Validation of a Prognostic Score for Steroid Therapy Response in Acute Severe Autoimmune Hepatitis

NCT ID: NCT05473403

Last Updated: 2024-03-13

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 150 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-06-01
• Study Completion Date: 2028-06-30

Brief Summary

Autoimmune hepatitis (AIH) is a chronic liver disease, which is characterized by the increase of immunoglobulin G (IgG) level, the presence of auto-antibodies and a typical histology, in the absence of other liver disease.

Due to the heterogeneity of AIH manifestations, different scoring systems have been validated in order to make a reliable diagnosis. The two most recent scoring systems are: the revised International Autoimmune Hepatitis Group (IAIHG) criteria and the IAIHG simplified criteria. The second one is recommended by the European Association for the Study of the Liver (EASL) clinical practice guidelines (CPGs).

The EASL clinical practice guidelines suggests that the treatment of ASAIH (Acute Severe AIH) is high doses of corticosteroids (superior to 1mg/kg/day) as early as possible and a lack of improvement within seven days should lead to listing for emergency liver transplantation (LT). However, the "lack of improvement" is not objectively defined and the grading of recommendation is III (Opinions of respected authorities).

The hypothesis of the study is that the previously developed decisional score on a retrospective series will prospectively allow the differentiation between patients with ASAIH (Acute Severe AIH) who respond to corticosteroid therapy and should be maintained on treatment and patients who do not respond and should be rapidly evaluated for LT. The score will be computed at day 3 since corticosteroid introduction.

Detailed Description

All the interventions (blood samples, imagery examinations, visits, liver biopsy, corticosteroid therapy, liver transplantation) will be performed following the standard of care for ASAIH. The investigators of the participating centers will not change their standard management for the study protocol. The management will follow the recommendation of EASL CPGs.

The prognostic score will allow to distinguish between patient's responders and non-responders to corticosteroid therapy in ASAIH. This knowledge will avoid the prolonged duration of the corticosteroid therapy in patients for whom this therapy is futile or harmful and rapidly select the patients for LT. Of course considering that the created score is decisional whether a patient is a candidate for LT, a prospective validation is mandatory to use it as a clinical tool for the day-to-day practice. This is the first prospective study on ASAIH.

Conditions

Liver Failure, Acute; Hepatitis, Autoimmune; Organ Dysfunction Scores; Risk Factors

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

Corticosteroid therapy

Prednisone or Prednisolone or Methylprednisolone : Patient with ASAIH will be treated in oral or intravenous (IV) with high doses ( ≥ 1mg/kg/day) of corticosteroids (Prednisone or Prednisolone or Methylprednisolone) until relapse (confirmed by blood tests and clinical status) requiring an emergency Liver Transplantation (LT) or death.

Group Type: EXPERIMENTAL

Corticosteroid therapy

Intervention Type: OTHER

Administration of high doses of corticosteroids as early as possible. Patient non-responder to treatment should lead to listing for emergency liver transplantation (LT).

Patient without corticosteroid therapy

Patient not treated will undergo to emergency Liver Transplantation (LT) or death.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Corticosteroid therapy

Administration of high doses of corticosteroids as early as possible. Patient non-responder to treatment should lead to listing for emergency liver transplantation (LT).

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Age ≥ 18 years
• Strong clinical suspicion of severe acute autoimmune hepatitis defined by the presence of increased IgG and/or autoantibodies and/or histology characteristic of the disease in the absence of other causes of severe acute hepatitis.
• International Normalized Ratio (INR) ≥ 1.5
• Informed, written consent
• Patient having the rights to French social insurance

Exclusion Criteria

• Previous medical history of chronic liver disease including autoimmune liver disease (AIH, Primary Biliary Cholangitis (PBC), Primary Sclerosing Cholangitis (PSC) , alcoholic hepatitis etc.)
• Other causes of acute severe hepatitis:

• Hepatitis A Virus (HAV) hepatitis, defined by HAV Immunoglobulin M (IgM) antibodies
• Hepatitis B Virus (HBV) hepatitis, defined by HBs antigen and HBV IgM antibodies
• Hepatitis E Virus (HEV) hepatitis, defined by HEV IgM antibodies or positive HEV-RNA in immunosuppressed patients
• Drug induced hepatitis, histologically proved or induced by well-known hepatotoxic substances
• Acute hypoxemic hepatitis, context of shock, hypoxemia or heat shock
• Budd-Chiari syndrome, diagnosed by imagery (Doppler ultrasound, CT scan)
• Acute hepatitis in the context of a HELLP (Hemolysis, Elevated Liver enzymes and a Low Platelet count) syndrome or acute fatty liver of pregnancy
• Use of corticosteroids 1 month before inclusion
• Pregnant or lactating woman
• Curator or guardianship or patient placed under judicial protection
• Participation in other interventional research during the study

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 99 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Eleonora DE MARTIN, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Assistance Publique - Hôpitaux de Paris

Locations

CHU Angers, Service Hepato-gastro-enterologie

Angers, , France

CHU Jean Minjoz Besançon, Service d'hepatologie et de soins intensifs digestifs

Besançon, , France

APHP, Hopital Avicenne, Service Hepatologie et Oncologie Hépatique

Bobigny, , France

CHU Brest, Hopital de la Cavale Blanche Service Gastro-enterologie

Brest, , France

CHU de Caen, Hopital de la Cote de Nacre, Service Hepato-Gastro-Enterologie et Nutrition

Caen, , France

CHU Trousseau Chambray, Service Gastro-enterologie et hepatologie

Chambray-lès-Tours, , France

CHU Dijon, Service Hepato-gastroenterologie et cancerologie digestive

Dijon, , France

CHRU de Lille, Hopital Claude Huriez, Service des maladies de l'appareil digestif et de la nutrition

