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

NCT05473403 | Not Yet Recruiting

• 2 other identifiers: D201801212021-A01869-32
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 26

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.

Conditions

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

Keywords

Acute Severe AutoImmune Hepatitis (ASAIH); Decisional score; Prognostic score

Outcome Measures

Primary Outcomes (1)

• Prospectively validate the previously elaborated SURFASA-score, evaluating its ability to predict non-response outcome to corticosteroid therapy in a new population of patients with acute severe autoimmune hepatitis.

  Patient response within 90 days to corticosteroid therapy defined as: responders (alive without LT) or non-responders (dead or transplanted) within 90 days since corticosteroid therapy introduction.

  Day 90

Secondary Outcomes (8)

• The association between infection occurrence and death during hospitalization

  participation period (treatment+follow-up): 12 months

• the management of infected ASAIH patients in usual practice

  participation period (treatment+follow-up): 12 months

• The risk factors for early AIH flair after corticosteroid therapy response.

  D90

• The risk factors for AIH recurrence after liver transplantation

  participation period (treatment+follow-up): 12 months

• The evolution of patients after LT

  participation period (treatment+follow-up): 12 months

Study Arms (2)

Corticosteroid therapy

EXPERIMENTAL

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.

Other: Corticosteroid therapy

Patient without corticosteroid therapy

NO INTERVENTION

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

Interventions

Corticosteroid therapy 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).

Corticosteroid therapy

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• Pregnant or lactating woman
• Curator or guardianship or patient placed under judicial protection
• Participation in other interventional research during the study

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (26)

CHU Angers, Service Hepato-gastro-enterologie

Angers, 49933, France

Location

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

Besançon, 25030, France

Location

APHP, Hopital Avicenne, Service Hepatologie et Oncologie Hépatique

Bobigny, 93000, France

Location

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

Brest, 29609, France

Location

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

Caen, 14033, France

Location

CHU Trousseau Chambray, Service Gastro-enterologie et hepatologie

Chambray-lès-Tours, 37170, France

Location

CHU Dijon, Service Hepato-gastroenterologie et cancerologie digestive

Dijon, 21079, France

Location

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

Lille, 59037, France

Location

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

Limoges, 87042, France

Location

CHU Hopital Edouard Herriot, Service Hepato-gastro-enterologie

Lyon, 69003, France

Location

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

Lyon, 69317, France

Location

Hopital Saint Joseph, Service Hepato-gastro-enterologie

Marseille, 13285, France

Location

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

Montpellier, 34295, France

Location

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

Nice, 06200, France

Location

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

Orléans, 45100, France

Location

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

Paris, 75012, France

Location

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

Paris, 75013, France

Location

AP-HP, Hopital Cochin Service Hepatologie

Paris, 75014, France

Location

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

Pessac, 33604, France

Location

CHU La Miletrie, Service Hepato-gastro-enterologie

Poitiers, 86000, France

Location

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

Reims, 51092, France

Location

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

Rennes, 35000, France

Location

CHU Rouen, Service d'hepatogastro-enterologie

Rouen, 76031, France

Location

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

Strasbourg, 67200, France

Location

CHU Toulouse, Hopital Rangueil, Service Hepatologie

Toulouse, 31059, France

Location

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

Villejuif, 94800, France

Location

MeSH Terms

Conditions

Liver Failure, Acute; Hepatitis, Autoimmune

Condition Hierarchy (Ancestors)

Liver Failure; Hepatic Insufficiency; Liver Diseases; Digestive System Diseases; Hepatitis, Chronic; Hepatitis; Autoimmune Diseases; Immune System Diseases

Study Officials

• Eleonora DE MARTIN, MD, PhD

  Assistance Publique - Hôpitaux de Paris

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Eleonora DE MARTIN, MD, PhD

CONTACT

33 (0)1.45.59.64.33; eleonora.demartin@aphp.fr

Jean-Charles DUCLOS-VALLEE, MD, PhD

CONTACT

33 (0)1.45.59.64.28; jean-charles.duclos-vallee@aphp.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a multicenter, prognostic, non-randomized, comparative, longitudinal, prospective, external validation cohort, which aims to evaluate a decisional score previously developed in a retrospective cohort.

Study Record Dates

• First Submitted: June 7, 2022
• First Posted: July 25, 2022
• Study Start: June 1, 2024
• Primary Completion (Estimated): May 31, 2027
• Study Completion (Estimated): June 30, 2028
• Last Updated: March 13, 2024

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

FR (26)