PredIcting SterOid DepeNdEnt LivEr InjuRy with Polyreactive Immunoglobulin G

Recruiting

• Conditions: Autoimmune Liver Disease; Autoimmune Hepatitis
• Interventions: Diagnostic Test: polyreactive immunoglobulin G

• Registration Number: NCT05810480
• Lead Sponsor: Hannover Medical School

Brief Summary

The investigators identified polyreactive immunoglobulin G (pIgG) in adults (published in Hepatology: https://doi.org/10.1002/hep.32134) and children (in preparation). Quantification of these pIgG using a "home-made" ELISA facilitates the diagnosis of autoimmune hepatitis (AIH) as compared to non-AIH liver diseases and healthy controls. Positivity for pIgG was independent from ANA/SMA positivity and equally diagnostic for AIH even when conventional autoantibodies (ANA/SMA/SLA/LKM) were negative.

Additionally, the frequency of pIgG was lower than conventional autoantibodies (ANA, SMA) in vaccinia/drug associated severe liver injury in a retrospective multicenter study after Covid-19 vaccination (https://doi.org/10.1016/j.jhepr.2022.100605).

Aims of the study The study aims to evaluate the diagnostic capacity of pIgG to predict AIH in comparison to other liver diseases prospectively. To avoid diagnostic inaccuracy between AIH with long-term need for an immunosuppression and drug induced liver injury with autoimmune features, which can be indistinguishable from AIH at baseline and which has a very low relapse rate after a short steroid course, a follow-up after six months is obligatory for inclusion.

Therefore, the investigators will collect one serum sample from every patient (without immunosuppressive treatment) that presents to the respective hospital for evaluation of liver disease by liver biopsy within one year after initiation of the study and that provided written informed consent. Follow-up for evaluation of steroid dependency at six months after diagnosis is obligatory.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-03-28
• Study First Submitted QC: 2023-04-11
• Study First Posted: 2023-04-12
• Study Start: 2023-06-06
• Status Verified: 2024-10
• Last Update Submitted: 2024-10-14
• Last Update Posted: 2024-10-16
• Primary Completion: 2026-07
• Study Completion: 2027-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 200

Inclusion Criteria

• Diagnostic liver biopsy for the work-up of any liver disease
• Informed consent
• Definition of any liver disease according to current societal guidelines

Exclusion Criteria

• No ongoing immunosuppression at the liver biopsy or prior to the liver biopsy
• Liver biopsies for the grading or staging of an already known liver disease (e.g. non-alcoholic fatty liver disease (NAFLD), Hepatitis B/D Virus Infections (HBV/HDV Infection), ...)

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
non-autoimmune hepatitis liver disease	polyreactive immunoglobulin G	This group includes patients with a diagnosis of any non-viral liver disease that is not autoimmune hepatitis and whose diagnosis necessitated a diagnostic liver biopsy in the work-up of the liver disease for local care. One serum sample will be stored for anonymized evaluation of serum autoantibodies
Autoimmune Hepatitis	polyreactive immunoglobulin G	This group includes patients with a diagnosis of Autoimmune Hepatitis according to the simplified diagnostic criteria by Hennes et al. made by the local treating physician. The diagnosis of autoimmune hepatitis additionally requires steroid dependency \> six months for this study to discriminate Autoimmune Hepatitis from autoimmune like drug-induced liver injury (DILI) which are hard to discriminate at diagnosis and with the latter often being treating with a short course of corticosteroids less than six months. One serum sample will be stored for anonymized evaluation of serum autoantibodies

Primary Outcome Measures

Name	Time	Method
Prediction of steroid dependent hepatitis	Assessment of steroid dependency at six months after enrollment	Prediction of steroid dependent hepatitis by elevated polyreactive immunoglobulin G

Secondary Outcome Measures

Name	Time	Method
Diagnostic discrimination between AIH and DILI by polyreactive IgG	At enrollment
Prediction of steroid dependent hepatitis by any other autoantibody	Assessment of steroid dependency at six months after enrollment	Prediction of steroid dependent hepatitis by any other elevated conventional autoantibody according to current guidelines (European Association for the study of the liver: EASL, American Association for the Study of Liver Diseases: AASLD)

Trial Locations

Locations (8)

University Hospital Bonn; 🇩🇪 Bonn, Germany

University Medical Centre Aachen; 🇩🇪 Aachen, Germany

University Medical Center Hamburg-Eppendorf; 🇩🇪 Hamburg, Germany

Hannover Medical School; 🇩🇪 Hannover, Germany

University Medical Center Heidelberg; 🇩🇪 Heidelberg, Germany

University Hospital Schleswig-Holstein, Location Lübeck; 🇩🇪 Lübeck, Germany

University Hospital Magdeburg; 🇩🇪 Magdeburg, Germany

Rostock University Medical Centre; 🇩🇪 Rostock, Germany