Metabolic dysfunction and alcohol-related liver disease (MetALD): Position statement by an expert panel on alcohol-related liver disease.

In this position statement, we explore the intricate relationship between alcohol intake and metabolic dysfunction in the context of the 2023 nomenclature update for steatotic liver disease (SLD). Recent and lifetime alcohol use should be accurately assessed in all patients with SLD to facilitate classification of alcohol use in grams of alcohol per week. Alcohol biomarkers (i.

Advanced three-dimensional X-ray imaging unravels structural development of the human thymus compartments.

Background: The thymus, responsible for T cell-mediated adaptive immune system, has a structural and functional complexity that is not yet fully understood. Until now, thymic anatomy has been studied using histological thin sections or confocal microscopy 3D reconstruction, necessarily for limited volumes.

Methods: We used Phase Contrast X-Ray Computed Tomography to address the lack of whole-organ volumetric information on the microarchitecture of its structural components.

High-Resolution Magic Angle Spinning Nuclear Magnetic Resonance Spectroscopy of Paired Clinical Liver Tissue Samples from Hepatocellular Cancer and Surrounding Region.

The global burden of liver cancer is increasing. Timely diagnosis is important for optimising the limited available treatment options. Understanding the metabolic consequences of hepatocellular carcinoma (HCC) may lead to more effective treatment options.

Adenosine signalling to astrocytes coordinates brain metabolism and function.

Brain computation performed by billions of nerve cells relies on a sufficient and uninterrupted nutrient and oxygen supply. Astrocytes, the ubiquitous glial neighbours of neurons, govern brain glucose uptake and metabolism, but the exact mechanisms of metabolic coupling between neurons and astrocytes that ensure on-demand support of neuronal energy needs are not fully understood. Here we show, using experimental in vitro and in vivo animal models, that neuronal activity-dependent metabolic activation of astrocytes is mediated by neuromodulator adenosine acting on astrocytic A2B receptors.

Availability of Alcohol on an Online Third-Party Delivery Platform Across London Boroughs, England: Exploratory Cross-Sectional Study.

Background: Higher availability of alcohol is associated with higher levels of alcohol consumption and harm. Alcohol is increasingly accessible online, with rapid delivery often offered by a third-party driver. Remote delivery and online availability are important from a public health perspective, but to date, relatively little research has explored the availability of alcohol offered by online platforms.

The early impact of the UK's new alcohol taxation system on product strength and price: an exploratory comparative descriptive study.

Objectives: We explored the early impact of changes to the UK alcohol tax system, implemented in August 2023, on the strength and price of alcoholic products available for sale on the website of the largest supermarket in England.

Study Design: Our comparative descriptive study using longitudinal brand-level data was not preregistered and should be considered exploratory.

Methods: Data were collected weekly (May to October 2023) using automated web scraping tools.

The relationship between the price and demand of alcohol, tobacco, unhealthy food, sugar-sweetened beverages, and gambling: an umbrella review of systematic reviews.

Background: The WHO highlight alcohol, tobacco, unhealthy food, and sugar-sweetened beverage (SSB) taxes as one of the most effective policies for preventing and reducing the burden of non-communicable diseases. This umbrella review aimed to identify and summarise evidence from systematic reviews that report the relationship between price and demand or price and disease/death for alcohol, tobacco, unhealthy food, and SSBs. Given the recent recognition as gambling as a public health problem, we also included gambling.

Effects of SGLT2 Ablation or Inhibition on Corticosterone Secretion in High-Fat-Fed Mice: Exploring a Nexus with Cytokine Levels.

Despite recent therapeutic advances, achieving optimal glycaemic control remains a challenge in managing Type 2 Diabetes (T2D). Sodium-glucose co-transporter type 2 (SGLT2) inhibitors have emerged as effective treatments by promoting urinary glucose excretion. However, the full scope of their mechanisms extends beyond glycaemic control.

Alcohol-Associated Liver Disease Outcomes: Critical Mechanisms of Liver Injury Progression.

Alcohol-associated liver disease (ALD) is a substantial cause of morbidity and mortality worldwide and represents a spectrum of liver injury beginning with hepatic steatosis (fatty liver) progressing to inflammation and culminating in cirrhosis. Multiple factors contribute to ALD progression and disease severity. Here, we overview several crucial mechanisms related to ALD end-stage outcome development, such as epigenetic changes, cell death, hemolysis, hepatic stellate cells activation, and hepatic fatty acid binding protein 4.

Beta-blockers or Placebo for Primary Prophylaxis (BOPPP) of oesophageal varices: study protocol for a randomised controlled trial.

