Sven Francque

University of Antwerp | UA · Gastroenterology & Hepatology

Metabolic dysfunction-associated steatotic liver disease (MASLD) exhibits considerable variability in clinical outcomes. Identifying specific phenotypic profiles within MASLD is essential for developing targeted therapeutic strategies. Here we investigated the heterogeneity of MASLD using partitioning around medoids clustering based on six simple c...

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. Methods: From 3016 patients with ACLD screened in 17 European and Chinese centers...

Introduction Primary biliary cholangitis (PBC) is a rare autoimmune cholestatic liver disease characterised by the destruction of interlobular bile ducts, resulting in cholestasis and biliary fibrosis. Elafibranor, a dual peroxisome proliferator-activated receptor-alpha/delta agonist, significantly improved prognostic biomarkers of cholestasis at W...

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-...

There is an unmet clinical need for pharmacologic treatment for metabolic dysfunction-associated steatotic liver disease (MASLD). Hepatocyte cell death is a hallmark of this highly prevalent chronic liver disease, but the dominant type of cell death remains uncertain. Here we report that ferroptosis, an iron-catalyzed mode of regulated cell death,...

Although metabolic dysfunction-associated steatohepatitis (MASH) is rapidly becoming a leading cause of cirrhosis worldwide, therapeutic options are limited and the number of clinical trials in MASH-related compensated cirrhosis is low as compared to those conducted in earlier disease stages. Moreover, designing clinical trials in MASH cirrhosis pr...

Introduction: 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 re-search consortium led a project to design and evaluate a patie...

Introduction & Objective: Type 2 diabetes (T2D) and obesity are associated with metabolic dysfunction-associated steatotic liver disease formerly known as NAFLD. Our aim was to understand stigma and disease burden among NAFLD patients with T2D. Methods: Members of the Global NASH Council created a 68-item survey about patients’ experience with NAFL...

Metabolic dysfunction-associated steatotic liver disease (MASLD), previously termed non-alcoholic fatty liver disease (NAFLD), is defined as steatotic liver disease (SLD) in the presence of one or more cardiometabolic risk factor(s) and the absence of harmful alcohol intake. The spectrum of MASLD includes steatosis, metabolic dysfunction-associated...

Metabolic dysfunction-associated steatotic liver disease (MASLD), previously termed non-alcoholic fatty liver disease (NAFLD), is defined as steatotic liver disease (SLD) in the presence of one or more cardiometabolic risk factor(s) and the absence of harmful alcohol intake. The spectrum of MASLD includes steatosis, metabolic dysfunction-associated...

Metabolic dysfunction-associated steatohepatitis (MASH) is characterised by cell death of parenchymal liver cells which interact with their microenvironment to drive disease activity and liver fibrosis. The identification of the major death type could pave the way towards pharmacotherapy for MASH. To date, increasing evidence suggest a type of regu...

INTRODUCTION The Baveno VI criteria have set the stage for noninvasive assessment of compensated advanced chronic liver disease (ACLD). The algorithm combining liver stiffness measurement (LSM, <20 kPa) and platelet count (>150,000/μL) safely avoids screening endoscopy for varices needing treatment (VNT) but identifies only a relatively low number...

Objective This study investigated whether the delta-over-baseline of exhaled 13CO2 (Δ13CO2), generated from a 13C glucose breath test (13C-GBT), measured insulin resistance (IR) in people with type 1 diabetes, using the hyperinsulinemic-euglycemic clamp (HEC) as reference method. Secondary objective was to compare the 13C-GBT with the estimated glu...

Aims Metabolic dysfunction Associated Steatotic Liver Disease (MASLD) outcomes such as MASH (metabolic dysfunction associated steatohepatitis), fibrosis and cirrhosis are ordinarily determined by resource-intensive and invasive biopsies. We aim to show that routine clinical tests offer sufficient information to predict these endpoints. Methods Usi...

