Corticosteroids in Alcoholic Hepatitis

Study Overview
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Brief Summary
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Approximately 50% of patients admitted for severe AH will have spontaneous improvement of liver function before initiation of therapy (ie decrease in mDF between hospital admission and initiation of steroids). These patients have a better prognosis than patients without spontaneous improvement of liver function. It has never been demonstrated that corticosteroids improve survival in severe AH patients with spontaneous improvement of liver function. Our hypothesis is that severe AH patients with spontaneous improvement of liver function represent a group who could most benefit from steroids

Official Title
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Corticosteroids in Severe Alcoholic Hepatitis Patients With Early Spontaneous Improvement

Conditions
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Alcoholic Hepatitis

Intervention / Treatment
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* Drug: Methylprednisolone or placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical syndrome of alcoholic hepatitis: recent jaudice or in recent aggravation (< 3 months) serum bilirubin > 5 mg/dL history of excess alcohol abuse (> 40g/day) Alcoholic hepatitis proven by a liver biopsy (histological criteria of alcoholic hepatitis defined according to EASL clinical practice guidelines : steatosis, hepatocyte ballooning, and an inflammatory infiltrate with PMNs). The results of the liver biopsy are not mandatory for inclusion. However, the biopsy must be planned at the latest on day 1. When the results become available and do not confirm alcoholic hepatitis, the patient must discontinue the study. Spontaneous liver function improvement, defined by a decrease in serum bilirubin level > 10% between admission and day 5-10 after admission less than 2 weeks since admission to hospital Maddrey discriminant function* greater than or equal to 32 Subjects must voluntarily sign and date an informed consent form, approved by an Institutional Review Board (IRB)/Independent Ethics Committee (IEC) prior to the initiation of any screening or study-specific procedures. Subjects must be able to understand and adhere to the study visit schedule and all other protocol requirements. Patients with significant hepatic encephalopathy are not excluded from participation to the trial. In this case, the patient should be accompanied by a legal representative that will decide participation in the clinical study and sign ICF. Exclusion Criteria: Other causes of liver disease including viral hepatitis (positive HBs antigen, HCV RNA positive), auto-immune hepatitis, biliary obstruction Other disease compromising 90-day survival Positive HIV serology Uncontrolled infection All patients will be screened for infection. This will involve chest radiography, urinalysis, PMNs count in ascites (if ascites present). All other sign or clinical suspicion of infection with or without antibiotherapy will be recorded as an infection. Positive culture and initiation of antibiotics with clinical or radiological signs of infection, as well as clinical suspicion, will be recorded as infection. Patients with evidence of sepsis will be treated for a minimum of 2 days with appropriate antibiotics. Once the local principal investigator considers that the sepsis is under control, the patient may be rescreened and randomised. Uncontrolled gastrointestinal bleeding Bleeding must be judged as controlled for at least 5 days Patient with serum creatinine > 2.5 mg/dL, under renal replacement therapy or under terlipressine (or other vasoactive drugs) Pentoxyphilline therapy Pregnant or lactating women

Ages Eligible for Study
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Minimum Age: 18 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: methylprednisolone<br>Patients will receive 28 days of methylprednisolone 32 mg/day | Drug: Methylprednisolone or placebo<br>* Patients will receive 28 days of methylprednisolone 32 mg/day<br>|
| Placebo Comparator: placebo<br>Patients will receive 28 days of matching placebo | Drug: Methylprednisolone or placebo<br>* Patients will receive 28 days of methylprednisolone 32 mg/day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality at 90 days | To determine whether Methylprednisolone compared to placebo improve the 90 day mortality from patients with severe AH and spontaneous improvement of liver function | 90 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality at 28 days | To determine the 28 day mortality from patients with severe AH and spontaneous liver function improvement treated with Methylprednisolone or placebo | 28 days | 
| Incidence of infections during the study period (90 days) | To determine the incidence of infections during the 90 day study period in corticosteroid-treated compared to placebo-treated patients | 90 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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alcoholic hepatitis, spontaneous improvement, corticosteroids