Autoimmune hepatitis associated with other autoimmune diseases

Autoimmune hepatitis (AIH) is a chronic inflammatory liver disorder driven by genetic predisposition, environmental triggers, and immune dysregulation. It is classified into type 1 (AIH-1) and type 2 (AIH-2), distinguished by specific autoantibodies. A notable feature of AIH is its frequent coexistence with other autoimmune conditions, reported in 20%–40% of patients. This review critically evaluates the evidence supporting these associations, focusing on prevalence, shared pathogenic mechanisms, diagnostic challenges, and therapeutic strategies.

AIH-Associated Endocrine Diseases
Autoimmune Thyroid Disease (AITD): AITD, particularly Hashimoto’s thyroiditis and Graves’ disease, is one of the most common comorbidities, affecting 6%–23% of AIH patients. Shared genetic factors, such as HLA-DR3, and immune dysregulation involving T-helper subsets (Th1, Th17) and regulatory T cells, contribute to this association. Diagnosing AIH in the context of thyroid dysfunction is challenging due to overlapping liver enzyme elevations. Treatment typically involves corticosteroids and azathioprine, with careful management of thyroid-specific manifestations.

Type 1 Diabetes Mellitus (T1DM): The prevalence of T1DM in AIH ranges from 1% to 10%. HLA-DRB1*03 and DRB1*04 are key genetic risk factors for both conditions. Diagnostic overlap exists with diabetes-related liver complications such as glycogenic hepatopathy and metabolic dysfunction-associated steatotic liver disease (MASLD). Liver biopsy is often necessary for differentiation. Steroid therapy for AIH may exacerbate hyperglycemia, necessitating steroid-sparing regimens and close endocrine collaboration.

AIH-Associated Hepatobiliary and Gastrointestinal Diseases
Primary Biliary Cholangitis (PBC) and Primary Sclerosing Cholangitis (PSC): Overlap syndromes (AIH-PBC and AIH-PSC) are diagnostically complex, with prevalence estimates ranging from 2% to 20%. Diagnostic criteria such as the Paris criteria are used, though their specificity is debated. No statistically significant association has been firmly established, partly due to diagnostic ambiguities and shared histologic features.

Inflammatory Bowel Disease (IBD) and Celiac Disease: Strong evidence supports associations between AIH and ulcerative colitis (UC), Crohn disease, and celiac disease. Mendelian randomization studies confirm genetic links. The "leaky gut" hypothesis and gut-liver axis interactions, mediated by cytokines like IL-17 and microbiome alterations (e.g., Lactobacillus), are proposed mechanisms. Treatment involves immunosuppression for AIH and disease-specific management for IBD or celiac disease. A gluten-free diet may aid in celiac-related liver enzyme normalization, but AIH often requires additional immunosuppression.

AIH-Associated Rheumatologic and Dermatologic Diseases
Systemic Lupus Erythematosus (SLE) and Rheumatoid Arthritis (RA): Reported prevalences of AIH-SLE and AIH-RA vary widely (1.6%–15% and 1.6%–7.8%, respectively). However, these associations are not well-supported due to inconsistent statistical significance and potential diagnostic overlap (e.g., lupus hepatitis). Histologic differentiation is essential.

Sjögren’s Syndrome (SS) and Vitiligo: Limited data exist for AIH-SS, and though one U.S. study reported a 4.9% prevalence, methodological limitations preclude definitive conclusions. Vitiligo has been observed in 1%–5% of AIH cases, but small sample sizes and lack of statistical rigor prevent confirmation of a true association.

Diagnostic and Therapeutic Considerations
Diagnosis of AIH relies on serologic markers (ANA, ASMA, LKM1), elevated IgG, and histologic findings such as interface hepatitis and emperipolesis. Overlap with other autoimmune diseases complicates diagnosis, especially when extrahepatic conditions cause secondary liver enzyme elevations. Liver biopsy remains crucial in ambiguous cases.

Treatment primarily involves corticosteroids and azathioprine. Steroid-sparing agents (e.g., mycophenolate mofetil) are used in intolerant patients. Biologics carry risks of drug-induced AIH. A multidisciplinary approach is essential for managing concurrent autoimmune diseases, particularly when treatments conflict (e.g., steroids in diabetes).

Conclusions
This review affirms significant associations between AIH and AITD, T1DM, UC, Crohn disease, and celiac disease. In contrast, links with PBC, PSC, SLE, RA, SS, and vitiligo are less substantiated. Future studies should prioritize precise diagnostic criteria and explore shared immunopathogenic pathways. An interdisciplinary management strategy is vital to optimize outcomes in patients with multi-organ autoimmune involvement.

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https://xiahepublishing.com/2310-8819/JCTH-2025-00153

The study was recently published in the Journal of Clinical and Translational Hepatology.

The Journal of Clinical and Translational Hepatology (JCTH) is owned by the Second Affiliated Hospital of Chongqing Medical University and published by XIA & HE Publishing Inc. JCTH publishes high quality, peer reviewed studies in the translational and clinical human health sciences of liver diseases. JCTH has established high standards for publication of original research, which are characterized by a study’s novelty, quality, and ethical conduct in the scientific process as well as in the communication of the research findings. Each issue includes articles by leading authorities on topics in hepatology that are germane to the most current challenges in the field. Special features include reports on the latest advances in drug development and technology that are relevant to liver diseases. Regular features of JCTH also include editorials, correspondences and invited commentaries on rapidly progressing areas in hepatology. All articles published by JCTH, both solicited and unsolicited, must pass our rigorous peer review process.

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