Active clinical trials for "Liver Diseases"

Investigators wishes to influence the gut microbiota in patients with alcoholic liver disease in a randomized controlled clinical trial. The investigators hypothesize that the alcohol-related dysbiosis seen in these patients can be changed and disease progression haltered by modulating microbiota with probiotics during 24 weeks.

Human microbiota is the set of microorganisms that, in a symbiotic way, coexist and develop in the different surfaces (skin and mucous membranes) of the human body. It is estimated that it is composed of approximately 10^14 bacteria and other unicellular life forms . The gastrointestinal (GI) tract is the organ in which the microbiota reaches its greatest complexity, influencing its metabolic activities in different organs and human systems. Human microbiota plays a role in multiple homeostatic and physiological functions including energy and intermediary metabolism, normal immune responses, and even appropriate bowel development and nervous system functioning. Given its vascular supply, the liver plays important roles in metabolism and immunological functions. It receives 70% of blood supply through the portal vein which carries all metabolic products derived from GI microbiota. Non alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in developed countries (with an estimated prevalence around 25 - 40% of adults) and it is expected that the burden of disease will increase in the near future. This condition can progress through a spectrum of progressive liver damage to non alcoholic steatohepatitis (NASH), liver fibrosis, cirrhosis and liver cancer. Around 20-30% of NAFLD patients develop NASH, with a lower rate progressing further to fibrosis and cirrhosis. Currently, there is no approved pharmacological or interventional treatment for the management of this so prevalent disease, apart from changes in lifestyle aiming weight loss. The aim of the present pilot study is to assess the efficacy and safety of microbiota manipulation by means of Fecal Microbiota Transplantation in the treatment of patients with NASH.

Liver cells play a major role in the regulation of lipid metabolism. They are the principal location for lipoprotein and cholesterol synthesis. In healthy individuals an equilibrium is preserved between utilization, biosynthesis and transfer of lipid fractions. Many diseases that affect the parenchyma of liver can lead to changes in the structure of lipoprotein and transport through blood. Non - alcoholic fatty liver disease (NAFLD) is an abnormal accumulation of fat in the liver in the absence of secondary causes of fatty liver, such as significant alcohol use, viral hepatitis or medications that induce fatty liver. NAFLD is the most common liver disorder worldwide and is present in approximately 25%of the world's population [3]. People with NAFLD often have no symptoms and NAFLD is often only detectable during routine blood tests or unrelated abdominal imaging or liver biopsy [4].in some cases NAFLD can cause symptoms such as fatigue, malaise and dull right upper quadrant abdominal discomfort. Non - alcoholic steatohepatitis can severely impair liver functions leading to cirrhosis, liver failure and hepatocellular carcinoma. Grading of NAFLD on ultrasound: when the echogenicity is only marginally increases, it is grade 1, when the echogenic liver obscures the echogenic walls of portal vein branches, it is grade 2, and when the echogenic liver obscures the diaphragmatic outlines, it is grade 3 fatty infiltrations.

Metabolic associated fatty liver disease(MEFLD) is a major chronic liver disease that can lead to various adverse events, such as liver cancer, cardiovascular disease, and chronic kidney disease. The present community-based cohort study enrolls subjects who take health physical examinations at the sub-center outpatient department, Beijing Friendship Hospital. Investigators collect their baseline information, including demographic data, clinical history, physical examination, laboratory results, imageological examination, and so on. Follow-up surveys are conducted annually and the information collected is the same as the baseline. The outcome information, including cardiovascular disease, malignancy, liver cirrhosis, liver decompensation, liver transplantation, and all-cause mortality, are obtained by linking to the hospital discharge database and death registration system of Beijing. The primary aim of the study is to build a risk-stratified evaluation system for MAFLD through the cohort.

The investigators seek to analyze the samples provided by patients with obesity-associated fatty liver disease at the multi-omics level and to integrate the results with clinical information, genotypic variants, and factors influencing inter-organ crosstalk. The main aim is to improve the interpretation of fatty liver disease associated with obesity and diabetes by developing predictive models built with algorithms from artificial intelligence. The challenge is to decipher the flow of information by exploring contributing factors, proximate causes of regulatory defects, and maladaptive responses that may promote therapeutic approaches.

Background: In Fontan Associated Liver Disease (FALD), congestion of blood in the liver causes cirrhosis. This condition can cause death. Researchers want to understand what triggers this process and find new treatments for it. Objective: To understand how long-term congestion of blood in the liver causes liver scarring that eventually leads to cirrhosis. Eligibility: People aged 18 and older who are at risk of developing FALD from the Fontan procedure. Design: Participants will be screened with: Medical history Physical exam Blood and urine tests Liver ultrasound. This uses sound waves to take pictures of the body. Participants will have an outpatient visit within 12 weeks after screening. Within 24 weeks later, they will have a 3-day hospital stay. About 2 weeks later, they will have a follow-up visit. Visits will include repeats of the screening tests and: Heart tests Stool collection Questionnaires MRI of the liver. Participants will lie on a bed that slides in and out of the scanner. They will receive a contrast agent injected into a vein. While in the scanner, they will also have an MRCP to view the bile ducts and the pancreatic duct. Fibroscan exam. This is an ultrasound that uses a special probe to look at the toughness of the liver. Upper endoscopy. This uses a thin scope to look inside the upper digestive tract. Liver biopsy. This will be taken through large vein in the neck or through the chest. Just before the biopsy, participants will have pressure measurements inside their liver. For this, a catheter will be inserted into a neck vein and guided into the liver.

People with liver disease report difficulties with attention and problem-solving skills. Diet plays an important role in the development of liver disease and/or pre-diabetes. The purpose of this study is to examine whether participation in a brief diet intervention (up to 3 weeks) can improve brain and liver health and function.

