Active clinical trials for "Liver Diseases"

The incidence of Non alcoholic fatty liver disease (NAFLD) continues to increase, and prevalence estimates for NAFLD range from 17-33%, making it is the most common cause of chronic liver disease in North America. It is associated with increased cardiovascular morbidity as well as progression to cirrhosis is a subset of patients. There is currently no approved treatment for NAFLD. A key barrier to the development of effective therapies is a lack of consensus on the criteria for diagnosis and endpoints for studies evaluating diagnostic markers, prognosis and therapeutic modalities. NAFLD encompasses an entire pathological spectrum of disease, from relatively benign accumulation of lipid (steatosis) to progressive non alcoholic steatohepatitis (NASH) associated with inflammation, fibrosis, and necrosis. It has been estimated that 20-30% of patients with NAFLD will exhibit biochemical and histological changes characteristic of NASH, and 15-20% of those patients will progress to have cirrhosis. NASH remains an important phenotypic state, because this sub-group of patients is deemed at high-risk for developing progressive disease resulting in cirrhosis, liver failure requiring transplantation, or death. Although NAFLD has not to date been included as a component of the metabolic syndrome, there is increasing evidence that NAFLD frequently accompanies the development of insulin resistance and therefore may be an indicator or predictor of future cardiometabolic risk. Moreover, recent findings in skeletal muscle of experimental insulin resistance (lipid infusion) as well as naturally occurring obese and type 2 diabetic, insulin resistant patients show that skeletal muscle inflammation leads to a pattern of extracellular matrix, structural, and remodeling abnormalities that closely resemble the TGFb, connective tissue growth factor (CTGF) mediated fibrotic response that differentiates simple steatotic liver from NASH. This suggests there may be a common underlying mechanism. Given the ready availability of skeletal muscle tissue using percutaneous needle muscle biopsies, compared to the more invasive liver biopsy, it may be possible to use characteristics of skeletal muscle to distinguish the severity of liver fibrosis. Given the preponderance of patients being identified with NAFLD, the recognition of less and non invasive tests that help to discriminate the different phenotypic types of NAFLD would be highly practical and useful. This would help identify patients at risk of progression to cirrhosis, and thus make them the target of any available therapeutic interventions. The investigators hypothesize that 1. Insulin resistance measured through glucose tolerance test directly correlates with the extent of liver and muscle fibrosis, and 2. Inflammation and fibrosis in the skeletal muscles correlates with the histopathological changes seen in patients with NAFLD, and potentially skeletal muscle inflammation may be used as a diagnostic predictor to differentiate patients with NASH from patients with simple steatosis. The overall goal of this project is to determine the extent to which inflammation and fibrosis in skeletal muscle mirrors and is predictive of the level of liver inflammation and can distinguish NASH from simple steatosis. Specifically, the investigators propose the following Aims: To use estimates of insulin sensitivity from modeling of oral glucose tolerance tests to test the hypothesis that the extent of liver and muscle fibrosis is directly related to insulin resistance. To use liver and muscle biopsies to characterize the changes in abundance of mRNAs and proteins that characterize inflammation, extracellular matrix remodeling, and fibrosis. The investigators will use quantitative rt-PCR and immunoblot analysis to compare mRNA expression and protein abundance of collagens I and III, fibronectin, and connective tissue growth factor (CTGF) to test the hypothesis that there is a direct relationship between the levels of these proteins in muscle and liver and the degree of fibrosis. To establish a biospecimen repository of serum, mRNA from circulating white blood cells, liver and muscle tissue, and DNA to serve as the substrate for future studies of the pathogenesis of NASH.

Background: - Fatigue is a common and often disabling symptom in people with chronic liver disease. Its causes are not well understood. Sleep disturbance may play a role in people with cirrhosis, but these factors have not been studied in people with other stages of liver disease. This study will look at the body's circadian rhythms (internal clock) to see if problems with these rhythms can contribute to fatigue. It will look at the causes and mechanisms of fatigue in people with chronic liver disease by comparing people with and without fatigue. Objectives: - To study reasons for fatigue in people with chronic liver disease. Eligibility: <TAB>Individuals at least 18 years of age who have chronic liver disease. <TAB>Participants with or without fatigue may enroll. Design: Participants will be screened with a physical exam and medical history. They will have a 2-day inpatient stay for the study. For the 7 days before the inpatient stay, participants will keep a sleep diary. They will record any caffeine or alcohol consumption, medicines, exercise, and sleep or naps. They will also wear an actigraph to measure their activity levels. During the inpatient stay, participants will answer questions about fatigue and sleep habits. They will have regular blood tests for 24 hours. Their body temperature will also be monitored. During the night, they will have a sleep study to look at how well or poorly they sleep. Treatment will not be provided as part of this study.