Background: Liver disease is within the top five causes of premature death in adults. Deaths caused by complications of cirrhosis continue to rise, whilst deaths related to other non-liver disease areas are declining. Portal hypertension is the primary sequelae of cirrhosis and is associated with the development of variceal haemorrhage, ascites, hepatic encephalopathy and infection, collectively termed hepatic decompensation, which leads to hospitalisation and mortality.

Clinical, experimental and pathophysiological effects of Yaq-001: a non-absorbable, gut-restricted adsorbent in models and patients with cirrhosis.

Objective: Targeting bacterial translocation in cirrhosis is limited to antibiotics with risk of antimicrobial resistance. This study explored the therapeutic potential of a non-absorbable, gut-restricted, engineered carbon bead adsorbent, Yaq-001 in models of cirrhosis and acute-on-chronic liver failure (ACLF) and, its safety and tolerability in a clinical trial in cirrhosis.

Design: Performance of Yaq-001 was evaluated .

The future of International Classification of Diseases coding in steatotic liver disease: An expert panel Delphi consensus statement.

Background: Following the adoption of new nomenclature for steatotic liver disease, we aimed to build consensus on the use of International Classification of Diseases codes and recommendations for future research and advocacy.

Methods: Through a two-stage Delphi process, a core group (n = 20) reviewed draft statements and recommendations (n = 6), indicating levels of agreement. Following revisions, this process was repeated with a large expert panel (n = 243) from 73 countries.

Human Precision-Cut Liver Slices: A Potential Platform to Study Alcohol-Related Liver Disease.

Alcohol-related liver disease (ALD) encompasses a range of pathological conditions that are complex to study at the clinical and preclinical levels. Despite the global burden of ALD, there is a lack of effective treatments, and mortality is high. One of the reasons for the unsuccessful development of novel therapies is that experimental studies are hindered by the challenge of recapitulating this multifactorial disorder in vitro, including the contributions of hepatotoxicity, impaired lipid metabolism, fibrosis and inflammatory cytokine storm, which are critical drivers in the pathogenesis of ALD in patients and primary targets for drug development.

Rat liver extracellular matrix and perfusion bioreactor culture promote human amnion epithelial cell differentiation towards hepatocyte-like cells.

Congenital and chronic liver diseases have a substantial health burden worldwide. The most effective treatment available for these patients is whole organ transplantation; however, due to the severely limited supply of donor livers and the side effects associated with the immunosuppressive regimen required to accept allograft, the mortality rate in patients with end-stage liver disease is annually rising. Stem cell-based therapy aims to provide alternative treatments by either cell transplantation or bioengineered construct transplantation.

Astrocytes produce nitric oxide via nitrite reduction in mitochondria to regulate cerebral blood flow during brain hypoxia.

During hypoxia, increases in cerebral blood flow maintain brain oxygen delivery. Here, we describe a mechanism of brain oxygen sensing that mediates the dilation of intraparenchymal cerebral blood vessels in response to reductions in oxygen supply. In vitro and in vivo experiments conducted in rodent models show that during hypoxia, cortical astrocytes produce the potent vasodilator nitric oxide (NO) via nitrite reduction in mitochondria.

The Role of Mass Spectrometry in Hepatocellular Carcinoma Biomarker Discovery.

Hepatocellular carcinoma (HCC) is the main liver malignancy and has a high mortality rate. The discovery of novel biomarkers for early diagnosis, prognosis, and stratification purposes has the potential to alleviate its disease burden. Mass spectrometry (MS) is one of the principal technologies used in metabolomics, with different experimental methods and machine types for different phases of the biomarker discovery process.

Serological response and breakthrough infection after COVID-19 vaccination in patients with cirrhosis and post-liver transplant.

Background: Vaccine hesitancy and lack of access remain major issues in disseminating COVID-19 vaccination to liver patients globally. Factors predicting poor response to vaccination and risk of breakthrough infection are important data to target booster vaccine programs. The primary aim of the current study was to measure humoral responses to 2 doses of COVID-19 vaccine.

Patient-derived precision cut tissue slices from primary liver cancer as a potential platform for preclinical drug testing.

Background: The exploitation of anti-tumour immunity, harnessed through immunomodulatory therapies, has fundamentally changed the treatment of primary liver cancer (PLC). However, this has posed significant challenges in preclinical research. Novel immunologically relevant models for PLC are urgently required to improve the translation from bench to bedside and back, explore and predict effective combinatorial therapies, aid novel drug discovery and develop personalised treatment modalities.