Metabolic Dysfunction Associated Steatotic Liver Disease

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease globally. While weight loss through lifestyle modification is the standard treatment, most patients regain weight limiting ultimate improvement in liver disease. On the other end of the spectrum, bariatric surgery has shown promise in the treatment of MASLD/metabolic dysfunction-associated steatohepatitis (MASH) due to its efficacy in inducing weight loss. Nevertheless, its adoption has been hindered by the perceived invasiveness of surgery. Over the past decade, endoscopic sleeve gastroplasty (ESG) has gained recognition as a promising minimally-invasive approach to weight loss. The procedure involves utilizing a Food and Drug Administration (FDA)-authorized endoscopic suturing device to reduce the gastric volume by 70%. Studies reveal that ESG is associated with approximately 18.2% weight loss at one year after the procedure, with sustained results for at least 10 years. Nevertheless, the effect of ESG on MASH remains unknown. In this study, the investigators will compare ESG + lifestyle modification versus lifestyle modification alone in treating histologic MASH. The study will randomize patients to one of two different treatment options: ESG + lifestyle modification or lifestyle modification alone.

The main purpose of the SYNERGY-OUTCOMES study is to find out whether retatrutide and tirzepatide can prevent major adverse liver outcomes (MALO) in people with high-risk metabolic dysfunction-associated steatotic liver disease (MASLD). The study will enroll adults who have MASLD based on non-invasive tests (NITs), which indicate they are more likely to develop MALO. Participants will be randomly assigned within a Master Protocol to receive either retatrutide (N1T-MC-RT01), tirzepatide (N1T-MC-TZ01) or placebo. The trial plans to enroll about 4,500 adults and will run for approximately 224 weeks. Participants may have up to approximately 25 to 30 clinic visits throughout the study to monitor their health, complete study procedures, and assess liver function and disease progression. Once the study is complete, eligible participants may participate in an optional 2-year extension study, in which all participants will receive either retatrutide or tirzepatide, even if they received placebo in the main study.

LiverSeek is a fully automated, passive case-finding programme for advanced liver fibrosis associated with metabolic dysfunction-associated steatotic liver disease (MASLD) in primary care. The programme operates through the Laboratory Information System (LIS; Modulab/Biwer Analytics) of the Clinical Biochemistry Laboratory at Hospital General Universitario Gregorio Marañón (HGUGM), covering approximately 350,000 inhabitants across 11 peri-urban primary care centres affiliated to SERMAS (Servicio Madrileño de Salud) in Madrid, Spain. When a high-risk patient (age 50-75 years with ≥1 of: ALT above ULN + HbA1c ≥6.5%; ALT above ULN + BMI \>30; BMI \>30 + HbA1c ≥6.5%) undergoes a routine blood test in primary care, the LIS automatically calculates FIB-4. If FIB-4 \>1.30, the system reflexively orders ELF and MASEF from the same serum sample, without any action required from the primary care clinician. Patients with a positive second-step NIT (ELF ≥9.8 or MASEF ≥0.33) receive an automatic alert directing them to the Hepatology Advanced Practice Nurse for VCTE (FibroScan) and clinical evaluation. The primary objective is to evaluate the prevalence of hepatic fibrosis in the high-risk population using this single-step automated strategy. Secondary objectives include head-to-head diagnostic comparison of FIB-4+ELF vs FIB-4+MASEF vs FIB-4+FAST for histologically-confirmed endpoints (significant fibrosis ≥F2, advanced fibrosis ≥F3, at-risk MASH), evaluation of the Liver Risk Score, and a health-economic analysis. A sub-study evaluates a nurse-led structured lifestyle intervention in NIT-positive patients.

This clinical trial aims to learn whether daidzein can improve liver tissue changes in adults with metabolic dysfunction-associated steatotic liver disease, also called MASLD. MASLD is a liver condition linked to extra fat in the liver and metabolic problems such as obesity, diabetes, abnormal blood lipids, or high blood pressure. Daidzein is a natural compound found in soy. Earlier laboratory studies suggest that daidzein may help protect the liver. This study will test whether taking daidzein for a short time before surgery can improve liver tissue findings in people with MASLD. The main questions this study aims to answer are: Does short-term daidzein treatment improve liver tissue injury in people with MASLD? Is daidzein safe and well tolerated before surgery? Are changes in blood or urine equol levels related to the effects of daidzein? Equol is a substance made by gut bacteria after some people take daidzein. Researchers will compare people who take daidzein before surgery with people who receive standard care without daidzein. Participants will: Be adults with MASLD who are scheduled for elective gallbladder surgery or another benign biliary surgery. Be randomly assigned to take daidzein or to receive standard care without daidzein. Take daidzein by mouth for 28 days before surgery if assigned to the daidzein group. Avoid soy foods during the study period. Provide blood and urine samples. Have a small liver tissue sample collected during surgery. Be followed for safety and recovery after surgery. The liver tissue sample will be used to check liver fat, inflammation, and liver cell injury. Researchers will also study markers related to liver injury, immune activity, and how the body responds to daidzein.

