Alcoholic Hepatitis Network Observational Study

What should I know about this research?

- Someone will explain this research to you.

- Taking part in this research is voluntary. Whether you take part is up to you.

- If you don't take part, it won't be held against you.

- You can take part now and later drop out, and it won't be held against you

- If you don't understand, ask questions.

- Ask all the questions you want before you decide.

How long will I be in this research? We expect that your taking part in this research will
last up to 6 months, after the 6 months we will look in your medical records every 180 days
for up to five years.

Why is this research being done? The purpose of this research is to create a clinical
database and bio-repository to study alcoholic hepatitis.

What happens to me if I agree to take part in this research? If you decide to take part in
this research study, the general procedures include: 1) allowing the investigators to review
your medical records, 2) answering questions about you and your health, 3) completing
questionnaires about alcohol use, 4) having a physical exam and blood drawn, and 5) providing
urine and stool samples.

Could being in this research hurt me? The most important risks or discomforts that you may
expect from taking part in this research include mild pain from blood draws and a small
chance for a loss of confidentiality (e.g., unauthorized users gain access to sensitive and
protected data about you).

Will being in this research benefit me? It is not expected that you will personally benefit
from this research. Possible benefits to others may include understanding specific health
conditions in patients with alcoholic hepatitis or other diseases.

CASES: Heavy drinkers with alcoholic hepatitis Inclusion criteria

1. A clinical diagnosis of alcoholic hepatitis

2. Serum total bilirubin >3 mg/dL

3. Subject or guardian ability to understand and willingness to provide written consent

4. Age greater or equal to 21 years

5. Re-enrolment of an alcoholic hepatitis donor is permissible up to 4 times if the donor
presents with a new episode of alcoholic hepatitis 24 weeks or longer after the most
recent enrolment in the study

Exclusion criteria

1. Liver disease significantly caused by hemochromatosis, autoimmune liver disease,
Wilson disease, NAFLD, and acute viral hepatitis

2. (NOTE: The presence of chronic hepatitis C, hepatitis B, or HIV is not exclusion to
participation.)Pregnant or breast feeding Based on the judgment of the investigator,
subject is not capable of understanding or complying with the study requirements.

CONTROLS: Heavy drinkers without significant liver disease Inclusion criteria

1. History of chronic alcohol consumption sufficient to cause liver damage. Generally,
this is considered to be >40 g/day or >280g/week on average for women and >60 g/day or
>420 g/week on average for men, for many years (usually decades). Judgement about
chronic alcohol consumption will be made by the site investigator.

2. Subject or guardian ability to understand and willingness to provide written consent

3. Age greater or equal to 21 years

Exclusion criteria

1. Past evidence of alcoholic liver disease, defined as a bilirubin > 2.0 mg/dL, an AST >
1.5 ULN, and any hospital admission for liver disease, or the presence of esophageal
varices or ascites (at any time in the past).

2. Liver disease significantly caused by hemochromatosis, autoimmune liver disease,
Wilson disease, NAFLD, and acute viral hepatitis (NOTE: The presence of chronic
hepatitis C, hepatitis B, or HIV is not exclusion to participation.)

3. Alcohol intake at less than 40 g/day or 280g/week on average for women and 60 g/day or
420 g/week on average for men for longer than the past 28 days

4. If liver stiffness has been assessed within the prior 90 days, then stiffness
suggesting fibrosis of F1 or greater is excluded. For Fibroscan, this is a fibrosis
score >7.0 kPa.

5. Pregnant or breast feeding

6. Any of the following laboratory abnormalities within 90 days prior to signing the
consent.

1. Total bilirubin: >ULN*

2. INR: > 1.4 5 *Individuals with a diagnosis of Gilbert's can have total bilirubin
up to 3.0 mg/dL and still be eligible for participation.

Healthy Controls

Inclusion criteria

1. AUDIT-C scores of <4 for men and <3 for women (signifying no alcohol misuse)

2. Abstinent (consumption of less than one standard drink/week) during the 6 months prior
to enrolment

3. Ability to understand and willingness to provide written consent.

Exclusion criteria

1. Clinical history or laboratory evidence of liver disease including alcoholic liver
disease, NAFLD, hemochromatosis, alcoholic hepatitis, autoimmune liver disease, Wilson
disease, hepatitis C, or hepatitis B.

2. Presence of diabetes (requiring treatment with oral agents or insulin).

3. Significant heart disease (prior history of heart disease, other than hypertension)

4. Chronic lung disease (requiring chronic treatment)

5. Immune related conditions (such as Crohn's disease, rheumatoid arthritis, ulcerative
colitis, systemic lupus erythematosus, severe psoriasis, etc.)

6. Known infection with HIV

7. Presumed infection, or use of antibiotics or other medications (e.g., corticosteroids)
that would affect immune function, within the past 14 days

8. BMI>35

9. Current or known history of cancer (except in situ carcinoma of the cervix or
adequately treated basal or squamous cell carcinoma of the skin) within 5 years prior
to enrollment

10. Pregnant or breast feeding

11. Any of the following laboratory abnormalities within 90 days prior to signing the
consent.

1. Hemoglobin: <10 g/dL

2. Conjugated bilirubin: > ULN

3. INR: > 1.4

4. AST: >40 IU/mL

5. ALT: >40 IU/mL

12. Based on the judgment of the investigator, subject is not capable of complying with
the study requirements