Intensive Enteral Nutrition and Acute Alcoholic Hepatitis

Study Overview
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Brief Summary
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To evaluate the effect of an intensive enteral nutrition (compared to clinical routine) in association with corticosteroïds in patients with severe acute alcoholic hepatitis.

Detailed Description
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Acute alcoholic hepatitis (AAH) is characterized by hepatocellular necrosis, ballooning degeneration and an inflammatory reaction with many polymorphonuclear leukocytes, and fibrosis (Mezey E. Treatment of alcoholic liver disease. Semin Liver Dis 1993). The presence of a severe AAH was identified by the presence of a discriminant function (DF) ≥ 32. DF ≥ 32 has been shown to prospectively identify patients with a 40 to 50 % risk of dying within 2 months (Ramond et al, NEJM 1992). The main treatment of AAH consists of abstinence from alcohol. Corticosteroids are generally recommended in patients with severe AAH. Indeed, a recent analysis of the individual data of the patients from the last three randomized controlled trials showed a significantly higher 1-month survival in corticosteroids compared to placebo treated patients with a severe AAH (Mathurin et al, J hepatol 2002). However, efficacy of this therapy is insufficient, since around 40 % of patients with a severe AAH do not respond to corticosteroids (Louvet et al, Hepatology 2007). Moreover, corticosteroïds are still contraindicated in case of active infection or gastrointestinal bleeding, which are relatively common complications in those patients. Therefore, alternative therapeutic options are needed and must be a medical priority. Alcoholic patients with severe AAH are frequently malnourished and usually remain anorectic for several weeks (DiCecco SR et al, Nutr Clin Pract 2006). Some data indicate that malnutrition is a factor of bad prognosis in this disease. Recent evidence was also provided that adequate enteral nutritional support might have an important impact on long-term survival in those patients (Cabré et al, Hepatology 2000). However, up to now, no study evaluated potential synergetic effect of intensive enteral nutrition and corticosteroids. Moreover, in clinical practice, in the majority of the centers, patients with alcoholic hepatitis receive alimentary supplements and dietetic counseling, which is often insufficient and difficult to apply and to follow. Aim : To evaluate the effect of an intensive enteral nutrition (compared to clinical routine which consists in oral supplements) in association with corticosteroïds in patients with severe acute alcoholic hepatitis.

Official Title
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Intensive Enteral Nutrition in Association With Corticosteroids in Severe Acute Alcoholic Hepatitis: a Multicenter, Randomized, Controlled Trial

Conditions
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Severe Alcoholic Hepatitis

Intervention / Treatment
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* Dietary Supplement: intensive nutrition
* Dietary Supplement: usual meals


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Acute alcoholic hepatitis proven by a liver biopsy (necessary histological findings : neutrophils infiltration, ballooned hepatocytes and Mallory bodies) Presence of a severe disease, defined by a Maddrey score higher than or equal to 32, at screening and in baseline (day 0). Maddrey score = total bilirubin in mg/dl + 4,6 X (Prothrombin time patient in sec - prothrombin time control in sec) Age between 18 and 75 years old, extremes included Recent jaundice or in recent aggravation (less than 3 months) Chronic alcohol consumption (more than 40 g/day) Informed consent read, understand and signed by the patient (in case of significant encephalopathy, a family representative can signed in place of the patient) Maximal delay between admission and randomization of 14 days. Exclusion Criteria: Other disease compromising 6 months survival of the patient Positive HIV or HCV serology, positive HBs Antigen Uncontrolled bacterial or fungal infection (infection must be judged controlled for at least 3 days) Uncontrolled upper GI bleeding (bleeding must be controlled for at least 5 days) Type 1 Hepatorenal syndrome (creatinin upper than 2,5 mg/dl), as defined by Salerno F et al, Gut 2007;56:1310-1318 History of bariatric surgery Pentoxyphilline therapy MARS therapy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: intensive arm<br>Corticosteroïds (Methylprednisolone 32 mg/d) for 28 days + intensive enteral nutrition by feeding tube for 14 days | Dietary Supplement: intensive nutrition<br>* Patients randomized in  intensive enteral nutrition  arm will receive by feeding tube (with the use of a microsonde), and in continuous administration, 2 liters of Fresubin HP Energy (1500 kcal/liter, 75 gr prot/liter) for patients with a weight of more than 90 kgs (after ascites removal), 1.5 liters of Fresubin HP Energy for patients with a weight between 60 and 90 kgs, and 1 liter of Fresubin HP Energy for patients of less than 60 kgs. Patients with significant encephalopathy despite therapy against encephalopathy will receive Fresubin Hepa in place of Fresubin HP Energy (1300 kcal/liter, 40 gr prot/liter, 44 % branched AA). Duration of enteral nutrition by feeding tube will be 14 days. The adaptation to the targeted volume must be achieved in maximum 3 days. Enteral nutrition will be administered by nasogastric microsonde.<br>|
| Active Comparator: control arm<br>Corticosteroïds (Methylprednisolone 32 mg/d) for 28 days +  classical  oral alimentation for 14 days | Dietary Supplement: usual meals<br>* Patients randomized in  classical oral nutrition  arm (control arm) will receive usual meals (estimated at 1750 kcal/day; 70 g protein/day), and alimentary supplements between meals to achieve the ESPEN recommandations (35-40 kcal/kg/day; protein 1.2-1.5 g/kg/day) (Plauth et al, Clinical Nutrition 2006). Calories and proteins intake must be recorded daily.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| survival |  | 6 months survival | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| survival |  | 1 month |