Lille, , France

CHU Limoges, Hopital Dupuytren, Service Hepato-gastroenterologie et nutrition

Limoges, , France

CHU Hopital Edouard Herriot, Service Hepato-gastro-enterologie

Lyon, , France

CHU Lyon, Hopital Croix Rousse, Service Hepato-gastro-enterologie

Lyon, , France

Hopital Saint Joseph, Service Hepato-gastro-enterologie

Marseille, , France

CHU Montpellier, Hopital Saint Eloi, Service Hepato-gastro-enterologie

Montpellier, , France

CHU Nice, Hopital de l'Archet 2, Service Hepatologie

Nice, , France

CHU Orleans, Hopital de la Source, Service Gastro-enterologie et hepatologie

Orléans, , France

AP-HP, Hopital St Antoine, Service Hepato-gastro-enterologie

Paris, , France

APHP, Hopital Pitie-Salpetriere, Service d'hepatologie et de gastroenterologie

Paris, , France

AP-HP, Hopital Cochin Service Hepatologie

Paris, , France

CHU Bordeaux, GH Sud Haut-Leveque, Service Hepato-gastro-enterologie

Pessac, , France

CHU La Miletrie, Service Hepato-gastro-enterologie

Poitiers, , France

CHU Reims, Hopital Robert Debré, Service Hepato-Gastroenterologie et de Cancerologie digestive

Reims, , France

CHU de Rennes, Hopital de Pontchaillou, Service Maladie du foie

Rennes, , France

CHU Rouen, Service d'hepatogastro-enterologie

Rouen, , France

CHU Strasbourg, Hopital de Hautepierre, Service Hepato-gastro-enterologie

Strasbourg, , France

CHU Toulouse, Hopital Rangueil, Service Hepatologie

Toulouse, , France

AP-HP, Paul Brousse Hospital, Centre Hepato-Biliaire

Villejuif, , France

Countries

France

Central Contacts

Eleonora DE MARTIN, MD, PhD

Role: CONTACT

eleonora.demartin@aphp.fr

33 (0)1.45.59.64.33

Jean-Charles DUCLOS-VALLEE, MD, PhD

Role: CONTACT

jean-charles.duclos-vallee@aphp.fr

33 (0)1.45.59.64.28

Facility Contacts

Adrien LANNES, MD

Role: primary

adrien.lannes@chu-angers.fr

33 (0)2.41.35.31.42

Vincent DI MARTINO, MD

Role: primary

Vdimartino@chu-besancon.fr

Nathalie GANNE, MD

Role: primary

nathalie.ganne@aphp.fr

33 (0)1.48.02.66.66

Noemi REBOUX, MD

Role: primary

noemi.reboux@chu-brest.fr

Isabelle OLLIVIER-HOURMAND, MD

Role: primary

ollivierhourmand-i@chu-caen.fr

33 (0)2.31.06.45.44

Helene BARRAUD, MD

Role: primary

h.barraud@chu-tours.fr

33 (0)2.47.47.59.16

Anne MINELLO, MD

Role: primary

anne.minello@chu-dijon.fr

33 (0)3.80.29.37.50

Alexandre LOUVET, MD

Role: primary

alexandre.louvet@chru-lille.fr

Marilyne DEBETTE-GRATIEN, MD

Role: primary

marilyne.gratien@chu-limoges.fr

33 (0)5.55.05.66.21

Jerome DUMORTIER, MD

Role: primary

jerome.dumortier@chu-lyon.fr

33 (0)4.72.11.01.09

Teresa Maria ANTONINI-MICHELLE, MD

Role: primary

teresa.antonini@chu-lyon.fr

Olivia PIETRI, MD

Role: primary

opietri@hopital-saint-joseph.fr

33 (0)4 91 80 70 61

Lucy MEUNIER, MD

Role: primary

lucy.meunier@chu-montpellier.fr

33 (0)4.67.33.66.33

Rodolphe ANTY, MD

Role: primary

anty.r@chu-nice.fr

33 (0)4.92.03.63.85

Pascal POTIER, MD

Role: primary

pascal.potier@chr-orleans.fr

33 (0)2.38.22.96.43

Olivier CHAZOULLIERES, MD

Role: primary

olivier.chazouilleres@aphp.fr

33 (0)1.49.28.29.23

Marika RUDLER, MD

Role: primary

Marika.rudler@aphp.fr

33 (0)1.42.17.56.91

Charlotte MOULIADE, MD

Role: primary

charlotte.mouliade@aphp.fr

Victor DE LEDINGHEN, MD

Role: primary

victor.deledinghen@chu-bordeaux.fr

33 (0)5.57.65.64.39

Christine SILVAIN, MD

Role: primary

c.silvain@chu-poitiers.fr

33 (0)5.49.44.44.38

Alexandra HEURGUE-BERLOT, MD

Role: primary

aheurgue@chu-reims.fr

33 (0)3.26.78.78.78

Pauline HOUSSEL-DEBRY, MD

Role: primary

pauline.houssel-debry@chu-rennes.fr

33 (0).99.28.42.98

Odile GORIA, MD

Role: primary

Odile.Goria@chu-rouen.fr

Camille BESCH, MD

Role: primary

camille.besch@chru-strasbourg.fr

33 (0)3.88.12.74.48

Christophe BUREAU, MD

Role: primary

bureau.c@chu-toulouse.fr

33 (0)5.61.77.25.27

Eleonora DE MARTIN, MD, PhD

Role: primary

eleonora.demartin@aphp.fr

33 (0)1.45.59.64.33

Other Identifiers

2021-A01869-32

Identifier Type: OTHER

Identifier Source: secondary_id

D20180121

Identifier Type: -

Identifier Source: org_study_id