Active clinical trials for "Non-alcoholic Fatty Liver Disease"

We hypothesize that insulin resistance is characteristic of nonalcoholic fatty liver disease as compared to age, gender, non-diabetic BMI-matched control subjects, both healthy and those with non-cirrhotic, non-steatotic liver disease.

Patients will be randomized to lifestyle changes alone or lifestyle changes associated with iron depletion. Iron depletion will be achieved by removing 350 cc of blood every 10-15 days according to baseline hemoglobin values and venesection tolerance, until ferritin < 30 ng/ml and transferrin saturation < 25%. Weekly phlebotomies will be allowed for carriers of the C282Y HFE mutation. Smaller phlebotomies (250 cc) will be allowed for carriers of beta-thalassaemia trait. Maintenance phlebotomies (as much as required) will then be instituted to keep iron stores depleted (ferritin < 50 ng/ml and transferrin saturation < 25%, MCV <85 fl). Before starting treatment, patients will undergo ECG, and in the presence of hyperglycemia or hypertension also echocardiography (see exclusion criteria). Change in diabetes medication dosage or start of new therapy will be allowed for HbA1C values <6% or ≥ 7%. According to accepted criteria, previously untreated patients should be treated with metformin. If possible, newly diagnosed hypertension should be treated with Ace-inhibitors.

The purpose of this study is to evaluate the efficacy of rosiglitazone alone compared with rosiglitazone plus metformin or rosiglitazone plus losartan in the treatment of biopsy proven nonalcoholic steatohepatitis (NASH). This study was designed to answer the question: are there differences in the efficacy (as measured by histopathology and insulin resistance) of three different therapeutic modalities used to treat NASH?

Non-Alcoholic Fatty Liver Disease (NAFLD), including its more pathologic consequence, non-alcoholic steatohepatitis (NASH), is believed to be the most common chronic liver disease worldwide, affecting between 6 to 37% of the population. NAFLD is a so called 'silent killer', as clinical symptoms only surface at late stages of the disease, when it is no longer treatable: untreated, NAFLD/NASH can lead to cirrhosis and hepatocellular carcinoma, culminating in liver failure. Several factors may contribute to the pathogenesis of NAFLD, including genetic assessment and mitochondrial dysfunction. Patients with NAFLD/NASH display disturbances of intestinal permeability, and gut microbiota. In the most of cases, NAFLD/NASH is strongly linked to other metabolic conditions, including visceral adiposity. Currently the best method of diagnosing and staging the disease is liver biopsy, a costly, invasive and somewhat risky procedure, not to mention unfit for routine assessment. Weight loss is the first step approach with reasonable evidence suggesting it is beneficial and safe in NAFLD/NASH patients. However, the efficacy of weight reduction for the treatment of NAFLD/NASH has not been carefully evaluated. Several studies on the effects of weight reduction on NAFLD/NASH have been uncontrolled, used poorly defined patient populations and non-standardized weight loss interventions, and lacked a well-accepted primary outcome for NASH. The objective of the project is to conduct a randomized controlled trial of 1 year-long weight reduction in the management of NAFLD/NASH patients using a lifestyle-dietary intervention program. Overweight or obese individuals with biopsy or ultrasonography (US) -proven NAFLD/NASH will be randomized to receive either standard medical care and educational sessions related to NAFLD/NASH, healthy eating, weight loss, and exercise (control group); or to an intensive weight management with a goal of at least 7-10 % weight reduction (lifestyle intervention group). The weight loss intervention will be modelled on Mediterranean-intervention-diet. The investigators hypothesize that a 7-10% weight reduction through intensive lifestyle intervention will lead to improvement of clinical, US, anthropometric, and biochemical features on patients diagnosed with NAFLD/NASH.

To study the effects of Hesperidin, flaxseed and both together on lipid profile, liver enzymes, inflammatory factors and hepatic fibrosis in patients with Nonalcoholic Steatohepatitis (NASH), 100 patients who referred to Gastrointestinal (GI) clinic with steatosis grade 2 and 3 will be randomly allocated to one of following four groups: control group, hesperidin group (2 capsules Hesperidin), flaxseed group (30 gram flaxseed) or flaxseed-hesperidin group (2 capsules Hesperidin and 30 gram flaxseed) for 12 weeks; both groups will be advised to adherence the investigators' diet and exercise program too. At the first and the end of the intervention, lipid profiles, liver enzymes, some inflammatory markers, and liver fibrosis will be assessed and compared between groups.

