Multimodal characterization of autoimmune hepatitis morbidity and metabolic phenotype

Background and Aims: Autoimmune hepatitis (AIH), as a chronic inflammatory liver disease posing significant diagnostic challenges due to its varied clinical manifestations and overlap with other liver diseases. We aim to elucidate the complex disease network associated with AIH using PheWAS analyses, as well as metabolic and serological alterations in patients with AIH.

Methods: 392 participants with AIH and 784 propensity score (age, sex, BMI, ethnicity) matched controls without liver diseases were included in the study. Comorbidities of individuals with AIH were studied using PheWAS. Moreover, we performed a comprehensive serological and metabolomic profiling comparing AIH patients with matched controls.

Results: Apart of direct liver-related complications (cirrhosis and portal hypertension), we also found a significant association of different autoimmune (systemic lupus erythematous HR: 18.9; KI95: 4.5-79.1), neoplastic (cancer of bronchus / lung HR: 4.1; KI95: 2-8.7), endocrine (type-2 diabetes HR: 2.5; KI95: 1.7-3.7), respiratory (pulmonary fibrosis HR: 11.3; KI95: 3.5-39) as well as extrahepatic gastrointestinal diseases with AIH. In lipidomic and metabolomic analyses among others the concentration of large HDL (HR: 1.04/SD) and VLDL diameter (HR: 0.96/SD), as well as tyrosine (HR: 1.02/SD) were significantly associated with AIH.

Conclusion: This study offers an in-depth view of the morbidity associated with AIH, which may improve patient counseling. Additionally, the identified metabolomic signature may provide insight into the complex pathophysiological mechanisms driving the development, progression, and related morbidity in AIH. Further we aim to validate our findings externally on a cohort from Hannover, to assure generalisability and validity.

Publication History

Article published online:
20 January 2025