Background: Nonalcoholic steatohepatitis (NASH) is a progressive liver disease with no approved treatment. Resmetirom is an oral, liver-directed, thyroid hormone receptor beta-selective agonist in development for the treatment of NASH with liver fibrosis. Methods: We are conducting an ongoing phase 3 trial involving adults with biopsy-confirmed...

Background Obesity is linked to several health complication, including Metabolic Dysfunction Associated Steatotic Liver Disease (MASLD). Adipose tissue hypoxia has been suggested as an important player in the pathophysiological mechanism leading to chronic inflammation in obesity, and in the progression of MASLD. The study aims to investigate the e...

Background and Aims Artificial intelligence-powered digital pathology offers the potential to quantify histologic findings in a reproducible way. This analysis compares the evaluation of histological features of non-alcoholic steatohepatitis (NASH) between pathologists and a machine learning (ML) pathology model. Approach and Results This post hoc...

The pathophysiology of Non-Alcoholic Steatohepatitis (NASH) encompasses a complex set of intra- and extrahepatic driving mechanisms, involving numerous metabolic, inflammatory, vascular and fibrogenic pathways. The Peroxisome Proliferator-Activated Receptors (PPARs) α, β and γ belong to the nuclear receptor family of ligand-activated transcription...

Background and aims: Polycystic liver disease (PLD) can lead to extensive hepatomegaly. Symptom relief is the primary goal of the treatment. The role of the recently developed disease-specific questionnaires for identification of the thresholds and the assessment of therapy needs further investigation. Methods: A five-year prospective multi-cent...

Background aims: With distinct mechanisms of action, the combination of tropifexor (TXR) and cenicriviroc (CVC) may provide an effective treatment for non-alcoholic steatohepatitis. This randomized, multicenter, double-blind, phase 2b study assessed the safety and efficacy of TXR and CVC combination, compared with respective monotherapies. Approa...

Background & aims: Roux-en-Y gastric bypass (RYGB), the most weight-loss effective surgical procedure, decreases obesity and comorbidities, such as non-alcoholic fatty liver (NAFLD) and cardiovascular (CVD) diseases. Cholesterol is a major CVD risk factor and modulator of NAFLD development, and the liver tightly controls its metabolism. How RYGB s...

Background and aims: Drug development in NASH is hampered by a high screening failure rate that reaches 60-80% in therapeutic trials, mainly because of the absence of fibrotic NASH on baseline liver histology. MACK-3, a blood test including three biomarkers (aspartate aminotransferase, homeostasis model assessment and cytokeratin 18), was recently...

Background aims: Detecting non-alcoholic steatohepatitis (NASH) remains challenging, while at-risk NASH (steatohepatitis and F≥ 2) tends to progress and is of interest for drug development and clinical application. We developed prediction models by supervised machine learning (ML) techniques, with clinical data and biomarkers to stage and grade no...

Background Gastric non‐Helicobacter pylori Helicobacter (NHPH) species naturally associated with animals have been linked with gastric disease in human patients. Aim The prevalence and clinical significance of zoonotic gastric NHPHs was determined in large and well‐defined, H. pylori‐negative, gastric patient populations. Methods Patients were re...

Purpose To study the association between testosterone and non-alcoholic fatty liver disease (NAFLD) since prior studies have reported inconsistent results. Methods A retrospective analysis was performed including obese men who underwent a liver biopsy and a metabolic and hepatological work-up. Free testosterone (CFT) was calculated by the Vermeule...

Background: The reference standard for detecting non-alcoholic steatohepatitis (NASH) and staging fibrosis-liver biopsy-is invasive and resource intensive. Non-invasive biomarkers are urgently needed, but few studies have compared these biomarkers in a single cohort. As part of the Liver Investigation: Testing Marker Utility in Steatohepatitis (LI...

The current document has been issued by the Liver Forum who mandated the NAFLD-Associated Comorbidities Working Group - comprised of multi-stakeholder, academic, industry and patient associations to identify aspects of diverse comorbidities frequently associated with NASH that can interfere with the conduct of therapeutic trials and, in particular,...

