Novel Therapies in Moderately Severe Acute Alcoholic Hepatitis

Study Overview
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Brief Summary
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This study is being done to find out whether a diet supplemented with a probiotic nutrient can improve alcoholic hepatitis and gut complications compared to routine standard care.

Detailed Description
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Aim 1: Evaluate the effects of probiotic supplements on improvement in MELD score and gut mucosal integrity in patients with MELD < 21. Patients will be randomized to receive daily probiotics for 6 months and standard of care treatment or placebo with standard care. Aim 2: Document the natural history of moderately severe alcoholic hepatitis. Patients who decline randomization will be offered the option of inclusion in the study prospectively for data collection purposes and research study procedures. Aim 3: Create a data and tissue biorepository. This biorepository will serve as a national resource for studies related to acute alcoholic hepatitis.

Official Title
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Novel Therapies in Moderately Severe Acute Alcoholic Hepatitis

Conditions
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Acute Alcoholic Hepatitis

Intervention / Treatment
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* Dietary Supplement: Lactobacillus Rhamnosus GG
* Drug: Placebo for Probiotic


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ability to provide informed consent by subject or appropriate family member Age between 21-70 years Recent alcohol consumption > 50 g/d for > 6 months, continuing within two months before enrollment At least 2 of the following symptoms or signs of acute alcoholic hepatitis: Anorexia, nausea, RUQ pain, jaundice, leukocytosis, hepatomegaly AND Elevation of AST > 80 U/L, but < 500 U/L at the time of admission or within 3 days of baseline visit; AST > ALT and ALT < 200 U/L; total bilirubin > 3 mg/dL AND Liver biopsy showing alcoholic hepatitis (steatohepatitis) OR ultrasound of liver showing increased echogenicity OR CT scan showing decreased attenuation of liver compared to spleen OR MRI showing fatty liver (decreased signaling intensity on T1 weighted images). If the liver biopsy (done within 60 days of inclusion) confirms diagnosis of AAH then inclusion e will be waived. Model for End-Stage Liver Disease (MELD) <20 Willingness to utilize two reliable forms of contraception (both males and females of childbearing potential) from screening through the first six weeks of study. Exclusion Criteria: Hypotension with BP < 80/50 after volume repletion Pregnancy; incarceration; inability to provide consent or lack of appropriate family member Signs of systemic infection: Fever > 38o C and positive blood or ascites cultures on appropriate antibiotic therapy for > 3 days within 3 days of inclusion Acute gastrointestinal bleeding requiring > 2 units blood transfusion within the previous 4 days Undue risk from immunosuppression: Positive HBsAg; a positive skin PPD skin test or history of treatment for tuberculosis; history of any malignancy including hepatocellular carcinoma; known HIV infection Treatment with corticosteroids or other immunosuppressive medications including specific anti-TNF therapy (not including pentoxifylline), calcineurin inhibitors for > 3 days within the previous 3 months. Evidence of acute pancreatitis: CT evidence and/or amylase or lipase > 5 X upper limit of normal Serious cardiac, respiratory or neurologic disease or evidence of autoimmune hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis, Wilsons disease, hemochromatosis, secondary iron overload due to chronic hemolysis, alpha-1-antitrypsin deficiency Acute or chronic kidney injury with serum creatinine > 3.0 mg/dl

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo for Probiotic<br>Placebo capsule that matches the probiotic capsule in appearance will be given once daily for 180 days. | Drug: Placebo for Probiotic<br>* Capsule manufactured without active ingredients.<br>* Other names: Dummy capsule;|
| Active Comparator: Lactobacillus Rhamnosus GG<br>Dietary supplement capsule (Lactobacillus Rhamnosus GG) will be given once daily for 180 days. | Dietary Supplement: Lactobacillus Rhamnosus GG<br>* Probiotic nutritional supplement; Lactobacillus Rhamnosus GG<br>* Other names: Culturelle;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MELD Score | Change in MELD scoring system for assessing the severity of chronic liver disease; MELD (Model of End Stage Liver Disease) scoring system for assessing the severity of chronic liver disease; calculated from serum bilirubin, serum creatinine, and the international normalized ratio for prothrombin time (INR) MELD = 3.8[Ln serum bilirubin (mg/dL)] + 11.2[Ln INR] + 9.6[Ln serum creatinine (mg/dL)] + 6.4. MELD score range from 6-40 with higher scores indicating more severe liver disease and a worse outcome. | 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MELD Score | Change in MELD scoring system over 180 day study duration. MELD (Model of End Stage Liver Disease) scoring system for assessing the severity of chronic liver disease; calculated from serum bilirubin, serum creatinine, and the international normalized ratio for prothrombin time (INR) MELD = 3.8[Ln serum bilirubin (mg/dL)] + 11.2[Ln INR] + 9.6[Ln serum creatinine (mg/dL)] + 6.4. MELD score range from 6-40 with higher scores indicating more severe liver disease and a worse outcome. | 180 days | 
| MELD Score | Change in MELD scoring system at 90 days study duration. MELD (Model of End Stage Liver Disease) scoring system for assessing the severity of chronic liver disease; calculated from serum bilirubin, serum creatinine, and the international normalized ratio for prothrombin time (INR) MELD = 3.8[Ln serum bilirubin (mg/dL)] + 11.2[Ln INR] + 9.6[Ln serum creatinine (mg/dL)] + 6.4. MELD score range from 6-40 with higher scores indicating more severe liver disease and a worse outcome. | 90 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Alcoholic Hepatitis, MELD < 20, Probiotic, Nutritional Supplement, Lactobacillus Rhamnosus GG