Patient case (clinical description): A 51-year-old man comes to the office complaining of fatigue and some sexual problems including lack of libido. The patient doesn't smoke or use any illicit drug.  Blood pressure is 120/80 mm Hg and pulse is 70/min.  Oxygen saturation is 99% on room air.  BMI is 24 kg/m2.  Skin examination shows increased pigmentation. Genotype testing is consistent with homozygosity for the C282Y mutation. Laboratory study shows transferrin saturation of 55% and serum ferritin of 550 μg/L. He is diagnosed as a case of hemochromatosis.

Patient's own account: I am 51 years old and I just came back from the doctor's office. I'm sick and tired of being that exhausted, reaching the point where me and my lovely wife are not touching each other anymore! I'm not smoking or doing drugs! My blood pressure was 120/80 mm Hg, and pulse was 70/min and my oxygen saturation 99%. My BMI is 24. My skin also turned a bit darker lately. He tested my genes and told me that I have a mutation of the C282Y gene. I also did lab tests where my transferrin saturation was 55% and serum ferritin was 550  μg/L. The doctor diagnosed me with iron overload.

Clinical trial: Effect of Iron Depletion by Phlebotomy Plus Lifestyle Changes vs. Lifestyle Changes Alone on Liver Damage in Patients With Nonalcoholic Fatty Liver Disease With Increased Iron Stores

Eligibility criteria:
Inclusion Criteria:

          -  Age ≥ 18 < 75 years

          -  Ferritin > 250 ng/ml and/or stainable iron at biopsy

          -  NAS ≥ 2 and/or NAS 1 and stage≥1 at liver histology

          -  Willingness to maintain diet and exercise during the full course of the study

          -  Written informed consent to participate to the study and to have the specific genetic
             tests performed

          -  Ability to comply with all study requirements

        Exclusion Criteria:

          -  Pregnant or lactating female

          -  Diagnosis of or a history of:

          -  Type 1 diabetes, diabetes that is a result of pancreatic injury, or secondary forms of
             diabetes, e.g. Cushing's syndrome or acromegaly

          -  Acute metabolic complication such as ketoacidosis or hyperosmolar state within the
             past 6 months

          -  Alcohol consumption > 20 g/day for females and > 30 g/day for males

          -  BMI ≥ 35 Kg/ m2

          -  Other liver disease such as viral hepatitis, autoimmune hepatitis, Wilson disease, as
             defined by ceruloplasmin below normal limits and liver histology consistent with
             Wilson disease. Alpha-1-antitrypsin deficiency as defined by alpha-1-antitrypsin level
             less than 80 mg/dl or PiZ/PiZ or PiZ/PiS genotype. *Hemochromatosis, as defined by
             homozygosity for the C282Y HFE mutation or compound heterozygosity for C282Y/H63D
             mutations or Hepatic Iron Index ≥ 1.9.

          -  Advanced liver disease (Child B/C cirrhosis), portal hypertension, hepatocellular
             carcinoma.

          -  Congestive heart failure (NYHA I-IV) and unstable ischemic heart disease, systolic
             dysfunction (ejection fraction < 45%)

          -  Any of the following ECG abnormalities: II or III degree Atrial Ventricular *Block,
             QT>500msec, repolarization defect suggestive of ischemia

          -  Malignancy within the last 5 years

          -  Serum creatinine levels > 1.5 mg/dl males, > 1.4 mg/dl females

          -  TSH outside of normal range

          -  Use of drugs known to induce NAFLD: corticosteroids, methotrexate, zidovudine,
             amiodarone, GH, estrogens, tamoxifene, tetracycline

          -  Lipodystrophy, dysbetalipoproteinemia, inflammatory bowel disease, HIV infection

          -  Basal hemoglobin levels < 11 g/dl
No condition on gender to be admitted to the trial.
No healthy subjects accepted to join the trial.
Subject must be at least 18 Years old.
Subject must be at most 65 Years

Eligibility (NLI label): Entailment