Role Of Brain Biomarkers S-100-Beta And Neuron-Specific Enolase For Detection And Follow-Up Of Hepatic Encephalopathy In Cirrhosis Before, During And After Treatment With L-Ornithine-L-Aspartate

Introduction: Hepatic encephalopathy (HE), in the context of liver cirrhosis, seems to result from low-grade cerebral edema of the astrocytes. Serum brain biomarkers S-100-beta und neuron-specific enolase (NSE) are often elevated in brain injury. We hypothesized that neuromarkers S-100-beta and NSE can be used in the diagnosis of HE, compared with standardized diagnostic tools. Material and Methods: A prospective non-randomized intervention study was performed using L-ornithine-L-aspartate (LOLA) for HE treatment. Primary endpoint was the evaluation of neuromarkers S-100-beta and NSE for detection and diagnosis of follow-up of HE. As secondary endpoints, the efficacy of LOLA on the course of HE and the diagnostic role of Portosystemic-Encephalopathy-Syndrome score (PHES) and critical flicker frequency (CFF) were analyzed. For diagnosis of covert (CHE) and overt (OHE) HE, West-Haven criteria (WHC), PHES and CFF were assessed at study entry. LOLA was applied (20 g i.v.) for 6 days. At the end of the study, HE evaluation was repeated. S-100-beta, NSE and ammonia were assessed in each patient before, during and after therapy with LOLA. Results: 30 patients were included. At study entry, CHE was diagnosed in 50% and OHE in 50% of all subjects. A total of 25 participants completed the study. After LOLA therapy, deterioration of HE occurred in <11%, while most patients showed improvement (e.g. improved CFF in 79%). No significant correlation with HE severity (as diagnosed by WHC, PHES and CFF) could be demonstrated for any biochemical parameter. In addition, there were no significant changes in brain biomarkers during the treatment period. Discussion: While CFF as well as PHES showed good correlation with treatment response, S-100-beta and NSE did not significantly correlate with HE severity compared to proven diagnostic methods, and do not seem reliable biochemical markers for the follow-up under therapy.