Double Trouble: Drug-Induced Autoimmune Hepatitis (AIH)-Primary Biliary Cholangitis (PBC) Overlap Syndrome Triggered...

The coexistence of autoimmune hepatitis (AIH) and primary biliary cholangitis (PBC) is termed AIH-PBC overlap syndrome, a rare but recognized clinical entity. Clinical presentation is often non-specific, including fatigue, myalgias, arthralgias, and cholestatic liver function test (LFT) abnormalities. Diagnosis is based on biochemical, histologic, and immunologic features commonly using the well-established Paris criteria. While the exact etiology is unclear, immune dysregulation triggered by medications may play a role.  We present the case of a 51-year-old male patient with hypertension and type 2 diabetes mellitus who developed elevated LFTs two weeks after starting hydralazine. Serologies revealed positive antimitochondrial antibody (AMA), antinuclear antibody (ANA), and anti-smooth muscle antibody (ASMA) while viral and acetaminophen toxicity were ruled out. An initial liver biopsy demonstrated mixed portal and lobular inflammation without definitive features of AIH or PBC. Despite discontinuing hydralazine, LFTs remained elevated. A repeat liver biopsy revealed florid duct lesions and interface hepatitis. Based on the Paris criteria and clinical judgement, the patient was diagnosed with AIH-PBC overlap syndrome. Treatment with prednisone and ursodiol led to near normalization of LFTs.  While DILI-induced AIH-PBC overlap has previously been reported with agents like infliximab and tuberculosis therapies, this is the first reported case potentially triggered by hydralazine. Immune dysregulation may have resulted from hepatic injury induced by hydralazine. This case highlights the importance of considering drug-induced liver injury as a potential precipitant of AIH-PBC overlap and the need for early recognition and treatment.