title: Pathology of flupirtine-induced liver injury: a histological and clinical study of six cases.
abstract: Drug-induced liver injury may cause impairment of liver function and is a leading cause of acute liver failure. Identification of the causative substance in patients receiving several drugs is often difficult in clinical practice. Evaluation of liver biopsies in suspected drug-induced injury is a challenging task that requires close clinico-pathological correlation. Recognizing a characteristic morphological pattern of liver injury may contribute to identification of the causative drug. Flupirtine, a non-opioid analgesic, has been reported to cause liver injury of idiosyncratic type in rare instances. We wished to characterize the histopathological features of flupirtine-induced liver injury, which have not been reported so far. Liver biopsies of five patients with severe liver injury and one explanted liver of a patient with flupirtine-induced acute liver failure that required transplantation were assessed. In addition clinical presentation and course were reviewed and clinical follow up was performed. Extensive perivenular necrosis with associated ceroid pigment-laden macrophages and a mild to moderate lymphocytic infiltrate was a common feature in all cases. Histological extent of liver necrosis corresponded well to serum amino-transferase levels. Accidental reexposure of one patient resulted in a plasma cell rich hepatitis with perivenular necrosis. This study provides evidence that flupirtine can cause substantial liver injury of hepatocellular type. Liver damage is associated with a characteristic morphological picture, the recognition of which will aid in causality assessment of drug-induced liver injury. Clinical and histological features raise the possibility of an immune-mediated toxicity.
authors: Department of Pathology, Hannover Medical School, Carl-Neuberg-Strasse 1, Hannover, Germany. Puls.Florian@mh-hannover.de
authors: Florian
authors: F
authors: Puls
authors: Clemens
authors: C
authors: Agne
authors: Fritz
authors: F
authors: Klein
authors: Martin
authors: M
authors: Koch
authors: Kinan
authors: K
authors: Rifai
authors: Michael P
authors: MP
authors: Manns
authors: Jürgen
authors: J
authors: Borlak
authors: Hans H
authors: HH
authors: Kreipe
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