study with heptral in subjects with liver disease due to alcohol consumption

Conditions: Intrahepatic Cholestasis Associated With Alcoholic Liver Disease

Summary: a research study of an approved drug called heptral®, ademetionine, to treat adults with intrahepatic cholestasis (a condition where bile cannot flow from the liver to the duodenum) in pre-cirrhotic and cirrhotic states. experience from clinical studies in subjects with liver disease has shown that ademetionine is effective.


Eligibility criteria:
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

Keywords: intrahepatic cholestasis