MASLD

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.

This single-center, prospective observational study aims to assess the accuracy of FIB-4 cut-offs in identifying liver fibrosis in obese patients attending an endocrinology outpatient clinic in Italy. All consecutive eligible patients undergo routine blood tests and liver elastography (FibroScan) as part of clinical practice; FIB-4 values will be calculated and compared with liver stiffness measurements to evaluate the performance of FIB-4 thresholds for directing patients to FibroScan and hepatology care.

The aim of this randomized interventional trial is to understand the effects of peanut consumption on patients with metabolic associated fatty liver. The main goal is to investigate if patients who consume peanuts have improved liver marker tests as well as metabolic profile. We will also investigate how peanuts alter the gut microbes and liver fat content in patients with metabolic associated fatty liver. * Participants will be randomized into intervention (peanut consumption for 12 weeks) and control (regular diet) arm. * Stool sample and blood (for biomarkers) collection across both arms at baseline and post-intervention * Daily log to be completed for tracking peanut consumption * 2-day Dietary recall at baseline, during Week 6 and Week 12 * Poat intervention Fibro scans for participants with baseline scans available

Metabolic dysfunction-associated steatotic liver disease (MASLD), commonly known as fatty liver disease, is increasingly prevalent worldwide. People living with HIV (PWH) face a higher risk of developing MASLD due to chronic immune activation and long-term antiretroviral therapy, yet whether the underlying biological changes differ from those in HIV-negative individuals with MASLD remains unknown. This prospective observational study will enroll three groups: PWH with MASLD, HIV-negative individuals with MASLD, and healthy controls without liver disease. A single fasting blood sample will be collected from each participant. Using targeted lipidomics, proteomics, and transcriptomics platforms, researchers will compare plasma molecular profiles across the three groups to identify MASLD-specific lipid signatures, characterize metabolic pathway dysregulation, and discover potential blood-based biomarkers for non-invasive diagnosis of MASLD. Findings from this study may help explain how HIV infection alters lipid metabolism in the context of MASLD and support the development of HIV-specific diagnostic tools for fatty liver disease.

Nonalcoholic steatohepatitis (NASH) is a severe subtype of nonalcoholic fatty liver disease (NAFLD) which affects 1 in 3 Americans. The mainstay of treatment for NASH, which was recently renamed metabolic associated steatohepatitis (MASH), involves lifestyle interventions to promote weight loss and to treat comorbidities such as hypertension, hyperlipidemia, and diabetes mellitus. There is thus, a substantial unmet need for pharmacological therapies that are effective for treatment of NASH, especially in those with fibrosis which is the main predictor of disease progression and mortality among NASH patients. The repurposing of presently available drugs would help expedite the search for agents effective in treating NASH. The cardiac glycoside digoxin is currently used in the management of heart failure and supraventricular tachyarrhythmias. The investigators and other groups have demonstrated that digoxin protects the liver from various forms of acute and chronic liver injury. The investigators preliminary data in healthy human subject indicate an immunomodulatory effect of low dose oral digoxin with no adverse side effects. This study proposes to demonstrate the clinical benefits of digoxin on NASH and on liver fibrosis, thus supporting the repurposing of digoxin as treatment for NASH.

Renal dysfunction is a frequent and clinically important complication in cirrhosis, and MASLD/NAFLD is associated with increased risk of incident CKD; however, finerenone has not been specifically studied in MASLD-cirrhosis populations despite proven cardiorenal benefits in diabetic CKD. This monocentric, open-label, randomized controlled trial at the Department of Hepatology, ILBS, New Delhi will enroll 160 adults (18-80 years) with MASLD/NAFLD cirrhosis, clinical grade I-II ascites, and stable eGFR ≥60 mL/min/1.73 m² (MDRD-6), with key exclusions including CTP class C, refractory ascites, significant coagulopathy, intrinsic kidney disease, recent major cardiovascular events, and other protocol-defined contraindications. Participants will receive standard medical treatment (dietary measures, diuretics as indicated, metabolic control, complication management, albumin/beta-blockers as needed) and will be randomized to finerenone (5 mg/day uptitrated to 10-20 mg/day) versus spironolactone (50 mg/day uptitrated to 100-200 mg/day). The primary endpoint is incident CKD at 6 months , defined as sustained eGFR \<60 mL/min/1.73 m² over 3 months. Secondary endpoints include MAKE/MACE/MALO at 6 months, drug-related adverse events (including hyperkalemia, hyponatremia, hypotension, hyperuricemia), AKI/AKD episodes, renal biomarkers (e.g., cystatin C, UPCR), ascites response, liver severity scores (MELD 3.0/MELD-Na/CTP), and metabolic/inflammatory/endothelial markers (e.g., HbA1c, HOMA-IR, hsCRP, vWF). Sample size (n=160; 80/arm) is powered to detect an absolute 20% reduction in CKD progression (35% to 15%) with 80% power and 5% alpha (10% dropout), with intention-to-treat analyses including Kaplan-Meier and Cox regression methods.

