S5870 Minocycline-Induced Autoimmune-Like Hepatitis With Rapid-Onset Bridging Fibrosis: First Report of Drug-Triggered Dynamic Fibrosis

Introduction: Minocycline is a commonly prescribed antibiotic for dermatologic conditions and is known to cause rare autoimmune hepatitis-like drug-induced liver injury (DILI). While transient transaminase elevations have been reported, progression to advanced fibrosis and persistent histologic inflammation despite biochemical normalization has not previously been described. Case Description/Methods: A 57-year-old obese man (body mass index 26) with no prior autoimmune disease, metabolic syndrome, or alcohol use presented with scleral icterus and elevated liver enzymes after 6–8 weeks of minocycline (100 mg daily) for presumed acneiform lesions. Labs showed aspartate aminotransferase 1,342 U/L, alanine aminotransferase 1,285 U/L, total bilirubin 7.4 mg/dL, albumin 2.6 g/dL, and alkaline phosphatase 299 U/L. Viral hepatitis and CMV/EBV PCRs were negative. Autoimmune workup revealed ANA 1:640 and elevated IgG (2,906 mg/dL); dsDNA was mildly elevated, with negative anti-Smith, SMA, and anti-RNP. Computed tomography showed hepatic steatosis without cirrhosis. Liver biopsy was performed to confirm diagnosis and assess reversibility, revealing severe interface hepatitis with plasma cells, rosettes, and bridging fibrosis (stage 3), consistent with autoimmune-like DILI. Minocycline was discontinued, and the patient responded to prednisone; azathioprine was later switched to mycophenolate mofetil (MMF) due to rash. Despite normalization of liver enzymes, a repeat biopsy 18 months later (to evaluate potential immunosuppression withdrawal) showed persistent grade 2 inflammation and stage 3 fibrosis. HVPG remained <5 mmHg, confirming no portal hypertension. MMF was continued, and the patient remains clinically stable. Discussion: This is the first reported case of minocycline-induced autoimmune-like DILI leading to advanced fibrosis within weeks of exposure. While severe necrosis can accelerate fibrogenesis, this case was notable for severe fibrosis at initial presentation, suggesting exceptionally rapid-onset dynamic fibrosis. Despite biochemical remission, persistent histologic activity reinforces the disconnect between labs and tissue resolution. Although the clinical course supports drug-induced injury, the possibility of de novo autoimmune hepatitis triggered or unmasked by minocycline cannot be excluded. This case underscores the aggressive fibrogenic potential of immune-mediated liver injury and the critical role of biopsy in guiding long-term immunosuppression decisions.