Immune Checkpoint Inhibitor-Related Hepatitis Versus Classical Autoimmune Hepatitis: A Retrospective Multidomain Phenotype Comparison

Background/Objectives: Immune checkpoint inhibitor-related hepatitis (ICI-H) can resemble classical autoimmune hepatitis (AIH), but comparative multidomain data remain limited. We compared their clinical, biochemical, and serological profiles and descriptively summarized histopathological findings. Methods: This single-centre retrospective cohort screened 100 records from January 2018 to October 2023; 79 patients met predefined criteria (40 ICI-H; 39 AIH). ICI-H required an updated RUCAM score of ≥6, whereas AIH required a simplified AIH score of ≥6 and compatible histology. Continuous and categorical variables were assessed using Mann–Whitney U and Fisher’s exact tests with Benjamini–Hochberg correction where applicable; histopathological findings were summarized descriptively because biopsy ascertainment was markedly unequal between groups. Results: Compared with AIH, ICI-H occurred more often in men (65.0% vs. 20.5%) and showed higher AST, ALT, ALP, GGT, INR, CRP, and neutrophil-to-lymphocyte ratio (all q < 0.001), but lower ANA positivity (12.5% vs. 74.4%; q < 0.001). Histopathological observations were limited to the biopsy-assessed subgroup (10 ICI-H; 39 AIH) and are reported descriptively because biopsy ascertainment was markedly unequal and non-random. Conclusions: ICI-H and classical AIH showed different observed clinical, biochemical, and serological profiles; however, these differences should not be interpreted as independent diagnostic discriminators because disease-specific criteria contributed to group assignment. Diagnosis after ICI exposure should integrate exposure timing, exclusion of competing causes, structured causality assessment, serology, and selective histology. Outcome comparisons require standardized longitudinal follow-up.