INTRODUCTION: Liver involvement manifested by increased liver enzymes has been reported in approximately 10% of cases of syphilis. Syphilitic hepatitis has been reported to cause cholestatic hepatitis, however has not been associated with hepatocellular injury. We present a case of autoimmune hepatitis flare after completion of treatment for biopsy proven syphilitic hepatitis. CASE DESCRIPTION/METHODS: Fifty-one-year-old Hispanic man with history of HTN presented for new onset jaundice and RUQ pain. Initial labs revealed Tbili 19.9, Dbili 15.5, ALP 147, ALT 1652 and INR 1.6. No new history of medications/herbs use, new sexual contact, body piercing, drug use or family history of liver disease. Work-up was negative for acute viral hepatitis, CMV and EBV. ANA positive (1:160), ASMA negative, anti-LKM 1.8, Anti-SLA 1.3 and IGG 1301. RPR reactive confirmed with FTA antibodies. Liver biopsy showed acute hepatitis with mixed infiltrates, confluent necrosis and cholestasis. Immunostaining for spirochetes was positive on liver biopsy. The patient received IM 2.4 million IU Benz Pen Q weekly x 3 doses with substantial improvement in liver enzymes (AST 481, ALT 422, Tbili 4.6) and INR 1.2. On 3-week follow-up, however liver enzymes were, AST 1007, ALT 1000, TBili 10.3, INR 1.6, requiring readmission. Further work-up showed: IgG 2275, ANA positive 1:160 and repeat liver biopsy revealed interface hepatitis with negative stains for spirochetes. The patient was treated with IV solumedrol 40 mg with significant improvement of liver enzymes and was discharged on prednisone 40 mg daily. Follow-up labs revealed: AST 90, ALT 139, Tbili 2.5 and INR 1.1. The prednisone dose was tapered with continued biochemical improvement. DISCUSSION: Treponema pallidum causes Syphilis and transmission is sexual and vertical. In cases of syphilitic hepatitis liver biopsy reveals focal hepatocyte necrosis and portal tracts with inflammatory infiltrates. Immunohistochemical stain for spirochetes is confirmatory but only identifies in about 50% of cases. Autoimmune hepatitis is T cell medicated immune attack on liver antigens with progressive necroinflammatory and fibrotic process in the liver. The diagnosis of AIH needs biochemical, immunologic and histologic confirmation. We report a unique case of biopsy proven syphilitic hepatitis with significant elevation of liver enzymes which improved with antibiotic therapy but subsequently triggered immunogenic response identical to AIH with recovery after steroid therapy.