Effect of Hypertension on Long-term Adverse Clinical Outcomes and Liver Fibrosis Progression in MASLD.

Background & Aims: Hypertension is common in metabolic dysfunction-associated steatotic liver disease (MASLD), but its impact on long-term clinical outcomes and disease progression remains unclear. This study investigated the association of hypertension and risk of adverse clinical outcomes and progression of liver stiffness/fibrosis in MASLD.

Methods: Three multicenter prospective cohorts were analyzed: the UK BioBank (UKBB) cohort to assess the risk of adverse clinical outcomes, the VCTE-Prognosis cohort to assess liver stiffness/fibrosis progression, and the Paired Liver Biopsy cohort to assess histologic liver fibrosis progression.

Longitudinal Changes in Fibrosis Markers: Monitoring Stiffness/Fibrosis Progression and Prognostic Outcomes in MASLD.

Background & Aims: Fibrosis-4 Index (FIB-4) is a noninvasive tool for assessing liver fibrosis in metabolic dysfunction-associated steatotic liver disease (MASLD). However, its role of dynamic FIB-4 for assessing fibrosis progression and predicting clinical outcomes remains unclear. The aim of this study was to examine the association between changes in FIB-4 and changes in liver stiffness, fibrosis progression, and outcomes in MASLD.

Modulation of metabolic, inflammatory and fibrotic pathways by semaglutide in metabolic dysfunction-associated steatohepatitis.

Metabolic dysfunction-associated steatohepatitis (MASH) is a chronic liver disease strongly associated with cardiometabolic risk factors. Semaglutide, a glucagon-like peptide-1 receptor agonist, improves liver histology in MASH, but the underlying signals and pathways driving semaglutide-induced MASH resolution are not well understood. Here we show that, in two preclinical MASH models, semaglutide improved histological markers of fibrosis and inflammation and reduced hepatic expression of fibrosis-related and inflammation-related gene pathways.

A Novel Risk Prediction Model for Hepatocellular Carcinoma in MASLD: A Multinational, Multicenter Cohort Study.

Background And Aims: It is unclear that which cardiometabolic risk factors (CMRFs) are significantly associated with hepatocellular carcinoma (HCC) development in metabolic dysfunction-associated steatotic liver disease (MASLD). We aimed to develop and validate a novel CMRF-based HCC risk prediction model in MASLD.

Methods: This multicenter cohort study recruited 77,677 MASLD patients from 20 medical centers in Korea and other Asian and Western countries (2004-2023).

Therapeutic horizons in metabolic dysfunction-associated steatohepatitis.

Metabolic dysfunction-associated steatohepatitis (MASH), the progressive inflammatory form of MASLD, is now a leading cause of chronic liver disease worldwide. Driven by obesity and type 2 diabetes, MASH significantly increases the risk of cirrhosis, hepatocellular carcinoma, and liver failure. While public health interventions remain essential, therapeutic strategies targeting metabolic dysfunction, inflammation, and fibrosis are urgently needed.

Non-invasive risk-based surveillance of hepatocellular carcinoma in patients with metabolic dysfunction-associated steatotic liver disease.

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) affects over 30% of the general population and is the fastest growing cause of hepatocellular carcinoma (HCC). Current guidelines recommend HCC surveillance in patients with cirrhosis when annual HCC incidence exceeds 1% without specifying the role of non-invasive tests in patient selection.

Objective: To define non-invasive test thresholds to select patients with MASLD for HCC surveillance.

Cardiovascular risk assessment tools are insufficient for patients with metabolic dysfunction associated steatotic liver disease.

Introduction: Risk for cardiovascular (CV) events is estimated by the Framingham Risk Score (FRS), Pooled Cohort Equation (PCE) and the American Heart Association Predicting Risk of CVD EVENTs (PREVENT) equation. The applicability of these risk tools in patients with MASLD is uncertain. This study sought to determine the accuracy of the FRS, PCE, and PREVENT in a real-world cohort of patients with MASLD.

Effect of Antidiabetic Drug Classes on the Risk of Liver-Related Events in Individuals With T2D and MASLD.

Background: We investigated the use of type 2 diabetes (T2D) medications, including pioglitazone, glucagon-like peptide-1 receptor agonists (GLP-1RAs), and sodium-glucose cotransporter-2 (SGLT-2) inhibitors, in individuals with T2D and metabolic dysfunction-associated steatotic liver disease (MASLD), and explored the effect of these medications on long-term risk of liver-related events (LREs) and progression of liver stiffness in a retrospective cohort study.

Methods: We enrolled 7867 individuals with T2D and MASLD from 16 tertiary referral centers between February 2004 and January 2023. We recorded the use of pioglitazone, GLP-1RAs, and SGLT-2 inhibitors and analyzed the effects of these antihyperglycemic medications on the risk of developing incident LREs and the progression of liver stiffness over a median of 5.

Anthropometric Measures and Mortality Risk in Individuals With Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD): A Population-Based Cohort Study.

Background/aims: As the primary anthropometric measure in metabolic dysfunction-associated steatotic liver disease (MASLD), waist circumference (WC) may more accurately reflect the visceral fat distribution than body mass index (BMI). This study aimed to compare the prognostic value of BMI, WC and WC-related indices including waist-hip ratio (WHR), body shape index (BSI) and weight-adjusted-waist index (WWI) in individuals with MASLD.

Methods: The study population was derived from four large-scale cohorts: the National Health and Nutrition Examination Survey (NHANES 2017-2020 and NHANES III), the Kailuan Cohort and the UK Biobank Cohort.

Phase 3 Trial of Semaglutide in Metabolic Dysfunction-Associated Steatohepatitis.

Background: Semaglutide, a glucagon-like peptide-1 receptor agonist, is a candidate for the treatment of metabolic dysfunction-associated steatohepatitis (MASH).

Methods: In this ongoing phase 3, multicenter, randomized, double-blind, placebo-controlled trial, we assigned 1197 patients with biopsy-defined MASH and fibrosis stage 2 or 3 in a 2:1 ratio to receive once-weekly subcutaneous semaglutide at a dose of 2.4 mg or placebo for 240 weeks.

From "Burnt-Out" to "Burning-Out": Capturing Liver Fat Loss in Patients With Advanced Metabolic Dysfunction-Associated Steatotic Liver Disease From a Dynamic Perspective.

Background & Aims: The absence of hepatic fat in advanced fibrosis has been documented in metabolic dysfunction-associated steatotic liver disease ("burnt-out" MASLD). However, whether hepatic fat loss occurs continuously with fibrosis progression is controversial. We proposed a "burning-out" concept to describe this process and analyze the long-term outcomes of "burnt-out" and "burning-out" MASLD.

Global burden of metabolic dysfunction-associated steatotic liver disease, 2010 to 2021.

Background & Aims: This study used the Global Burden of Disease data (2010-2021) to analyze the rates and trends of point prevalence, annual incidence, and years lived with disability (YLDs) for metabolic dysfunction-associated steatotic liver disease (MASLD) in 204 countries.

Methods: Total numbers and age-standardized rates per 100,000 population for MASLD prevalence, annual incidence, and YLDs were compared across regions and countries by age, sex, and sociodemographic index (SDI). Smoothing spline models were used to evaluate the relationship between the burden of MASLD and SDI.

NAFLD vs MASLD (Metabolic Dysfunction-Associated Steatotic Liver Disease)-Why the Need for a Change of Nomenclature?

Several reasons led to the change in the nomenclature from nonalcoholic fatty liver disease (NAFLD) to metabolic dysfunction-associated steatotic liver disease (MASLD); the most important being limitations due to the reliance on exclusionary confounder terms and the use of potentially stigmatizing language (the terms "nonalcoholic" and "fatty"). The new name was decided through a Delphi process and now includes in the name, and definition, the metabolic origin (the presence of at least 1 of 5 cardiometabolic risk factors) without the stigmatizing terms. The recognition of a new category termed "metabolic and alcohol related/associated liver disease" (MetALD) opens up a new area for exploration although the relative contribution of alcohol and metabolic risk factors requires further evaluation as does the evidencing at a patient rather than population level.

Prognostic performance of the two-step clinical care pathway in metabolic dysfunction-associated steatotic liver disease.

Background & Aims: Current guidelines recommend a two-step approach for risk stratification in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) involving Fibrosis-4 index (FIB-4) followed by liver stiffness measurement (LSM) by vibration-controlled transient elastography (VCTE) or similar second-line tests. This study aimed to examine the prognostic performance of this approach.

Methods: The VCTE-Prognosis study was a longitudinal study of patients with MASLD who had undergone VCTE examinations at 16 centres from the US, Europe and Asia with subsequent follow-up for clinical events.

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.

Glycated haemoglobin is a major predictor of disease severity in patients with NAFLD.

Objectives: Currently, non-invasive scoring systems to stage the severity of non-alcoholic fatty liver disease (NAFLD) do not consider markers of glucose control (glycated haemoglobin, HbA1c); this study aimed to define the relationship between HbA1c and NAFLD severity in patients with and without type 2 diabetes.

Research Design And Methods: Data were obtained from 857 patients with liver biopsy staged NAFLD. Generalized-linear models and binomial regression analysis were used to define the relationships between histological NAFLD severity, age, HbA1c, and BMI.

The impact of stigma on quality of life and liver disease burden among patients with nonalcoholic fatty liver disease.

Background & Aims: Patients with nonalcoholic fatty liver disease (NAFLD)/metabolic dysfunction-associated steatotic liver disease (MASLD) face a multifaceted disease burden which includes impaired health-related quality of life (HRQL) and potential stigmatization. We aimed to assess the burden of liver disease in patients with NAFLD and the relationship between experience of stigma and HRQL.

Methods: Members of the Global NASH Council created a survey about disease burden in NAFLD.

A Phase 2 Randomized Trial of Survodutide in MASH and Fibrosis.

Background: Dual agonism of glucagon receptor and glucagon-like peptide-1 (GLP-1) receptor may be more effective than GLP-1 receptor agonism alone for treating metabolic dysfunction-associated steatohepatitis (MASH). The efficacy and safety of survodutide (a dual agonist of glucagon receptor and GLP-1 receptor) in persons with MASH and liver fibrosis are unclear.

Methods: In this 48-week, phase 2 trial, we randomly assigned adults with biopsy-confirmed MASH and fibrosis stage F1 through F3 in a 1:1:1:1 ratio to receive once-weekly subcutaneous injections of survodutide at a dose of 2.

Circulating myeloid populations have prognostic utility in alcohol-related liver disease.

Introduction: Alcohol-related liver disease (ARLD) accounts for over one third of all deaths from liver conditions, and mortality from alcohol-related liver disease has increased nearly five-fold over the last 30 years. Severe alcohol-related hepatitis almost always occurs in patients with a background of chronic liver disease with extensive fibrosis or cirrhosis, can precipitate 'acute on chronic' liver failure and has a high short-term mortality. Patients with alcohol-related liver disease have impaired immune responses, and increased susceptibility to infections, thus prompt diagnosis of infection and careful patient management is required.