Active clinical trials for "Liver Diseases"

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.

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

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

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

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.

More than 1.5 millions individuals are infected with HCV in Italy. They are at risk to develop related morbidity and mortality from cirrhosis and hepatocellular carcinoma, unless the evolution of their disease is halted by treatment-induced HCV RNA clearance. Indeed, it is well recognized that a curative antiviral treatment, leading to HCV RNA undetectability 24 weeks after the end of therapy, may prevent the occurrence of complications of HCV chronic liver disease. Several pre-treatment host and viral factors have been associated with the outcome of pegylated Interferon and Ribavirin treatment. These predictors are relevant as the ability to identify patients with the highest likelihood of achieving HCV RNA clearance may increase the number of patients who agree to be treated and who maintain their adherence to treatment. Several pre-treatment predictors as HCV genotype, HCV viral load, age, gender, body mass index, stage of fibrosis and race are very well recognized and have been used for many years during the treatment decision-making process. Based on studies of viral kinetics, HCV RNA undetectable at week 4 on treatment has been shown to represent the best on treatment predictor of response. In addition to these well known factors, very recently, a single nucleotide polymorphism (SNP) upstream of the gene IL28B on chromosome 19, coding for IFN-lambda 3 has been identified as associated with both spontaneous and treatment induced HCV RNA clearance. We have developed the molecular technique needed to evaluate this polymorphism in our laboratory. This technical process was a consequence of the genetics expertise of our research Institute. We have also performed a valuable comparison of the different methods to evaluate this polymorphism. Comparison of different technologies allow us to know the rate of variability between the different assays used. With this methodology we have evaluated "a posteriori" patients previously enrolled in Randomized Controlled Trial. The results of these studies confirmed the association between IL28B CC allele and a favorable outcome of HCV infection in our geographic area (Mangia et al Gastroenterology 2010; Mangia et al Hepatology 2010, AASLD presentation). We are now interested in prospective evaluation of patients referring to our center at the aim of understanding whether there are differences in the rates of IL28B frequencies in patients with different HCV genotypes. In fact, we hypothesize that the frequency of IL28B might be different according with different HCV genotypes and that this difference may explain the different rates of response to antiviral treatment reported in patients with HCV infection. Since we lead a collaborative group of hepatologists named AL-LIVER operating in Puglia, Lazio, Basilicata, Sicilia and Campania regions in Italy we would like to extend this evaluation to our collaborative group to explore in a large number of patients whether the prevalence of CC, CT and TT genotypes is inversely associated with HCV G1, 4, 3 and 2.

The purpose of this study is to gather information regarding the use of Myfortic, Prograf, and corticosteroids in new liver transplant recipients. These three medicines help to prevent the body from rejecting the transplanted liver. The information the investigators are obtaining is data relating to the process of Myfortic absorption by the body, its distribution in the body, the breakdown of Myfortic in the body, and its elimination from the body. This absorption, distribution, breakdown, and elimination is called pharmacokinetics.

The main objective of the study is to gain insight in the early dynamics and mechanisms of recovery of liver disease and sex steroid metabolism during weight loss in obese men and women and to investigate whether surgical weight loss has differential effects as compared to weight loss with life style measures. In addition, we want to evaluate the postprandial hypoglycemic reactive syndrome (PPHRS) in these patients using a standard chewable meal. Secondary objectives are investigating determinants for the changes in sex steroids, liver disease and PPHRS. Possible determinants to be investigated are adipocytokine secretion patterns, body composition, resting metabolism rate, weight loss per se and changes in fat distribution, parameters of fatty acid metabolism, … .