitation
- Gastrointestinal motility and disorders
- Liver Diseases and Immunity
- Drug-Induced Hepatotoxicity and Protection
- Immune cells in cancer
- Macrophage Migration Inhibitory Factor
- COVID-19 Impact on Reproduction
- Hepatitis B Virus Studies
- Gout, Hyperuricemia, Uric Acid
- Clinical Nutrition and Gastroenterology
- Advanced Glycation End Products research
- Drug Transport and Resistance Mechanisms
- Psoriasis: Treatment and Pathogenesis
Aarhus University Hospital
2014-2025
Aarhus University
2025
King's College Hospital
2017-2018
King's College London
2015-2018
Rifaximin-α is efficacious for the prevention of recurrent hepatic encephalopathy (HE), but its mechanism action remains unclear. We postulated that rifaximin-α reduces gut microbiota-derived endotoxemia and systemic inflammation, a known driver HE.
Introduction Liver cirrhosis is a progressive disease with high mortality. Gut microbiota derangement, increased gut permeability, bacterial translocation and chronic inflammation all drive progression. This trial aims to investigate whether faecal transplantation (FMT) may improve the course in patients acute decompensation of liver cirrhosis. Methods analysis In this Danish, multicentre, randomised, double-blinded, placebo-controlled trial, 220 Child-Pugh score≤12 will be randomised (1:1)...
OBJECTIVES: Inflammatory activation of resident hepatic macrophages (Kupffer cells) by portal-derived lipopolysaccharide (LPS) has a primary role in animal models alcoholic liver disease, but it not been systematically or longitudinally studied human hepatitis (AH). METHODS: We followed 50 patients with AH for 30 days. 26 stable cirrhosis and 20 healthy individuals were controls. measured the plasma (P) concentrations soluble CD163 (sCD163; specific marker inflammatory macrophage activation)...
Th17 cells, a subset of CD4+ T cells that produce interleukin (IL)-17A, IL-17F, IL-21, IL-22, IL-26, and the chemokine CCL20 are critically involved in mucosal inflammation observed Crohn's disease (CD). However, their role as mediators CD has been questioned by recent clinical trial which anti-IL-17A (secukinumab) treatment was ineffective. Besides being pro-inflammatory, Th17-related cytokines mediate protective functions. We aimed to investigate inflammation.Blood samples from 26 patients...
Background: Chronic liver disease (CLD) is a progressive condition that, in its advanced stages, leads to cirrhosis with related clinical complications, and can lead acute-on-chronic failure (ACLF) - syndrome marked by critical illness, multi-organ dysfunction high mortality. Systemic inflammation ACLF occur without overt infection, indicating alternative pathways of immune activation microbial translocation. Intestinal perturbations, bacterial translocation, the resulting systemic are...
IL-22 facilitates mucosal healing by directly inducing epithelial regeneration and barrier integrity, which is essential for achieving remission thereby treating inflammatory bowel disease. Here, we evaluated efficacy of a novel lipidated alone in combination with immunomodulatory agents addressing chronic dextran sodium sulfate (DSS)-induced colitis mice demonstrated action on healing. Mice were treated DSS, followed various doses IL-22, anti-TNF antibody, fingolimod, or anti-mouse α4β7...
Background and aims Hepatic macrophages (Kupffer cells) are involved in the immunopathology of alcoholic liver disease (ALD). The mannose receptor (MR, CD206), expressed primarily by macrophages, mediates endocytosis, antigen presentation T-cell activation. A soluble form, sMR, has recently been identified humans. We aimed to study plasma sMR levels its correlation with severity survival ALD patients. Methods included 50 patients hepatitis (AH), 68 cirrhosis (AC) (Child-Pugh (23), B (24), C...
Abstract Background & Aims A simultaneous decline in pro‐ and anticoagulant drivers patients with liver diseases results a “rebalanced” haemostatic system, even acutely ill patients. Nevertheless, both bleeding thrombotic events are common. Here, we explored efficacy of antihaemostatic strategies compensated cirrhotics which may be unpredictable given the profound changes. Methods We tested effects vitro addition clinically relevant doses commonly used plasma from healthy individuals (n...
The dynamics and role of cytotoxic T lymphocytes (CTLs), natural killer (NK) cells, NKT cells in the life-threatening inflammatory disease alcoholic hepatitis is largely unknown. These directly kill infected damaged through, e.g., degranulation interferon-γ (IFNγ) production, but cause tissue damage if overactivated. They also assist repair via IL-22 production. We, therefore, aimed to investigate frequency, functionality, activation state such hepatitis. We analyzed blood samples from 24...
