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Elevated Serum Levels of Astroglial S100β in Patients with Liver Cirrhosis Indicate Early and Subclinical Portal-Systemic Encephalopathy

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Abstract

Portal-systemic encephalopathy is the prototype among the neuropsychiatric disorders that fall under the term Hepatic Encephalopathies. Ammonia toxicity is central to the pathophysiology of Portal-systemic encephalopathy, and neuronal ammonia toxicity is modulated by activated astrocytes. The calcium-binding astroglial key protein S100β is released in response to glial activation, and its measurement in serum only recently became possible. Serum S100β was determined by an ultrasensitive ELISA in patients (n=36) with liver cirrhosis and transjugular intrahepatic portosystemic stent-shunt. Subclinical portal-systemic encephalopathy and overt portal-systemic encephalopathy were determined by age-adjusted psychometric tests and clinical staging, respectively. Serum S100β was specifically elevated in the presence of subclinical or early portal-systemic encephalopathy, but not arterial ammonia. S100β levels elevated above a reference value (S100β ≤ 110pg/ml) or the cut off value determined in our group of patients (112pg/ml) predicted subclinical portal-systemic encephalopathy with a specificity and sensitivity of 100 and 56.5%, respectively. Serum S100β was significantly dependent on liver dysfunction (Child-Pugh score), but was more closely related to cognitive impairments than the score. Serum S100β seems to be a promising biochemical surrogate marker for mild cognitive impairments due to portal-systemic encephalopathy.

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Authors and Affiliations

  1. Department of Psychiatry, Department of Internal Medicine, Division of Gastroenterology, University of Göttingen, D-37075, Göttingen, Germany

    Jens Wiltfang, Wilhelm Nolte, Jens Wildberg & Eckhard Rüther

  2. Department of Psychiatry, Department of Internal Medicine, Division of Endocrinology, University of Göttingen, D-37075, Göttingen, Germany

    Heinz Hartmann & Giuliano Ramadori

  3. Department of Neurology, Department of Cardiology, University of Göttingen, D-37075, Göttingen, Germany

    Markus Otto & Erik Bahn

  4. Department of Pulmonology, University of Göttingen, D-37075, Göttingen, Germany

    Hans Reiner Figulla

  5. Department of Medical Statistics, University of Göttingen, D-37075, Göttingen, Germany

    Lars Pralle

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  1. Jens Wiltfang
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  2. Wilhelm Nolte
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Correspondence to Jens Wiltfang.

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Wiltfang, J., Nolte, W., Otto, M. et al. Elevated Serum Levels of Astroglial S100β in Patients with Liver Cirrhosis Indicate Early and Subclinical Portal-Systemic Encephalopathy. Metab Brain Dis 14, 239–251 (1999). https://doi.org/10.1023/A:1020785009005

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