Non-alcoholic fatty liver disease (NAFLD) is a multifactorial disease affecting a quarter of the world population. Pathological accumulation of fat, into the hepatocytes, is the first hit and is due to altered hepatic and extrahepatic lipogenesis, lipolysis and lipophagy of the large lipid droplets. Lipophagy plays a key role in the onset of NAFLD, in the autolysosomes, small droplets of fat are catabolized by Lysosomal Acid Lipase (LAL) enzyme which hydrolyzes cholesterol esters and triglycerides forming cholesterol and free fatty acids. Our research group demonstrated that, subjects affected by NAFLD, present a reduced enzymatic activity either compared to patients with chronic liver disease of different etiology, but comparable staging, either compared to healthy control subjects. Leukocytes are the main site of enzymatic activity in the blood, however, our research group has shown that it can also be detected inside the platelets, demonstrating how the LAL activity can be exchanged between cells. Furthermore, our group has shown, for the first time, how the intracellular enzymatic activity is reduced, independently of the platelets and leukocytes count and progressively from chronic liver disease up to cirrhosis. Among factors which contribute to altered lipid metabolism, the genetic predisposition to the accumulation of hepatic fat must be counted. Several variants of genes that code for proteins implicated in the digestion or storage of fats, are involved. In this study were considered: patatin-like phospholipase domain-containing 3 (PNPLA3), Transmembrane 6 superfamily 2 (TM6SF2) and 17β-Hydroxysteroid dehydrogenase type 13 (HSD17B13). The rs738409 variant (C> G, p.I148M) of the PNPLA3 gene consists of a protein in which the catalytic site is not entirely accessible to the substrate which, consequently, accumulates in the storage site. This variant is commonly found in NAFLD subjects and it has been widely reported how the variant carriers progress faster towards severe disease (steatohepatitis) than wild type subjects. The TM6SF2 gene encodes a membrane transporter involved in the triglycerides movement, the rs58542926 (C> T E167K) variant has been associated with an increased predisposition towards liver fibrosis in NAFLD subjects. This is likely due to the loss of protein function resulting in hepatic retention of triglycerides and cholesterol. Unlike PNPLA3 and TM6SF2, the rs72613567 (TA> TAA) variant of the HSD17B13 gene has a protective effect against NAFLD progression. It is characterized by a protein loss of function that protects against chronic liver damage and mitigates the progression of the disease although how the protective effect occurs is still under study. Due to the multifactorial etiology of the disease, to the need of carrying out a targeted surveillance in predisposed genetic subjects and, in order to prevent NALFD progression towards severe pathological forms characterized by an increased mortality, in this study, 316 subjects will be enrolled. They will be divided as follows: Italian Caucasians, aged> 18 and <70 years, with non-cirrhotic NAFLD and carriers of the PNPLA3 I148M variant, and, 158 Italian Caucasian subjects, aged> 18 and <70 years, with non-cirrhotic NAFLD and carriers of the wild type allele. The following exclusion criteria will be considered: any type of malignant disease in the past 5 years, any type of inflammatory or autoimmune disease, corticosteroids for systemic use, any type of drug that may affect body weight or body composition, insufficiency kidney (GFR <90 mL / min), heart failure (NYHA classes II-IV), any type of liver disease rather than NAFLD, excessive alcohol intake (> 140 g / week for men and 70 g / week for women), participation in a weight reduction program in the past 3 months, bile salts, cholestyramine in the last 6 months prior to enrollment, previous cholecystectomy, gallbladder disease. Peripheral blood will be withdrawn in order to measure haematic lipids (total cholesterol and fractions, triglycerides), total blood LAL activity, to perform genetic analysis and finally to evaluate lipase activity into the platelets. Hepatic elastography will be also executed, in 100 patients, according to the presence/absence of the PNPLA3 variant, in order to weigh up the genetic predisposition on NAFLD development or progression Finally, in subjects who present a lipase activity 30% lower than the normal value (0.88 ± 0.38 (mean ± SD), the methylation of the LIPA promoter will be studied.

Prospective, observational study to define precipitants and predictors of development of Acute-on-Chronic Liver Failure (ACLF) after surgical interventions, allowing to develop a risk stratification for elective procedures in cirrhotic patients. As well as identifying molecular mechanisms of post-interventional ACLF and thus preparing the ground for development of new therapeutic approaches.

Non-alcoholic fatty liver disease (NAFLD) has become a major health problem worldwide with an increasing prevalence ranging from 13% in Africa to 42% in South-East Asia. The term NAFLD includes a variety of diseases, ranging from liver fat deposition in more than 5% of hepatocytes (steatosis-non-alcoholic fatty liver (NAFL)) to necroinflammation and fibrosis (non-alcoholic steatohepatitis (NASH)), which can progress into NASH-cirrhosis, and eventually to hepatocellular carcinoma 1 Lifestyle modifications remain the cornerstone of NAFLD treatment, even though various pharmaceutical interventions are currently under clinical trial. Among them, sodium-glucose co-transporter type-2 inhibitors (SGLT-2i) are emerging as promising agents. Processes regulated by SGLT-2i, such as endoplasmic reticulum (ER) and oxidative stress, low-grade inflammation, autophagy and apoptosis are all implicated in NAFLD pathogenesis 2 In non-DM patients, only a small single center study exists which studied 12 patients under dapagliflozin and 10 patients under teneligliptin, a DPP4 inhibitor, for a total of 12 weeks, showing that after this intervention period, serum transaminases were decreased in both groups, while in the dapagliflozin group, total body water and body fat decreased, leading to decreased total body weight.3