Double-barreled drug-induced liver injury and the unmasking of latent primary biliary cholangitis: A case of amoxicillin-clavulanate and warfarin interaction.

BACKGROUND

Drug-induced liver injury (DILI) remains a diagnostic challenge, particularly in the setting of polypharmacy. Amoxicillin-clavulanate is the most frequent cause of idiosyncratic DILI worldwide, typically producing a delayed cholestatic pattern. Warfarin-associated hepatotoxicity is rare but recognized, and coadministration of potentially hepatotoxic or interacting agents may exacerbate hepatic injury or coagulopathy.

CASE PRESENTATION: A 60-year-old woman with atrial fibrillation on long-term warfarin therapy presented with progressive jaundice two weeks after completing a 10-day course of amoxicillin-clavulanate for otitis media. Laboratory tests revealed marked hepatocellular injury (ALT 2023 U/L [ULN 45], AST 2194 U/L [ULN 40], bilirubin 6 mg/dL [ULN 1.2], INR 7). Viral hepatitis serologies, including hepatitis E, were negative. Autoimmune testing showed ANA 1:640, AMA 1:80, ASMA 1:80, and elevated IgG (3000 mg/dL). Liver biopsy demonstrated features of resolving hepatocellular and canalicular damage on a background of early primary biliary cholangitis (PBC). Warfarin withdrawal and vitamin K administration normalized INR and improved liver enzymes.

CONCLUSION

This case illustrates a multifactorial liver injury wherein amoxicillin-clavulanate served as the primary hepatotoxin, with possible warfarin-related hepatotoxicity and coagulopathy superimposed on latent PBC. It emphasizes the need for vigilance when prescribing interacting with or hepatotoxic agents to patients on chronic anticoagulation. The case further demonstrates the supportive-but not definitive-role of RUCAM in polypharmacy-related DILI assessment, reinforcing the primacy of comprehensive clinical judgment.