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

Risk Factors Clinical Trial

— PRO-SURFASA  

Official title:

Validation of a Prognostic Score for Steroid Therapy Response in Acute Severe Autoimmune Hepatitis, a National Prospective Multicentre Study

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05473403
• Other study ID #: D20180121
• Secondary ID: 2021-A01869-32
• Status: Not yet recruiting
• Phase: N/A
• Start date: June 1, 2024
• Est. completion date: June 30, 2028

Study information

• Verified date: September 2023
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: Eleonora DE MARTIN, MD, PhD
• Phone: 33 (0)1.45.59.64.33
• Email: eleonora.demartin[@]aphp.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 150
• Est. completion date: June 30, 2028
• Est. primary completion date: May 31, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

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

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis A
• Hepatitis, Autoimmune
• Liver Failure
• Liver Failure, Acute
• Risk Factors

Intervention

Other:
• 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).

Locations

Country	Name	City	State
France	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 Cochin Service Hepatologie	Paris
France	AP-HP, Hopital St Antoine, Service Hepato-gastro-enterologie	Paris
France	APHP, Hopital Pitie-Salpetriere, Service d'hepatologie et de gastroenterologie	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

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

Outcome

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