Study With Heptral in Subjects With Liver Disease Due to Alcohol Consumption

Inclusion criteria

• Signed informed consent given by the subject
• Age ≥ 18 years to 75 years
• Chronic liver disease due to alcoholic liver disease
• Compensated alcoholic liver disease, defined as having a Maddrey Score < 32 and not being treated with pentoxifylline or prednisolone within 6 months prior to the study
• History of chronic alcohol use, defined as, history of consumption of > 40 g of alcohol per day for females and > 80 g alcohol per day for males for more than 5 years prior to enrolment
• Subjects who abstain from alcohol for more than 2 weeks and will not consume alcohol during the study
• Subjects with Intrahepatic Cholestasis (IHC):
• ALP: more than 1.5 x upper normal limit and
• γGT: more than 3 x upper normal limit
• Subjects with additional serum conjugated bilirubin (SCB) > Upper Limit of Normal (ULN) will be selected for initial IV treatment

Exclusion criteria

• Subjects with a known hypersensitivity to the active substance of ademetionine or to any of the inactive ingredients
• Subjects with extrahepatic cause of cholestasis (proven by ultrasound or described in medical history)
• Diagnosis of human immunodeficiency virus (HIV) in medical history
• Subjects with chronic liver disease Child-Pugh class C
• Subjects in the decompensation stage of ALD (such as Maddrey Score >32)
• 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
• Subjects with drug-induced liver disease
• 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 or > 150 µmol/l)
• 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) or known folate, Vitamin B6 or B12 deficiency
• 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)
• 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 or Hepatitis C Virus (HCV) RNA)
• Evidence of autoimmune liver disease
• Wilson´s disease
• Hemochromatosis
• Alpha-1-antitrypsin deficiency
• Subjects with history of biliary diversion
• History of major depression 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 other than ALD with likely life-expectancy less than five years