Study of N-Acetylcysteine in Acute Liver Failure (ALF)

A Multi-Center Trial to Study Acute Liver Failure: N-Acetylcysteine (NAC) Open Label Use Study

This proposed study is a multi-center open label study to determine if N-acetylcysteine has any survival benefits in patients with acute liver failure.

Patients admitted to study sites with carefully defined criteria for acute liver failure and who are thought not to have acetaminophen toxicity, mushroom poisoning, pregnancy-related liver failure, or malignancy will be eligible. Each patient will receive intravenously in solution of 5% dextrose in water containing N-acetylcysteine, beginning at a dose of 150 mg/kg bodyweight in 250 ml 5% dextrose over one hour, and in declining doses over a total of 72 hours. Care of patients and consideration of transplantation or other clinical decisions will not be affected by the study or the use of study drug.

Inclusion Criteria:

• Written Informed consent from patient's next of kin
• Altered mentation of any degree (encephalopathy)
• Evidence of moderately severe clotting abnormalities (international normalized ratio ≥ 1.5)
• A presumed acute illness onset of less than 26 weeks
• Admitted to study site hospital intensive care units with acute liver failure and who can be evaluated and started on treatment within the first 24 hours of hospitalization
• All subjects will be between 18 and 70 years
• The NIH guidelines on the inclusion of women and minorities as subjects will be observed

Exclusion Criteria:

• Patients less than age 18 or over 70 years of age
• Acetaminophen or mushroom poisoning induced liver failure
• Patients with a diagnosis of shock liver (ischemic hepatopathy)
• Acute liver failure of pregnancy
• Acute liver failure thought secondary to intra-hepatic malignancy
• Cerebral herniation
• Intractable arterial hypotension
• Severe sepsis (temperature >39º C and/or significant bacteremia) present at the time of enrollment