Ensayos clínicos

CASES: Heavy drinkers with alcoholic hepatitis.

Inclusion Criteria:

• A clinical diagnosis of alcoholic hepatitis.
• Serum total bilirubin >3 mg/dL.
• Subject or guardian ability to understand and willingness to provide written consent.
• Age greater or equal to 21 years.
• 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:

• 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).
• 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

• 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. 
• Subject or guardian ability to understand and willingness to provide written consent.
• Age greater or equal to 21 years.

Exclusion Criteria:

• 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).
• 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.
• 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.
• 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.
• Pregnant or breast feeding.
• Any of the following laboratory abnormalities within 90 days prior to signing the consent:
  • 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:

• AUDIT-C scores of <4 for men and <3 for women (signifying no alcohol misuse).
• Abstinent (consumption of less than one standard drink/week) during the 6 months prior to enrolment.
• Ability to understand and willingness to provide written consent.

Exclusion Criteria:

• 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. 
• Presence of diabetes (requiring treatment with oral agents or insulin). 
• Significant heart disease (prior history of heart disease, other than hypertension).
• Chronic lung disease (requiring chronic treatment).
• Immune related conditions (such as Crohn's disease, rheumatoid arthritis, ulcerative colitis, systemic lupus erythematosus, severe psoriasis, etc.).
• Known infection with HIV.
• Presumed infection, or use of antibiotics or other medications (e.g., corticosteroids) that would affect immune function, within the past 14 days.
• BMI>35.
• 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.
• Pregnant or breast feeding.
• Any of the following laboratory abnormalities within 90 days prior to signing the consent:
  • Hemoglobin: <10 g/dL;
  • Conjugated bilirubin: > ULN;
  • INR: > 1.4;
  • AST: >40 IU/mL;
  • ALT: >40 IU/mL.
• Based on the judgment of the investigator, subject is not capable of complying with the study requirements.