Trial of Anakinra (Plus Zinc) or Prednisone in Patients With Severe Alcoholic Hepatitis

Inclusion criteria

• AH, as defined by the NIAAA pan-consortia for AH:

• Onset of jaundice (defined as serum total bilirubin >3 mg/dL) within the prior 8 weeks to screening visit
• 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
• AST > 50 IU/l
• AST:ALT > 1.5 and both values < 400 IU/l
• and/or histological evidence of AH*
• MELD 20-35 on day of randomization.
• Ages >21

• In patients with possible AH or AH with confounding factors such as possible ischemic hepatitis, possible DILI, uncertain history of alcohol use (e.g., patient denies excessive alcohol use), and atypical/abnormal laboratory tests (e.g., AST < 50 IU/L or > 400 IU/L, AST/ALT ratio < 1.5), antinuclear antibody > 1:160 or SMA > 1:80, a standard of care liver biopsy may be performed during current hospital admission to confirm AH and exclude competing etiologies

Exclusion criteria

• MELD SCORE <20 or > 35
• Active sepsis (positive blood or ascitic cultures) with Systemic Inflammatory Response Syndrome (SIRS) or hemodynamic compromise requiring intravenous pressors to maintain tissue perfusion
• Pneumonia as evidenced by radiological exam
• Multi-organ failure
• Renal failure defined by GFR <35 mL/min by CKD-EPI.
• Clinically active C. diff infection
• History of imaging of the liver (ultrasound, computerized tomography or magnetic resonance) showing other causes of jaundice
• History of other liver diseases including hepatitis B (positive HBsAg or HBV DNA), hepatitis C (positive HCV RNA), autoimmune hepatitis, Wilson disease, genetic \\hemochromatosis, alpha1-antitrypsin deficiency or strong suspicion of Drug Induced Liver Injury (DILI). Previously treated hepatitis C that was cured (sustained virological response with negative RNA ≥24 weeks following treatment) is not an exclusion.
• History of HIV infection (positive HIV RNA or on treatment for HIV infection)
• History or presence of cancer (including hepatocellular carcinoma) other than non- melanoma skin cancer
• History of other significant medical problems such as autoimmune diseases, severe asthma, psoriasis, Inflammatory Bowel Disease (IBD), etc. that might require immunosuppressive treatments
• Pregnancy or breastfeeding
• Prior exposure to experimental therapies in last 3 months
• Prior exposure to systemic corticosteroid (glucocorticoid) or immunosuppressive therapy for more than 4 days within previous 30 days
• Need for inotropic pressor support to maintain perfusion to critical organs within prior 48 hours before randomization and initiation of experimental treatment
• Clinically significant pancreatitis- abdominal pain, elevated lipase (> 3 X ULN) and at least edema of pancreas with fat-stranding on CT scan
• Total WBC count > 30,000/mm3
• Known allergy or intolerance to therapeutic agents to be tested
• Inability to voluntarily obtain informed consent from participant or guardian
• Perceived inability to follow study procedures and comply with protocol
• Platelet count < 40,000 k/cumm.
• Positive PCR test for COVID -19 within 7 days prior to the baseline day 0 visit
• Active gastrointestinal bleeding defined as hematemesis or melena with a decrease in hemoglobin more than 2 g/dl in 24 hrs. Due to gastrointestinal bleeding, or with a decrease in mean arterial BP to < 65 mmHg.

• Positive test is exclusionary only during screening period. If a patient tests positive any time after baseline randomization, a positive PCR test for COVID-19 will be considered as a SAE.