Metabolic Associated Fatty Liver Disease

The goal of this clinical trial is to investigate the sensitivity to glucagon in patients with type 2 diabetes mellitus (T2DM), with and without metabolic associated fatty liver disease (MASLD). The main questions it aims to answer are: 1. Is the sensitivity to glucagon with respect to hepatic FA oxidation and suppression of VLDL-TG secretion impaired in humans with T2DM and MASLD? 2. Is glucagon resistance and MASLD reflected in an aberrated lipidomic/metabolomic profile in blood and adipose tissue? Researchers will compare patients with T2DM with and without MASLD to see if the response to basal and high levels of glucagon differs between the groups. Participants will attend 2 short visits and 1 full-day visit, including: * Body scan (DXA) to check fat and bone composition * MRI to measure liver fat. * Blood tests. * Ultrasound to check liver stiffness and scarring. * Fat biopsies * 8-hour hormone (including glucagon) and tracer infusion * PET-CT scans

Study Objective: to evaluate the efficacy and safety of rifaximin in the treatment of metabolic-associated fatty liver disease (MAFLD), and investigate the underlying mechanisms by which rifaximin influence MAFLD progression. Target Population: patients diagnosed with MAFLD. Intervention: this single-center, single-arm exploratory study will enroll up to 40 eligible MAFLD patients who meet the inclusion criteria, do not meet any exclusion criteria, and provide written informed consent. Participants will receive oral rifaximin at a dosage of 1200 mg/day (400 mg, three times daily) for 24 weeks. Patients will be advised to maintain their usual physical activity and adhere to a recommended dietary plan (e.g., Mediterranean diet). Concurrent therapies such as hepatoprotective agents, lipid-lowering medications, and antihypertensive treatments will remain unchanged, with close monitoring of relevant parameters. No additional prescription or over-the-counter drugs that may affect fatty liver progression or alter gut microbiota composition will be permitted during the study. The primary endpoint will be assessed at 24 weeks. If liver proton density fat fraction (PDFF) remains ≥ 8% after 24 weeks of rifaximin therapy, treatment will be extended for an additional 12 weeks, followed by reevaluation of PDFF changes. The maximum total treatment duration will not exceed 48 weeks. All patients will undergo a 24-week post-treatment follow-up period after discontinuation of rifaximin. Investigational Drug: Rifaximin (Alfa Wassermann S.p.A., Italy).

The purpose of this study is to explore the value of new MR technology in assessing the systemic metabolism, disease status, and prognostic risk of metabolism-related fatty liver disease. By obtaining clinical, imaging, laboratory examination and pathological data of metabolism-related fatty liver disease, image processing software is used to analyze the images, explore the relationship between imaging parameters, body composition and metabolic diseases and metabolism-related fatty liver disease, and achieve non-invasive diagnosis, efficacy evaluation, and prognosis prediction of metabolism-related fatty liver disease. Thereby guiding clinical treatment and improving the prognosis and quality of life of patients with metabolism-related fatty liver disease

The Non-Invasive Biomarkers for Metabolic Liver Disease (NIMBLE) study is a comprehensive, multi-year collaborative effort to standardize, validate and advance the regulatory qualification of blood- and imaging-based biomarkers to diagnose and stage Metabolic dysfunction-associated steatohepatitis (MASH), previously known as nonalcoholic steatohepatitis (NASH). MASH is characterized by liver inflammation accompanied by simultaneous fat accumulation in the liver.

This study aimed to explore the effects of ordinary meal replacements and low-valine meal replacements on the weight and risk of related metabolic diseases in overweight/obese patients through a randomized double-blind controlled clinical trial.

The goal of this clinical trial is to improve the treatment of hepatic steatosis associated with obesity with pharmacological and nutritionnal approaches. The main question it aims to answer is: Does an individualized nutritionnal approach with a dietician combined with medication targeting obesity is the most efficient way to treat hepatic steatosis associated with obesity? Participants will either participate in one of three groups: * Nutrition: Participant will only have a regular follow-up with a registered dietician; * Nutrition + Semaglutide: Participants will start a new medication targeting obesity and will have a regular follow-up with a registered dietician; * Semaglutide: Participants will start a new medication targeting obesity.

In 2019, the number of patients with diabetes was about 463 million in the world, accounting for 8.3% of the total population, and it is expected to rise to 578 million (9.2%) by 2030 and 700 million (9.6%) by 2045. According to the WHO diagnostic criteria, the prevalence of diabetes among adults in China from 2015 to 2017 was 11.2%, of which over 90% were type 2 diabetes mellitus (T2DM). The global prevalence of non-alcoholic fatty liver disease (NAFLD) is also very high, which was approximately 25% in 2016. The prevalence of NAFLD may continue to rise. NAFLD is often accompanied by clinical manifestations of metabolic syndrome, such as obesity, T2DM, hyperlipidemia and hypertension.

Metabolic dysfunction-associated fatty liver disease (MAFLD) is a new concept proposed in 2020. Unlike non-alcoholic fatter liver disease (NAFLD), the diagnosis of MAFLD requires the presence any of the following 3 metabolic risks, including overweight/obesity, presence of diabetes mellitus, and evidence of metabolic dysregulation. However, there are patients that have hepatic steatosis but no metabolic risk, who thus do not meet the diagnostic criteria of MAFLD. Besides, there are patients with both MAFLD and other liver diseases. The clinical features and the management of these patients remain unclear. Thus, further histopathological and clinical study is required to elucidate and compare the characteristics of MAFLD and NAFLD. Here, in this single-center, prospective clinical study, investigators are planning to establish a long-term follow-up cohort of patients with either MAFLD or NAFLD. In order to understand the risk of developing liver-related complications and important extra-hepatic outcomes (e.g. cardiovascular disease), and also to better elucidate the risk of disease progression in "lean" NAFLD individuals without any metabolic dysregulation and MAFLD individuals with dual or multiple causes. Ultimately, investigators aim to improve the diagnosis of MAFLD and improve patients' outcomes.