Clinical trial NCT05473403: Validation of a Prognostic Score for Steroid Therapy Response in Acute Severe Autoimmune Hepatitis
Official title: Validation of a Prognostic Score for Steroid Therapy Response in Acute Severe Autoimmune Hepatitis, a National Prospective Multicentre Study
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Liver Failure, Acute
Hepatitis, Autoimmune
Organ Dysfunction Scores
Risk Factors
Keywords: Acute Severe AutoImmune Hepatitis (ASAIH)
Decisional score
Prognostic score
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2022-07-25
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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.
Primary purpose: OTHER

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.

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

Primary outcomes:
measure: 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.
timeFrame: Day 90
Secondary outcomes:
measure: The association between infection occurrence and death during hospitalization
timeFrame: participation period (treatment+follow-up): 12 months
measure: the management of infected ASAIH patients in usual practice
timeFrame: participation period (treatment+follow-up): 12 months
measure: The risk factors for early AIH flair after corticosteroid therapy response.
timeFrame: D90
measure: The risk factors for AIH recurrence after liver transplantation
timeFrame: participation period (treatment+follow-up): 12 months
measure: The evolution of patients after LT
timeFrame: participation period (treatment+follow-up): 12 months
measure: The evolution of patients not treated with corticosteroids but meeting the inclusion and non-inclusion criteria
timeFrame: participation period (treatment+follow-up): 12 months
measure: The prognostic factors for survival in patients treated with corticosteroids who underwent or not LT
timeFrame: participation period (treatment+follow-up): 12 months
measure: The association of histological features (liver biopsy) with response to corticosteroids and survival at 90 days since admission
timeFrame: 90 days
Other outcomes:
Locations:
city: Angers
country: France
facility: CHU Angers, Service Hepato-gastro-enterologie
city: Besançon
country: France
facility: CHU Jean Minjoz Besançon, Service d'hepatologie et de soins intensifs digestifs
city: Bobigny
country: France
facility: APHP, Hopital Avicenne, Service Hepatologie et Oncologie Hépatique
city: Brest
country: France
facility: CHU Brest, Hopital de la Cavale Blanche Service Gastro-enterologie
city: Caen
country: France
facility: CHU de Caen, Hopital de la Cote de Nacre, Service Hepato-Gastro-Enterologie et Nutrition
city: Chambray-lès-Tours
country: France
facility: CHU Trousseau Chambray, Service Gastro-enterologie et hepatologie
city: Dijon
country: France
facility: CHU Dijon, Service Hepato-gastroenterologie et cancerologie digestive
city: Lille
country: France
facility: CHRU de Lille, Hopital Claude Huriez, Service des maladies de l'appareil digestif et de la nutrition
city: Limoges
country: France
facility: CHU Limoges, Hopital Dupuytren, Service Hepato-gastroenterologie et nutrition
city: Lyon
country: France
facility: CHU Hopital Edouard Herriot, Service Hepato-gastro-enterologie
city: Lyon
country: France
facility: CHU Lyon, Hopital Croix Rousse, Service Hepato-gastro-enterologie
city: Marseille
country: France
facility: Hopital Saint Joseph, Service Hepato-gastro-enterologie
city: Montpellier
country: France
facility: CHU Montpellier, Hopital Saint Eloi, Service Hepato-gastro-enterologie
city: Nice
country: France
facility: CHU Nice, Hopital de l'Archet 2, Service Hepatologie
city: Orléans
country: France
facility: CHU Orleans, Hopital de la Source, Service Gastro-enterologie et hepatologie
city: Paris
country: France
facility: AP-HP, Hopital St Antoine, Service Hepato-gastro-enterologie
city: Paris
country: France
facility: APHP, Hopital Pitie-Salpetriere, Service d'hepatologie et de gastroenterologie
city: Paris
country: France
facility: AP-HP, Hopital Cochin Service Hepatologie
city: Pessac
country: France
facility: CHU Bordeaux, GH Sud Haut-Leveque, Service Hepato-gastro-enterologie
city: Poitiers
country: France
facility: CHU La Miletrie, Service Hepato-gastro-enterologie
city: Reims
country: France
facility: CHU Reims, Hopital Robert Debré, Service Hepato-Gastroenterologie et de Cancerologie digestive
city: Rennes
country: France
facility: CHU de Rennes, Hopital de Pontchaillou, Service Maladie du foie
city: Rouen
country: France
facility: CHU Rouen, Service d'hepatogastro-enterologie
city: Strasbourg
country: France
facility: CHU Strasbourg, Hopital de Hautepierre, Service Hepato-gastro-enterologie
city: Toulouse
country: France
facility: CHU Toulouse, Hopital Rangueil, Service Hepatologie
city: Villejuif
country: France
facility: AP-HP, Paul Brousse Hospital, Centre Hepato-Biliaire
Study officials:
affiliation: Assistance Publique - Hôpitaux de Paris
name: Eleonora DE MARTIN, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: