Alterations in one-carbon metabolism in metabolic dysfunction associated steatotic liver disease may be modified by semaglutide.

Introduction And Objectives: Disruptions in one-carbon metabolism (OCM) have been linked to cardiometabolic diseases. We evaluated alterations in OCM metabolites and enzymes and the impact of semaglutide in MASLD.

Materials And Methods: Using targeted metabolomics and bulk-transcriptomics, we analyzed components of OCM in plasma samples and liver biopsies from MASLD patients (n=100 with F0-F4 fibrosis, 51% type 2 diabetes) and healthy controls (n=50).

Diagnostics of Autoimmune Hepatitis Enabled by Non-Invasive Clinical Proteomics.

Background: Autoimmune hepatitis (AIH) may be difficult to diagnose and distinguish clinically and biochemically from other chronic liver diseases like metabolic dysfunction-associated steatotic liver disease (MASLD).

Aims: To identify pathways involved in the pathogenesis and identify disease-specific biomarkers of AIH.

Methods: We recruited 19 newly diagnosed patients with AIH, 17 with MASLD, and 19 healthy controls.

Circulating and hepatic levels of growth differentiation factor 15 in patients with metabolic dysfunction-associated steatotic liver disease.

Aim: Increased growth differentiation factor 15 (GDF15) may reflect impaired metabolic health and an inflammatory state in metabolic dysfunction-associated steatotic liver disease (MASLD). We investigated the role of GDF15 in histologically verified MASLD in a meal test (discovery) cohort (n = 20) and a prospective (validation) cohort with 2 years of follow-up (n = 276).

Methods: Participants were evaluated clinically and histologically in both cohorts.

Hepatic steatosis and not type 2 diabetes, body mass index, or hepatic fibrosis associates with hyperglucagonemia in individuals with steatotic liver disease.

Increased plasma concentrations of glucagon (hyperglucagonemia) are reported in patients with type 2 diabetes (T2D) and are considered a diabetogenic risk factor. Emerging evidence suggests that hepatic steatosis in obesity is causing a condition of resistance toward glucagon's effects on amino acid metabolism, resulting in an amino acid-induced hyperglucagonemia. We investigated the presence of hyperglucagonemia in individuals with biopsy-verified metabolic dysfunction-associated steatotic liver disease (MASLD), and whether body mass index (BMI), T2D, hepatic steatosis, and/or fibrosis contribute to this relationship.

Glucagon Clearance Is Decreased in Chronic Kidney Disease but Preserved in Liver Cirrhosis.

It is not completely clear which organs are responsible for glucagon elimination in humans, and disturbances in the elimination of glucagon could contribute to the hyperglucagonemia observed in chronic liver disease and chronic kidney disease (CKD). Here, we evaluated kinetics and metabolic effects of exogenous glucagon in individuals with stage 4 CKD (n = 16), individuals with Child-Pugh A-C cirrhosis (n = 16), and matched control individuals (n = 16), before, during, and after a 60-min glucagon infusion (4 ng/kg/min). Individuals with CKD exhibited a significantly lower mean metabolic clearance rate of glucagon (14.

Use of PNPLA3, TM6SF2, and HSD17B13 for detection of fibrosis in MASLD in the general population.

Background: Genetic testing can be used to evaluate disease risk. We evaluated if the use of three Single Nucleotide Polymorphisms (SNPs), alone or combined into a genetic risk score (GRS), can aid identify significant fibrosis in subjects with metabolic dysfunction-associated steatotic liver disease (MASLD).

Methods: We assessed three known risk variants: PNPLA3 rs738409, TM6SF2 rs58542926, and HSD17B13 rs72613567.

Patients with autoimmune liver disease have glucose disturbances that mechanistically differ from steatotic liver disease.

Autoimmune liver diseases are associated with an increased risk of diabetes, yet the underlying mechanisms remain unknown. In this cross-sectional study, we investigated the glucose-regulatory disturbances in patients with autoimmune hepatitis (AIH, = 19), primary biliary cholangitis (PBC, = 15), and primary sclerosing cholangitis (PSC, = 6). Healthy individuals ( = 24) and patients with metabolic dysfunction-associated steatotic liver disease (MASLD, = 18) were included as controls.

Low sphingolipid levels predict poor survival in patients with alcohol-related liver disease.

Background & Aims: Alcohol-related hepatitis (AH) and alcohol-related cirrhosis are grave conditions with poor prognoses. Altered hepatic lipid metabolism can impact disease development and varies between different alcohol-related liver diseases. Therefore, we aimed to investigate lipidomics and metabolomics at various stages of alcohol-related liver diseases and their correlation with survival.

Suboptimal diagnostic accuracy of ultrasound and CT for compensated cirrhosis: Evidence from prospective cohort studies.

Introduction: Abdominal ultrasound (US) and CT are important tools for the initial evaluation of patients with liver disease. Our study aimed to determine the accuracy of these methods for diagnosing cirrhosis.

Methods: In all, 377 participants from 4 prospective cohort studies evaluating patients with various liver diseases were included.

Impaired Cerebral Autoregulation during Head Up Tilt in Patients with Severe Brain Injury.

Early mobilization is of importance for improving long-term outcome for patients after severe acquired brain injury. A limiting factor for early mobilization by head-up tilt is orthostatic intolerance. The purpose of the present study was to examine cerebral autoregulation in patients with severe acquired brain injury and a low level of consciousness.

Transient hyperoxia does not affect regional cerebral tissue oxygen saturation in moderately preterm or term newborns.

Aim: Even short periods of hyperoxia may induce prolonged cerebral vasoconstriction in newborn infants, and this could theoretically lead to cerebral ischaemia even once normoxia is re-established. This study aimed to investigate the effect of brief hyperoxic exposures on regional cerebral tissue oxygen saturation (rStO2 ) and to evaluate whether any observed prolonged cerebral vasoconstriction was related to maturity.

Methods: The study included 30 infants with a postmenstrual age of more than 32 weeks, who were treated with nasal continuous positive airway pressure and a fraction of inspired oxygen of ≤0.