PredIcting sterOid depeNdEnt livEr injuRy With Polyreactive Immunoglobulin G
Trial statusRecruiting
Trial phaseNot listed
Trial typeObservational
Biological sexAll
AgeNot listed
SponsorHannover Medical School
About this trial
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.
Eligibility criteria
This trial accepts healthy volunteersQualifiers
Diagnostic liver biopsy for the work-up of any liver disease
Informed consent
Definition of any liver disease according to current societal guidelines
Disqualifiers
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
Trial population
Any patient that presents to the respective hospital for evaluation of a so far unknown-liver disease and consents is eligible if the treating physician orders a liver biopsy for the diagnostic evaluation of the liver disease. Patients are not eligible if a liver biopsy is performed for staging or grading of an already known liver disease or if the patient is treated with immunosuppressive drugs at the time of the liver biopsy.
Trial design
Design model
Case-control
Time perspective
Prospective
Treatments tested in this trial
polyreactive immunoglobulin G
Diagnostic testPolyreactive 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.
Treatment groups
400 Participants
are divided into 2 treatment groupsGroup A: Autoimmune Hepatitis1 intervention
Group B: non-autoimmune hepatitis liver disease1 intervention
Trial outcomes
Primary outcomes
1
Sensitivity of new simplified pIgG AIH Score
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.
Time frame
Assessment of steroid dependency at six months after enrollment2
Specificty of pIgG simplified AIH Score
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.
Time frame
Assessment at baselineSecondary outcomes
1
Diagnostic discrimination between AIH and DILI by polyreactive IgG
Time frame
At enrollment2
Prediction of steroid dependent hepatitis by any other autoantibody
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)
Time frame
Assessment of steroid dependency at six months after enrollment3
Age-dependency of autoantibodies
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
Time frame
Assessment of autoantibodies at baselineOther outcomes
1
Concordance of different testing methods for autoantibodies
Different methodology to assess presence of autoantibodies (e.g. ELISA, Immunofluorescence on tissue sections) will be tested head-to-head for their diagnostic capacity
Time frame
At enrollmentSponsors and contacts
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Source ClinicalTrials.gov