LAUSR

A 68-year-old man presented to a district emergency department with a 3-day history of jaundice and vomiting. He was urgently transferred to our centre for management of acute liver injury (ALI). On arrival in the intensive care unit he was in atrial fibrillation (rate 120 b.p.m.), normotensive and not encephalopathic. He was jaundiced without other significant examination findings. Laboratory investigations were consistent with ALI (Table 1). His medical history included atrial fibrillation anticoagulated with rivaroxaban, dilated cardiomyopathy and type 2 diabetes mellitus. He had no risk factors for acute or chronic liver disease and had normal liver biochemistry 6 months before presentation. He consumed 2–3 standard drinks/week. His weight was 70 kg (body mass index 22 kg/m). His other prescription medications were bisoprolol 10 mg mane, spironolactone 25 mg mane, metformin SR 500 mg daily and sacubitril/ valsartan 24 mg/26 mg BD, all of which he had been taking for over 12 months. On further questioning, he reported commencing berberine 500 mg BD 3 weeks prior. A rivaroxaban trough concentration was supratherapeutic at 284 ng/mL (20–150 ng/mL), despite the last dose being 4 days prior. Viral, genetic and autoimmune aetiologies of ALI were excluded on serological assessment. Paracetamol level was undetectable (Table 1). Ultrasonography demonstrated hepatic steatosis but was otherwise normal. An echocardiogram showed stable mild left ventricular dysfunction. He received supportive care with intravenous fluids and vitamin K. He did not require ventilatory support, vasopressors or renal replacement therapy, and did not have any bleeding events. His liver biochemistry and coagulation parameters improved rapidly (Table 1). He was discharged to the referring hospital on day 7. At 6 months follow up, his liver biochemistry had normalised completely. Berberine is a complementary and alternative medicine (CAM) with a rapidly expanding range of purported benefits. Rivaroxaban is a direct acting oral anticoagulant and has been identified as a cause of acute liver failure; however, this has generally been described on drug commencement. Our patient had been on a stable dose for several years. Berberine is a potent inhibitor of Pglycoprotein (P-gp) and the cytochrome p450 system, including CYP3A4. Of note, rivaroxaban is metabolised by CYP3A4/3A5/2 J2 and P-gp. Co-administration of dual CYP3A4 and P-gp inhibitors has been shown to increase rivaroxaban concentrations by up to 50%. Therefore, we hypothesised that in the present case, berberine inhibited the metabolism of rivaroxaban, resulting in ALI. This was supported by the temporal commencement of berberine, supratherapeutic