Validation of a Prognostic Score for Steroid Therapy Response in Acute Severe Autoimmune Hepatitis (PRO-SURFASA)

March 11, 2024 updated by: Assistance Publique - Hôpitaux de Paris

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

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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Estimated)

150

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • France
      • Angers, France, 49933
        • CHU Angers, Service Hepato-gastro-enterologie
        • Contact:
        • Principal Investigator:
          • Adrien LANNES, MD
      • Besançon, France, 25030
        • CHU Jean Minjoz Besançon, Service d'hepatologie et de soins intensifs digestifs
        • Contact:
        • Principal Investigator:
          • Vincent DI MARTINO, MD
      • Bobigny, France, 93000
        • APHP, Hopital Avicenne, Service Hepatologie et Oncologie Hépatique
        • Contact:
        • Principal Investigator:
          • Nathalie GANNE, MD
      • Brest, France, 29609
        • CHU Brest, Hopital de la Cavale Blanche Service Gastro-enterologie
        • Contact:
        • Principal Investigator:
          • Noemi REBOUX, MD
      • Caen, France, 14033
        • CHU de Caen, Hopital de la Cote de Nacre, Service Hepato-Gastro-Enterologie et Nutrition
        • Contact:
        • Principal Investigator:
          • Isabelle OLLIVIER-HOURMAND, MD
      • Chambray-lès-Tours, France, 37170
        • CHU Trousseau Chambray, Service Gastro-enterologie et hepatologie
        • Contact:
        • Principal Investigator:
          • Helene BARRAUD, MD
      • Dijon, France, 21079
        • CHU Dijon, Service Hepato-gastroenterologie et cancerologie digestive
        • Contact:
        • Principal Investigator:
          • Anne MINELLO, MD
      • Lille, France, 59037
        • CHRU de Lille, Hopital Claude Huriez, Service des maladies de l'appareil digestif et de la nutrition
        • Contact:
        • Principal Investigator:
          • Alexandre LOUVET, MD
      • Limoges, France, 87042
        • CHU Limoges, Hopital Dupuytren, Service Hepato-gastroenterologie et nutrition
        • Principal Investigator:
          • Marilyne DEBETTE-GRATIEN, MD
        • Contact:
      • Lyon, France, 69003
        • CHU Hopital Edouard Herriot, Service Hepato-gastro-enterologie
        • Contact:
        • Principal Investigator:
          • Jerome DUMORTIER, MD
      • Lyon, France, 69317
        • CHU Lyon, Hopital Croix Rousse, Service Hepato-gastro-enterologie
        • Contact:
        • Principal Investigator:
          • Teresa Maria ANTONINI-MICHELLE, MD
      • Marseille, France, 13285
        • Hopital Saint Joseph, Service Hepato-gastro-enterologie
        • Contact:
        • Principal Investigator:
          • Olivia PIETRI, MD
      • Montpellier, France, 34295
        • CHU Montpellier, Hopital Saint Eloi, Service Hepato-gastro-enterologie
        • Principal Investigator:
          • Lucy MEUNIER, MD
        • Contact:
      • Nice, France, 06200
        • CHU Nice, Hopital de l'Archet 2, Service Hepatologie
        • Principal Investigator:
          • Rodolphe ANTY, MD
        • Contact:
      • Orléans, France, 45100
        • CHU Orleans, Hopital de la Source, Service Gastro-enterologie et hepatologie
        • Contact:
        • Principal Investigator:
          • Pascal POTIER, MD
      • Paris, France, 75012
        • AP-HP, Hopital St Antoine, Service Hepato-gastro-enterologie
        • Contact:
        • Principal Investigator:
          • Olivier CHAZOULLIERES, MD
      • Paris, France, 75013
        • APHP, Hopital Pitie-Salpetriere, Service d'hepatologie et de gastroenterologie
        • Contact:
        • Principal Investigator:
          • Marika RUDLER, MD
      • Paris, France, 75014
        • AP-HP, Hopital Cochin Service Hepatologie
        • Contact:
        • Principal Investigator:
          • Charlotte MOULIADE, MD
      • Pessac, France, 33604
        • CHU Bordeaux, GH Sud Haut-Leveque, Service Hepato-gastro-enterologie
        • Contact:
        • Principal Investigator:
          • Victor DE LEDINGHEN, MD
      • Poitiers, France, 86000
        • CHU La Miletrie, Service Hepato-gastro-enterologie
        • Contact:
        • Principal Investigator:
          • Christine SILVAIN, MD
      • Reims, France, 51092
        • CHU Reims, Hopital Robert Debré, Service Hepato-Gastroenterologie et de Cancerologie digestive
        • Contact:
        • Principal Investigator:
          • Alexandra HEURGUE-BERLOT, MD
      • Rennes, France, 35000
        • CHU de Rennes, Hopital de Pontchaillou, Service Maladie du foie
        • Contact:
        • Principal Investigator:
          • Pauline HOUSSEL-DEBRY, MD
      • Rouen, France, 76031
        • CHU Rouen, Service d'hepatogastro-enterologie
        • Contact:
        • Principal Investigator:
          • Odile GORIA, MD
      • Strasbourg, France, 67200
        • CHU Strasbourg, Hopital de Hautepierre, Service Hepato-gastro-enterologie
        • Contact:
        • Principal Investigator:
          • Camille BESCH, MD
      • Toulouse, France, 31059
        • CHU Toulouse, Hopital Rangueil, Service Hepatologie
        • Contact:
        • Principal Investigator:
          • Christophe BUREAU, MD
      • Villejuif, France, 94800
        • AP-HP, Paul Brousse Hospital, Centre Hepato-Biliaire
        • Contact:
        • Principal Investigator:
          • Eleonora DE MARTIN, MD, PhD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 99 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Time Frame: 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.
Day 90

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Assistance Publique - Hôpitaux de Paris

Investigators

  • Principal Investigator: Eleonora DE MARTIN, MD, PhD, Assistance Publique - Hôpitaux de Paris

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

June 1, 2024

Primary Completion (Estimated)

May 31, 2027

Study Completion (Estimated)

June 30, 2028

Study Registration Dates

First Submitted

June 7, 2022

First Submitted That Met QC Criteria

July 22, 2022

First Posted (Actual)

July 25, 2022

Study Record Updates

Last Update Posted (Actual)

March 13, 2024

Last Update Submitted That Met QC Criteria

March 11, 2024

Last Verified

September 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • D20180121
  • 2021-A01869-32 (Other Identifier: IDRCB)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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