We report the case of an 80-year-old male who developed severe cholestatic jaundice following two courses of flucloxacillin prescribed for a soft-tissue infection. Despite discontinuation of the antibiotic, serum bilirubin remained markedly elevated eight weeks later, accompanied by persistent pruritus. Comprehensive evaluation for acute liver injury, including viral, autoimmune, and metabolic studies as well as abdominal imaging, was unremarkable. A liver biopsy demonstrated preserved hepatic architecture with prominent hepatocellular cholestasis, consistent with hepatocellular secretory failure.

After consulting with a specialist hepatology centre, the patient was initiated on rifampicin monotherapy, resulting in gradual symptomatic improvement and a progressive decline in bilirubin levels over subsequent weeks. This case highlights the importance of maintaining a high index of suspicion for hepatocellular secretory failure in patients with persistent hyperbilirubinemia following withdrawal of a potential hepatotoxic agent. Targeted therapy with rifampicin can result in both symptomatic and biochemical improvement in hepatic function.

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