Please select the eligibility criteria that correspond to the clinical trial below.
Title: Non-alcoholic Fatty Liver Disease (NAFLD) in Overweight and Obese People Under Nutritional and Lifestyle Follow-up: a Randomized Controlled Trial
Brief Summary: 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.


Options:
A: Inclusion Criteria:

* Age 18-65 with Nonalcoholic Fatty Liver Disease as determined by MRS

Exclusion Criteria:

* Medical History

  * Diabetes
  * Heart Disease
  * Asthma/Lung disease
  * Injury that prevents exercise
* Social history

  * Drinking
  * More than one drink per day
  * Binge drinking on the weekends (more than 3 or 4 drinks per weekend day)
* Smoking
* It's OK if they were a previous smoker, but they need to have quit more than 6 months ago
* Exercise

  * They must exercise less than one hour per week
  * Medications: must be on stable regimen of ANY medication for at least 3 months
* Beta-Blockers

  * Lipid/cholesterol lowering medications:
  * Oral hypoglycemics (anti-diabetes medications - some like metformin are indicated for pre-diabetes)
* Hormone replacement therapy
* If the woman is pre-menopausal, it is OK if she is on birth control as long as she has been on it over 3 months
* Weight history

  * Weight \<300 lbs
  * BMI 30 to 45
  * Weight stable - \<10lbs weight loss or gain in the last 3 months
B: Inclusion Criteria:

* Sedentary, non smoking, male subjects,
* Alcohol consumption men \<21 units/week,
* BMI 27-35. (Lean individuals do not suffer from NAFLD, so are not suitable for this study. Conversely, we are restricted to a maximum BMI of 35 due to the size limitations of the MR scanner.)
* A clinical diagnosis of NAFLD based upon the following criteria: i) exclusion of other causes of liver disease i.e. negative Hepatitis B and C serology, a negative auto-immune profile and normal caeruloplasmin concentrations, ii) Ultrasound appearances suggestive of a fatty, echo-bright liver with no evidence of cirrhosis (in some cases, the diagnosis will have been confirmed histologically after liver biopsy.
* Being willing to engage and motivated to follow an exercise program.

Exclusion Criteria:

* Prescription of corticosteroids, amiodarone, tamoxifen, methotrexate (drugs known to cause secondary steatohepatitis) or fibrates. Statin is Ok as long as the patients are on stable therapy for a while, if changed then the patient will be excluded.
* Alcohol consumption for men 21 units/week.
* A contraindication to exercise (such as unstable ischaemic heart disease),
* Type 2 diabetes (type 2 diabetes patients are excluded so that we are examining the involvement of insulin resistance at a reversible stage before β-cell failure has occurred).
* Patients who are on medications that will interact with GTN (glyceryl trinitrate) will be excluded from the GTN dilatation (endothelial independent NO mediated function) aspect of the study.
* Individuals who suffer from claustrophobia and have metal implants will be excluded from the MRI aspect of the study.
* Patients who smoke will also be excluded from the study.
* Total cholesterol \>7
C: Inclusion Criteria:

* Age ≥ 18 years
* Body mass index ≥ 28 kg/m2
* Fatty liver index ≥ 60
* Fructose intake ≥45 grams/day

Exclusion Criteria:

* Medical history of liver disease
* (History of) excessive alcohol consumption (defined as \> 2 units/day for women, and \> 3 units/day for men)
* Major change in weight and/or physical activity prior to the study
* Use of glucose lowering drugs
* Recent illness
* Pregnancy and/or lactation
* Contraindications for magnetic resonance imaging
* Inability to give informed consent

Protocol change (implemented on July 18, 2018): in order to increase the inclusion of study participants, subjects with an average daily fructose intake \< 45 gram/day will also be eligible for participation. In subjects who have an average daily fructose intake \< 45 gram/day, supplementation of either fructose or glucose (see 'Arms and Interventions') will be increased to 45 gram/day.
D: Inclusion Criteria:

* Overweight or obese
* Diagnosis of NAFLD
* Age: 30-80 years
* Female / Male

Exclusion Criteria:

* Known liver disease (other than NAFLD)
* Abuse of alcohol (\>21 and \>14 units of alcohol a week for men and women, respectively, eg 1 unit = 125 mL of wine);
* Drug treatments: immunosuppressants, cytotoxic agents, systemic corticosteroids, agents potentially causing fatty liver disease or abnormal liver tests or weight modifiers
* Active cancer or a history of malignancy in the last 5 years
* Problems of massive edemas
* Obesity known endocrine origin (except treated hypothyroidism)
* Surgical procedure for weight loss
* ≥ 3kg weight loss in the last 3 months
* Severe psychiatric disorders
* Lack of autonomy or inability to follow the diet (including food allergies or intolerances) or/and lifestyle recommendations as well as to follow scheduled visits.
* Consumption of any type of food supplements (antioxidants, prebiotics, probiotics, etc.)

Answer: D