PredIcting SterOid DepeNdEnt LivEr InjuRy with Polyreactive Immunoglobulin G

NCT05810480 | Recruiting

• 1 other identifier: PIONEER
• Study Type: observational
• Target: 200
• Locations: 1 country
• Sites: 8

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.

Conditions

Autoimmune Hepatitis; Autoimmune Liver Disease

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• 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

Other Outcomes (1)

• Concordance of different testing methods for autoantibodies

  At enrollment

Study Arms (2)

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

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

Interventions

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.

Also known as: Conventional diagnostic autoantibodies

Autoimmune Hepatitis; non-autoimmune hepatitis liver disease

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• Diagnostic liver biopsy for the work-up of any liver disease
• Informed consent
• Definition of any liver disease according to current societal guidelines

You may not qualify if:

• 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), …)

Sponsors & Collaborators

• Hannover Medical School: lead

Study Sites (8)

University Medical Centre Aachen

Aachen, 52074, Germany

RECRUITING

University Hospital Bonn

Bonn, Germany

RECRUITING

University Medical Center Hamburg-Eppendorf

Hamburg, 20251, Germany

RECRUITING

Hannover Medical School

Hanover, 30625, Germany

RECRUITING

University Medical Center Heidelberg

Heidelberg, 69120, Germany

RECRUITING

University Hospital Schleswig-Holstein, Location Lübeck

Lübeck, 23562, Germany

RECRUITING

University Hospital Magdeburg

Magdeburg, 39120, Germany

RECRUITING

Rostock University Medical Centre

Rostock, 18057, Germany

RECRUITING

Related 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.

  PMID: 34473365 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

Serum

MeSH Terms

Conditions

Hepatitis, Autoimmune

Condition Hierarchy (Ancestors)

Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Bastian Engel, Dr.

  Hannover Medical School

  PRINCIPAL INVESTIGATOR

• Richard Taubert, Dr.

  Hannover Medical School

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Bastian Engel, Dr.

CONTACT

+49 511 532 6766; Engel.Bastian@mh-hannover.de

Richard Taubert, Dr.

CONTACT

+49 511 532 6766; Taubert.Richard@mh-hannover.de

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 28, 2023
• First Posted: April 12, 2023
• Study Start: June 6, 2023
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): January 1, 2027
• Last Updated: October 16, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

DE (8)