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

This is an interventional treatment trial for Intrahepatic Cholestasis Associated With Alcoholic Liver Disease focused on measuring Intrahepatic Cholestasis Read More

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