This phase 2 trial is a single-site sequential, multiple assignment, randomized trial (SMART) to test and construct a high-quality adaptive intervention of essential amino acids (EAA) and/or Low Sugar Diet for children with metabolic dysfunction associated steatotic liver disease (MASLD) and increased cardiometabolic risk. The basis for the trial includes high-quality pilot data in both EAA for hepatic steatosis and a low sugar diet for hepatic steatosis. In the trial, children aged 11-17 years old will be eligible to participate if their BMI is greater than or equal to 95th% at baseline and hepatic steatosis is greater than or equal to 8% at baseline by Magnetic Resonance Imaging Proton Density Fat Fraction (MRI-PDFF) because this is the most common age group diagnosed with metabolic-dysfunction associated steatotic liver disease.

This study is a Phase Ib, multicenter randomized, double-blind, dose-escalation, placebo-controlled trial designed to evaluate the safety, tolerability, PK, and PD profiles of multiple-dose ACT500 in participants with metabolic dysfunction-associated steatotic liver disease (MASLD) complicated with chronic hepatitis B (CHB). The trial plans to enroll 24 participants with MASLD complicated with CHB across three dose cohorts initially, each consisting of 8 participants who will receive oral ACT500 tablets once daily.

Type of Study: Clinical Trial Goal: The goal of this clinical trial is to investigate how performing exercise at different times of day (morning vs. evening) affects liver fat, cardiometabolic health, and gut microbiota in postmenopausal women. Participant Population/Health Conditions: The study will involve 63 sedentary postmenopausal women (aged 45-75) diagnosed with metabolic dysfunction-associated steatotic liver disease. Main Questions: The main questions this study aims to answer are: * Does morning exercise reduce hepatic fat more effectively than evening exercise? * How does time-of-day-specific exercise influence cardiometabolic markers? * Do changes in gut microbiota contribute to the metabolic effects of exercise timing? Participants Will: Be randomized into one of three groups: morning exercise, evening exercise, or a usual-care control group. Follow the assigned regimen for 12 weeks. The exercise groups will perform supervised aerobic and resistance training three times per week. Provide blood, stool, and imaging data before and after the intervention to determine the effects of the intervention. Comparison Group: Researchers will compare the effects of morning vs. evening exercise (and usual care) on hepatic fat reduction and cardiometabolic improvement, as well as changes in gut microbiota.

The aim of this study is to evaluate mean platelet volume (MPV) as a predictor of acute coronary syndrome (ACS) in patients with metabolic dysfunction-associated steatotic liver disease (MASLD to evaluate mean platelet volume (MPV) as a predictor of acute coronary syndrome (ACS) in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) in Sohag University Hospital.

This study is researching an experimental drug called ALN-CIDEB, also referred to as "study drug". The study is focused on participants with metabolic dysfunction-associated steatotic liver disease (MASLD) (Part A) and metabolic dysfunction-associated steatohepatitis (MASH) (Part B). MASLD and MASH are long-lasting liver conditions caused by having too much fat in the liver. The aim of the study is to see how safe and tolerable the study drug is. The study is looking at several other research questions, including: * What side effects may happen from taking the study drug * How the study drug works to change liver fat content * How much study drug and study drug metabolites (byproducts of the body breaking down the study drug) are in the blood at different times

Steatotic liver disease (SLD) is one of the most common chronic liver diseases worldwide. Distinguishing simple steatosis from metabolic dysfunction-associated steatohepatitis (MASH) with significant fibrosis is clinically important, but liver biopsy - the current standard - is invasive. Recent ultrasound technology allows noninvasive measurement of tissue viscoelasticity, which has been linked to liver inflammation. Samsung Medison's HERA W12 system (S-Viscosity) and Canon Aplio i800 (Dispersion Slope Imaging) both provide vendor-specific viscoelasticity parameters derived from shear-wave dispersion analysis, but their relationship and agreement have not been compared in SLD patients. This prospective single-center observational study will enroll approximately 95-100 participants in three cohorts: (A) 15-20 living-donor candidates as a healthy reference, (B+C) approximately 80 adults with sonographically suspected or confirmed SLD recruited consecutively. SLD participants will be classified post-hoc into low-MASH-risk (Cohort B) and at-risk MASH (Cohort C) subgroups using a multi-parametric stratification combining liver stiffness (LSM), DeepUSFF (deep-learning-based ultrasound fat fraction), and serum AST. All participants will undergo same-day ultrasound examination with both Samsung HERA W12 and Canon Aplio i800. The primary objective is to evaluate the correlation and agreement between Samsung S-Viscosity and Canon Dispersion Slope. Secondary objectives include deriving a normal reference range from the healthy cohort, comparing viscoelasticity parameters across cohorts, and exploring a Modified US-FAST score.

