S100β and Neuron Specific Enolase Levels in Liver Transplantation

Neurologic disorders that affect the liver transplantation candidates when they are on the waitlist not only significantly affect preoperative morbidity and even mortality but also present important predictive factors for post-op neurologic manifestations. Attentive neurological evaluation before transplantation plays a significant role in defining seriousness level and distribution of neurologic disorders besides current treatable anomalies and potentially prescribe postoperative prognosis. Preferred specific indexes of neurological evaluation before transplantation can vary according to centers but correct diagnosis and definitive diagnosis of some syndromes can be difficult despite using current biochemical, neurophysiologic, neuropsychological and neuroimaging diagnosis tools.

Liver transplant receivers constitute the group with the most frequent central nervous system complication (incidence: 10%-85%) amongst the organ transplantation patients. They are focal or diffuse neurologic deficits creating a significant obstacle for short and long term recovery. Neurologic deficits which can develop are cerebral edema, increase of intracranial pressure, metabolic encephalopathy, cerebrovascular complications, osmotic demyelination syndrome and opportunistic infections. Moreover, several preoperative neurologic disorders (such as dysarthria akinetic mutism, confusion and seizures) can get worse due to neurotoxic side effect of the medicines which are used for preventing graft rejection (calcineurin inhibitors).

Neurologic findings and pathophysiology of end stage liver failure cannot be understood completely. Multiple factors such as long term brain "neuroinflammation", brain microglia, activation of inflammatory cells, accumulation of manganese and ammonia, changing blood-brain barrier permeability, changed nerve conduction and inflammation of peripheric nerve system inflammation are held responsible from brain damage. Other negative direct or indirect neurologic effects are chronical malnutrition, gastrointestinal bleeding, cerebral hypoperfusion and renal dysfunction. The most commonly accepted neurological complications of serious hepatocellular insufficiency are complex syndromes of hepatic encephalopathy (HE).

S100β is 10.4 kDa (kilodalton) protein. Synthesized with end feet processes of astrocytes in the brain S100β belongs to low molecular weight EF-hand type acidic calcium binding protein superfamily. This protein is metabolized in the kidneys and removed with urine. It is shown that S100β does not show differences due to ethnical groups or genders and is not affected by circadian rhythm. Although S100β is also found in other tissues, it is in higher concentrations in the brain so it can be used as an early indicator for brain damage.

Astrocytes are the keys to homeostasis regulation in central nervous system (CNS) and release S100β after brain damage. Some studies conducted that, increased S100β levels as an early indicator for intracerebral changes within patients with acute or chronical liver failure and before cerebral edema is developed in HE.

Moreover, it is also asserted that S100β increase in serum concentration can foresee HE. Additionally, there are limited evidences to prove S100β levels and existence of HE.

NSE is an CNS protein which exists in neurons and neuroendocrine tissues. NSE plays a role in glycolytic route in neurons as intracytoplasmic enzyme increasing serum level in case of neuron damage. Whilst S100β is the marker of astroglia dysfunction, NSE is the marker of neuronal dysfunction.

The aim of the study is analyzing S100β serum concentrations and correlate neurologic damage of liver transplantation patients besides evaluating its effect on prognosis.