Impact of biochemical markers NSE and S100beta for detection and monitoring of subclinical and manifest hepatic encephalopathy

Background and Aims: Proton magnetic resonance spectroscopy (¹H-MRS) studies of the human brain gave an indication of the presence of low grade cerebral edema in patients with cirrhosis (1). Based on this observation it was hypothesized that hepatic encephalopathy (HE) reflects the clinical manifestation of a low grade cerebral edema, which may worsen under the influence of precipitating factors and thereby trigger cell hydration-dependent alterations of astrocyte function and volume homeostasis. Such alterations may affect glial-neuronal communication, whose disturbance is considered to be relevant to the pathogenesis of HE. In adults, serum concentrations of neuron-specific enolase (NSE) and S100beta have served as markers of neuronal damage. NSE is a glycolytic enzyme that is localized primarily to the neuronal cytoplasm while S100beta is a calcium-binding protein localized to astroglial cells. The aim of this study was to evaluate circulating NSE and S100beta levels as potential biochemical markers of HE prior to and following treatment with L-ornithin-L-aspartat (LOLA). The aim of this study was to evaluate circulating NSE and S100beta levels as potential biochemical markers for diagnosis of HE and treatment response.

Methods: 25 patients with liver cirrhosis and subclinical (n=8 grade 0, West-Haven criteria) and manifest HE (n=9 grade I, n=8 grade II) were enrolled in a prospective clinical trial of L-ornithin-L-aspartat (LOLA) administered intravenously in a dose of 20g/d during 6 consecutive days. HE was evaluated by psychometric tests (number connection tests A, B; figure connection tests A, B; line-tracing-test) and critical flicker frequency (CFF) before and after LOLA-treatment. Daily blood samples were obtained from venous blood for analysis of NSE and S100beta (150 serum samples each) with an ultrasensitive chemoluminescence method.

Results: LOLA showed significant efficacies in patients with manifest HE with respect to improvement in psychometric test times and CFF (p<0.001). Serum levels of NSE and S100beta were neither elevated in subclinical and manifest HE nor dependent on liver dysfunction (Child-Pugh score), origin of cirrhosis and severity of HE (p>0.05). Treatment with LOLA revealed no significant changes in the serum marker levels before, during and after therapy.

Conclusions: NSE and S100beta represent no promising biochemical markers for detection and monitoring of subclinical and manifest HE and do not correlate with the West-Haven criteria.

Reference: [1] Spahr L, Burkhard PR, Grötzsch H, Hadengue A. Clinical significance of basal ganglia alterations at brain MRI and 1H MRS in cirrhosis and role in the pathogenesis of hepatic encephalopathy. Metab Brain Dis. 2002;17:399–413.