This proposal evaluates the implementation of a novel, non-interruptive, electronic health record alert for metabolic dysfunction-associated steatotic liver disease (MASLD) fibrosis risk assessment in primary care patients with MASLD using a stepped wedge, cluster randomized design. This work will generate generalizable data to dramatically enhance MASLD management in primary care.

Metabolic dysfunction-associated steatotic liver disease (MASLD), redefined in 2020, is an improved diagnostic standard evolved from non-alcoholic fatty liver disease (NAFLD), emphasizing the correlation between hepatic steatosis and metabolic dysfunction. Compared to NAFLD, which relies on exclusion-based diagnosis, MASLD criteria enhance population homogeneity in studies and accommodate patients with coexisting liver diseases, thereby improving the efficiency and relevance of drug development. MASLD affects approximately one-quarter of the global population. If left untreated, it may progress to liver fibrosis, cirrhosis, or hepatocellular carcinoma. Given its high clinical burden and the current lack of FDA-approved therapies, effective treatments for MASLD are urgently needed. Previous studies suggest that diet and gut microbiota play crucial roles in the pathogenesis of MASLD. Dietary composition influences microbial balance and intestinal barrier function. In dysbiosis, gut-derived harmful substances such as pathogen-associated molecular patterns (PAMPs) and microbiota-derived metabolites (MDMs) may translocate via a leaky gut to the liver through the portal vein, contributing to hepatic injury. These processes, often described as the gut-liver axis, remain incompletely understood. Animal studies have shown that dietary components regulating gut microbiota may help alleviate MASLD. While clinical evidence remains limited, incorporating microbiota-modulating and immune-regulating food ingredients holds potential. Next-generation probiotics have demonstrated benefits in improving hepatic lipid metabolism and modulating gut microbiota, potentially slowing MASLD progression through gut-liver axis modulation. Our previous research investigated a pasteurized Akkermansia muciniphila strain, NTUH\_Amuc03 (pAKK\_LWHK0003), which attenuated fatty liver progression in preclinical models. In mice subjected to a high-fat, high-fructose, high-cholesterol diet, pAKK\_LWHK0003 administration resulted in reduced body weight, improved dyslipidemia, lowered NAFLD activity scores, and improved HOMA-IR. These findings support the potential of pAKK\_LWHK0003 in slowing MASLD progression. This study aims to evaluate further the clinical efficacy and safety of pAKK\_LWHK0003 in individuals with MASLD.

The goal of this pilot randomized controlled trial is to evaluate the trial feasibility and acceptability of LLM-based chatbot for reducing alcohol use among patients with metabolic alcohol-related liver disease. Specific objectives include: 1. To assess how many MetALD patients accept the invitation to participate in the trial 2. To assess the retention rate of the participants through 3 and 6 months after treatment initiation 3. To assess the acceptability of the LLM-based chatbot in terms of participants' compliance and usability rating 4. To estimate the intervention effect on alcohol reduction 5. To explore the participants' perception and experiences in the chatbot