Background Alcoholic hepatitis (AH) has a severe prognosis due to hepatic inflammatory injury. The cytokine interleukin-22 (IL-22) is reported exert anti-apoptotic and proliferative effects, but IL-22 not been studied during the course of AH. mainly produced by CD4+ (helper) T cells, including Th17 cells. In addition, cells produce proinflammatory IL-17A, which implicated in Aims We aimed study levels circulating IL-22- IL-17A-producing helper plasma cytokines patients with AH examine...
Abstract Activated macrophages shed the haemoglobin–haptoglobin scavenger receptor CD163 into circulation as soluble(s)‐CD163. We measured s CD 163 an in vivo macrophage activation marker patients with Crohn's disease (CD) or ulcerative colitis (UC) receiving antitumour necrosis factor (TNF)‐ α antibody prednisolone treatment. also investigated expression on circulating monocytes. 58 CD, 40 UC and 90 healthy controls (HC) were included. All had active at inclusion followed for 6 weeks of...
In alcoholic hepatitis (AH), translocation of gut bacteria may drive hepatic macrophage activation and systemic inflammation. We investigated the effect oral non-absorbable, broad-spectrum antibiotic treatment on bacterial liver inflammation in AH.We consecutively recruited 31 patients with AH. Fourteen were given vancomycin 500 mg, gentamycin 40 meropenem mg once daily for 7 days. Seventeen a reference group receiving standard-of-care. Circulating markers measured at baseline, by day 90....
The complement system is activated in liver diseases including acute failure (ALF); however, the role of lectin pathway has scarcely been investigated ALF. initiated by soluble pattern recognition molecules: mannan-binding (MBL), M-, L-, and H-ficolin collectin-liver-1 (CL-L1), which are predominantly synthesized liver. We aimed to study levels ALF patients associations with clinical outcome.Serum samples from 75 enrolled US Study Group were collected on days 1 3. included healthy blood...
Thrombocytopenia and circulating dysfunctional immune cells are commonly observed in patients with cirrhosis. Platelets may form complexes neutrophils, monocytes T modulating their function. We recently reported increased frequencies of platelet-complexed neutrophils cirrhosis evidence neutrophil activation upon contact healthy platelets vitro. Whether this occurs vivo following platelet transfusion contributes to systemic inflammation endothelial is unknown.To characterise...
The role of sterile inflammation caused by release damage‐associated molecular patterns ( DAMP ) remains unclear in human alcoholic hepatitis AH ). , high mobility group box‐1 protein HMGB 1) is released tissue damage and inflammation. We aimed to investigate whether 1 a primary inflammatory driver determining serum levels effects on cells from patients. measured 34 patients 10 healthy controls using ELISA . Toll‐like receptor 4 TLR 4) CD 14 expressions were assessed flow cytometry...
INTRODUCTION: In alcoholic hepatitis (AH), high interleukin (IL)-22 production is associated with disease improvement, purportedly through enhanced infection resistance and liver regeneration. IL-22 binding protein (BP) binds antagonizes bioactivity, but data on IL-22BP in suggest a complex interplay. Despite the scarcity of human data, clinical trial as treatment AH. We, therefore, patients AH, described system focusing associations course, mechanistically pursued vitro . METHODS: We...
Acute alcoholic hepatitis (AH) is a life-threatening disease and its course often determined by infections. However, the pattern of pathogens has not been studied. We examined microbiological that caused blood-borne infection in patients with AH. included 32 AH without at inclusion. Patients were followed for 1 month their status was recorded based on clinical records, radiologic exams cultures different secreta. Nine (28%) developed blood culture-positive The agents heterogeneous aetiology...
In non-alcoholic fatty liver disease (NAFLD), neutrophils in infiltrates are activated, which may contribute to progression towards steatohepatitis (NASH). However, the functional status of blood remains unknown and their role mechanisms is thus uncertain. We therefore characterized activation function patients with NAFLD relation clinical markers plasma milieu.We studied 20 NAFLD, among these 6 NASH, 14 healthy persons. Neutrophil activation, interleukin (IL)-8 production oxidative burst...
Objectives: During alcoholic hepatitis (AH) monocytes traverse the vascular boundaries and massively invade liver. In principle, tissue extravasation can be limited through shedding of CD18 integrins from leukocytes, including monocytes. The soluble (s) product sCD18 conceals adhesion receptors on endothelium, which reduces monocyte extravasation. AH, are dysfunctional, but whether this involves their self-generated anti-migration is unknown. Our aim was, therefore, to investigate dynamics...
Alcoholic hepatitis (AH) holds a high mortality, and vast macrophage infiltration of the liver is involved in progressive injury. No efficient medical treatment exists, macrophages may be future target. Here, we examine associations between non-classical monocyte subsets cell surface markers migration with disease activity patients severe AH.We analyzed samples from two cohorts AH. Cohort 1 included 15 AH patients, followed for 30 days, 8 healthy controls (HCs). 2 23 90 9 HCs. Peripheral...