Autoimmune HepatitisPIONEERNCT05810480
PredIcting sterOid depeNdEnt livEr injuRy With Polyreactive Immunoglobulin G
An observational study of Autoimmune Hepatitis and Autoimmune Liver Disease, run by Hannover Medical School at 6 sites in Germany.
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… Read more about this study
- Who is it for?
- Any ageHealthy volunteers can take part
- Conditions the study is for
- Autoimmune Hepatitis, Autoimmune Liver Disease
- What is being tested?
- polyreactive immunoglobulin G
- How many people
- 400 participants
- Where
- 6 sitesGermany
- Study dates
- 6 Jun 2023to Jan 2029
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
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.
Who may be able to join
- Diagnostic liver biopsy for the work-up of any liver disease
- Informed consent
- Definition of any liver disease according to current societal guidelines
Who cannot join
- 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
Trial locations and contacts
6 sites in 1 country. Contact the study team or a site near you to ask about taking part.
6 sites in 1 country
Germany6 sites, 6 recruiting
- Not yet recruiting
RWTH Aachen
Aachen
Tony Bruns, MD, tbruns@ukaachen.de
Karsten Große, MD, kargrosse@ukaachen.de
- Not yet recruiting
University Medical Center Hamburg-Eppendorf
Hamburg, 20251
Marcial Sebode, MD
- Recruiting
Hannover Medical School
Hanover, 30625
Bastian Engel, MD, +495115326766, Engel.Bastian@mh-hannover.de
Richard Taubert, MD, +495115326766, Taubert.Richard@mh-hannover.de
- Not yet recruiting
University Medical Center Heidelberg
Heidelberg, 69120
Uta Merle, MD, Prof.
Jessica Seessle, MD
- Not yet recruiting
University Hospital Schleswig-Holstein, Location Lübeck
Lübeck, 23562
Carolin Zimpel, MD
- Not yet recruiting
Rostock University Medical Centre
Rostock, 18057
Theresia Blattmann, MD
About this study
Official title: Prospective Multicenter Study: PredIcting sterOid depeNdEnt livEr Injury (PIONEER) 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).
Read more
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
- Being tested
- polyreactive immunoglobulin G
- Medical subject headings
- Hepatitis, Autoimmune
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
polyreactive immunoglobulin GDiagnostic test
Also called Conventional diagnostic autoantibodies
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.
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: Diagnostic Test: polyreactive immunoglobulin G |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Assessment of steroid dependency at six months after enrollment
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.
Measured: Assessment at baseline
Secondary outcomes (3)
Diagnostic discrimination between AIH and DILI by polyreactive IgG
Measured: At enrollment
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)
Measured: Assessment of steroid dependency at six months after enrollment
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
Measured: Assessment of autoantibodies at baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Apr 2023
- Study start6 Jun 2023
- Primary completionJul 2028 (estimated)
- Study completionJan 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Autoimmune HepatitisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 400 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hannover Medical School
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Engel, Bastian Dr., Hannover Medical School
- Investigators
- Bastian Engel, Dr., Principal investigator, Hannover Medical SchoolRichard Taubert, Dr., Principal investigator, Hannover Medical School
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05810480
- Sponsor's protocol ID
- PIONEER
- Acronym
- PIONEER
- Status last verified
- Jul 2026
- First submitted
- 28 Mar 2023
- Last updated
- 15 Jul 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: IPD are not shared with collaborators. Data, in general, is only provided anonymized by contributing centers.
Publications
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.
PubMed 34473365
Study at a glance
From the registry record, last updated by the sponsor on 15 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prospective Multicenter Study: PredIcting sterOid depeNdEnt livEr Injury (PIONEER) With Polyreactive Immunoglobulin G
- ClinicalTrials.gov ID
- NCT05810480
- Acronym / sponsor ID
- PIONEER / PIONEER
- Conditions
- Autoimmune Hepatitis, Autoimmune Liver Disease
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 400 participants (estimated)
- Lead sponsor
- Hannover Medical SchoolUniversity, hospital or other
- Study start
- 6 Jun 2023 (actual)
- Primary completion
- Jul 2028 (estimated)
- Study completion
- Jan 2029 (estimated)
- First posted
- 12 Apr 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Autoimmune Hepatitis | – | Diagnostic Test: polyreactive immunoglobulin GThis 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 |
| non-autoimmune hepatitis liver disease | – | Diagnostic Test: polyreactive immunoglobulin GThis 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 |
Who may qualify
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
- 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.
Key inclusion criteria (3 listed)
- Diagnostic liver biopsy for the work-up of any liver disease
- Informed consent
- Definition of any liver disease according to current societal guidelines
Key exclusion criteria (5 listed)
- 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), …)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| polyreactive immunoglobulin GAlso: Conventional diagnostic autoantibodiesPolyreactive 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. | Diagnostic test | Autoimmune Hepatitis, non-autoimmune hepatitis liver disease |
Primary outcome
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.
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.
3 secondary outcomes
Diagnostic discrimination between AIH and DILI by polyreactive IgG
Time frame: At enrollment
Prediction of steroid dependent hepatitis by any other autoantibody
Time frame: Assessment of steroid dependency at six months after enrollment
Age-dependency of autoantibodies
Time frame: Assessment of autoantibodies at baseline
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jul 2026.
- Background: PubMed 34473365Taubert 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.
- Individual participant dataSharing planned: No. IPD are not shared with collaborators. Data, in general, is only provided anonymized by contributing centers.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Bastian Engel, Dr. principal investigator
Hannover Medical School
Richard Taubert, Dr. principal investigator
Hannover Medical School
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Autoimmune Hepatitis and Autoimmune Liver Disease, run by Hannover Medical School at 6 sites in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 15 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Bastian Engel, Dr. (+49 511 532 6766, Engel.Bastian@mh-hannover.de), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Sensitivity of new simplified pIgG AIH Score (time frame: Assessment of steroid dependency at six months after enrollment). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05810480, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Jul 2026.