Liver is an important organ in maintaining energy homeostasis. Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD), formerly known as non-alcoholic fatty liver disease (NAFLD), is the most common chronic liver disease locally and globally. MASLD and type 2 diabetes mellitus (T2DM) are closely related with alarmingly high prevalence of MASLD in people with T2DM, along with the escalated risk of adverse clinical outcomes. Our group has reported that around 70% of people with T2DM have increased controlled attenuation parameter (CAP) suggestive of hepatic steatosis and one out of six had advanced liver fibrosis as evidenced by increased liver stiffness measurements (LSM). Despite its prevalence, close relationships and potential consequences, the mechanisms underlying the complex interconnections between MASLD and T2DM are not fully understood. MASLD is associated with a twofold higher risk of developing T2DM, independent of obesity and other common metabolic risk factors. This risk increases with the severity of MASLD, such that patients with more advanced stages of liver fibrosis are at a higher risk of developing T2DM. Moreover, the progression from hepatic steatosis to fibrosis is an important, yet not fully understood, step towards cirrhosis and end-stage liver disease. Identification of clinical predictors and biomarkers to select individuals with MAFLD for close monitoring is pivotal to prevent the sinister outcomes. To date, longitudinal cohorts with paired biobank focused on people with diabetes and comorbid MASLD for investigating the clinical courses and biomarkers for prediction of outcomes are lacking. We hypothesized that Hong Kong Chinese T2DM with comorbid steatotic liver disease have unique clinical courses and special biomarkers for predicting the progression to advanced liver fibrosis. The aims of this study are: 1) establish a prospective cohort of people with T2DM and comorbid steatotic liver disease accompanied with the setting up of a biobank; 2) elucidate the clinical courses and outcomes of Hong Kong Chinese T2DM with comorbid steatotic liver disease; 3) identify potential diagnostic markers of advanced liver fibrosis in people with T2DM and comorbid steatotic liver disease in Hong Kong. The primary outcome measure will be all-cause mortality and secondary outcome measure will be fatal and non-fatal CVD, heart failure, hospitalizations, NT-proBNP levels, and novel diagnostic markers of MASH in people with T2DM comorbid with MASLD.

The goal of this observational study is to create a detailed virtual model to better understand how Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) develops. This model will also help predict heart problem at different stage of the disease.

This is a single-center, prospective, randomized, controlled (crossover) clinical study designed to investigate the impact of lowering insulin levels on hepatic glucose production (HGP) vs de novo lipogenesis (DNL) in people with insulin resistance. The investigators will recruit participants with a history of overweight/obesity and evidence of insulin resistance (i.e., fasting hyperinsulinemia plus prediabetes and/or impaired fasting glucose and/or Homeostasis Model Assessment of Insulin Resistance \[HOMA-IR\] score \>=2.73), and with evidence of metabolic dysfunction-associated steatotic liver disease (MASLD). Participants will undergo two pancreatic clamp procedures -- one in which serum insulin levels are maintained near hyperinsulinemic baseline (Maintenance Hyperinsulinemia or "MH" Protocol) and the other in which serum insulin levels are lowered by 50% (Reduction toward Euinsulinemia or "RE" Protocol). In both clamps the investigators will use stable-isotope tracers to monitor hepatic glucose and triglyceride metabolism. The primary outcome will be the impact of steady-state clamp insulinemia on HGP vs DNL.

Menopause increases the risk of metabolic dysfunction-associated steatotic liver disease (MASLD), possibly owing to the abrupt lack of estrogen. Gonadotropin-releasing hormone (GnRH) treatment in endometriosis is regarded as a model of pharmaceutical menopause. Thus, the effect of goserelin acetate, a GnRH analog that results in transient menopause, on hepatic steatosis and fibrosis will be evaluated in this study.

Study Objective: To evaluate the efficacy and safety of Rifaximin-α in the treatment of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD), and investigate the underlying mechanisms by which Rifaximin-α influences MASLD progression. Target Population: Patients diagnosed with MASLD. Intervention: This trial is a multicenter, prospective, randomized, controlled study. Enrolled MASLD patients who meet the inclusion criteria, do not meet any exclusion criteria, and provide written informed consent will be randomized in a 2:1 ratio to the Rifaximin-α treatment group (40 cases) or the control group (20 cases). All patients are advised to maintain daily physical activity and follow a recommended dietary plan (e.g., Mediterranean diet). The Rifaximin-α treatment group will receive oral Rifaximin-α at a dose of 1200 mg per day for 24 weeks. Both groups of patients will enter a 24-week follow-up period after completing the 24-week treatment. During the study, patients' existing foundational treatments (such as liver-protecting, lipid-lowering, glucose-lowering, and antihypertensive therapies) will be maintained. Relevant indicators will be closely monitored. And avoid the use of medications known to alter the gut microbiota, such as lactulose, antibiotics, and various types of intestinal microecological preparations. Investigational Drug: Rifaximin-α (Alfa Wassermann S.p.A., Italy).

Tissue elasticity and viscosity correlate with pathology. These tissue properties are typically evaluated subjectively using palpation. The purpose of "elastography" is to provide an objective elasticity image that is equivalent to the remote palpation of tissue. The investigators have developed elastography imaging systems based on ultrasound and magnetic resonance imaging and have applied them previously to prostate imaging, breast imaging in patients and liver imaging in healthy volunteers. A first objective of this study is to compare the investigators' ultrasound shear wave absolute vibro-elastography (S-WAVE) technology with the existing clinical standard, FibroScan, and magnetic resonance elastography to quantify liver stiffness in healthy volunteers and in patients suspected of fatty liver disease. A second objective of this study is to compare ultrasound-based liver tissue fat measurement with MRI-based measurements. A third objective of this study is to determine whether ultrasound can be used to assess liver inflammation.

