Alcoholic Hepatitis Network Observational Study

CASES: Heavy drinkers with alcoholic hepatitis Inclusion criteria 1. A clinical diagnosis of alcoholic hepatitis as defined by the NIAAA pan-consortia for AH: 1. Onset of jaundice (defined as serum total bilirubin \>3 mg/dL) within the prior 8 weeks to screening visit 2. Regular consumption of alcohol with an intake of \> 40 gm daily or \>280gm weekly on average for women and \> 60 gm daily or \>420gm weekly on average for men for 6 months or more, with less than 8 weeks of abstinence before onset of jaundice 3. AST \> 50 IU/l 4. AST:ALT \> 1.5 and both values \< 400 IU/l 5. and/or histological evidence of AH\* 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, and acute viral hepatitis (NOTE: The presence of chronic hepatitis C, hepatitis B, HIV, or stage 1 (one lesion \<2 cm) HCC is not exclusion to participation) 2. Pregnant or breast feeding 3. Received liver transplant 4. 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 6 months or more. 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.) \*Individuals with a diagnosis of Gilbert's can have total bilirubin up to 3.0 mg/dL and still be eligible for 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. Received liver transplant 6. Pregnant or breast feeding 7. Any of the following laboratory abnormalities within 90 days prior to signing the consent. 1. Total bilirubin: \>ULN\* 2. INR: \> 1.4 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. 4. Age greater or equal to 21 years 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. Received liver transplant 11. Pregnant or breast feeding 12. 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 13. Based on the judgment of the investigator, subject is not capable of complying with the study requirements