This prospective observational cohort study aims to evaluate the association between liver fat fraction measured by ultrasound-derived fat fraction (UDFF) and cardiac functional parameters assessed by 2D and 4D HeartAI in adult patients with metabolic dysfunction-associated steatotic liver disease (MASLD). Participants will undergo baseline assessment and repeat evaluations at 6, 12, and 36 months. The study will assess the diagnostic performance of integrated UDFF-HeartAI analysis for detecting subclinical cardiac abnormalities and identify predictors of cardiovascular risk progression and major adverse cardiovascular events in patients with MASLD.

This research study is being conducted to find out more about techniques to non-invasively evaluate liver disease. This is the second phase of a project in which we are testing a new technology to evaluate the liver (LiverScope®). We will compare LiverScope® to other methods to evaluate the liver, including advanced conventional liver MR exams. MR exams are common exams used to monitor MASLD (also known as NAFLD). Conventional MR scanners use magnetic fields and radio waves to make pictures of the liver. LiverScope® is a small, portable MR-based device that uses similar, but simplified technology, and can be used on top of an exam table in an outpatient setting. LiverScope® currently is not approved for clinical use. In this second phase of the study, we took what we learned in the first phase to optimize the LiverScope® device and are now testing to see how LiverScope® measurements compare to MR after these optimizations. Study participants will be asked to complete a one-time visit which includes: * LiverScope exam * MR exam * FibroScan exam (optional) * Blood draw * Completion of study questionnaires

The overall objectives of this study are to determine the effectiveness of a participant-specific guided electronic decision support system on provider decision making for participants with metabolic-dysfunction associated steatotic liver disease (MASLD), and to determine the acceptance and barriers for use of an electronic health record embedded algorithm for MASLD care management within ambulatory primary care, endocrinology, and general gastroenterology settings.

This research study is being conducted to find out more about advanced ultrasound techniques to non-invasively evaluate liver disease in children. The investigators are developing advanced techniques for analyzing ultrasound data and images of the liver, and they will compare it to other established methods used to evaluate the liver, including liver MRI. The investigators plan to develop and test the advanced analysis techniques using conventional full-size ultrasound machines and, if possible, small handheld devices. Our goals are: * To assess the accuracy of the advanced ultrasound analysis techniques in children * To implement and assess these advanced technique on small handheld ultrasound devices, if possible

The goal of this clinical trial is to learn how the liver responds to sugar in people with obesity who are having bariatric surgery. Researchers want to understand differences between people with and without metabolic associated steatotic liver disease (MASLD). The main question is: Does giving sugar directly into the vein change how liver genes work in people with and without MASLD? Researchers will compare: * People with MASLD who receive sugar * People with MASLD who receive saline (salt water) * People without MASLD who receive sugar * People without MASLD who receive saline During surgery, participants will: * Receive either a sugar solution (35 grams of glucose in 150 mL fluid) or saline * Have small samples (biopsies) taken from the liver and fat tissue before and 45 minutes after the infusion * Provide blood samples to measure sugar, insulin, and other metabolites * Provide a one-time sample of intestinal tissue that is normally removed during surgery This study may help explain why MASLD develops and how the liver reacts to sugar. The results could lead to new ways to understand and treat liver disease in people with obesity.

