"Overlap" Syndromes in Autoimmune Liver Disease: Definitions, Clinical Challenges and Future Directions

Autoimmune liver diseases, including autoimmune hepatitis, primary biliary cholangitis, and primary sclerosing cholangitis, are rare chronic conditions characterized by immune-mediated hepatobiliary injury. While traditionally viewed as distinct entities, they exist along a continuous spectrum, manifesting in some cases as "overlap" or "variant" syndromes. These variants are considered phenotypic variations of shared pathways rather than unique diseases. The rarity of these conditions and an incomplete understanding of their underlying pathophysiology have prevented standardized definitions, and ultimately hinder the development of robust, evidence-based clinical protocols for these patient populations. This review aims to offer a pragmatic clinical approach to these complex cases.