Digoxin In Treatment of Alcohol Associated Hepatitis

Inclusion Criteria:

1. Diagnosis of alcohol associated hepatitis based on clinical criteria or histologicevidence

2. Clinical criteria:

• Onset of jaundice (bilirubin >3 mg/dL) within the prior 8 weeks

• Regular alcohol use > 6 months, with intake of > 40 g/day (>280 g/week) forwomen; and > 60 g/day (>420 g/week) for men

• AST > 50 IU/l

• AST: ALT > 1.5 and both values < 400 IU/l

2. Histological evidence of alcohol associated hepatitis*

3. MDF >32 or MELD ≥ 20 to ≤ 35 on Day 0 of the trial

4. Age between 21 and 70 years, inclusive

• In patients with possible alcohol associated hepatitis with confounding factorssuch as possible ischemic hepatitis, possible DILI, uncertain history of alcoholuse, or atypical/abnormal laboratory tests (e.g., AST < 50 IU/IU/L or > 400 IU/IU/L,AST/ALT ratio < 1.5), antinuclearantibody > 1:160 or SMA > 1:80, standard of careliver biopsy may be performed as per discretion of the primary attending physicianto confirm alcohol associated hepatitis and exclude competing etiologies. Thedecision to perform liver biopsy will be made by the primary team and will occurregardless of the study. As per current SOC, a liver biopsy may be obtained toconfirm suspected alcohol-associated hepatitis and to rule out other potentialetiologies of liver disease. If a liver biopsy is performed for clinically indicated reasons, we will store livertissue that is left over after the portion needed for the primary indication hasbeen identified.

Exclusion Criteria:

1.

• Currently pregnant or breastfeeding

2.

• Inability of patient, legally authorized representative or next-of-kin toprovide informed consent

3.

• Allergy or intolerance to digoxin

4.

• Clinically active C. diff infection

5.

• Positive test for COVID-19 within 14 days prior to the screening visit

6.

• Acute hepatitis E, Cytomegalovirus, Epstein Barr Virus, Herpes SimplexVirus

7- History of other liver diseases including hepatitis B (positive HBsAg or HBVDNA), hepatitis 8-C (positive HCV RNA), autoimmune hepatitis, Wilson disease,genetic hemochromatosis, alpha1-antitrypsin deficiency.

8-Diagnosis of Drug Induced Liver Injury (DILI), or other etiologies seen on liverimaging.

9 - History of HIV infection (positive HIV RNA or on treatment for HIV infection)

10 - Current diagnosis of cancer

11- Renal failure defined by GFR <30 mL/min

12 - Refractory ascites, defined as having more than 4 paracenteses in the preceding 8 weeks despite diuretic therapy

13 - Prior exposure to experimental therapies or other clinical trial in last 3months

14 - Current acute or chronic pancreatitis

15 - Active gastrointestinal bleeding unless resolved for >48 hours

16 - Experiencing withdrawal seizures or considered at high risk for alcoholwithdrawal seizures or delirium tremens

17 - Heart rate less than 60 bpm at screening visit or at baseline

18 - Current diagnosis of atrial fibrillation

19 - Cardiomyopathy

20 - Heart failure

21 - Severe aortic valve disease

22 - Presence of Accessory arterio-ventricular pathway (eg Wolf-Parkinson-Whitesyndrome)

23 - Complete heart block or second degree arterio-ventricular block withoutpacemaker or implantable cardiac device

24 - Any of the following within the previous 6 months: myocardial infarction,percutaneous intervention, pacemaker/implantable cardiac device implantation,cardiac surgery or stroke

25 - Current use of the following medications:

• Antiarrhythmic (amiodarone, dofetilide, sotalol, dronedarone)

• Parathyroid hormone analog (teriparatide)

• Thyroid supplement (thyroid, levothyroxine sodium)

• Sympathomimetics or ionotropic drugs (epinephrine, norepinephrine, dopamine,dobutamine, milrinone)

• Neuromuscular blocking agents (succinylcholine)

• Calcium supplement

• Ivabradine

• Disulfiram