Nash

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 researchers want to learn how androgens, a type of sex hormone, might affect nonalcoholic fatty liver (NAFLD) in young women over time. NAFLD happens when fat builds up in the liver which can cause damage to the liver such as inflammation or scarring. Young women with a condition called polycystic ovary syndrome (PCOS) have a high risk for NAFLD, and they often have high androgen levels too. So the researchers are recruiting young women with PCOS as well as those without PCOS, and will compare changes in NAFLD over time between young women with and without PCOS. This study is funded by the National Institutes of Health

This project aims to evaluate the roles of the autonomic nervous system (ANS) and gut microbiota as correlates of clinical improvement in metabolic dysfunction-associated fatty liver disease (MAFLD) and non-alcoholic fatty liver disease (NAFLD) in response to a therapeutic regimen comprising resistance exercise and probiotic supplementation. The primary objective is to investigate the effects of these non-pharmacological interventions on MAFLD/NAFLD and to identify patient phenotypes based on baseline ANS profiles and gut microbiota composition that predict clinical responses.

The goal of this clinical trial is to learn if CS060380 tablets works to treat non-alcoholic steatohepatitis(NASH) in adults.It will also learn about the safety of CS060380 tablets.The main questions it aims to answer are: * After 12 weeks of administration, what was the percentage change in fat content evaluated by MRI-PDFF compared to the baseline？ * What medical problems do participants have when taking CS060380 tablets? Researchers will compare CS060380 tablets to a placebo (a look-alike substance that contains no drug) to see if CS060380 tablets works to treat NASH. Participants will: * Take CS060380 tablets or a placebo every day for 12 weeks * Visit the clinic for checkups and tests at the frequency required by the protocol * Keep a diary of their symptoms and the number of tablets taken

Hepatocellular carcinoma (HCC) is the fifth most common solid cancer and the second cause of cancer-related mortality worldwide. Nonalcoholic fatty liver disease (NAFLD), that is hepatic accumulation of fat in excess of 5% not explained by at risk alcohol intake, is projected to become the leading cause of HCC in Western countries within 2025.NAFLD is most frequently caused by insulin resistance due to unhealthy lifestyle. Due to the epidemics of obesity and type 2 diabetes, NAFLD now affects one in three individuals worldwide. NAFLD-HCC frequently develops without overt cirrhosis suggesting that steatosis directly promotes hepatic carcinogenesis.

First-in-human, single centre, two parts, dose-escalation, parallel-group, safety, tolerability, pharmacokinetic and pharmacodynamic Phase I study. Part A: randomised, double-blind, placebo-controlled, single ascending dose study. Part B: open label, multiple ascending dose study.

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.

The prevalence of Metabolic dysfunction-associated steatotic liver disease (MASLD) and its severe form, Metabolic dysfunction-associated steatohepatitis (MASH), is high and they are increasingly becoming major causes of cirrhosis, hepatocellular carcinoma (HCC), and the need for liver transplantation. Due to the lack of noticeable symptoms during the early stages, the detection of MASLD is often delayed until the disease has advanced. Currently, the treatment options MASLD are limited to lifestyle interventions such as dietary changes and physical activity. Despite the increasing prevalence of MASLD, there are no drugs available on the market specifically for this condition. The goal is to made new model care which integrates the standard clinical procedures with a digital approach, namely a mobile application for patients and a clinical dashboard for healthcare professionals (HCPs), integrated with simple clinical data (anthropometric, laboratory and imaging data). This study wants to test the feasibility of integrating a digital intervention to improve the patient engagement and linkage to care in order to identify the advanced MASLD at earliest stage (secondary prevention) and mitigate the impact of ongoing advanced liver disease helping patients to manage the long-term effect of disease. To achieve this goal the study will leverage on a mobile app named OpenTele in order to test the adherence to lifestyle changes in patient with MASLD and on the connected clinical dashboard. The app aims at integrating the standard clinical practice with digital technologies able to guide and support patients in order to seamlessly integrate secondary prevention strategies in their everyday life with 2 main aims: * to implement a strategy for delay progression of liver disease; * to reduce the effect of cirrhosis (tertiary prevention).

