Study to Investigate the Effects of Different Doses of S-adenosyl-L-methionine (SAMe) in Subjects With Nonalcoholic Fatty Liver Disease and Non-treated Matched Healthy Volunteers as Control Group

Investigation the Effects of Different Doses of SAMe in Subjects with Nonalcoholic Fatty Liver Disease and non-treated matched healthy volunteers as control group


Eligibility Criteria:
Inclusion Criteria

* Subjects with non-alcoholic steatohepatitis based on histology in medical history within the last 3 years
* Subjects in a stable metabolic condition since histology for NASH (Non-alcoholic Steatohepatitis)

Exclusion Criteria

* Subjects with extrahepatic biliary obstruction
* Subjects with primary sclerosing cholangitis (PSC)
* Subjects with primary biliary cirrhosis (PBC)
* Any form of malignancy within the past 5 years and/or basal cell carcinoma and squamous cell carcinoma of the skin within the past two years
* History of active substance abuse (oral, inhaled or injected) within one year prior to the study
* Subjects with renal impairment (creatinine level of \>2.0 mg/dL)
* Subjects with a known hypersensitivity to the active substance (ademetionine) or methionine or to any of the inactive ingredients
* Subjects with known genetic defects affecting the methionine cycle and/or causing homocystinuria and/or hyperhomocysteinemia (e.g., cystathionine beta-synthase deficiency, Vitamin B12 metabolism defect)
* Subjects on total parenteral nutrition in the year prior to screening
* Subjects after or planned for bariatric surgery (jejunoileal bypass or gastric weight loss surgery)
* Extrahepatic cholestasis (proven by ultrasound)
* Subjects with alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) \> 5 upper limit of normal (ULN)
* Subject with serum total bilirubin (STB) \> 5 ULN
* Subjects after liver transplantation and subjects on the waiting list for liver transplantation
* Subjects with any of the following disease in medical history:
* Viral hepatitis (serum positive HBcAb (hepatitis B core antibody) or Hepatitis C Virus (HCV) ribonucleic acid (RNA)
* Evidence of autoimmune liver disease
* Wilson's disease
* Hemochromatosis
* Alpha-1-antitrypsin deficiency
* Known positivity for antibody to human immunodeficiency virus (HIV)
* Known heart failure of New York heart Association class 3 or 4
* Current or history of significant alcohol consumption for a period of more than three consecutive months within five years prior to screening (significant alcohol consumption is defined as \> 3 U (unit)/day for men and \> 2 U/day for women, on average) or binge drinking or inability to reliably quantify alcohol consumption.
* Clinical or histological evidence of cirrhosis F4
* Subjects with history of biliary diversion
* Subjects with uncontrolled diabetes mellitus defined by HbA1c (hemoglobin A1c) \> 8.0 % at screening
* Concomitant medication of B12, folate, betaine or choline
* Concomitant treatment with glitazone within the past year prior to the study
* Subjects with known folate or B12 deficiency
* BMI (body mass index) \> 40 kg/m2
* History of major depression diagnostic and statistical manual of mental disorders (DSM-IV) or bipolar disease
* Women of childbearing potential: positive urine pregnancy test during screening or unwillingness to use an effective form of birth control during the study.
* Breastfeeding women
* Any condition that, in the opinion of the investigator, does not justify the patient's inclusion into the study
* Investigational drug intake within one month prior to the study
* Active, serious medical disease with likely life-expectancy less than five years
* Uncooperative attitude or reasonable likelihood for non-compliance with the protocol or any other reason that, in the investigator's opinion, prohibits the inclusion of the subject into the study
* Legal incapacity or limited legal capacity, or who are incarcerated.
* Inability to return for scheduled visits.
* Inability to understand and follow the requirements of the protocol in the local language