SETH-HA: Liver Transplantation in Alcoholic Hepatitis

Sponsor

Sociedad Española de Trasplante Hepático (Other)

Overall Status

Suspended

CT.gov ID

NCT01768715

Collaborator

Fundación Mutua Madrileña (Other)

Enrollment

Locations

Duration (Months)

2.4

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Alcoholic Hepatitis

Detailed Description

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

Inclusion criteria for patients:

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

Exclusion criteria :

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

Criteria for liver transplantation.

Absence of response to steroid therapy (Lille score ≥ 0.45 7 days after initiation of steroid therapy).
Adequate social and familiar environment.
Complete agreement in the medical staff about the candidate to transplantation.
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 Design

Study Type:

Observational

Anticipated Enrollment :

40 participants

Observational Model:

Case-Control

Time Perspective:

Prospective

Official Title:

Applicability of Liver Transplantation in Alcoholic Hepatitis

Study Start Date :

Jan 1, 2013

Anticipated Primary Completion Date :

Dec 1, 2014

Anticipated Study Completion Date :

Dec 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Good response Patients with severe alcoholic hepatitis and good response to therapy.
Non transplant candidates Patients with severe alcoholic hepatitis and poor response to therapy, that are not candidates to transplantation, according to the specified criteria.
Transplant candidates Patients with severe alcoholic hepatitis and poor response to therapy, that are candidates to transplantation, according to the specified criteria.

Outcome Measures

Primary Outcome Measures

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

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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

Exclusion Criteria:

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

Criteria for liver transplantation.

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

Contacts and Locations

Locations

	Site	City	State	Country
1	Hospital Central de Asturias	Oviedo	Asturias	Spain
2	Hospital Marqués de Valdecilla	Santander	Cantabria	Spain
3	Hospital Clínico Universitario de Santiago	Santiago de Compostela	La Coruña	Spain
4	Hospital Puerta de Hierro	Majadahonda	Madrid	Spain
5	Clínica Universidad de Navarra	Pamplona	Navarra	Spain
6	Hospital Vall d'Hebrón	Barcelona		Spain
7	Hospital Reina Sofía	Córdoba		Spain
8	Hospital Virgen de la Nieves	Granada		Spain
9	Complejo Hospitalario Universitario de la Coruña	La Coruña		Spain
10	Hospital Gregorio Marañón	Madrid		Spain
11	Hospital Ramón y Cajal	Madrid		Spain
12	Hospital Virgen de la Arrixaca	Murcia		Spain
13	Hospital Carlos Haya	Málaga		Spain
14	Hospital Virgen del Rocío	Sevilla		Spain
15	Hospital La Fe	Valencia		Spain
16	Hospital Río Hortega	Valladolid		Spain
17	Hospital Lozano Blesa	Zaragoza		Spain