Machine Learning for Prediction of Therapy Response in Autoimmune Hepatitis

The 5th International Autoimmune Hepatitis Group (IAIHG) research workshop emphasized the integration of large clinical cohorts with artificial intelligence (AI) for enhanced prediction of therapy responses and outcomes in Autoimmune Hepatitis (AIH). This project aims to develop and validate machine learning (ML) models using data from the R-Liver registry and other international cohorts. After rigorous preprocessing to ensure data uniformity and quality, the investigators will identify and characterize factors influencing therapy response. They will then implement ML models to predict complete biochemical response (CBR) at 6 and 12 months, using five-fold cross-validation, and validate these models in external cohorts from Spain, Canada, and the international AIH group, ensuring robustness and generalizability.

Finally, the investigators will prospectively validate the models in newly registered cases, assessing both short-term and long-term outcomes. This project seeks to advance personalized treatment strategies in AIH, facilitating timely adjustments in therapy and improving patient prognosis through AI-driven decision support. This projects' interdisciplinary team, with expertise in clinical AI and hepatology, is well-equipped to address these challenges and enhance the clinical management of AIH.

Study Overview

• Status: Active, not recruiting
• Conditions: Autoimmune Hepatitis

• Study Type: Observational
• Enrollment (Estimated): 5000

Contacts and Locations

Study Locations

• Germany
  • Dresden, Germany
    • Else Kroener Fresenius Center for Digital Health, Technical University Dresden
  • Hanover, Germany, 30625
    • Hannover Medical School

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

This project utilizes already established registries of patients with autoimmune hepatitis (AIH) from the international autoimmune hepatitis group (IAIHG), the European Reference Network on Rare liver diseases (R-LIVER), the spanish network on autoimmune hepatitis (colHAI) and the canadian network on autoimmune hepatitis (CANAL). Initial reports on the patient populations within the respective registries were separately published (doi: 10.1111/liv.16035, doi: 10.1097/HEP.0000000000000589, 10.1016/j.jhep.2024.03.021, 10.1097/HEP.0000000000000018 ).

Description

Inclusion Criteria:

• Diagnosis of Autoimmune hepatitis
• Consent to provide data to the specific registry
• available follow-up data at least within the first 12 months

Exclusion Criteria:

• variant syndromes
• extrahepatic autoimmune disease
• immunosuppressive treatment at diagnosis

Study Plan

How is the study designed?

Number of groups / cohorts

5

Cohorts and Interventions

Group / Cohort
R-LIVER Registry
AIH registry from Edmonton, Canada
CANAL Registry
IAIHG Registry
ColHAI Registry

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients with complete biochemical response at 6 months after diagnosis	Complete biochemical response is defined as normal aspartate amino transferase (AST), alanine aminotransferase (ALT) and immunoglobulin G (IgG).	6 months
Number of patients with complete biochemical response at 12 months after diagnosis	Complete biochemical response is defined as normal aspartate amino transferase (AST), alanine aminotransferase (ALT) and immunoglobulin G (IgG).	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients experiencing liver-related death or liver transplantation		From enrolment until the end of the study
Number of patients with decompensation of liver disease	Decompensation meaning a composite of new/worsening ascites, infection requiring hospitalization, acute-on-chronic liver failure, variceal bleeding, hepatic encephalopathy.	From enrolment until the end of the study
Number of patients with complete biochemical response through study completion	Complete biochemical response is defined by normal AST, normal ALT and normal IgG	through study completion, an expected average of 1 year
Number of patients with histological remission of AIH through study completion	Histological remission is defined as modified hepatitis activity index below 4.	through study completion, an expected average of 1 year
Number of patients that develop cirrhosis through study completion	Cirrhosis is defined by imaging findings indicative of cirrhosis, histological staging indicating fibrosis or liver stiffness measurement that is in line with a cirrhotic liver.	through study completion, an expected average of 1 year
Number of patients with intolerance to primary treatment necessitating regimen change	Intolerance to treatment is reported by respective patients and assessed by respective treating physicians. It is expected to be gastrointestinal side effects and hematological side effects (cytopenias) that may typically occur from treatment with azathioprine or mycophenolate mofetil which lead to change of treatment regimens in patients with autoimmune hepatitis.	12 months
Number of patients with non-response to primary treatment necessitating treatment change	Non-Response ist defined as persistently elevated aspartate aminotransferase, alanine aminotransferase and/or immunoglobulin G. It is considered a reason to change the therapeutic regimen.	12 months
Number of patients with third line treatment due to non-response to obtain biochemical response through study completion	Non-response is defined as persistently elevated aminotransferases and/or immunoglobulin G.	through study completion, an expected average of 1 year
Number of patients with normalization of aminotransferase levels in the blood irrespective of Immunoglobulin G levels	Aminotransferases are alanine aminotransferase and asparatate aminotransferase. These enzymes indicate liver injury and are considered response markers measured from blood in clinical routine to assess therapeutic response in autoimmune hepatitis.	6 months
Number of patients with normalization of aminotransferase levels irrespective of Immunoglobulin G levels	Aminotransferases are alanine aminotransferase and asparatate aminotransferase. These enzymes indicate liver injury and are considered response markers measured from blood in clinical routine to assess therapeutic response in autoimmune hepatitis.	12 months
Number of patients with steroid-free complete biochemical response	Complete biochemical response is defined by normal blood levels for aminotransferases and normal immunoglobulin G. This outcome measure assesses this parameter in relation to the fact if the patient needed corticosteroid-therapy to obtain this outcome or if the patient only needed other immunosuppressive drugs (e.g. azathioprine, mycophenolate mofetil).	6 months
Number of patients with steroid-free complete biochemical response	Complete biochemical response is defined by normal blood levels for aminotransferases and normal immunoglobulin G. This outcome measure assesses this parameter in relation to the fact if the patient needed corticosteroid-therapy to obtain this outcome or if the patient only needed other immunosuppressive drugs (e.g. azathioprine, mycophenolate mofetil).	12 months

Collaborators and Investigators

• Sponsor: Hannover Medical School
• Collaborators: Technische Universität Dresden
• Investigators: Principal Investigator: Bastian Engel, MD, Hannover Medical School, Hannover, Germany

Study record dates

Study Major Dates

• Study Start (Actual): January 5, 2026
• Primary Completion (Estimated): January 5, 2027
• Study Completion (Estimated): January 1, 2028

Study Registration Dates

• First Submitted: January 5, 2026
• First Submitted That Met QC Criteria: January 28, 2026
• First Posted (Actual): January 30, 2026

Study Record Updates

• Last Update Posted (Actual): January 30, 2026
• Last Update Submitted That Met QC Criteria: January 28, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: machine learning; registry; therapeutic response
• Additional Relevant MeSH Terms: Autoimmune Diseases; Immune System Diseases; Digestive System Diseases; Liver Diseases; Hepatitis, Chronic; Hepatitis; Hepatitis, Autoimmune
• Other Study ID Numbers: AIH_ML_v1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Anonymized IPD will be shared for the purpose of the study by the respective registries with the research team of this study. IPD request need to be directed directly to the respective officials of the different registries.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No