Americans commonly consume excess amounts of dietary fructose. Added fructose has been shown to have an adverse impact on metabolic health, including increased insulin resistance and type 2 diabetes (T2D) risk. However, the mechanisms that link dietary fructose and metabolic health are poorly understood. Malabsorption or incomplete metabolism of fructose in the small intestine is common in the population. Excess fructose reaches the colon where it may change the structure and function of the gut microbiome, alter bacterial metabolites and trigger inflammatory responses impacting T2D risk. To elucidate whether commonly consumed levels of dietary fructose influence metabolic outcomes through altering the gut microbiome, the research team will randomize 30 participants to a controlled cross-over dietary intervention, in which the participants will consume 12-day isocaloric, added fructose or glucose diets (25% of total calories) separated by a 10-day controlled diet washout period. The research team aims to: 1. Determine the relationships between high fructose consumption, the gut microbiome and metabolic risk. 2. Characterize the causal role(s) that fructose-induced alterations to the gut microbiome have on metabolic risk using a germ-free mouse model. The research team will measure 1) microbiota community structure and function via metagenomic sequencing of stool, 2) fecal metabolites via targeted and untargeted metabolomics, 3) anthropometrics, 4) insulin resistance, serum markers of T2D risk and inflammatory cytokines, 5) fecal microbial carbohydrate oxidation capacity and 6) liver fat via MRI elastography. The research team will use novel statistical approaches, including Distributed Lag Modeling, to understand the complex relationships between diet, the microbiome, metabolites and health outcomes. The research team will then conduct controlled dietary interventions and fecal microbiome transplantation studies in germ-free mice. Donor fecal samples from human participants in both the glucose and fructose arms of the clinical intervention will be transplanted into germ-free and colonized mice to establish a causal relationship between fructose-induced changes to the gut microbiome, liver fat and metabolic and inflammatory changes known to increase risk for T2D. The research team aims to comprehensively assess the structural and functional changes to the gut microbiome brought about by a high fructose diet. Determining the impact of excess fructose on the microbiome will help identify novel means by which fructose contributes to metabolic disease risk. In addition to identifying strategies to improve metabolic health in adults, data from this proposal could help inform targeted approaches to mitigate future disease risk in vulnerable populations that consume high levels of fructose, such as children.

The goal of this clinical trial is to learn whether an artificial intelligence (AI) tool called FibroX can help primary care providers better diagnose significant liver fibrosis (≥F2) and clinically significant portal hypertension in adults with metabolic dysfunction-associated steatotic liver disease (MASLD). The main questions it aims to answer are: * Can FibroX improve the accuracy of diagnosing significant liver fibrosis (≥F2) and clinically significant portal hypertension compared to usual care? * Is FibroX easy to use and acceptable to primary care providers in simulated clinical settings? * Do providers trust FibroX as a decision-support tool? Researchers will compare FibroX-assisted care to usual care to see if FibroX improves diagnostic accuracy, provider trust, and supports better decision-making. Participants will: * Be primary care providers (MDs, DOs, NPs, PAs) from diverse clinics * Review simulated patient cases with MASLD risk factors * Use either usual care tools (standard labs and optional FIB-4 calculator) or FibroX (AI-generated risk score, triage band, and explainability panel) * Make diagnostic and referral decisions for each case * Complete surveys on usability, trust in AI, confidence, and cognitive workload This study will help determine whether FibroX can be integrated into real-world primary care workflows to support earlier and more accurate detection of liver fibrosis and portal hypertension, potentially reducing missed diagnoses, unnecessary referrals, and improving patient outcomes.

The Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) is a leading cause of chronic liver disease globally, with a prevalence exceeding 30% in the population. MASLD is strictly associated with insulin resistance and cardiometabolic conditions, and in 20-30% of cases, it can progress to steatohepatitis (MASH), which is characterized by progressive liver damage and inflammation. In patients at higher risk, the disease can lead to the onset of advanced fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). One of the main problems in the clinical management of MASLD is the absence of specific risk biomarkers and the lack of effective treatments, especially for patients with advanced-stage disease. MASLD has a well-documented and enormous genetic component, with studies having identified several common variants associated with this pathology, such as those in the PNPLA3, TM6SF2, and MBOAT7 genes. However, these variants identified so far only explain a small part of MASLD's heritability, suggesting the contribution of rare loss-of-function (LoF) variants as well. Furthermore, scientific evidence indicates that the accumulation of somatic variants, both in hepatocytes and myeloid cells, could also play a key role in MASLD progression. In particular, clonal hematopoiesis of indeterminate potential (CHIP), which is a condition characterized by the presence of hematopoietic clones with somatic mutations often associated with leukemia and cardiovascular diseases, might favor the onset of hepatocellular carcinoma. However, the evidence available to date is still limited and requires further investigation and studies on larger cohorts. The current study therefore aims to deepen this aspect through the analysis of the genetic profile using a Whole-Genome Sequencing (WGS) approach. DNA samples from peripheral blood from patients with advanced MASLD and peripheral blood DNA samples from controls presenting various associated metabolic risk factors will be sequenced. In addition, 80 liver tissue samples from patients with advanced MASLD will also be sequenced to identify specific somatic mutations. The expected results from this study include the identification of new genetic variants associated with MASLD progression, the improvement of risk stratification through the development of polygenic risk scores, and the identification of potential therapeutic targets. This study represents a fundamental step for understanding the biology of MASLD and could have important clinical implications for disease management.

The goal of this clinical trial is to study the effect of a time-restricted eating (TRE) dietary pattern combined with a time of consumption restriction about the daily portions of fruits and vegetables in people diagnosed with metabolic dysfunction-associated steatotic liver disease (MASLD). The protocol of the study is an intention to treat protocol. The main research questions are: 1. Does compliance in a TRE dietary scheme (positively) affect changes in body weight and body fat mass in people diagnosed with MASLD? 2. Does an additional time restriction on the consumption of fruits and vegetables within the "light-window" of the day affects the metabolism of food contaminants? Participants will be asked to: 1. Adhere to a TRE dietary pattern for 3 months. TRE consists of an 8-hour eating vs 16 hours fasting within the day. First meal of the day should not occur at least an hour after wake-up time and last meal of the day should occur not later than 2 hours before bed-time. 2. Adhere to a further time restricted consumption of a "5-a-day" portions of fruits and vegetables between the "light-window hours" between 9am to 4pm. 3. Visit the Nutrition \& Dietetics Clinic once every month for anthropometric measurements (on 4 time points). 4. Collect and deliver first morning urine samples (on 7 time points). 5. Collect and deliver saliva samples at baseline and at the end of the trial (Saliva collection should occur every 4-hours for 48-hours including fasting collection at baseline and at the end of three months) 5\) Complete a compliance and lifestyle questionnaire questionnaire via telephone interview to the research team every 2 weeks. 6\) Share photos to the research team with the use of an application on time of actual fruit and vegetables consumption, 3-4 times per week throughout the study protocol. Researchers will compare the designed intervention package of this TRE with the Standard of Care (SoC) protocol (based on the international guidelines) that is currently used in daily practice for the management of MASLD.

Non-alcoholic fatty liver disease (NAFLD) is a new condition that has become the most common chronic liver disease in the world and a main cause of liver cirrhosis, liver failure and liver cancer. Obesity and diabetes, conditions that are very common among Veterans are the main risk factors for NAFLD. Therefore, the burden of NAFLD and its complications among Veterans is substantial. However, most VA patients with NAFLD are undiagnosed and untreated, and their care is not consistent with practice guidelines. The NAFLD Clinical Care Pathway (NCCP) intervention seeks to close this major gap in the care of Veterans by automatically identifying patients at risk of NAFLD, calculating their risk scores of having severe NAFLD, and educating the primary care providers on the diagnosis and treatment of NAFLD. This clinical trial will test the benefit of this NCCP intervention against usual care in increasing the rates of NAFLD diagnosis as well as referral to and enrollment in appropriate treatment. The study will also identify barriers and promotors of future NCCP implementation.