The purpose of this study is to examine whether non-alcoholic fatty liver disease (NAFLD) is associated with hepatic glucagon resistance and hyperglucagonemia.

Postoperative pain caused by surgery-associated tissue injury is a major concern for all the clinical practitioners. Because it affects multiple systems and induces physiological, immunological and psychological changes. Previous literature showed surgical injury induces a systemic inflammatory metabolic-endocrine response that is proportional to the severity of the surgical stress. In surgeries such as liver transplantation, the patients suffer not only from postoperative pain but also an additional oxidative stress caused by ischemia reperfusion. Previous report have proved that an adequate postoperative pain control improves the recovery and reduces the inflammatory cascade by suppression of physiological and psychological stresses. However, the effect of postoperative pain management on ischemia reperfusion injury is unclear so far. In this three year study, we plan to continue our previous study to test the following two hypothesis: (1) postoperative pain exacerbate remote organ injury caused by ischemia reperfusion, (2) the interaction of different antinociceptive modalities on ischemia reperfusion injury.

Living donor liver transplantation (LDLT), involves complex systems and processes of care that are particularly vulnerable to medical errors and preventable complications. This ancillary study of the Adult-to-Adult Living Liver Transplantation Cohort Study (A2ALL) will focus on conducting a proactive, systematic, and comprehensive assessment of the vulnerabilities in the systems and process of LDLT care to reduce medical errors and preventable complications thereby improving the safety of LDLT care. This project will address an important gap in the knowledge needed to achieve high quality and safe LDLT care of patients by developing a process to: 1) proactively, systematically and comprehensively identify areas of vulnerabilities in LDLT care that can result in medical errors, 2) design and implement solutions to mitigate these weaknesses, and 3) evaluate the effectiveness of these solutions to improve the safety of LDLT care by measuring clinical and process outcomes before and after solution implementation across four A2ALL participating transplant centers

Non-alcoholic fatty liver disease (NAFLD) comprises a spectrum ranging from simple fatty liver over steatohepatitis (NASH) to liver cirrhosis and cancer (HCC) and is a major and increasing health problem affecting nearly 40% of the general population. Moreover, NAFLD is an important risk factor for progression of diabetes and atherosclerosis. However, the pathomechanisms determining disease progression are poorly understood. The overall aim of this project is to test the central hypothesis that excessive fructose consumption provides a multiple metabolic hit in the pathogenesis and progression of NAFLD/NASH by impairment of hepatic lipid homeostasis and mitochondrial function resulting in hepatic lipotoxicity with inflammasome activation and disturbed interorgan cross-talk among insulin sensitive tissues.

To determine if ultrasound measurements can accurately measure the blood pressure of flow across a stent that has been placed in a portal vein to reduce portal vein pressure known as Transjugular Intrahepatic Porto-Systemic shunts or TIPS.

In an open-label trial, 20 otherwise healthy morbidly obese patients scheduled for bariatric surgery will be administered 20 mg/kg/day ursodeoxycholic acid for three weeks until the day before surgery. The maximum dose will be 3 g/day. Twenty other patients will serve as controls. Serum from days 1 and 21 will be analyzed for routine liver tests, bile acids, a complete lipid profile including FA and in addition for 7α-hydroxy-4-cholesten-3-one and fibroblast growth factor 19 (FGF-19), markers for bile acid synthesis its intestinal stimulation. For the evaluation of insulin resistance and possible pre-diabetes, plasma will be taken for the estimation of homeostasis model assessment (HOMA) index and oral glucose tolerance test (OGTT) will be performed at days 1 and 21. At surgery, a liver biopsy (0.5-1 g) and a white adipose tissue (WAT) specimen (1 cm2) will be taken and immediately frozen in liquid nitrogen for messenger ribonucleic acid (mRNA) and protein preparation for quantitative real-time polymerase chain reaction (RT-PCR) and Western analysis, respectively, histopathological Non-alcoholic fatty liver disease (NAFLD) grading, and measuring of hepatic and white adipose tissue (WAT) lipase activity. In all patients at randomization, abdominal ultrasound will be performed for the detection of NAFLD and gallstones and a blood sample will be taken for the analysis of polymorphisms of hepatic lipid synthesis, storage, fatty acid (FA) oxidation and export genes. Six month after operation, HOMA, OGTT and abdominal ultrasound will be repeated.

