Clinical trial NCT05810480: PredIcting SterOid DepeNdEnt LivEr InjuRy with Polyreactive Immunoglobulin G
Official title: Prospective Multicenter Study: PredIcting SterOid DepeNdEnt LivEr Injury (PIONEER) with Polyreactive Immunoglobulin G
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Autoimmune Hepatitis
Autoimmune Liver Disease
Lead sponsor: Hannover Medical School
Sponsor class: OTHER
First posted: 2023-04-12
Enrollment: 200
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study 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.

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.


Eligibility criteria: 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), ...)

Primary outcomes:
measure: Prediction of steroid dependent hepatitis
timeFrame: Assessment of steroid dependency at six months after enrollment
Secondary outcomes:
measure: Diagnostic discrimination between AIH and DILI by polyreactive IgG
timeFrame: At enrollment
measure: Prediction of steroid dependent hepatitis by any other autoantibody
timeFrame: Assessment of steroid dependency at six months after enrollment
Other outcomes:
measure: Concordance of different testing methods for autoantibodies
timeFrame: At enrollment
Locations:
city: Aachen
country: Germany
facility: University Medical Centre Aachen
city: Bonn
country: Germany
facility: University Hospital Bonn
city: Hamburg
country: Germany
facility: University Medical Center Hamburg-Eppendorf
city: Hannover
country: Germany
facility: Hannover Medical School
city: Heidelberg
country: Germany
facility: University Medical Center Heidelberg
city: Lübeck
country: Germany
facility: University Hospital Schleswig-Holstein, Location Lübeck
city: Magdeburg
country: Germany
facility: University Hospital Magdeburg
city: Rostock
country: Germany
facility: Rostock University Medical Centre
Study officials:
affiliation: Hannover Medical School
name: Bastian Engel, Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Hannover Medical School
name: Richard Taubert, Dr.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Taubert R, Engel B, Diestelhorst J, Hupa-Breier KL, Behrendt P, Baerlecken NT, Suhs KW, Janik MK, Zachou K, Sebode M, Schramm C, Londono MC, Habes S; UK-AIH Consortium; Oo YH, Lalanne C, Pape S, Schubert M, Hust M, Dubel S, Thevis M, Jonigk D, Beimdiek J, Buettner FFR, Drenth JPH, Muratori L, Adams DH, Dyson JK, Renand A, Graupera I, Lohse AW, Dalekos GN, Milkiewicz P, Stangel M, Maasoumy B, Witte T, Wedemeyer H, Manns MP, Jaeckel E. Quantification of polyreactive immunoglobulin G facilitates the diagnosis of autoimmune hepatitis. Hepatology. 2022 Jan;75(1):13-27. doi: 10.1002/hep.32134. Epub 2021 Dec 5.