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

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