MASH

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.

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.

The purpose of this research study is to validate (check the accuracy of) laboratory assays, intravenous catheter insertion, and equipment or devices and their reproducibility, which is necessary to perform high quality research on chronic diseases, nutrition, and metabolism (the process by which a substance is handled in the body) at the University of Missouri. As technology changes and uses new testing methods, it is necessary to compare results from old tests, equipment and devices and new tests, equipment, or devices and the reproducibility of these measurements to make sure the results are accurate. Reproducibility means performing the same test more than once to see if the same results can be achieved each time. This study will look at the validation and reproducibility of tests and laboratory assays in participants who are healthy or affected by relevant endocrine, cardiometabolic, and musculoskeletal disorders.

Two-part Phase 1/2 study of OPK-88006, including an open-label SAD phase in healthy participants and a double-blind, randomized, placebo-controlled MAD phase in participants with presumed MASH, to evaluate safety, PK, and MASH related pharmacodynamic changes compared to placebo.

Approval study Trans-Duodenal Barrier The goal of this clinical trial is to determin the safety and performance of the newly developed Trans-Duodenal Barrier in adult Tryp 2 diabetic and obese patients. The Trans-Duodenal Barrier is an endoscopic implant which can be placed to the gastric outlet and the upper small bowel by interventional endoscopy. It consists of a 60 cm long foil tube , a transpyloric shaft and and two ringlike balloons to fix it at the pylorus. It will be removed after 6 months via gastroscopy. The main questions it aims to answer are: * Does the Trans-Duodenal Barrier lower the HbA1c of the participants ? * How frequent are adverse side effects related to the device? * How much ist the excessive wight loss of treated patients ? * Show patients with Metabolic assiociated Hepatosteatitis (MASH) improvements in liver elasticity (elastography) ? Researchers implant the Trans-Duodenal Barrier to enclosed patients and follow up them till 4 weeks after explantation. Participants will: * Get the Trans-Duodenal Barrier as an implant for 6 moths * Visit the clinic 3 times in the implant period and once for explant. * Receive a telefon interview 4 weeks after explant

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 goal of this observational study is to establish a unified cohort for retrospective and prospective high quality baseline and follow-up data registration of patients with a diagnosis of NAFLD/NASH/MAFLD, according to standardized criteria. This will allow future studies aimed at elucidate clinical presentation, natural history, response to treatment, genetic and metabolic risk factors, treatment options and outcomes of the disease. The cohort will allow investigators to carry out genetic, serological, microbiologic and immunological studies.

The goal of this clinical trial is to use positron emission tomography (PET) to evaluate and compare the binding of the novel tracer \[68Ga\]Ga-DOTA-Cys-ATH001 in the liver and/or gastrointestinal tract between healthy volunteers and different patient groups including patients with metabolically caused steatohepatitis (MASH), patients with fibrostenotic Crohn´s Disease (CD) and patients with primary sclerosing cholangitis (PSC).The study will also assess the safety of a microdose of 68Ga\]Ga-DOTA-Cys-ATH001 and how it is distributed in different parts of the body. The main questions the study aims to answer are: * What does the uptake of the \[68Ga\]Ga-DOTA-Cys-ATH001 PET-tracer look like in the liver of healthy subjects, and in that of patients with MASH and PSC? * What does the uptake of the \[68Ga\]Ga-DOTA-Cys-ATH001 PET-tracer look like in the GI tract of healthy subjects, and that of patients with fibrostenotic CD? * How much \[68Ga\]Ga-DOTA-Cys-ATH001 PET-tracer can be found in the blood after injection? * How is \[68Ga\]Ga-DOTA-Cys-ATH001 uptake distributed in the body? * What medical problems do participants have when receiving \[68Ga\]Ga-DOTA-Cys-ATH001? Participants will: Receive one administration of \[68Ga\]Ga-DOTA-Cys-ATH001, after which examination with PET is performed. Magnetic Resonance Imaging (MRI) is also used in the study to create a detailed picture of the body and its function which will facilitate the interpretation of the results of the PET examination. A subset of participants will have blood samples collected after the tracer administration to assess the blood levels of the tracer over time. A subset of participants will come back for a second visit where they will receive a second administration of \[68Ga\]Ga-DOTA-Cys-ATH001, followed by PET and MRI. A health check-up is performed before dosing, and a safety assessment will be performed after dosing. A remote follow-up visit is performed the day after the dosing visit.

GRIPonMASH will assist (primary) health care providers clinicians to implement the latest patient care pathway, as described by the European Association for the Study of the Liver (EASL), to identify patients at risk of severe metabolic dysfunction-associated steatotic liver disease (MASLD) and to raise awareness. The primary objective is to implement a transmural patient care pathway, in order to identify patients with MASLD and its progressive form metabolic dysfunction-associated steatohepatitis (MASH) in primary care centres and clinics in 10 European countries.

Steatosis is the building of fat in the liver. Steatotic liver disease (SLD) regroups MASLD (metabolic dysfunction-associated steatotic liver disease) and MASH (metabolic dysfunction-associated steatohepatitis) i.e. MASLD with inflammation. An estimated 30% of the population worldwide has MASLD and 5% of Canadians have MASH. MASH is a leading cause of liver transplantation in Canada. There is no cure for SLD, and the treatment relies on diet, weight loss, and physical activity (PA). Is a counselling intervention to help patients progressively engage in more PA a feasible and acceptable approach? Objectives. This proposal has three primary objectives: 1) To assess the feasibility of our PA counselling intervention (to be delivered online) with SLD patients; 2) To evaluate the acceptability of our intervention; 3) To evaluate the feasibility of the study methods/procedures. Methodology. This study is an open-label, mono-centred, single-case experimental design with multiple base levels. The study will comprise 3 phases, alternating periods of observation (A) and 1 period of counselling (B) with an A1-B-A2 design. PA will be assessed continuously using an accelerometer for 7 to 14 days per (A) phase. During phase (B), participants will receive the intervention, i.e. 6 x 45-minute, real-time, face-to-face, virtual sessions with a PA counsellor. Based on past studies, our sample size will be 12 participants. They will be recruited through the hepatology clinic at Hôpital Montfort. The primary outcomes of the project are to evaluate the feasibility and acceptability of the trial and intervention. The secondary outcomes are Daily PA time and biological/imaging data evolution