As the prevalence of obesity is reaching epidemic proportions, the prevalence of non-alcoholic fatty liver disease (NAFLD), including non-alcoholic steatohepatitis (NASH), increases concomitantly and becomes a major global health hazard. Successful pharmacological interventions to treat or prevent NASH are not available and so far only weight loss has clear benefits, but sustained weight-loss is difficult to achieve on the longer-term. We recently demonstrated in mice that plant sterol and stanol ester consumption inhibited the development of liver inflammation, which needs to be validated in humans in a translational approach. In the current proposed pilot study, the effect of consuming plant sterol or plant stanol esters on biopsy proven liver inflammation will be investigated in NAFLD patients. The objective is to assess the effect of consuming plant sterol or plant stanol esters (3 grams/day) for 12 months on biopsy proven liver inflammation in NAFLD patients. This study is a randomized, placebo-controlled, double blinded pilot study with a run-period of 2 weeks, an intervention period of 12 months and a wash-out period of 1 month. The study population consists of 15 patients with biopsy-proven liver inflammation, aged 18-75 years. All subjects will start a run-in period of two weeks during which they consume daily 20 grams of control margarine after which they will be randomly allocated to consume 20 grams control margarine or plant sterol or plant stanol enriched margarine on a daily basis for a period of 12 months. The primary outcome parameter in this study is biopsy proven liver inflammation.

Nonalcoholic fatty liver disease (NAFLD) is a global health concern with a suspected increasing prevalence due to the rise in obesity and diabetes mellitus. The vast majority of patients will have isolated steatosis or steatosis with mild inflammation that is very unlikely to progress in severity. However, about 25% of patients with NAFLD have non-alcoholic steatohepatitis (NASH), the more aggressive form of the disease that is associated with fibrosis progression and potential risk for cirrhosis and end-stage liver disease complications. Additionally, multiple studies have demonstrated an association between NAFLD and the presence of coronary artery disease by either coronary CT angiography (CCTA) or coronary artery calcium (CAC) score. Cardiovascular disease is the most important cause of mortality in patients with the entire spectrum of NAFLD. In the era of advanced imaging and functional vascular assessment it is possible that novel risk assessments are poised to refine overall prognostic estimation in this population. Multiple analyses have suggested that NAFLD is an independent and strong predictor of significant CAD independent of cardiovascular risk factors, including a significant burden of high risk CCTA findings in one analysis of symptomatic patients in the emergency department. Given the multiple metabolic derangements inherent in the NAFLD population, endothelial dysfunction is also an important contributor to global cardiovascular dysfunction. Furthermore, data suggests that patients with NAFLD may be at increased risk of adenomatous polyp formation and colorectal adenocarcinoma. In addition, it is suboptimal to require a liver biopsy to diagnose NASH. Recent imaging advances have made it possible to assess liver fibrosis but have yet to be fully studied in NAFLD. The purpose of this study is to assess the current prevalence and severity of NAFLD in adult subjects. Secondary endpoints include correlation to new vascular function (cine scan of the abdominal aorta) and echocardiographic imaging modalities available at BAMC and to circulating biomarker panels as well as to determine the prevalence and severity of CAD by multidetector coronary CT angiography with subject outcomes being monitored prospectively. Additionally, correlation of NAFLD diagnosis to colonoscopy findings will be performed.

Non-alcoholic fatty liver disease (NAFLD) is a condition of excessive hepatic lipid accumulation in subjects that consume less than 20g ethanol per day, without other known causes as drugs consumption or toxins exposure. In Western countries, the rate of this disease lies about 30% in the general adult population. The process of developing NAFLD can start from simple steatosis to non-alcoholic steatohepatitis (NASH), which eventually can lead to cirrhosis and hepatocellular carcinoma in the absence of alcohol abuse. Liver biopsy is considered the "gold standard" of steatosis, fibrosis and cirrhosis. However, it is rarely performed because it is an invasive procedure and investigators are focusing in the application of non-invasive liver damage scores for diagnosis. The pathogenesis of NAFLD is multifactorial and triggered by environmental factors such as unbalanced diets and overnutrition as well as by lack of physical activity in the context of a genetic predisposition. Nowadays, the treatment of NAFLD is based on diet and lifestyle modifications. Weight loss, exercise and healthy eating habits are the main tools to fight NAFLD. Nevertheless, there is no a well characterized dietary pattern and further studies are necessary. With this background, the general aim of this project is to increase the knowledge on the influence of nutritional/lifestyle interventions in obese patients with NAFLD, as well as contribute to identify non-invasive biomarkers/scores to early diagnosis of this pathology in future obese people.

