Intensive Enteral Nutrition and Acute Alcoholic Hepatitis

Not Applicable

Completed

• Conditions: Severe Alcoholic Hepatitis
• Interventions: Dietary Supplement: intensive nutrition; Dietary Supplement: usual meals

• Registration Number: NCT01801332
• Lead Sponsor: Erasme University Hospital

Brief Summary

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

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.

Study Timeline

• Study Start: 2010-02
• Status Verified: 2013-02
• Primary Completion: 2013-02
• Study First Submitted: 2013-02-27
• Study First Submitted QC: 2013-02-27
• Last Update Submitted: 2013-02-27
• Study First Posted: 2013-02-28
• Last Update Posted: 2013-02-28

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 136

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
intensive arm	intensive nutrition	Corticosteroïds (Methylprednisolone 32 mg/d) for 28 days + intensive enteral nutrition by feeding tube for 14 days
control arm	usual meals	Corticosteroïds (Methylprednisolone 32 mg/d) for 28 days + " classical " oral alimentation for 14 days

Primary Outcome Measures

Name	Time	Method
survival	6 months survival

Secondary Outcome Measures

Name	Time	Method
survival	1 month

Trial Locations

Locations (19)

Cliniques universitaires Saint-Luc; 🇧🇪 Brussels, Belgium

CHR La Citadelle; 🇧🇪 Liège, Belgium

Hôpitaux Iris-Sud; 🇧🇪 Brussels, Belgium

ULG Sart Tilman; 🇧🇪 Liège, Belgium

Hôpital Saint-Joseph; 🇧🇪 Liège, Belgium

Hôpital Ottignies; 🇧🇪 Ottignies-Louvain-La-Neuve, Belgium

Hôpital Ambroise Paré; 🇧🇪 Mons, Belgium

AZ Brugge; 🇧🇪 Brugge, Belgium

CHU Brugmann; 🇧🇪 Brussels, Belgium

UZ Antwerpen; 🇧🇪 Antwerp, Belgium

CHU Saint-Pierre; 🇧🇪 Brussels, Belgium

AZ VUB; 🇧🇪 Brussels, Belgium

Erasme University Hospital; 🇧🇪 Brussels, Belgium

KU Leuven; 🇧🇪 Leuven, Belgium

UZ Gent; 🇧🇪 Gent, Belgium

Hôpital de Jolimont; 🇧🇪 La Louvière, Belgium

CHR Saint Joseph-Warquignies; 🇧🇪 Mons, Belgium

CHU Caen; 🇫🇷 Caen, France

CHU Lille; 🇫🇷 Lille, France