PIONEER: PredIcting sterOid depeNdEnt livEr injuRy With Polyreactive Immunoglobulin G
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Autoimmune Hepatitis 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 |
Diagnostic Test: polyreactive immunoglobulin G
Polyreactive immunoglobulin G will be tested centralized in Hannover as published (Taubert, Engel et al., Hepatology, 2022). The current standard diagnostic autoantibodies (e.g. ANA, anti-SMA, anti-LKM, anti-LC1, anti-SLA/L) will be tested centrally in Hannover according to current guidelines.
Other Names:
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| non-autoimmune hepatitis liver disease 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 |
Diagnostic Test: polyreactive immunoglobulin G
Polyreactive immunoglobulin G will be tested centralized in Hannover as published (Taubert, Engel et al., Hepatology, 2022). The current standard diagnostic autoantibodies (e.g. ANA, anti-SMA, anti-LKM, anti-LC1, anti-SLA/L) will be tested centrally in Hannover according to current guidelines.
Other Names:
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Outcome Measures
Primary Outcome Measures
- 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
- 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)
Other Outcome Measures
- Concordance of different testing methods for autoantibodies [At enrollment]
Different methodology to assess presence of autoantibodies (e.g. ELISA, Immunofluorescence on tissue sections) will be tested head-to-head for their diagnostic capacity
Eligibility Criteria
Criteria
Inclusion Criteria:
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Diagnostic liver biopsy for the work-up of any liver disease
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Informed consent
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Definition of any liver disease according to current societal guidelines
Exclusion Criteria:
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No ongoing immunosuppression at the liver biopsy or prior to the liver biopsy
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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), …)
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Hannover Medical School
Investigators
- Principal Investigator: Bastian Engel, Dr., Hannover Medical School
- Principal Investigator: Richard Taubert, Dr., Hannover Medical School
Study Documents (Full-Text)
None provided.More Information
Publications
- PIONEER