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

Sponsor

Assistance Publique - Hôpitaux de Paris (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05473403

Collaborator

(none)

150

Enrollment

Locations

Arms

Anticipated Duration (Months)

5.6

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Liver Failure, Acute Hepatitis, Autoimmune Organ Dysfunction Scores Risk Factors	Other: Corticosteroid therapy	N/A

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 Design

Study Type:

Interventional

Anticipated Enrollment :

150 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

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.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.

Masking:

None (Open Label)

Primary Purpose:

Other

Official Title:

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

Anticipated Study Start Date :

Sep 1, 2022

Anticipated Primary Completion Date :

Sep 1, 2025

Anticipated Study Completion Date :

Dec 1, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	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).
No Intervention: Patient without corticosteroid therapy Patient not treated will undergo to emergency Liver Transplantation (LT) or death.

Arm

Intervention/Treatment

Experimental: 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.

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).

No Intervention: Patient without corticosteroid therapy

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

Outcome Measures

Primary Outcome Measures

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

To evaluate the association between infection occurrence and death during hospitalization [participation period (treatment+follow-up): 15 months]
Documented infections during hospitalization
To describe the management of infected ASAIH patients in usual practice [participation period (treatment+follow-up): 15 months]
Antibiotic therapy : doses
To describe the management of infected ASAIH patients in usual practice [participation period (treatment+follow-up): 15 months]
Antifungal therapy : doses
To describe the management of infected ASAIH patients in usual practice [participation period (treatment+follow-up): 15 months]
Antibiotic therapy : duration
To describe the management of infected ASAIH patients in usual practice [participation period (treatment+follow-up): 15 months]
Antifungal therapy : duration
To study risk factors for early AIH flair after corticosteroid therapy response [participation period (treatment+follow-up): 15 months]
The frequency of AIH flair - defined as the increase of bilirubin and/or transaminase > 3 times the upper limit of normal after corticosteroid response (alive and non-transplanted 90 days since therapy initiation - will be described with clinical and biological characteristics of patients who present this event.
To study risk factors for AIH recurrence after liver transplantation [participation period (treatment+follow-up): 15 months]
AIH recurrence after LT will be defined by the International Autoimmune Hepatitis Group (IAIHG) simplified criteria and/or increase of cholestasis (Bilirubin, Alkaline Phosphatase (ALP), GGT) and/or transaminase > 3 times the upper limit of normal, presence of auto-antibodies with titer > 1:80, IgG > 1.5 times the upper limit of normal and histological features of AIH. The frequency AIH recurrence will be described and clinical and biological characteristics of patients who present this event will be searched.
To describe the evolution of patients after LT [participation period (treatment+follow-up): 15 months]
Retransplantation, alive, death
To describe the evolution of patients not treated with corticosteroids but meeting the inclusion and non-inclusion criteria [participation period (treatment+follow-up): 15 months]
Retransplantation, alive, death
Factors associated with a survival [participation period (treatment+follow-up): 15 months]
quality of the graft, immunosuppression, rejection episode,
To evaluate 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
Evaluate the association of histological features (liver biopsy) with response to corticosteroids and survival at 90 days since admission [90 days]
Proportion of centrilobular necrosis and inflammatory infiltration

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 99 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age ≥ 18 years
Acute autoimmune hepatitis defined by IAIHG score as "definite" or "probable" with a score ≥ 6.
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
Pregnant or lactating woman
Curator or guardianship or patient placed under judicial protection
Participation in other interventional research during the study

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	CHU Angers, Service Hepato-gastro-enterologie	Angers	France	49933
2	CHU Jean Minjoz Besançon, Service d'hepatologie et de soins intensifs digestifs	Besançon	France	25030
3	APHP, Hopital Jean Verdier, Service Hepatologie	Bondy	France	93140
4	CHU Brest, Hopital de la Cavale Blanche Service Gastro-enterologie	Brest	France	29609
5	CHU de Caen, Hopital de la Cote de Nacre, Service Hepato-Gastro-Enterologie et Nutrition	Caen	France	14033
6	CHU Trousseau Chambray, Service Gastro-enterologie et hepatologie	Chambray-lès-Tours	France	37170
7	CHU Dijon, Service Hepato-gastroenterologie et cancerologie digestive	Dijon	France	21079
8	CHU Grenoble Alpes Hopital Nord, Service Hepato-gastro-enterologie	La Tronche	France	38700
9	CHRU de Lille, Hopital Claude Huriez, Service des maladies de l'appareil digestif et de la nutrition	Lille	France	59037
10	CHU Limoges, Hopital Dupuytren, Service Hepato-gastroenterologie et nutrition	Limoges	France	87042
11	CHU Hopital Edouard Herriot, Service Hepato-gastro-enterologie	Lyon	France	69003
12	CHU Lyon, Hopital Croix Rousse, Service Hepato-gastro-enterologie	Lyon	France	69317
13	Hopital Saint Joseph, Service Hepato-gastro-enterologie	Marseille	France	13285
14	CHU Montpellier, Hopital Saint Eloi, Service Hepato-gastro-enterologie	Montpellier	France	34295
15	CHU Nice, Hopital de l'Archet 2, Service Hepatologie	Nice	France	06200
16	CHU Orleans, Hopital de la Source, Service Gastro-enterologie et hepatologie	Orléans	France	45100
17	AP-HP, Hopital St Antoine, Service Hepato-gastro-enterologie	Paris	France	75012
18	APHP, Hopital Pitie-Salpetriere, Service d'hepatologie et de gastroenterologie	Paris	France	75013
19	AP-HP, Hopital Cochin Service Hepatologie	Paris	France	75014
20	CHU Bordeaux, GH Sud Haut-Leveque, Service Hepato-gastro-enterologie	Pessac	France	33604
21	CHU La Miletrie, Service Hepato-gastro-enterologie	Poitiers	France	86000
22	CHU Reims, Hopital Robert Debré, Service Hepato-Gastroenterologie et de Cancerologie digestive	Reims	France	51092
23	CHU de Rennes, Hopital de Pontchaillou, Service Maladie du foie	Rennes	France	35000
24	CHU Rouen, Service d'hepatogastro-enterologie	Rouen	France	76031
25	CHU Strasbourg, Hopital de Hautepierre, Service Hepato-gastro-enterologie	Strasbourg	France	67200
26	CHU Toulouse, Hopital Rangueil, Service Hepatologie	Toulouse	France	31059
27	AP-HP, Paul Brousse Hospital, Centre Hepato-Biliaire	Villejuif	France	94800