Gradual DNA methylation changes reveal transcription factors implicated in metabolic dysfunction-associated steatotic liver disease progression and epigenetic age acceleration.

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease worldwide, but its pathophysiological mechanisms remain elusive. It is a progressive disease, encompassing hepatic steatosis, steatohepatitis with (out) fibrosis, and ultimately cirrhosis and hepatocellular carcinoma. DNA methylation (DNAm) is dysregulated in MASLD and may play a central role in its pathogenesis.

Real-World Evidence of the Effect of Adjunctive Semaglutide on Weight Change, Glycemic Control, and Metabolic Dysfunction-Associated Steatotic Liver Disease in People with Type 1 Diabetes.

Obesity is increasingly prevalent in type 1 diabetes (T1D), contributing to insulin resistance and metabolic dysfunction-associated steatotic liver disease (MASLD). While semaglutide has demonstrated weight loss, improved glycemic control, and cardiovascular benefits in type 2 diabetes, its use in T1D remains unapproved. This real-world study evaluates the effects of once-weekly semaglutide in overweight/obese adults with T1D after 12 months of follow-up.

Altered liver sinusoidal endothelial cells in MASLD and their evolution following lanifibranor treatment.

Background & Aims: Data on changes in liver sinusoidal endothelial cells (LSECs) in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) and their response to treatment are limited. This study aimed at determining (i) features associated with LSEC capillarisation in patients with MASLD; (ii) whether LSEC changes can regress with the pan-peroxisome proliferator-activated receptor (PPAR) agonist lanifibranor; (iii) the role of the different PPAR isotypes on LSEC changes in MASLD.

Methods: We analysed CD34 expression, a marker of LSEC capillarisation, on liver biopsies from patients considered for inclusion in the NATIVE trial at baseline (n = 249), and after 24 weeks of placebo or lanifibranor (n = 173).

Global research initiative for patient screening on MASH (GRIPonMASH) protocol: rationale and design of a prospective multicentre study.

Introduction: The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) may be as high as 38% in the adult population with potential serious complications, multiple comorbidities and a high socioeconomic burden. However, there is a general lack of awareness and knowledge about MASLD and its progressive stages (metabolic dysfunction-associated steatohepatitis (MASH) and fibrosis). Therefore, MASLD is still far underdiagnosed.

Increased prevalence and risk of atherosclerotic cardiovascular disease in individuals with Type 1 diabetes and metabolic dysfunction-associated steatotic liver disease.

Objective: This study aimed to investigate the correlation between metabolic dysfunction-associated steatotic liver disease (MASLD) and atherosclerotic cardiovascular disease (ASCVD) in individuals with type 1 diabetes (T1D).

Methods: Adults with T1D (n = 659) were consecutively screened for liver steatosis via abdominal ultrasound. The presence of macrovascular disease (including coronary artery disease [CAD], peripheral artery disease [PAD], or ischaemic stroke [CVA, cerebrovascular accident]) was identified via electronic medical records.

Comparison of diagnostic accuracy and utility of non-invasive tests for clinically significant liver disease in a general population with metabolic dysfunction.

Background And Aims: Screening for liver disease in the general population requires accurate non-invasive tests (NITs). A head-to-head comparison of NITs for early detection of clinically relevant liver disease among the target population for screening is lacking.

Aproach And Results: Among the meta-cohort (Rotterdam Study and National Health and Nutrition Examination Survey) with metabolic dysfunction aged 18-80 years, 10 NITs were investigated.

Non-invasive tests for fibrotic MASH for reducing screen failure in therapeutic trials.

Background & Aims: Therapeutic trials in metabolic dysfunction-associated steatohepatitis (MASH) are hampered by a high 70-80% screen failure rate mostly because of the absence of fibrotic MASH on baseline liver biopsies, underscoring the need for better selection of candidates. We compared the performance of eight non-invasive tests, designed or not for the diagnosis of fibrotic MASH.

Methods: A total of 1,005 patients with histologically proven MASLD were included in five tertiary care centers.

Biomarkers of Histological Response in Lanifibranor-treated Patients With Metabolic Dysfunction-associated Steatohepatitis.

Background & Aims: Lanifibranor, a pan-peroxisome proliferator-activated receptor agonist, has demonstrated therapeutic efficacy on metabolic dysfunction-associated steatohepatitis (MASH) resolution and fibrosis improvement in the Phase IIb NATIVE study. The histologic endpoints of MASH resolution and fibrosis improvement (E1), MASH resolution without worsening of fibrosis (E2), and fibrosis improvement without worsening of MASH (E3) were investigated with the aim of identifying biological signatures of E1, E2, and E3 responders based on serum biomarkers in patients treated with lanifibranor.

Methods: NATIVE evaluated lanifibranor 800 and 1200 mg daily vs placebo in patients with non-cirrhotic MASH treated over 24 weeks.

