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Pathology of flupirtine-induced liver injury:

a histological and clinical study of six cases

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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.

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Authors and Affiliations

  1. Department of Pathology, Hannover Medical School, Carl-Neuberg-Str.1, 30625, Hannover, Germany

    Florian Puls & Hans H. Kreipe

  2. Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Carl-Neuberg-Str.1, 30625, Hannover, Germany

    Clemens Agne, Kinan Rifai & Michael P. Manns

  3. Department of General, Visceral, and Transplantation Surgery, Charité, Augustenburger Platz 1, 13353, Berlin, Germany

    Fritz Klein

  4. Department of Pathology, Charité, Charitéplatz 1, 10117, Berlin, Germany

    Martin Koch

  5. Fraunhofer Institute of Toxicology and Experimental Medicine, Centre for Drug Research and Medical Biotechnology, Nicolai-Fuchs-Strasse 1, 30625 , Hannover, Germany

    Jürgen Borlak

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  1. Florian Puls
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  2. Clemens Agne
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  3. Fritz Klein
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Correspondence to Florian Puls.

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Florian Puls and Clemens Agne contributed equally to this work.

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Puls, F., Agne, C., Klein, F. et al. Pathology of flupirtine-induced liver injury:. Virchows Arch 458, 709–716 (2011). https://doi.org/10.1007/s00428-011-1087-9

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  • DOI: https://doi.org/10.1007/s00428-011-1087-9

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