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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Risk Factors, Liver Failure, Acute, Hepatitis, Autoimmune, Organ Dysfunction Scores

Intervention / Treatment
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* Other: Corticosteroid therapy


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Corticosteroid therapy<br>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<br>* Administration of high doses of corticosteroids as early as possible. Patient non-responder to treatment should lead to listing for emergency liver transplantation (LT).<br>|
| No Intervention: Patient without corticosteroid therapy<br>Patient not treated will undergo to emergency Liver Transplantation (LT) or death. | |

What is the study measuring?
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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. | 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 association between infection occurrence and death during hospitalization | Documented infections during hospitalization | participation period (treatment+follow-up): 15 months | 
| the management of infected ASAIH patients in usual practice | Antibiotic therapy : doses | participation period (treatment+follow-up): 15 months | 
| The risk factors for early AIH flair after corticosteroid therapy response. | The frequency of AIH flair | D90 | 
| The risk factors for AIH recurrence after liver transplantation | AIH recurrence | participation period (treatment+follow-up): 15 months | 
| The evolution of patients after LT | Retransplantation, alive, death | participation period (treatment+follow-up): 15 months | 
| The evolution of patients not treated with corticosteroids but meeting the inclusion and non-inclusion criteria | Retransplantation, alive, death | participation period (treatment+follow-up): 15 months | 
| 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): 15 months | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute Severe AutoImmune Hepatitis (ASAIH), Decisional score, Prognostic score