Drug induced liver injury associated with Flupirtine in 6 cases

Background & aims: Drug-induced liver injury is a frequent diagnostic consideration in daily practice in hepatology. To date, Flupirtine, a non-opioid analgesic, has only been rarely described to cause liver injury. The aim of this case series was to characterize clinical and morphological features of Flupirtine-associated liver injury.

Methods: Clinical presentation of six patients with Flupirtine-associated liver injury was reviewed, clinical follow up and review of histological features were performed.

Results: Six patients (4 females) presented with clinical signs of hepatitis. All used Flupirtine for pain management since 3 weeks up to 2 years. Four of the five patients presented with jaundice (Bilirubin 123–555µmol/L) and severe impairment of liver function (INR 1,53–3,65). Distinct elevation of aminotransferases was found in all five patients (max. AST 330–2089U/l, max. ALT 775–2902U/l). Extent of histological injury corresponded well to severity of clinical disease. Extensive perivenular necrosis with associated ceroid-laden macrophages was a shared histological feature in all cases. All patients fully recovered after discontinuation of flupirtine medication. One patient was reexposed to Flupirtine and developed a second hepatitis episode.

Conclusion: Flupirtine can cause substantial liver injury in form of severe cholestatic hepatitis. Clinical information and a characteristic morphological picture are important in establishing the right diagnosis.