Liver Transplantation in Alcoholic Hepatitis

Suspended

• Conditions: Alcoholic Hepatitis

• Registration Number: NCT01768715
• Lead Sponsor: Sociedad Española de Trasplante Hepático

Brief Summary

Patients with alcoholic hepatitis non-responsive to steroids have a poor prognosis. Recently a French-Belgian prospective study has obtained good results (acceptable survival with a low rate of alcohol recidivism).

The hypothesis of the present study is that carefully selected Spanish patients with alcoholic hepatitis that do not respond to steroid therapy may have a good survival if they receive a liver transplant. The expected rate of alcohol recidivism in such a selected population will be low.

Detailed Description

This is a open prospective multicenter study. Nineteen liver transplant units in Spain will take part in it.

Inclusion criteria for patients:

1. Diagnosis of alcoholic hepatitis (liver biopsy will be advisable).

2. First episode of clinical decompensation of alcoholic liver disease (defined as jaundice, variceal bleeding, ascites or portal-systemic encephalopathy).

3. Absence of a high risk of alcoholic recidivism (according to De Gottardi, et al).

4. Severe alcoholic hepatitis (ABIC score \> 6.71)

5. Informed consent

Exclusion criteria :

1. Age over 65 years.

2. Hepatitis B or C or HIV infections.

3. Uncontrolled bacterial infection

4. Other liver diseases, such as alpha-1-antitrypsin deficiency, primary biliary cirrhosis, ...

5. Morbid obesity (BMI \> 35 kg/m2)

6. Major uncontrolled psychiatric disease

7. Drug addiction (excluding tobacco) in the last two years.

8. Absence of informed consent.

9. Acute-on-chronic liver disease.

10. Paracetamol consumption over 10 grams in the last week.

Criteria for liver transplantation.

1. Absence of response to steroid therapy (Lille score ≥ 0.45 7 days after initiation of steroid therapy).

2. Adequate social and familiar environment.

3. Complete agreement in the medical staff about the candidate to transplantation.

4. Absence of bacterial or fungal infection.

Three groups of patients will be formed:

Group 1. Patients with severe alcoholic hepatitis and good response to therapy. Group 2. Patients with severe alcoholic hepatitis and poor response to therapy, that are not candidates to transplantation.

Group 3. Patients with severe alcoholic hepatitis and poor response to therapy, that are candidates to transplantation.

A complete follow-up of the patients would be extended to five years. The survival of these three groups will be compared. Survival of liver transplant recipients should also be compared with survival of other liver transplant recipients.

Alcohol recidivism should also be studied in all the patients of the study. Sample size estimation: According to the data published by Mathurin et al, 28 patients treated with liver transplantation and 28 non-transplanted patients with severe alcoholic hepatitis should be necessary.

Interim analysis after every 10 transplanted patients should be performed. The study will be interrupted if the differences in the survivals between groups 2 and 3 reaches a significance of 0.01. In case this significance is not reached the inclusion of patients should end when 40 patients are transplanted. This sample size is estimated to be reached in 18-24 months.

Study Timeline

• Study First Submitted: 2012-12-29
• Study Start: 2013-01
• Study First Submitted QC: 2013-01-13
• Study First Posted: 2013-01-15
• Status Verified: 2014-06
• Last Update Submitted: 2014-06-02
• Last Update Posted: 2014-06-03
• Primary Completion: 2014-12
• Study Completion: 2017-12

Recruitment & Eligibility

• Status: SUSPENDED
• Sex: All
• Target Recruitment: 40

Inclusion Criteria

1. Diagnosis of alcoholic hepatitis (liver biopsy will be advisable).
2. First episode of clinical decompensation of alcoholic liver disease (defined as jaundice, variceal bleeding, ascites or portal-systemic encephalopathy).
3. Absence of a high risk of alcoholic recidivism (according to De Gottardi, et al).
4. Severe alcoholic hepatitis (ABIC score > 6.71)
5. Informed consent

Exclusion Criteria

1. Age over 65 years.
2. Hepatitis B or C or HIV infections.
3. Uncontrolled bacterial infection
4. Other liver diseases, such as alpha-1-antitrypsin deficiency, primary biliary cirrhosis, ...
5. Morbid obesity (BMI > 35 kg/m2)
6. Major uncontrolled psychiatric disease
7. Drug addiction (excluding tobacco) in the last two years.
8. Absence of informed consent.
9. Acute-on-chronic liver disease.
10. Paracetamol consumption over 10 grams in the last week.

Criteria for liver transplantation.

1. Absence of response to steroid therapy (Lille score ≥ 0.45 7 days after initiation of steroid therapy).
2. Adequate social and familiar environment.
3. Complete agreement in the medical staff about the candidate to transplantation.
4. Absence of bacterial or fungal infection.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Evaluate survival of patients with severe alcoholic hepatitis non responsive to therapy after liver transplantation	1 year after the diagnosis of alcoholic hepatitis	The survival of patients transplanted with alcoholic hepatitis is going to be compared with the survival of patients with alcoholic hepatitis that are not considered adequate for liver transplantation

Secondary Outcome Measures

Name	Time	Method
Evaluate the applicability of liver transplantation in patients with alcoholic hepatitis non responsive to steroid therapy	1 year	The applicability of liver transplantation is defined as the ratio between the number of patients transplanted for alcoholic hepatitis and the number of patients with severe alcoholic hepatitis that do not respond to steroid therapy.
Evaluate the mortality in waiting list for transplantation of patients with alcoholic hepatitis unresponsive to steroid therapy	1 year	Proportion of patients who are accepted as candidates for liver transplantation who die before transplantation.
Evaluate the rate of alcohol recidivism after liver transplantation for alcoholic hepatitis	1, 2, 3, 4 and 5 years	Proportion of patients transplanted for alcoholic hepatitis that have a recurrence in alcohol consumption
Evaluate survival of patients with alcoholic hepatitis after liver transplantation.	2, 3, 4 and 5 years after the diagnosis of alcoholic hepatitis	The survival of patients transplanted with alcoholic hepatitis is going to be compared with the survival of patients with alcoholic hepatitis that are not considered adequate for liver transplantation

Trial Locations

Locations (17)

Hospital Central de Asturias; 🇪🇸 Oviedo, Asturias, Spain

Hospital Marqués de Valdecilla; 🇪🇸 Santander, Cantabria, Spain

Hospital Clínico Universitario de Santiago; 🇪🇸 Santiago de Compostela, La Coruña, Spain

Hospital Puerta de Hierro; 🇪🇸 Majadahonda, Madrid, Spain

Clínica Universidad de Navarra; 🇪🇸 Pamplona, Navarra, Spain

Hospital Vall d'Hebrón; 🇪🇸 Barcelona, Spain

Hospital Reina Sofía; 🇪🇸 Córdoba, Spain

Hospital Virgen de la Nieves; 🇪🇸 Granada, Spain

Complejo Hospitalario Universitario de la Coruña; 🇪🇸 La Coruña, Spain

Hospital Gregorio Marañón; 🇪🇸 Madrid, Spain

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