Non-alcoholic fatty liver disease (NAFLD) is responsible for a significant proportion of liver-related deaths and healthcare costs in the United States, accounting for approximately 36% of liver-related deaths and over one billion dollars in annual healthcare expenses. \[PMID: 34863359\] A recent analysis of healthcare costs in Italy showed that out of the 9,729 NAFLD/NASH patients who were hospitalized and analyzed, the vast majority (97%) did not have advanced liver disease, while 1.3% had compensated advanced liver disease (cACLD), 3.1% had decompensated cirrhosis, 0.8% had hepatocellular carcinoma, and 0.1% underwent liver transplantation. The burden of comorbidities was high across all patient cohorts, and patients with cACLD required a greater number of inpatient services, outpatient visits, and the pharmacy fills compared to those without advanced liver disease. As disease severity increased, mean total annual costs also increased primarily due to higher inpatient services costs. In Italy, as in other EU countries, most of the healthcare costs for patients were attributed to NAFLD/NASH-related liver complications. Thus, the optimization of the non-invasive diagnosis of cACLD represents an urgent need in dysmetabolic liver disease. These advancements will play a crucial role in early detection, risk stratification, and effective management of highly prevalent liver diseases such as NAFLD/NASH and their progression.

This study will evaluate the efficacy and safety and the best effective dose of HuHuangLianzonggan capsule in subjects with nonalcoholic steatohepatitis.

It is an observational study of NASH patients with a calculated sample size of 220. Liver biopsy-proven NASH fibrosis with stage F2-F4 will be recruited in this study. A second biopsy will be performed after clinical trials or 1-3 years of lifestyle intervention. Patients will be followed up at baseline and every six months with h-CRP, liver function tests, fasting blood glucose, fasting insulin, ferritin, liver ultrasonography, and liver stiffness measurements.

The purpose of the KETONASH study is to evaluate, in patients with metabolic-associated fatty liver disease (MAFLD) with non-alcoholic steatohepatitis (NASH) and significant liver fibrosis, the effect of a very low-calorie ketogenic diet (VLCKD) compared to that of a standard low-calorie diet (standard Mediterranean LCD - in accordance with the European Association for the Study of the Liver/European Society for Clinical Nutrition and Metabolism guidelines on MAFLD/NAFLD).

The investigators hypothesize that weight loss obtained with the French RNPC weight reduction program is beneficial for the general health of overweight/obese patients in the medium term. The objective of this cohort study is to demonstrate the effectiveness of the RNPC program on the reduction of drug or instrumental treatments (for example, continuous positive pressure ventilation for the treatment of sleep apnea syndrome) and the improvement of overweight/obesity-associated comorbidities in the medium term. This is a multicenter clinical study, as part of routine care, with standardized nutritional care (RNPC Program) in all RNPC centers in France. A cohort will be formed based on the clinical and biological data usually collected in the centers, enriched by data from additional clinical and biological examinations as well as by self-questionnaires completed by the participants. About 10,000 overweight or obese participants will be included for 2 years and followed 5 years. The SCOOP-RNPC study will have benefits for individual participants, for the scientific community in terms of knowledge acquired and for society with a better definition of the impact of treatments. Responding to the major public health issue represented by overweight, this prospective cohort of overweight or obese patients will make it possible to evaluate, in real-life conditions, the effects of weight loss obtained by the RNPC Program in the short, medium and long term on biological parameters predictive of cardiometabolic risk, drug consumption, quality of life, diet and eating behavior, sleep, physical activity, stress/anxiety, as well as depression. This cohort will make it possible to identify clinical phenotypes and biomarkers to optimize the personalization of the management of overweight or obese patients, in particular those at risk of developing comorbidities associated with excess weight.

The European NAFLD Registry is a prospectively recruited, observational study supporting the study of the clinical phenotype, natural history, disease outcomes and pathophysiology of Non-Alcoholic Fatty Liver Disease and Non-Alcoholic Steatohepatitis. The ultimate goals are to better understand the drivers of interpatient variation in disease pathophysiology and severity and to utilise this information to develop and validate biomarkers that, singly or in combination, enable detection and monitoring of disease progression and/or from NAFL through NASH to fibrosis and cirrhosis.

The main objective of this cohort study is to determine genetic, clinical biologic and metabolic factors associated with patient heterogeneity in regards to severity of NAFLD at diagnosis as well as during the clinical course. * at diagnosis, with the aim to better characterize patients of different severity and improve our understanding of clinical and histological heterogeneity at diagnosis * during the clinical course to better understand and predict disease progression in terms notably of fibrosis progression and progression to cirrhosis