Overlap Syndromes in Autoimmune Hepatitis: Experience from a Moroccan Tertiary Care Center

Introduction: Overlap syndromes associated with autoimmune hepatitis are rare and heterogeneous conditions that combine features of autoimmune hepatitis and autoimmune cholangiopathies, primarily primary biliary cholangitis or primary sclerosing cholangitis. Their diagnosis relies on a multidimensional approach integrating clinical, laboratory, immunological, radiological, and histological data. The objective of this study was to describe the characteristics of overlap syndromes observed in a Moroccan cohort of patients with autoimmune hepatitis and to compare them with forms of isolated autoimmune hepatitis. Materials and Methods: We conducted a retrospective descriptive and analytical study in the Hepatogastroenterology Department of Hassan II University Hospital, Fez, from January 2012 to December 2025. The full cohort included 78 AIH patients and the analysis compared 33 overlap cases with 45 isolated AIH cases. Results: Overlap syndromes represented 42.3% of AIH cases. AIH-primary biliary cholangitis overlap was predominant, occurring in 30 patients (90.9%), while AIH-primary sclerosing cholangitis overlap was observed in 3 patients (9.1%). The mean age at diagnosis was 47.3 years, with marked female predominance (91%). Cytolysis and cholestasis were frequent. Antinuclear antibodies were positive in 72% of cases and anti-mitochondrial antibodies in 66%. Liver biopsy showed fibrosis, inflammatory infiltrates, interface hepatitis, and biliary lesions. All patients received corticosteroids and ursodeoxycholic acid, and 90.9% received azathioprine. Complete biochemical remission at 12 months was achieved in 84.8% of patients. Compared with isolated AIH, overlap syndromes were significantly associated with cholestasis, anti-mitochondrial antibodies, and histological biliary lesions. Conclusion: Overlap syndromes account for a significant proportion of autoimmune hepatitis cases in our setting, with a clear predominance of AIH-PBC forms. Their early recognition is essential for tailoring therapeutic management, particularly through the combination of immunosuppressive therapy and ursodeoxycholic acid. Prospective multicenter studies are needed to better define their long-term prognosis.