Recent progress in our understanding of the pathogenic mechanisms that drive progression of nonalcoholic steatohepatitis as well as lessons learned from several clinical trials that have been conducted over the past 15 years guide our current regulatory framework and trial design. Targeting the metabolic drivers should probably be the backbone of t...

Background & aims: The LIVIFY trial investigated the safety, tolerability, and efficacy, of Vonafexor, a second-generation, non-bile acid farnesoid X receptor agonist in patients with suspected fibrotic non-alcoholic steatohepatitis (NASH). Methods: This double-blind phase 2a study was conducted in two parts. Patients were randomised (1:1:1:1) t...

To test the hypothesis that the gut microbiota of individuals with nonalcoholic fatty liver disease (NAFLD) produce enough ethanol to be a driving force in the development and progression of this complex disease, we performed one prospective clinical study and one intervention study. Ethanol was measured while fasting and 120 min after a mixed meal...

Background The efficacy of nucleos(t)ide analogs (NAs) in non-cirrhotic chronic hepatitis B (CHB) patients is well-established. However, their impact on complications of portal hypertension in advanced chronic liver disease (ACLD) is less well characterized.MethodsMEDLINE/PubMed, EMBASE, Web of Science, Cochrane Central Register of Controlled Trial...

Background & Aims Non-invasive tests (NITs) are practical methods of advanced fibrosis identification in non-alcoholic fatty liver disease (NAFLD). Despite increasing implementation, their use is not standardised, which can lead to inconsistent interpretation and risk-stratification. We aim to assess the types of NITs and the corresponding cut-offs...

Background: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide. The landscape of the systemic treatment for advanced HCC is changing quickly, and recently, the standard of care became either atezolizumab plus bevacizumab or tremelimumab plus durvalumab in the single tremelimumab regular interval durvaluma...

Background Peroxisome proliferator‐activated receptors (PPARs) are ligand‐activated transcription factors known to regulate glucose and fatty acid metabolism, inflammation, endothelial function and fibrosis. PPAR isoforms have been extensively studied in metabolic diseases, including type 2 diabetes and cardiovascular diseases. Recent data extend t...

Initially a condition that received limited recognition and whose clinical impact was controversial, non-alcoholic steatohepatitis (NASH) has become a leading cause of chronic liver disease. Although there are no approved therapies, major breakthroughs, which will be reviewed here, have paved the way for future therapeutic successes. The unmet medi...

Background: NAFLD is strongly associated with type 2 diabetes. Insulin resistance is proposed as a major contributor. NAFLD is increasingly reported in type 1 diabetes (T1D) , but whether insulin resistance is linked to NAFLD in this population needs elucidation. Furthermore, T1D is an excellent model to investigate insulin resistance in relation t...

Background: Non-alcoholic fatty liver disease (NAFLD) affects nearly 25% of the global population. Cardiovascular disease (CVD) is the most common cause of death among patients with NAFLD, in line with highly prevalent dyslipidemia in this population. Increased plasma triglyceride (TG)-rich lipoprotein (TRL) concentrations, an important risk facto...

Purpose: Immunotherapy for hepatocellular carcinoma (HCC) shows considerable promise in improving clinical outcomes. HepaVac-101 represents a single-arm, first-in-man Phase I/II multicenter cancer vaccine trial for HCC (NCT03203005). It combines multi-peptide antigens (IMA970A) with the TLR7/8/RIG I agonist CV8102. IMA970A includes 5 HLA-A*24 and...

Background The multifactorial nature of non-alcoholic fatty liver disease cannot be explained solely by genetic factors. Recent evidence revealed that DNA methylation changes take place at proximal promoters within susceptibility genes. This emphasizes the need for integrating multiple data types to provide a better understanding of the disease’s p...

Background The factors affecting intra-operator variability of two-dimensional shear wave elastography (2D-SWE) have not been clearly established. We evaluated 2D-SWE variability according to the number of measurements, clinical and laboratory features, and liver stiffness measurements (LSM). Methods At least three LSM were performed in 452 patien...