MASH to cirrhosis: bridging the gaps in MASLD management.

Metabolic dysfunction-associated steatohepatitis (MASH) represents a critical stage in the progression of metabolic dysfunction-associated steatotic liver disease (MASLD), significantly increasing the risk of cirrhosis, hepatocellular carcinoma (HCC), and liver-related mortality. Despite the rising global prevalence of MASLD, gaps in understanding the pathophysiological mechanisms driving MASH to cirrhosis persist, leading to challenges in early diagnosis, prevention, and treatment. This review explores the current knowledge on MASH, focusing on its pathophysiology, clinical management, and treatment strategies in the advanced stages.

Co-existing regeneration mechanisms in severe alcohol-related steatohepatitis.

Background: Keratin 7 positive (K7) cells are considered to be activated in case of impaired hepatocyte replication. Their exact role and their interaction with hepatocytes and macrophages also implicated in liver regeneration remain poorly characterized in humans. The aim of this study is to evaluate hepatocyte, K7 cells and macrophage populations in severe alcohol-related steatohepatitis (sASH) and to link them with liver injury and patients' outcomes.

Insights into the results of Resmetirom trials: Can a thyroid hormone receptor agonist be the holy grail of MASH therapy?

Despite the heavy individual patient and socioeconomic burden of metabolic dysfunction-associated steatohepatitis (MASH), until recently, no pharmacological therapy for MASH was approved, with available treatment options geared towards associated cardiometabolic risk factors. Accelerated approval of resmetirom, a thyroid hormone receptor-β agonist to be used in conjunction with diet and exercise, marks a significant step forward in the treatment of MASH, offering tempered optimism to healthcare providers and millions of patients around the world for more effective management. Evidence from phase 2 and 3 clinical trials suggests that resmetirom has the potential to alleviate hepatic fibrosis and inflammation and significantly reduce liver lipid content.

The Lipidomic Profile Discriminates Between MASLD and MetALD.

Background: The recent consensus statement redefined steatotic liver diseases. Metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction and alcohol-related liver disease (MetALD) now represent distinct disease entities. However, biomarkers that differentiate MASLD and MetALD remain largely unknown.

Precision in Liver Diagnosis: Varied Accuracy Across Subgroups and the Need for Variable Thresholds in Diagnosis of MASLD.

Background And Aims: The performance of non-invasive liver tests (NITs) is known to vary across settings and subgroups. We systematically evaluated whether the performance of three NITs in detecting advanced fibrosis in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) varies with age, sex, body mass index (BMI), type 2 diabetes mellitus (T2DM) status or liver enzymes.

Methods: Data from 586 adult LITMUS Metacohort participants with histologically characterised MASLD were included.

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.

Steatotic liver disease.

Steatotic liver disease is the overarching term for conditions characterised by abnormal lipid accumulation in the liver (liver or hepatic steatosis). Steatotic liver disease encompasses what was previously termed non-alcoholic fatty liver disease (NAFLD), which is now called metabolic dysfunction-associated steatotic liver disease (MASLD). Additionally, steatotic liver disease includes alcohol-related liver disease (ALD) and MetALD, the new classification for the overlap between MASLD and ALD, and rare causes of liver steatosis.

Hepatocellular Cancer Surveillance in Patients with Advanced Chronic Liver Disease.

Background: Patients with advanced chronic liver disease (ACLD) are at high risk of developing hepatocellular carcinoma (HCC). Therefore, biannual surveillance is recommended. This large-scale multicenter study aimed to stratify the risk of HCC development in ACLD.

A Case-Control Study Supports Genetic Contribution of the Gene Family in Obesity and Metabolic Dysfunction Associated Steatotic Liver Disease.

The paraoxonase () gene family (including PON1, PON2, and PON3), is known for its anti-oxidative and anti-inflammatory properties, protecting against metabolic diseases such as obesity and metabolic dysfunction-associated steatotic liver disease (MASLD). In this study, the influence of common and rare variants on both conditions was investigated. A total of 507 healthy weight individuals and 744 patients with obesity including 433 with histological liver assessment, were sequenced with single-molecule molecular inversion probes (smMIPs), allowing the identification of genetic contributions to obesity and MASLD-related liver features.

Practice Recommendations for the Management of MASLD in Primary Care: Consensus Results.

Background: Despite its high prevalence and impact on health, metabolic dysfunction-associated steatotic liver disease (MASLD) is inadequately addressed in European primary care (PC), with a large proportion of cases going undiagnosed or diagnosed too late. A multi-country European research consortium led a project to design and evaluate a patient-centered, integrated model for MASLD screening, diagnosis, and linkage to specialty care for European PC settings. Based on the lessons from this project, the latest research evidence, and existing guidelines for the management of MASLD, we sought to develop a set of practice recommendations for screening, referral, and management of MASLD in PC.