Autoimmune Hepatitis, Autoimmune Liver Disease
Conditions
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.
Interventions
DIAGNOSTIC_TESTpolyreactive 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.
Sponsors
Hannover Medical School
Study design
Observational model
CASE_CONTROL
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Healthy volunteers
Yes
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
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Sensitivity of new simplified pIgG AIH Score | 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 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 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) |
| Age-dependency of autoantibodies | Assessment of autoantibodies at baseline | 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 |
Countries
Germany
Contacts
CONTACTBastian Engel, Dr.
CONTACTRichard Taubert, Dr.
PRINCIPAL_INVESTIGATORBastian Engel, Dr.
Hannover Medical School
PRINCIPAL_INVESTIGATORRichard Taubert, Dr.
Hannover Medical School
Outcome results
None listed