The purpose of this study is to collect epidemiological data in children and adolescents with chronic hepatitis B(CHB), in particular data on the prevalence of HBeAg positive disease with associated ALT levels , active HBeAg negative disease and decompensated CHB in the pediatric population. Family history and history of HBV transmission is essential to assess the course of the disease and can be used to determine the best mode of treatment This information will be used to assist with the feasibility and design of studies for the Novartis clinical pediatric development program, as the current epidemiology of ediatric CHB is not accurately known in Western countries or the rest of the world making pediatric studies difficult to plan and conduct. This study forms part of the Novartis Pediatric Investigational Plan, a post marketing approval commitment to the EMEA Pediatric Committee.

All subjects will be evaluated by the Research Nurse at the Clinical Translational Research Center (CTRC) Outpatient Clinic to obtain informed consent, a brief medical history, weight, body mass index, waist/hip circumference and vital signs. Additionally, blood will be drawn at this visit to screen for renal dysfunction (Chem 10), liver disease (liver function tests (LFT's)), thyroid dysfunction (TSH), diabetes mellitus (HbA1C), and chronic inflammatory states (erythrocyte sedimentation rate). Subjects recruited to the study will be placed on a low-carbohydrate diet (<20 g/d without caloric restriction) designed either to promote weight loss or maintain weight stability for fourteen days prior to the protocol or they will consume a typical "Western" diet designed either to promote weight loss (restricted by 1300 kcal/d in the final fourteen days) or maintain weight stability for twenty-one days. Subjects recruited to the study will be lean, overweight, or obese and also may carry a diagnosis of NAFLD. Target accrual for total enrollment for this project will be set to 80 subjects to accommodate attrition and screen failures. The details of the low-carbohydrate diet have been discussed in consultation with Linda Brinkley, nutrition staff of the CTRC. Subjects chosen to undergo carbohydrate-restriction will have a teaching session with a CTRC dietician. Subjects will then initiate dietary carbohydrate-restriction on their own and keep a daily dietary record for seven days. At the end of seven days, the dietary record will be analyzed. The CTRC will then prepare all meals for the final seven days of the diet in accordance with daily caloric intake calculated from the dietary record. Calorie-restricted participants will keep a dietary record for one week while eating a typical "Western" diet. The dietician will analyze this record and meals restricted by 1300 kcal/d will be prepared by the CTRC for the final fourteen days of the diet. Alternatively, some subjects eating a typical "Western" diet may consume prepared meals with a fixed content of carbohydrate, fat, and protein that is unrelated to their pre-study dietary intake. In this scenario, the dietary carbohydrate content may be varied between 30 and 60% to provide information on differences in hepatic metabolism under conditions of differing, but clinically sustainable, carbohydrate intake. All participants will be admitted to the CTRC the night prior to the study and begin an overnight fast after dinner. Between 18:00 and 09:00, subjects will receive two stable isotope tracers orally: [U-13C]propionate at 08:00 (three 400 mg doses given over 1 hour) and 70% 2H2O at 22:00, 02:00, and 06:00. During the study subjects will also be given 0.5% 2H2O ad libitum. Two 500 mg acetaminophen tablets will also be given at 08:00. Between 08:00 and 09:00 subjects will undergo measurement of their respiratory quotient (RQ) using the CTRC indirect calorimeter (Delta Trac II).. Subjects will then have an intravenous catheter placed and an infusion of tracer amounts of [3,4-13C2]glucose, [1,2-13C]β-hydroxybutyrate and [3,4-13C]acetoacetate will be initiated. At 1 ½ and 2 hours after initiation of the infusion, a 50 cc blood draw will be performed. Voided urine will be collected every hour after ingestion of acetaminophen until the protocol concludes. The subject will then be given a meal and discharged from the CTRC, marking the completion of the protocol. The collected blood and urine will be transported by the research coordinator to the Advanced Imaging Research Center lab for analysis by MRS. Another blood draw (approximately 10 cc) will be done in conjunction with the final MRI in order to measure changes in the lipid profile after the diet intervention. The visits in their entirety will be as follows: 1 screening visit: 20 minutes dietician visit: 20 minutes MRS visits: 45 minutes each 1 (optional) overnight visit: 20 hours