Triple autoimmune overlap syndrome of the liver: a rare case of concomitant PBC, PSC, and AIH

Triple overlap syndrome involving autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), and primary sclerosing cholangitis (PSC) is an exceptionally rare autoimmune hepatopathy, posing major diagnostic and therapeutic challenges. A 51-year-old woman initially diagnosed with AIH-PBC overlap presented persistent hepatocellular cytolysis despite corticosteroids and ursodeoxycholic acid. Autoimmune screening revealed ANA, anti-M2, and anti-gp210 positivity. Repeat liver biopsy showed interface hepatitis, ductopenic lymphocytic cholangitis, and periductal fibrosis. Magnetic resonance cholangiography demonstrated an attenuated intrahepatic biliary tree with a "pruned-tree" appearance, confirming PSC features. The diagnosis of AIH-PBC-PSC triple overlap was established. Due to azathioprine intolerance and hepatotoxicity, therapy was switched to mycophenolate mofetil with UDCA and low-dose corticosteroids, resulting in biochemical stabilization. This case represents one of the few well-documented instances of AIH-PBC-PSC overlap. It underscores the importance of integrating serology, histology, and advanced imaging for accurate diagnosis and individualized therapy. In the absence of standardized guidelines, management relies on tailored immunosuppression and supportive care to prevent progression toward liver failure.