NASH and Type 2 Diabetes: Role of the Receptor Activator of Nuclear Factor-κB (RANK) and Its Ligand...
Diabetes type2NASH - Nonalcoholic Steatohepatitis1 moreNon-alcoholic fatty liver diseases (NAFLD) include several entities ranging from simple steatosis to hepatic fibrosis or cirrhosis. Steatosis, considered benign and the first stage of the disease, is characterized by the accumulation of triglycerides in the liver. It may in some cases progress to nonalcoholic steatohepatitis (NASH), which is characterized by the presence of a marked inflammation with or without fibrosis. NAFLD is the most common liver disease in the world and is particularly associated with type 2 diabetes (T2D) (80% in the diabetic population). While NASH is characterized by a higher prevalence of mortality from a cardiac and hepatic (cirrhosis and cancer) origin, therapeutic resources are almost non-existent. RANK (receptor activator of NF-kB) and its ligand RANKL (a member of the TNFalpha family) have emerged in recent years as new players in bone pathophysiology. By binding to its receptor, RANKL induces a number of signaling pathway and in particular the NF-kB pathway (Nuclear factor-kB), a major player in inflammation. Recent literature shows that the role of RANK / RANKL is not confined to the bone but may be involved in the genesis of inflammation in other tissues. It has been shown recently that a high circulating level of RANKL was a risk factor predictor of T2DM. Furthermore, the invalidation of RANK specifically in hepatocytes protects from insulin resistance and hepatic steatosis induced by a high fat diet in mice. The aim of our project is to provide a proof of concept that the RANKL / RANK system plays an important role in the pathogenesis of NAFLD and in the progression of this disease to NASH. The aim of our project is to provide a proof of concept that the RANKL / RANK system plays an important role in the pathogenesis of NAFLD and in the progression of this disease to NASH. The investigator propose to study the RANKL / RANK expression in serum and liver biopsies of type 2 diabetic patients at different stages of NAFLD.
Evaluation of Pancreatic Steatosis in Patients With Cancer of Pancreas
Cancer of PancreasPrognostic Importance of Quantitative Magnetic Resonance Imaging for Evaluation of Pancreatic Steatosis in Patients with Pancreatic Cancer
Role of New Adipokines and Hepatokines in Prediction of Patients With Metabolic Syndrome or NAFLD...
Non-alcoholic Fatty Liver DiseaseType 2 Diabetes1 moreTo investigate the predictive roles of adipokines and hepatokines to detect non-alcoholic fatty liver disease (NAFLD), diabetes, or dyslipidmia. To examine the association or effects of clinical and biochemical factors (lab results and medication, etc.) on serum levels of adipokines and hepatokines in certain subjects with non-alcoholic fatty liver disease (NAFLD), diabetes, or dyslipidmia.
THE ASSOCIATION BETWEEN FATTY LIVER (NAFLD) DISEASE AND PCOS
Polycystic Ovarian Syndrome,Nonalcoholic Fatty Liver DiseaseSince both pathologies (PCOS and NAFLD) involve disturbed carbohydrate economy, which revolve around insulin resistance, it is tempting to examine the specific "liver profile" of women with PCOD. Furthermore, it would be of great importance if lean women who suffer from PCOD would be revealed to shere cardiovascular risks with their more overweight peers. Patients - women who will be diagnosed with PCOD following their initial referal to our fertility clinic. Controls - normal ovulatory women who approached our fertility clinic due to either unexplained or male factor infertility. Workup - history for menstrual pattern; Clinical evaluation for features of hyperandrogenism; ultrasonographic documentation of ovarian morphology; follicular phase hormonal profile for validation of the diagnosis and for ruling out other pathologies which may cause anovulation. Liver profiling - The following blood tests will be used for the biochemical profiling: fasting glucose and insulin, CRP, HDL-cholesterol, triglycerides, AST, ALT, GGT, LDH, alkaline phosphatase, total bilirubin, direct bilirubin, ferritin, HBA1C and micro albumin ratio. FibroScan® will be used to measure liver stiffness.
Development of Kinetic Biomarkers of Liver Fibrosis Measuring NAFLD
Non-alcoholic Fatty Liver DiseaseThis is a small preliminary study conducted to explore new methods for the potential of aiding in diagnosis of liver fibrotic disease as well as predicting disease progression. There will be a total of 4 visits spread out over approximately 8 weeks. You will be asked to drink "heavy water" during most of that time. "Heavy Water" also known as deuterated water, is physically and chemically very similar to ordinary drinking water. It tastes and feels exactly like regular water. It is odorless and has no known harmful effects at the doses given here. Heavy water occurs naturally, and is a minor component of the water we all ingest daily.
Hepatic Histology and Metabolism Following Total Pancreatectomy and Pancreaticoduodenectomy
Total PancreatectomyPancreaticoduodenectomy4 moreThe objective of the study is to investigate the development of NAFLD following total pancreatectomy and pancreaticoduodenectomy and to explore the histological and metabolic changes following the procedures.
