PredIcting sterOid depeNdEnt livEr injuRy With Polyreactive Immunoglobulin G

Autoimmune Hepatitis Clinical Trial

— PIONEER  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05810480
• Other study ID #: PIONEER
• Status: Recruiting
• Start date: June 6, 2023
• Est. completion date: January 2025

Study information

• Verified date: July 2023
• Source: Hannover Medical School
• Contact: Bastian Engel, Dr.
• Phone: +49 511 532 6766
• Email: Engel.Bastian[@]mh-hannover.de
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: January 2025
• Est. primary completion date: July 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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), …)

Related Conditions & MeSH terms

• Autoimmune Hepatitis
• Autoimmune Liver Disease
• Hepatitis, Autoimmune
• Liver Diseases

Intervention

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.

Locations

Country	Name	City	State
Germany	University Medical Centre Aachen	Aachen
Germany	University Hospital Bonn	Bonn
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

Sponsors (1)

Lead Sponsor	Collaborator
Hannover Medical School

Country where clinical trial is conducted

Germany, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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	At enrollment
Primary	Prediction of steroid dependent hepatitis	Prediction of steroid dependent hepatitis by elevated polyreactive immunoglobulin G	Assessment of steroid dependency at six months after enrollment
Secondary	Diagnostic discrimination between AIH and DILI by polyreactive IgG		At enrollment
Secondary	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)	Assessment of steroid dependency at six months after enrollment