A Multi-Center Trial to Study Acute Liver Failure in Adults

Although ALF is truly an orphan disease affecting only about 2,000 persons per year, its
severity, its frequency among young adults, and its high resource utilization justifies the
attention paid to it. In addition, ALF has captured the interest and attention of researchers
because of its unique pathogenesis and extreme severity, encouraging us to understand the
processes underlying all forms of liver injury, by focusing on this most lethal
manifestation.

The etiologies associated with ALF have continued to change further over the years with an
apparent decline in viral hepatitis, and a remarkable increase in acetaminophen toxicity to
its current level of ~44-50% of cases. A further problem in studying ALF is that the number
of cases of a specific etiology observed at any one institution are vanishingly small. The
earliest goals of the ALF Study then were to more carefully define the etiologies of ALF on a
national scale, and to finally allow in-depth study of specific ALF causes such as autoimmune
ALF, viral hepatitis and Wilson disease (WD).

A second group of patients worthy of study are those with acute liver injury.It would be of
value to study patients destined to possibly have ALF earlier in their illness for several
reasons: first, we might be able to better predict who will progress to full liver failure;
second, the current definition requiring encephalopathy limits the number of patients
available for study at any site; finally, therapeutic trials might have greater efficacy if
begun at earlier disease stages.

Patients who are enrolled are referred to ALFSG clinical sites by
gastroenterologist/hepatologist and fellows. Detailed clinical data and bio-specimen (sera,
urine, plasma, DNA and tissue if available) are collected. Subjects are followed long-term at
6 months and 12 months. Detailed clinical data and sera are collected.

ALF Inclusion Criteria:

- Written Informed consent from patient's next of kin

- Altered mentation of any degree (encephalopathy)

- Evidence of moderately severe coagulopathy (INR ≥ 1.5)

- A presumed acute illness onset of less than 26 weeks

- The NIH guidelines on the inclusion of women and minorities as subjects in clinical
research will be observed

ALF Exclusion Criteria:

- Cirrhosis patients

- Alcohol induced liver failure

- Known pre-existing chronic liver disease

ALI Inclusion Criteria:

Acetaminophen (APAP) etiology: acute illness < 2 wks

- INR ≥ 2.0, ALT ≥ 10X ULN Non-acetaminophen etiology: acute illness < 26 wks

- INR≥ 2.0, ALT≥ 10X ULN, TBili ≥ 3 mg/dl

ALI Exclusion Criteria:

• Altered mentation of any degree (encephalopathy)