NASH - Nonalcoholic Steatohepatitis

This is a multi-center evaluation of efruxifermin (EFX) in a randomized, double-blind, placebo-controlled study in subjects with compensated cirrhosis due to NASH/MASH.

Participants meeting study entry criteria are randomized with equal probability to one of two study groups: (1) Lifestyle modification or (2) Vertical Sleeve Gastrectomy (VSG) with Iifestyle modification, followed for 12 months. The primary goal for the trial is to determine if the investigators can recruit, randomize, and retain participants to perform invasive and non-invasive measurements of NASH and fibrosis, deliver lifestyle modification and demonstrate the safety of VSG. The investigators wish to also understand which of these two interventions is more effective in achieving, 12 months after entry into the trial, a reduction in NAS composed of the non-weighted scores: (1) steatosis 0-3 (2) Inflammation 0-3 and (3) ballooning 0-2. Secondary goals include comparing the two treatment groups for changes in other measured outcomes including MRI assessments of intrahepatic triglyceride and liver elasticity and serum markers. As a pilot study, a sample size of 20 in each group should offer significant information as to the difference in NAS score reduction between to two groups and achieve adequate power to distinguish clinically significant changes in the primary and secondary outcome measures. These data support the overarching objective i.e. to provide evidence that a larger, longer-term clinical outcomes trial is feasible. A goal is for a longer term follow up for 5 years to assess the durability of treatment effects and treatment differences.

To evaluate, in patients with suspected NASH referred for liver biopsy, the diagnostic performance of CT1 at discriminating those with NAS≥4 \& F≥2 from those without.

The aim of the study is to demonstrate the superiority of bariatric surgery on the disappearance of NASH without worsening of fibrosis in comparison to medical standard treatment in obese patients (35 kg/m² \> BMI ≥ 30 kg/m²) with NASH complicated of advanced fibrosis (F3 and F4 fibrosis grade according to Brunt score).

The primary objective of the study is to compare the changes in serum ALT level among patients with non-alcoholic steatohepatitis (NASH) following 3-month treatment of 800 mg SNP-610 or the placebo. The secondary objectives will be to compare the changes in liver fat fraction, other liver function tests, cytokeratin-18 (CK-18) fragment level and adverse event / serious adverse event rates among the interventional and placebo arms.

This study is being done to better understand the relationship between inflammation in adipose tissue (AT), abnormal deposition of fat around the liver and how this affects its appearance and function and ultimately insulin resistance.

Non-alcoholic fatty liver disease (NAFLD) is a growing epidemic in the United States. Despite this, the treatment options remain limited. Preclinical and preliminary clinical data suggest that estrogen deficiency plays an important role in the pathology of steatosis, inflammation and fibrosis in non-alcoholic steatohepatitis (NASH), the progressive form of NAFLD. Post-menopausal women are a growing population with particularly high risk of NASH due to their lack of estrogen. This study will examine the effect of estradiol on hepatic fibrosis and fat in post-menopausal women with NASH.

Objective of the study Our working hypothesis is that platelets activated by gut-derived metabolites dock in the liver of NAFLD patients and amplify the inflammatory state by releasing pro-inflammatory cytokines/chemokines, which in turn recruit and activate leukocytes in the liver sinusoids. Combined stimuli from leukocytes and platelets would then lead to metabolic reprogramming of hepatocytes, progression to NASH and eventually cirrhosis. To test this hypothesis, the investigators propose 2 objectives. Primary objective: To identify platelet features that correlate with liver disease progression. Secondary objective: To study the mechanistic relationship between gut dysbiosis, metabolome composition, inflammation, and platelet activation in chronic liver disease.

Subjects with biopsy-proven NASH will be randomly assigned in a 2:1 ratio to oral doses of namodenoson 25 mg every 12 hours or matching placebo every 12 hours for 36 weeks. Subjects will be evaluated regularly for safety, and efficacy biomarkers will be measured at Baseline and Weeks 6, 12, 24, and 36. At Week 36, all subjects will undergo liver biopsy.

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

The main aim of the study is to set up an observational cohort with NAFLD (Non-alcoholic fatty liver disease) at different stage of disease (from simple steatosis to cirrhosis and/or HCC-Hepatocellular carcinoma) and for comparative purpose a cohort of subjects with diabetes and/or obesity and/or other risk factors (i.e. psoriasis, IBD (inflammatory bowel disease), dyslipidemia) without NAFLD in order to have a clinical phenotypical characterization and the collection of biological specimens. We will collect clinical data, biological samples and imaging results in order to perform future cross-sectional studies and/or longitudinal studies for elucidating pathways of the disease and develop and validate biomarkers for diagnosis, prognosis and monitoring liver disease and comorbidities in order to contribute to precision medicine in this field.