Genetical Background of Non-alcoholic Fatty Liver Disease (NAFLD) in Diabetes Mellitus and in Chronic...
Non-alcoholic Fatty Liver DiseaseChronic Kidney Disease1 moreThe present study investigates relationship between non-alcoholic fatty liver disease and its risk factors, such as genetic background and diseases, such as chronic kidney disease and diabetes mellitus.
NASH: Non-invasive Diagnostic Markers and Imaging
Nonalcoholic Fatty Liver DiseaseNonalcoholic SteatohepatitisRationale: Non-alcoholic fatty liver disease (NAFLD) is the most widespread liver disorder in Western society (prevalence 20-30%). It is strongly associated with overweight and obesity. The majority of patients have simple steatosis. However, in about 15-30% of the subjects, a chronic inflammatory state develops that is referred to as non-alcoholic steatohepatitis (NASH), which leads to an overall increase in morbidity and mortality due to the progression to fibrosis, cirrhosis and in some cases, hepatocellular carcinoma (HCC). The term NAFLD comprises both simple steatosis and NASH. Most patients with NAFLD have no or few, mainly aspecific symptoms; and generally there is a silent progression of simple steatosis to NASH and in the end, liver-related morbidity and mortality. To date, liver biopsy is the most sensitive test for detecting and staging NAFLD, and is the only reliable method for differentiating between NASH and simple steatosis. However, the procedure of obtaining a liver biopsy is invasive and associated with patient discomfort, significant complications and high costs. In addition, liver biopsy is prone to sampling error and inter- and intra-observer variability, due to the small size of liver biopsy samples. This method is therefore not suitable for screening large numbers of subjects at risk, or for follow-up of patients with NASH over time. Hence, only subjects at high risk (usually based upon elevated aminotransferase levels, which is not specific for the presence of NASH) are biopsied, leading to an underestimation of NASH prevalence and undertreatment. Further insight into disease mechanisms and risk factors for NAFLD and in particular NASH is warranted, to enable early diagnosis, adequate therapy and preventive measures to improve health status of these individuals. Accurate and less invasive methods to evaluate NASH, and NAFLD, are urgently needed. Objective: The primary objective of this study is to establish non-invasive tools (e.g. biomarkers and imaging) to accurately diagnose patients with NASH. The secondary objective is to show an association between the levels of identified markers and disease severity. Study design: Eligible subjects will be included via the outpatient clinics Zuyderland in Heerlen, the Catharina hospital in Eindhoven and MUMC+ in Maastricht. A subset of eligible subjects has undergone a liver biopsy for clinical reasons. It is estimated that about 85% of subjects will be asked to undergo a biopsy for study purposes only. Liver biopsies for study purposes will be performed during a surgical procedure, e.g. bariatric surgery or cholecystectomy. Blood, faeces and exhaled air will be collected and a FibroScan (+CAP) will be performed during a study visit. An MRI will be performed, to estimate the degree of steatosis. Furthermore, anthropometric data (weight, height, abdominal and waist circumference and blood pressure (BP)) will be collected. The participants in the group undergoing liver biopsy during bariatric surgery will be asked permission to be approached for follow-up measurements 3 months post-surgery. As they will lose weight, which is associated with improvement of hepatic steatosis, this enables assessment of possible changes over time. A routine follow-up visit post-surgery will take place after 3 months. The follow-up measurements will be combined with this visit, minimizing the burden for the participant. The measurements will consist of blood, faeces and exhaled air collection and a FibroScan (+CAP) will be performed during a study visit. Furthermore, weight, height, BP and abdominal and waist circumference will be measured. Study population: Subjects with proven NAFLD by histology or NAFLD proven by imaging, who are undergoing surgery (i.e. bariatric surgery or cholecystectomy) will be asked to participate in this study. Furthermore, all subjects have to be between 18 and 65 years old. Main study parameters/endpoints: Non-invasive tool based on biomarkers and imaging to diagnose NASH.
Role of Regulatory B Cells in the Pathogenesis of Metabolic Associated Fatty Liver Disease
Non-Alcoholic Fatty Liver DiseaseTo evaluate the role of regulatory B cells in the pathogenesis of metabolic associated fatty liver disease patients.
Diagnosis and Characterization of Non-Alcoholic Fatty Liver Disease Based on Artificial Intelligence....
Non-alcoholic Fatty Liver Disease (NAFLD)A key element in the diagnosis of non-alcoholic fatty liver disease (NAFLD) is the differentiation of non-alcoholic steatohepatitis (NASH) from non-alcoholic fatty liver (NAFL) and the staging of the liver fibrosis, given that patients with NASH and advanced fibrosis are those at greatest risk of developing hepatic complications and cardiovascular disease. There are still no available non-invasive methods that allow for correct diagnosis and staging of NAFLD. The implementation of Artificial Intelligence (AI) techniques based on artificial neural networks and deep learning systems (Deep Learning System) as a tool for medical diagnoses represents a bona fide technological revolution that introduces an innovative approach to improving health processes.