This study shall be a prospective, multicenter, single arm, consecutive, interventional study conducted in a post-market setting using commercially available devices. Consecutive, eligible patients with clinical suspicion of MASLD or MASH reporting for an endoscopic ultrasound and liver biopsy for evaluation of fibrosis will be enrolled. EUS Shear Wave Elastography and Attenuation Imaging technologies will be compared to liver biopsy and FibroScan results and other non-invasive fibrosis screening modalities . The data collected during this study will be evaluated in accordance with the procedures set forth in the protocol. The main question\[s\] it aims to answer are: * Establish optimal cutoffs for EUS-SWE in reference to liver biopsies staging system for liver fibrosis * Evaluate the diagnostic performance of EUS-SWE compared to FibroScan (VCTE) and to other non-invasive fibrosis screening modalities (screening scores). Participants will undergo: * Endoscopic Ultrasound with Shear Wave Elastography (SWE) and Attenuation Imaging (ATI) * Liver biopsy * FibroScan

The objective of the study is to evaluate an ultraportable ultrasound device, Hepatoscope, for the non-invasive assessment of hepatic steatosis in patients with metabolic-dysfunction associated liver diseases (MASLD), by comparing its measurements with current diagnostic modalities, such as MRI-PDFF.

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

A generic screening study to establish structural and/or functional baselines of specific organs.

Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) is the most common cause of chronic liver disease worldwide and predominately affects individuals with overweight and obesity, as well as those with type 2 diabetes and cardiovascular disease. Tirzepatide is a medication used to treat type 2 diabetes and obesity. It has also been shown to help with MASLD. The purpose of this study is to study how tirzepatide affects the liver in patients with MASLD. Participants will be asked to: * Take tirzepatide for 12 months. * Come in for clinic visits every 3 months. * Have blood drawn at baseline, 6, and 12 months. * Complete a liver ultrasound at baseline and at 12 months.

This study focuses on developing an explainable machine learning model based on cardiopulmonary interaction characteristics to achieve early prediction of acute lung injury (ALI) in patients undergoing major liver surgery. The research will establish a digital early-warning system for ALI to provide support for clinical diagnosis and treatment decisions, thereby reducing the incidence and fatality rate of ALI.

Diet can play a key role in atherosclerosis and coronary heart disease (CHD), but little interventional data exists, and the mediators of possible anti-atherosclerotic effects of diet are unclear. The investigators will investigate if a healthy Nordic diet (HND) reduces plaque volume, coronary artery calcification (CAC), and plaque inflammation (FAI) in CHD, and examine if changes in gut microbiota may be linked to plaque progression over time. The investigators will also explore if the diet response can be predicted by the metabolic phenotype. In total 150 CHD patients is randomized to a HND rich in unsaturated fat and fibre from plants, or to a "usual care diet" for 18 months. Plaque volume and composition is assessed by CT, and fecal microbiota composition is determined by deep metagenome shotgun sequencing. CHD and metabolic risk factors, liver fat, muscle fat and biomarkers of diet adherence (plasma fatty acids, whole-grain metabolites) are measured. Machine-learning is used to identify diet "responders" on plaque progression, based on the individual microbiome and metabolome. If a HND reduces plaque progression, this would be novel information of clinical importance. Also, if the diet alters microbiota that are linked to plaque progression, this would be of high scientific interest. Finally, potential prediction of the diet-response would open up for more personalized treatment of atherosclerosis.

The aim of this clinical trial is to investigate the development of cardiac decompensation following transjugular intrahepatic portosystemic shunt (TIPSS) implantation in order to draw conclusions for future treatment methods or exclusion criteria prior to TIPS implantation. The main questions to be answered are: How often do symptoms of cardiac decompensation develop over a one year period? What laboratory, clinical or imaging morphological changes are associated with this? In addition to the standardised clinical procedure for TIPSS implantation, participants will undergo 3 cardiac magnetic resonance imaging (MRI), extended echocardiographic examinations (both just before, 3 days after and 3 months after implantation) and laboratory chemistry tests for specific endothelial and inflammatory markers (just before, on the day of implantation, 1 day after, 1, 3, 6 and 12 months after implantation).

In this study the investigators aim is to explore the dynamics of (small) intestinal fructose catabolism in humans and ethanol production in relation to small intestinal signalling pathways and changes in pH, using 13C fructose isotope tracing techniques complemented with direct luminal sampling via small intestinal catheter in biopsy proven MASLD/MASH patients vs healthy (BMI\<25) subjects. Additionally the investigators will repeat the experiment after four weeks of administering omeprazole at a dose of 40 mg twice daily. Omeprazole is a proton pump inhibitor, known to elevate pH from 2-6.