Clinical trial NCT01768715: Liver Transplantation in Alcoholic Hepatitis
Official title: Applicability of Liver Transplantation in Alcoholic Hepatitis
Study type: OBSERVATIONAL
Overall status: SUSPENDED
Conditions: Alcoholic Hepatitis
Keywords: Alcoholic hepatitis
Liver transplantation
Survival
Alcoholism
Lead sponsor: Sociedad Española de Trasplante Hepático
Sponsor class: NETWORK
Collaborators: name: Fundación Mutua Madrileña
First posted: 2013-01-15
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with alcoholic hepatitis participating in this trial are going to be selected from patients admitted to the hospital (from the emergency department or referred from other hospital)

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Evaluate survival of patients with severe alcoholic hepatitis non responsive to therapy after liver transplantation
timeFrame: 1 year after the diagnosis of alcoholic hepatitis
Secondary outcomes:
measure: Evaluate the applicability of liver transplantation in patients with alcoholic hepatitis non responsive to steroid therapy
timeFrame: 1 year
measure: Evaluate the mortality in waiting list for transplantation of patients with alcoholic hepatitis unresponsive to steroid therapy
timeFrame: 1 year
measure: Evaluate the rate of alcohol recidivism after liver transplantation for alcoholic hepatitis
timeFrame: 1, 2, 3, 4 and 5 years
measure: Evaluate survival of patients with alcoholic hepatitis after liver transplantation.
timeFrame: 2, 3, 4 and 5 years after the diagnosis of alcoholic hepatitis
Other outcomes:
Locations:
city: Oviedo
country: Spain
facility: Hospital Central de Asturias
state: Asturias
city: Santander
country: Spain
facility: Hospital Marqués de Valdecilla
state: Cantabria
city: Santiago de Compostela
country: Spain
facility: Hospital Clínico Universitario de Santiago
state: La Coruña
city: Majadahonda
country: Spain
facility: Hospital Puerta de Hierro
state: Madrid
city: Pamplona
country: Spain
facility: Clínica Universidad de Navarra
state: Navarra
city: Barcelona
country: Spain
facility: Hospital Vall d'Hebrón
city: Córdoba
country: Spain
facility: Hospital Reina Sofía
city: Granada
country: Spain
facility: Hospital Virgen de la Nieves
city: La Coruña
country: Spain
facility: Complejo Hospitalario Universitario de la Coruña
city: Madrid
country: Spain
facility: Hospital Gregorio Marañón
city: Madrid
country: Spain
facility: Hospital Ramón y Cajal
city: Murcia
country: Spain
facility: Hospital Virgen de la Arrixaca
city: Málaga
country: Spain
facility: Hospital Carlos Haya
city: Sevilla
country: Spain
facility: Hospital Virgen del Rocío
city: Valencia
country: Spain
facility: Hospital La Fe
city: Valladolid
country: Spain
facility: Hospital Río Hortega
city: Zaragoza
country: Spain
facility: Hospital Lozano Blesa
Study officials:
affiliation: Clinica Universidad de Navarra
name: Ignacio Herrero, MD
role: STUDY_CHAIR
affiliation: Complejo Hospitalario Universitario de Santiago
name: Santiago Tome, MD
role: STUDY_CHAIR
affiliation: Hospital Central de Asturias
name: Ignacio Gonzalez-Pinto, MD
role: STUDY_CHAIR
References:
citation: Dominguez M, Rincon D, Abraldes JG, Miquel R, Colmenero J, Bellot P, Garcia-Pagan JC, Fernandez R, Moreno M, Banares R, Arroyo V, Caballeria J, Gines 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.
citation: Tome S, Martinez-Rey C, Gonzalez-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. doi: 10.1016/s0168-8278(02)00047-8.
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. doi: 10.1002/lt.21298.
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-Vallee JC. Early liver transplantation for severe alcoholic hepatitis. N Engl J Med. 2011 Nov 10;365(19):1790-800. doi: 10.1056/NEJMoa1105703.