CONTROLLED TRIAL ON THE EFFECT OF TOMATO PRODUCTS IN OBESE CHILDREN WITH NON ALCOHOLIC FATTY LIVER DISEASE Aim of the study To evaluate the effect of the addition of a daily dose of lycopene enriched tomato sauce on the progress of NAFDL in obese children. Participants Children with obesity referred to the Hepatology unit of Dept.of Pediatric Clinic of the University Federico II of Naples. Diagnosis of NAFLD is made on the presence of fatty liver at ultrasound examination, with or without hypertransaminasemia. Patients are eligible on the basis of: Age 4-14 years BMI > 85°percentile Liver Steatosis evaluated as mild, moderate or severe by US (hyperechogenic liver tissue compared with the adjacent kidney cortex) Patients are excluded on the basis of: Liver disease Diabetes or manifest metabolic alterations Associated diseases Informed consent is obtained from the parents of the participating children. Sample size estimation To provide an 80% power to detect a 25% or greater relative shift of outcome variables, with a first degree error of .05 a sample of 50 cases is estimated in a cross over trial. Study design This is a randomized, crossover, one side open trial with blinded outcome evaluation. A statistician who is not otherwise involved in the trial generated the randomized assignment sequence. At the enrollment all participants received a low carotenoids diet for two weeks (wash out), then children are assigned to the first intervention for 8 weeks, and subsequently, in the crossover phase, they are switched to the second intervention for the next 8 weeks. No wash out is planned between the two treatments. Interventions Supplemented diet: 100 gr/day of Lycopene enriched tomato products (weekly average) Control diet: ordinary healthy diet, with no special encouragement to eat carotenes products All children are put on a 'mediterranean style' diet, with a controlled amount of calories: a dedicated dietitian for the whole study, irrespective of the treatment, checked their diet twice a week. At beginning (T0) and at the end of each treatment (T1 and T2) all patients underwent anthropomorphic measurements, including weight, height, waist, abdomen and hips circumferences. BMI and its standard deviation score are calculated. Regardless of group assignment, all participants are seen by a hepatologist at the end of each intervention and checked for liver steatosis, by US. Fasting blood samples are collected at beginning (T0) and at the end of each treatment (T1 and T2) to evaluate IR (assessed by HOMA), transaminases levels, lipids profile, oxidative state (assessed by antioxidant enzymes activity, serum levels of MDA and carbonylated proteins), inflammatory state (by cytokines serum levels, typing of lymphocytes subpopulations, metabolism of lymphocytes). Data collection are performed in a partially blind fashion: the statistician performing data analysis is blind to treatment. Outcomes: The primary outcome is reduction of the liver steatosis estimated by US Scan, according to the following parameters: parenchyma echogenicity (compared with that of the cortical of the right kidney), far gain attenuation, diaphragm blurring. steatosis. Secondary outcomes is reduction in Insulin resistance, Oxidative state, Inflammatory state. Statistical Analysis Data are inspected for normality and paired t-test (before/after) of each phase of the trial are performed when appropriate. The Median % change of each variable between the values at Time 8 and 16 weeks and values at enrollment are also looked. Ordinal logistic regression analysis, hierarchical, mixed model with adjustment variables are adopted to estimate the size of the effect. The study is approved by the Ethical Committee of University Federico II of Naples.

To study the effects of a low free sugar diet on lipid profile, glycemic indices, liver enzymes, inflammatory factors and hepatic steatosis and fibrosis in patients with Nonalcoholic fatty liver disease, 50 patients who referred to Gastrointestinal (GI) clinic with steatosis grade 2 and 3 will be randomly allocated to receive low free sugar diet or regular diet for 12 weeks; both groups will be advised to adherence the investigators' nutrition recommendation and exercise program too. At the first and the end of the intervention, lipid profiles, liver enzymes,glycemic indices, some inflammatory markers, and liver fibrosis will be assessed and compared between groups.