Liver Transplantation in Alcoholic Hepatitis

Alcoholic Hepatitis Clinical Trial

— SETH-HA  

Official title:

Applicability of Liver Transplantation in Alcoholic Hepatitis

Clinical Trial Details — Status: Suspended

Administrative data

• NCT number: NCT01768715
• Other study ID #: SETH-HA
• Status: Suspended
• Phase: N/A
• First received: December 29, 2012
• Last updated: June 2, 2014
• Start date: January 2013
• Est. completion date: December 2017

Study information

• Verified date: June 2014
• Source: Sociedad Española de Trasplante Hepático
• Contact: n/a
• Is FDA regulated: No
• Health authority: Spain: Comité Ético de Investigación Clínica
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Suspended
• Enrollment: 40
• Est. completion date: December 2017
• Est. primary completion date: December 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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

Observational Model: Case Control, Time Perspective: Prospective

Related Conditions & MeSH terms

• Alcoholic Hepatitis
• Hepatitis
• Hepatitis A
• Hepatitis, Alcoholic

Locations

Country	Name	City	State
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	Hospital Ramón y Cajal	Madrid
Spain	Hospital Puerta de Hierro	Majadahonda	Madrid
Spain	Hospital Carlos Haya	Málaga
Spain	Hospital Virgen de la Arrixaca	Murcia
Spain	Hospital Central de Asturias	Oviedo	Asturias
Spain	Clínica Universidad de Navarra	Pamplona	Navarra
Spain	Hospital Marqués de Valdecilla	Santander	Cantabria
Spain	Hospital Clínico Universitario de Santiago	Santiago de Compostela	La Coruña
Spain	Hospital Virgen del Rocío	Sevilla
Spain	Hospital La Fe	Valencia
Spain	Hospital Río Hortega	Valladolid
Spain	Hospital Lozano Blesa	Zaragoza

Sponsors (2)

Lead Sponsor	Collaborator
Sociedad Española de Trasplante Hepático	Fundación Mutua Madrileña

Country where clinical trial is conducted

Spain, 

References & Publications (4)

Dominguez M, Rincón D, Abraldes JG, Miquel R, Colmenero J, Bellot P, García-Pagán JC, Fernández R, Moreno M, Bañares R, Arroyo V, Caballería J, Ginès P, Bataller R. A new scoring system for prognostic stratification of patients with alcoholic hepatitis. Am J Gastroenterol. 2008 Nov;103(11):2747-56. doi: 10.1111/j.1572-0241.2008.02104.x. Epub 2008 Aug 21. — View Citation

Mathurin P, Moreno C, Samuel D, Dumortier J, Salleron J, Durand F, Castel H, Duhamel A, Pageaux GP, Leroy V, Dharancy S, Louvet A, Boleslawski E, Lucidi V, Gustot T, Francoz C, Letoublon C, Castaing D, Belghiti J, Donckier V, Pruvot FR, Duclos-Vallée JC. Early liver transplantation for severe alcoholic hepatitis. N Engl J Med. 2011 Nov 10;365(19):1790-800. doi: 10.1056/NEJMoa1105703. — View Citation

Tomé S, Martinez-Rey C, González-Quintela A, Gude F, Brage A, Otero E, Abdulkader I, Forteza J, Bustamante M, Varo E. Influence of superimposed alcoholic hepatitis on the outcome of liver transplantation for end-stage alcoholic liver disease. J Hepatol. 2002 Jun;36(6):793-8. — View Citation

Wells JT, Said A, Agni R, Tome S, Hughes S, Dureja P, Lucey MR. The impact of acute alcoholic hepatitis in the explanted recipient liver on outcome after liver transplantation. Liver Transpl. 2007 Dec;13(12):1728-35. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Evaluate survival of patients with severe alcoholic hepatitis non responsive to therapy after liver transplantation	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	1 year after the diagnosis of alcoholic hepatitis	No
Secondary	Evaluate the applicability of liver transplantation in patients with alcoholic hepatitis non responsive to steroid therapy	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.	1 year	No
Secondary	Evaluate the mortality in waiting list for transplantation of patients with alcoholic hepatitis unresponsive to steroid therapy	Proportion of patients who are accepted as candidates for liver transplantation who die before transplantation.	1 year	No
Secondary	Evaluate the rate of alcohol recidivism after liver transplantation for alcoholic hepatitis	Proportion of patients transplanted for alcoholic hepatitis that have a recurrence in alcohol consumption	1, 2, 3, 4 and 5 years	Yes
Secondary	Evaluate survival of patients with alcoholic hepatitis after liver transplantation.	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	2, 3, 4 and 5 years after the diagnosis of alcoholic hepatitis	No