Modeling the Health and Economic Impact of Pharmacologic Therapies for MASLD in the United States.

Background And Aims: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a common condition leading to chronic liver disease which generates substantial health care costs. Our aim was to model the impact on disease and economic burden of a hypothetical pharmacologic therapy which halts MASLD fibrosis progression.

Methods: The U.

Metabolomics at the cutting edge of risk prediction of MASLD.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a major public health threat globally. Management of patients afflicted with MASLD and research in this domain are limited by the lack of robust well-established non-invasive biomarkers for diagnosis, prognostication, and monitoring. The circulating metabolome reflects both the systemic metabo-inflammatory milieu and changes in the liver in affected individuals.

Sexual dimorphism of MASLD-driven bone loss.

Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) is highly prevalent with major risk of progression to Metabolic Dysfunction-Associated Steatohepatitis (MASH) and Hepatocellular Carcinoma (HCC). Recently, osteoporosis and bone fracture have emerged as sexually-dimorphic comorbidities of MASLD yet the mechanisms of this bone loss are unknown. Herein, we address these knowledge gaps using DIAMOND mice which develop MASLD, MASH, and HCC via Western diet exposure.

Aramchol attenuates fibrosis in mouse models of biliary fibrosis and blocks the TGFβ-induced fibroinflammatory mediators in cholangiocytes.

Background: Fibroinflammatory cholangiopathies, such as primary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC), are characterized by inflammation and biliary fibrosis, driving disease-related complications. In biliary fibrosis, cholangiocytes activated by transforming growth factor-β (TGFβ) release signals that recruit immune cells to drive inflammation and activate hepatic myofibroblasts to deposit the extracellular matrix (ECM). TGFβ regulates stearoyl-CoA desaturase (SCD), an enzyme that catalyzes the synthesis of monounsaturated fatty acids, in stimulating fibroinflammatory lipid signaling.

A Pragmatic Management Approach for Metabolic Dysfunction-Associated Steatosis and Steatohepatitis.

Obesity and associated insulin resistance induce a chronic metaboinflammatory state that lead to injury and dysfunction of multiple organs resulting in a cluster of noncommunicable diseases such as type 2 diabetes mellitus, hypertension, cardiovascular disease, chronic kidney disease, and metabolic dysfunction-associated steatotic liver disease (MASLD). Metabolic dysfunction-associated steatohepatitis (MASH) is a histologically active form of MASLD and characterized by greater injury and inflammation and progresses to cirrhosis with greater certainty than steatosis alone. The progression to cirrhosis is characterized by increasing fibrosis.

Semaglutide 2.4 mg in Participants With Metabolic Dysfunction-Associated Steatohepatitis: Baseline Characteristics and Design of the Phase 3 ESSENCE Trial.

Background: Semaglutide, a glucagon-like peptide-1 receptor agonist, has demonstrated potential beneficial effects in metabolic dysfunction-associated steatohepatitis (MASH).

Aims: To describe the trial design and baseline characteristics of the 'Effect of Semaglutide in Subjects with Non-cirrhotic Non-alcoholic Steatohepatitis' (ESSENCE) trial (NCT04822181).

Methods: ESSENCE is a two-part, phase 3, randomised, multicentre trial evaluating the effect of subcutaneous semaglutide 2.

Novel eicosanoid signature in plasma provides diagnostic for metabolic dysfunction-associated steatotic liver disease.

There is a clinical need for a simple test implementable at the primary point of care to identify individuals with metabolic dysfunction-associated steatotic liver disease (MASLD) in the population. Blood plasma samples from adult patients with varying phenotypes of MASLD were used to identify a minimal set of lipid analytes reflective of underlying histologically confirmed MASLD. Samples were obtained from the NIDDK Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) NAFLD Database prospective cohort study (MASLD group; N = 301).

Reproducibility and Repeatability of US Shear-Wave and Transient Elastography in Nonalcoholic Fatty Liver Disease.

Background US shear-wave elastography (SWE) and vibration-controlled transient elastography (VCTE) enable assessment of liver stiffness, an indicator of fibrosis severity. However, limited reproducibility data restrict their use in clinical trials. Purpose To estimate SWE and VCTE measurement variability in nonalcoholic fatty liver disease (NAFLD) within and across systems to support clinical trial diagnostic enrichment and clinical interpretation of longitudinal liver stiffness.

Integrating liver endpoints in clinical trials of cardiovascular and kidney disease.

The intersection of cardiovascular disease, metabolic disorders and chronic kidney disease represents a complex clinical picture challenging healthcare systems worldwide. Metabolic-dysfunction-associated steatotic liver disease (MASLD) often manifests sequentially or concomitantly with these diseases, and may share underlying mechanisms and risk factors. Growing evidence suggests that new therapies could have benefits across these diseases, but trial sponsors and investigators tend to be reluctant to include patients with comorbidities-particularly liver diseases-in clinical trials.

Liver stiffness progression in biopsy-proven metabolic dysfunction-associated steatotic disease among people with diabetes versus people without diabetes: A prospective multicenter study.

Background And Aims: There are limited data on the progression of liver stiffness measurement (LSM) by vibration-controlled transient elastography (VCTE) in people with type 2 diabetes mellitus (T2DM) versus those without T2DM in biopsy-proven metabolic dysfunction-associated steatotic liver disease. We examined LSM progression in participants with T2DM versus those without T2DM in a large, prospective, multicenter cohort study.

Approach And Results: This study included 1231 adult participants (62% female) with biopsy-proven metabolic dysfunction-associated steatotic liver disease who had VCTEs at least 1 year apart.

Acute kidney injury in severe alcohol-associated hepatitis treated with anakinra plus zinc or prednisone.

Background And Aims: In a recent trial, patients with severe alcohol-associated hepatitis treated with anakinra plus zinc (A+Z) had lower survival and higher acute kidney injury (AKI) rates versus prednisone (PRED). We characterize the clinical factors and potential mechanisms associated with AKI development in that trial.

Approach And Results: Data from 147 participants in a multicenter randomized clinical trial (74 A+Z, 73 PRED) were analyzed.

The Liver Cirrhosis Network Cohort Study: Cirrhosis Definition, Study Population, and Endpoints.

Introduction: One of the primary goals of the Liver Cirrhosis Network (LCN) is to develop a cohort study to better understand and predict the risk of hepatic decompensation and other clinical and patient-reported outcomes among patients with Child A cirrhosis.

Methods: The LCN consists of a Scientific Data Coordinating Center and 10 clinical centers whose investigators populate multiple committees. The LCN Definitions and Measurements Committee developed preliminary definitions of cirrhosis and its complications by literature review, expert opinion, and reviewing definition documents developed by other organizations.