S100 Beta as a Marker of Section Hepatic Encephalopathy: A Case-control Study

Abstract

Introduction: Hepatic Encephalopathy (HE) is a term used to describe a reversible syndrome of impaired brain function involving a complex spectrum of non specific neurological and psychiatric manifestations occurring in patients of severe acute or Chronic Liver Disease (CLD). The current clinical standard employed is psychometric analysis by computing Psychometric Hepatic Encephalopathy Score (PHES), which is cumbersome to perform. Hence, this necessitates the requirement of a serum biomarker which could correlate with the grades of HE. Following a metabolic injury, the earliest response involving the glial response and astrocyte activation results in the secretion of S100 Beta. Hence, estimation of serum S100 beta levels is considered as a strong marker of Central Nervous System (CNS) injury. Aim: To verify S100 Beta as a marker of HE. Materials and Methods: This was a case-control study conducted from 1st April 2021 to 31st July 2022. All diagnosed cases of cirrhosis of liver in the Medicine Department of a tertiary care hospital of North India. A total of 40 age and sex matched healthy controls were recruited after due consent and application of exclusion criteria. They were subjected to psychometric analysis (Five pen and paper tests) and on basis of PHES were divided into four groups on the basis of grades of encephalopathy. Serum samples of patients were run for all routine biochemical parameters in line with Child Turcotte Pugh (CTP) score and S100 Beta levels estimation. Statistical analysis was done to find correlation between S100 Beta levels, PHES and CTP score. Results: A total of 150 patients and 40 controls were recruited in the study. A progressive deterioration of PHES score was found in the various groups of the study population with worsening of grade of HE. S100 Beta levels correlated with the PHES and also Receiver Operating Characteristic (ROC) curve analysis showed that the sensitivity of the marker stood at 92.7% and specificity at 84.8%. S100 Beta levels could fairly differentiate between patients with and without HE. Hence, S100 Beta levels correlated more with grades of HE than with hepatic functional status (CTP Score). At higher grades of HE when it becomes more clinically apparent, S100 Beta levels would help, when other causes of behaviour changes like psychiatric illness coexist or cannot be ruled out. In the diagnosis of low-grade HE whenever neuro psychometric tests are suboptimal, or when competing psychiatric differential diagnoses are in place, S100 beta levels would have a role over and above the PHES score. Conclusion: Currently, psychometric analysis holds to be the best clinical standard for diagnosis of HE. S100 Beta holds promising results as a marker for establishing a liquid diagnosis of HE.

Keywords

• chronic liver disease
• hepatic encephalopathy
• diagnosis
• marker
• psychometric hepatic encephalopathy score