Clinicopathological Features of Autoimmune Hepatitis Stratified by Extrahepatic Autoimmune Diseases

Background/Objectives: Autoimmune hepatitis (AIH) often coexists with extrahepatic autoimmune diseases (EADs); however, the clinical significance of EAD comorbidity and its subtypes remains incompletely understood. In addition, an increasing proportion of AIH without EAD (NEAD-AIH) has been suggested but not systematically evaluated. Methods: We retrospectively analyzed 46 patients diagnosed with AIH between 2014 and 2023. Clinical features were compared between EAD-associated AIH (EAD-AIH) and NEAD-AIH. Analyses were performed focusing on major EAD subtypes, including Sjögren’s syndrome (SS), autoimmune thyroid disease (AITD), and systemic sclerosis (SSc). Steroid-treated cases were further evaluated for treatment response and renal outcomes. Results: Among the 46 patients (median age, 63 years; 89% female), 61% had concomitant EADs. Compared with EAD-AIH, NEAD-AIH showed significantly higher AST, ALT, IgG, and bilirubin levels, together with lower albumin and prothrombin activity. Acute-onset hepatitis and corticosteroid use were more frequent in NEAD-AIH, and all cases of liver failure occurred in this group. The proportion of NEAD-AIH increased over time (from 21% to 54%). A small number of recent NEAD-AIH cases occurred after COVID-19 vaccination or immune checkpoint inhibitor therapy, although causality could not be established. Among EAD subtypes, SSc-AIH was characterized by relatively low IgG levels, whereas SS-AIH showed favorable biochemical profiles with low relapse rates. No excess renal deterioration was observed in SSc-AIH after steroid therapy. Conclusions: AIH exhibits substantial clinical heterogeneity according to EAD status and subtype. NEAD-AIH tends to present with a more acute and severe phenotype and appears to be increasing, whereas EAD-AIH shows distinct immunologic characteristics. These findings underscore the importance of considering autoimmune background in the clinical evaluation of AIH.