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

Not Applicable

Not yet recruiting

• Conditions: Organ Dysfunction Scores; Liver Failure, Acute; Hepatitis, Autoimmune; Risk Factors
• Interventions: Other: Corticosteroid therapy

• Registration Number: NCT05473403
• Lead Sponsor: Assistance Publique - Hôpitaux de Paris

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.

Study Timeline

• Study First Submitted: 2022-06-07
• Study First Submitted QC: 2022-07-22
• Study First Posted: 2022-07-25
• Status Verified: 2023-09
• Last Update Submitted: 2024-03-11
• Last Update Posted: 2024-03-13
• Study Start: 2024-06-01
• Primary Completion: 2027-05-31
• Study Completion: 2028-06-30

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 150

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Corticosteroid therapy	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.

Primary Outcome Measures

Name	Time	Method
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.	Day 90	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.

Secondary Outcome Measures

Name	Time	Method
the management of infected ASAIH patients in usual practice	participation period (treatment+follow-up): 12 months	Antibiotic therapy : doses
The risk factors for early AIH flair after corticosteroid therapy response.	D90	The frequency of AIH flair
The association between infection occurrence and death during hospitalization	participation period (treatment+follow-up): 12 months	Documented infections during hospitalization
The evolution of patients after LT	participation period (treatment+follow-up): 12 months	Retransplantation, alive, death
The evolution of patients not treated with corticosteroids but meeting the inclusion and non-inclusion criteria	participation period (treatment+follow-up): 12 months	Retransplantation, alive, death
The prognostic factors for survival in patients treated with corticosteroids who underwent or not LT	participation period (treatment+follow-up): 12 months	quality of the graft, immunosuppression, rejection episode,
The risk factors for AIH recurrence after liver transplantation	participation period (treatment+follow-up): 12 months	AIH recurrence
The association of histological features (liver biopsy) with response to corticosteroids and survival at 90 days since admission	90 days	Presence of centrilobular necrosis and inflammatory infiltration

Trial Locations

Locations (26)

CHU Jean Minjoz Besançon, Service d'hepatologie et de soins intensifs digestifs; 🇫🇷 Besançon, France

CHU de Caen, Hopital de la Cote de Nacre, Service Hepato-Gastro-Enterologie et Nutrition; 🇫🇷 Caen, France

CHU Dijon, Service Hepato-gastroenterologie et cancerologie digestive; 🇫🇷 Dijon, France

CHU La Miletrie, Service Hepato-gastro-enterologie; 🇫🇷 Poitiers, France

CHU Toulouse, Hopital Rangueil, Service Hepatologie; 🇫🇷 Toulouse, France

AP-HP, Paul Brousse Hospital, Centre Hepato-Biliaire; 🇫🇷 Villejuif, France

CHU Angers, Service Hepato-gastro-enterologie; 🇫🇷 Angers, 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

APHP, Hopital Avicenne, Service Hepatologie et Oncologie Hépatique; 🇫🇷 Bobigny, France

CHU Brest, Hopital de la Cavale Blanche Service Gastro-enterologie; 🇫🇷 Brest, France

CHU Trousseau Chambray, Service Gastro-enterologie et hepatologie; 🇫🇷 Chambray-lès-Tours, France

CHU Montpellier, Hopital Saint Eloi, Service Hepato-gastro-enterologie; 🇫🇷 Montpellier, France

CHU Strasbourg, Hopital de Hautepierre, Service Hepato-gastro-enterologie; 🇫🇷 Strasbourg, France

CHU Limoges, Hopital Dupuytren, Service Hepato-gastroenterologie et nutrition; 🇫🇷 Limoges, France

CHU Orleans, Hopital de la Source, Service Gastro-enterologie et hepatologie; 🇫🇷 Orléans, France

CHU Rouen, Service d'hepatogastro-enterologie; 🇫🇷 Rouen, France

CHU Hopital Edouard Herriot, Service Hepato-gastro-enterologie; 🇫🇷 Lyon, France

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

CHU Lyon, Hopital Croix Rousse, Service Hepato-gastro-enterologie; 🇫🇷 Lyon, France

Hopital Saint Joseph, Service Hepato-gastro-enterologie; 🇫🇷 Marseille, France

CHU Nice, Hopital de l'Archet 2, Service Hepatologie; 🇫🇷 Nice, France

CHU Bordeaux, GH Sud Haut-Leveque, Service Hepato-gastro-enterologie; 🇫🇷 Pessac, 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