Elevated serum levels of astroglial S100 beta in patients with liver cirrhosis indicate early and subclinical portal-systemic encephalopathy

Portal-systemic encephalopathy is the prototype among the neuropsychiatric disorders that fall under the term Hepatic Encephalopathies. Ammonia toxici ty is central to the pathophysiology of Portal-systemic encephalopathy, and neuronal ammonia toxicity is modulated by activated astrocytes. The calciu m-binding astroglial key protein S100 beta is released in response to glial activation, and its measurement in serum only recently became possible. Se rum S100 beta was determined by an ultrasensitive ELISA in patients (n=36) with liver cirrhosis and transjugular intrahepatic portosystemic stent-shun t. Subclinical portal-systemic encephalopathy and overt portal-systemic enc ephalopathy were determined by age-adjusted psychometric tests and clinical staging, respectively. Serum S100 beta was specifically elevated in the pr esence of subclinical or early portal-systemic encephalopathy, but not arte rial ammonia. S100 beta levels elevated above a reference value (S100 beta less than or equal to 110pg/ml) or the cut off value determined in our grou p of patients (112pg/ml) predicted subclinical portal-systemic encephalopat hy with a specificity and sensitivity of 100 and 56.5%, respectively. Serum S100 beta was significantly dependent on liver dysfunction (Child-Pugh sco re), but was more closely related to cognitive impairments than the score. Serum S100 beta seems to be a promising biochemical surrogate marker for mi ld cognitive impairments due to portal-systemic encephalopathy.