Active clinical trials for "Fatty Liver"

The first aim of this study is to assess oxidative stress and nutritional status in patients with elevated liver enzymes who were found to have either simple steatosis (SS) or nonalcoholic steatohepatitis (NASH) or normal histological findings on liver biopsy by measuring liver lipid peroxides and tumor necrosis factor (TNF)-α, liver pathology and immunohistochemistry, liver function tests, liver and red blood cell membrane fatty composition, insulin resistance (IR) parameters, plasma lipid peroxides, plasma antioxidant vitamins and antioxidant power, lipid profile, subject demographics, medical history and medication use. The second aim is to detect differences in hepatic gene expression (messenger RNA, mRNA) and epigenetic regulation (micro RNA, miRNA) between patients with SS or NASH and healthy controls, in addition to determine in patients with non-alcoholic fatty liver disease (NAFLD = SS+NASH combined) whether there is an association between hepatic n-3 PUFA content and gene expression. The third aim is to determine the intestinal microbiome (microbial composition and metagenome) in patients with SS or NASH and healthy controls.

In the past decades, obesity in children is much more prevalent in the world. Given the increasing prevalence of pediatric obesity worldwide, fatty liver incidence is on the rise. Genetic variant in apolipoprotein C3 (APOC3) gene is associated with increased liver fat content in adults. The aim of this study is to find out whether APOC3 single nucleotide polymorphism (SNP) influence fatty liver in obese children and adolescent.

The main objective of this study is to analyze the pathophysiological implications of glucagon and the incretin hormones in patients with liver disease (Non alcoholic fatty liver disease (NAFLD) or cirrhosis) with and without diabetes compared with healthy controls. The present study will contribute significantly to the understanding of the pathophysiology of liver disease and glucose metabolism. The final goal is that the results could pave the way for new treatment modalities for patients with liver disease.

The pathogenesis of nonalcoholic fatty liver disease has not been fully elucidated. The most widely supported theory implicates insulin resistance as the key mechanism leading to hepatic steatosis, and perhaps also to steatohepatitis. Selenoprotein P(SeP) is a secretory protein primarily produced by the liver. Previous studies demonstrated that SeP, a liver-derived secretory protein, causes insulin resistance. Therefore, the purpose of this study is to determine the different Sep levels between healthy normal group and NAFLD group.

Hepatitis C virus infection (HCV) is a major health concern in Canada and worldwide. Chronic HCV can cause progressive liver damage leading to inflammation, scarring and, in some cases, cirrhosis or liver cancer. It has been shown that fat accumulation in the liver can accelerate the disease progression and is therefore a risk factor in HCV patients. However, the exact mechanism(s) by which fat accumulation in the liver is involved in disease progression are not clear yet. It is possible that the presence of fat provides a liver susceptible to a second injurious process which leads to scarring. Candidates for this second "hit" may include insulin resistance, leading to accumulation of fat within the liver cells and secondly oxidation of these lipids. In turn, lipid peroxidation can lead to production of reactive oxygen species (unstable molecules that can damage cells) and cytokines (signal molecules that promote inflammation) resulting in more oxidative stress and liver damage. Aim of the study is to find out, whether patients with HCV and fatty liver have increased oxidative stress and inflammation than patients with HCV without fatty liver, and whether this is associated with a different nutritional status.

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in affluent countries. It may progress to cirrhosis and liver cancer. At present, there is no approved drug for NAFLD. Although healthy diet and exercise is often recommended, there is little supportive evidence. Therefore, the investigators plan to conduct a randomized controlled trial comparing a low glycemic index dietary intervention program and simple lifestyle advice in NAFLD patients. The primary endpoint is resolution of NAFLD. Non-invasive tests will be used to assess the study subjects. Proton-magnetic resonance spectroscopy is used to quantify hepatic triglyceride content, and transient elastography is used to quantify liver fibrosis.

In patients with NAFLD/NASH, changes in liver lipid composition and function tests following a short dietary intervention are associated with changes in gut microbiota

Non-alcoholic fatty liver disease (NAFLD) covers a spectrum from reversible hepatic steatosis to inflammation and fibrosis termed steatohepatitis (NASH) and cirrhosis. New evidence indicates that NAFLD is associated with development of heart failure, abnormal ventricular glucose and fatty acid (FA) utilisation and cardiosteatosis. The mechanisms behind cardiac involvement and the progression from NAFL to NASH are poorly understood but must include altered cardiac and intrahepatic lipid handling. In collaboration with renowned research groups from Oxford, Mayo Clinic and Copenhagen we plan comprehensive kinetic studies of heart and liver FA uptake and oxidation, ventricular function and substrate utilisation, and hepatic triglyceride (TG) secretion in order to assess mechanisms governing cardiac and hepatic lipid and glucose trafficking in subjects with NAFL and NASH and the relationship with heart function. In addition, we will assess skeletal muscle and adipose tissue enzyme activities, gene expression and protein concentrations in these subjects to define mechanisms involved in the cross-talk between heart, liver, muscle and adipose tissues. We will address these questions using innovative tracer techniques (11Cpalmitate, 11C acetate, 18FDG glucose PET tracers and TG tracers) in combination with hepatic vein catherisation to study cardiac and liver substrate trafficking, as well as NMR spectroscopy, echocardiography, muscle and fat biopsies in combination with state-of-the art muscle and adipose tissue enzyme kinetics, gene- and protein expression. Effects of acute exercise as well as GLP-1 agonist and SGLT-2 inhibitor treatment (alone and in combination) will be assessed. The overarching goals are to define abnormalities and differences between NAFLD and NASH in hepatic lipid (FA and TG) metabolism and to assess hepatic, adipose and skeletal muscle lipid and substrate utilisation.

Vitamin D deficiency is very common in patients with fatty liver disease as evidenced by our observations in the Metabolic Liver Clinic and that reported by others. We also observed that patients with more severe fatty liver disease had lower Vitamin D concentrations. Others have shown that replacing Vitamin D in patients with cirrhosis is effective and even patients with Vitamin D replete status have lowering of Vitamin D over time if not supplemented. One of the measures of liver injury in NAFLD is the plasma concentration of ALT and we will use this to follow patients as is currently done as standard of care. All patients in the Metabolic Liver Clinic are being routinely screened for Vitamin D deficiency as standard of care and treatment is being started with oral supplementation, but there are not standardized protocols to determine success of therapy. We hypothesize that patients with NAFLD with low Vitamin D levels will respond appropriately to Vitamin D supplementation for 6 months.

The aim of our study is to evaluate the effect of coffee consumption on the risk of severe liver fibrosis in French patients with NASH.