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

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.

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