The main research hypothesis is that alterations in the communication between the endoplasmic reticulum (ER) and the mitochondria at contact sites called mitochondria-associated membranes (MAMs) occurs in different hepatic cell types of patients with Metabolic Dysfunction-Associated Steatotic Liver Disease (MALSD) and is involved in the progression towards MASH and could also influence the process of improvement of MASH. This study aims to investigate the link between Metabolic Dysfunction-Associated Steatohepatitis (MASH) and Mitochondria-Associated Membranes (MAMs) in liver cells and peripheral blood mononuclear cells (PBMCs) in patients undergoing bariatric surgery. The primary objective is to analyze MAMs alterations in hepatocytes in MASH patients compared to non-MASH patients. Secondary objectives include evaluating the correlation between MAMs in PBMCs and liver cells and assessing MAMs changes post-bariatric surgery.

NAFLD encompasses the entire spectrum of Fatty liver disease in individuals without significant alcohol consumption, ranging from fatty liver to steatohepatitis to cirrhosis. A high prevalence of NAFLD (62.5%) was observed in overweight/obese Indian adolescent (1). Lifestyle modification consisting of diet, exercise and weight loss has been advocated to treat patients with NAFLD (2). EASL guidelines recommends that the macronutrient in the diet should be adjusted according to the Mediterranean diet for weight loss (3). Mediterranean diet helps to decrease hepatic fat by decreasing lipogenesis, fibrogenesis, inflammation, oxidative stress and by increasing fatty acids beta oxidation (4). There are various studies showing benefits of using other diets such as Low Fat Diet, Low Carbdohydrate diet, Low Fructose Diet, et. Though there are numerous studies in adults comparing Mediterranean diet vs Low Fat diet, date regarding the same in children are lacking. The aim of this study will be to compare the Effect of Indianized version of Mediterranean diet vs. Low Fat Diet on Hepatic Steatosis in Overweight children and adolescent with MASLD.

This multicenter prospective study aims to evaluate the correlation between quantitative ultrasound fat fraction (USFF) and MRI-PDFF (Proton Density Fat Fraction) for liver fat quantification in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). The study will compare the diagnostic accuracy of quantitative ultrasound imaging against MRI-PDFF as the reference standard.

Steatotic liver disease associated with metabolic dysfunction (MASLD) is a disease caused by excess fat storage in the liver. Excessive fat delivery to the liver and MASLD typically occurs in people with abdominal obesity and type 2 diabetes. Type 1 diabetes (T1D) is also associated with a marked increase in the release of fat from adipose tissues and MASLD is increased in T1D and significantly increases the risk of heart, kidney and eye diseases.

The goal of this clinical trial is to learn if daily supplementation with Low-methoxy (LM) pectin (polysaccharides extracted from citrus peels), which are commonly found in the UK diet (not pharmacological agents), can reduce systemic inflammation and improve gut microbiota composition in adults recently diagnosed with Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD). The main question it aims to answer is: -How does dietary Low-methoxy (LM) pectin supplementation affect systematic inflammation pathways such as those mediated by gut microbiota composition and what are the impacts on general metabolic indicators in individuals with MASLD? Researchers will compare a group taking 15g of LM-pectin with 10g of cocoa powder to a placebo group receiving 10g of placebo with 10g of cocoa powder to see if LM-pectin has measurable effects on inflammation and gut microbiota. Participants will: * Take a daily supplement for 6 weeks: either 15g of LM-pectin with 10g of cocoa powder (intervention), or 10g of placebo with 10g of cocoa powder (control) * Provide stool and fasting blood samples before and after the intervention * Undergo anthropometric measurements (weight, height, waist/hip ratio, and blood pressure) * Complete a case report form (CRF) including demographics and health/medical history * Undergo a FibroScan™ to assess liver health * (Optional) Participate in MRI scans to evaluate gut permeability

This study enrolled 228 patients with MASLD-related cirrhosis confirmed by histopathology or clinical diagnosis. Follow-up was conducted every 3-6 months. The primary endpoint was cumulative incidence of liver-related events (including decompensation events, hepatocellular carcinoma, liver transplantation, and liver-related mortality) and all-cause mortality. Secondary endpoints included cumulative incidence of metabolic events and changes in non-invasive fibrosis markers.