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NCT Number: NCT05810480

PredIcting sterOid depeNdEnt livEr injuRy With Polyreactive Immunoglobulin G

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.

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Key information

Sex eligibility

All sexes

Study type

Observational

Primary location

RWTH Aachen, Aachen, Germany

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Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

  • 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), …)
  • known liver disease
  • missing informed consent
  • patients or caregivers who can not provide informed consent

Treatment and study plan

polyreactive immunoglobulin G

Diagnostic Test

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: Conventional diagnostic autoantibodies

Primary outcomes

  1. Sensitivity of new simplified pIgG AIH Score

    Time frame: Assessment of steroid dependency at six months after enrollment

    Autoimmune serology will be substituted by pIgG in the 2021 simplified AIH Score. Sensitivity of the new score will be compared to the old score, primarily for non-inferiority and second for superiority if non-inferiority was met.

  2. Specificty of pIgG simplified AIH Score

    Time frame: Assessment at baseline

    Autoimmune serology will be substituted by pIgG in the 2021 simplified AIH Score. Sensitivity of the new score will be compared to the old score, primarily for non-inferiority and second for superiority if non-inferiority was met.

Secondary outcomes

  1. Diagnostic discrimination between AIH and DILI by polyreactive IgG

    Time frame: At enrollment

  2. Prediction of steroid dependent hepatitis by any other autoantibody

    Time frame: 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)

  3. Age-dependency of autoantibodies

    Time frame: Assessment of autoantibodies at baseline

    Presence of autoantibodies will be descriptively evaluated with regard to age of the patients as currently it is proposed that lower antibody titers/levels are diagnostic in children (dependent on age) than in adults

Other outcomes

  1. Concordance of different testing methods for autoantibodies

    Time frame: 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

Study contacts

Contact information is provided by the study sponsor or research team.

Bastian Engel, Dr.

CONTACT

[email protected]

+49 511 532 6766

Richard Taubert, Dr.

CONTACT

[email protected]

+49 511 532 6766

Sponsors and collaborators

Lead sponsor

Hannover Medical School

Other

Registry information

Official study title

Prospective Multicenter Study: PredIcting sterOid depeNdEnt livEr Injury (PIONEER) With Polyreactive Immunoglobulin G

Acronym: PIONEER

Important dates

Study start
2023
Primary completion
2028
Study completion
2029
First posted
Apr 12, 2023
Registry last updated
Jul 15, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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