S5794 An Uncommon Link: Autoimmune Hepatitis Following Doxycycline Therapy

Introduction: Drug-induced autoimmune hepatitis (DI-AIH) is a rare but important cause of acute liver injury. Although more commonly associated with minocycline, other antibiotics such as doxycycline have been implicated. Early recognition is critical, as DI-AIH can resemble classic autoimmune hepatitis but may resolve with drug withdrawal alone. This case illustrates the clinical features, diagnostic workup, and spontaneous resolution of DI-AIH in a patient following a short course of doxycycline. Case Description/Methods: A 63-year-old man with a history of hypertension, chronic kidney disease, BPH, morbid obesity, and gout presented with a one-week history of jaundice, dark urine, acholic stools, pruritus, and fatigue. Two weeks prior, he had completed a 7-day course of doxycycline for acute prostatitis. He denied alcohol use, herbal supplements, or other recent medication changes. Initial labs revealed total bilirubin of 18.2 mg/dL, aspartate aminotransferase (AST) 578 U/L, alanine aminotransferase (ALT) 575 U/L, alkaline phosphatase 176 U/L, and international normalized ratio 1.28. Abdominal imaging showed hepatic steatosis without biliary obstruction. Workup for viral hepatitis was negative. Autoimmune panel revealed positive ANA, elevated IgG (2500 mg/dL), and marginally positive ASMA. Liver biopsy demonstrated moderate portal inflammation with interface hepatitis, Mallory-Denk bodies, mild steatosis, and stage 2–3 fibrosis—findings consistent with autoimmune hepatitis. Given the temporal relationship to doxycycline, a diagnosis of DI-AIH was favored. Doxycycline and diclofenac were discontinued. Although prednisone was initiated, it was held after one dose as liver enzymes began trending down spontaneously. At follow-up, liver tests normalized (AST 40 U/L, ALT 37 U/L, bilirubin 3.1 mg/dL), and symptoms resolved. The patient was counseled to avoid doxycycline and was scheduled for repeat imaging. Discussion: Diagnosing DI-AIH can be tricky because its presentation often mimics other types of liver injury. In this case, doxycycline appeared to be the likely culprit, raising awareness of its role in triggering autoimmune-like reactions—especially in patients with other risk factors like fatty liver or multiple medications. The diagnosis came into focus after correlating the timing of symptoms with autoimmune markers and liver biopsy findings. In contrast to classic autoimmune hepatitis, the liver injury resolved after discontinuing the medication, without the need for long-term immunosuppression. Early recognition and appropriate management are key to preventing disease progression and avoiding unnecessary therapies.