Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT03453047 |
| Other study ID # |
LIVER |
| Secondary ID |
|
| Status |
Completed |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
June 20, 2017 |
| Est. completion date |
May 20, 2021 |
Study information
| Verified date |
July 2021 |
| Source |
Akdeniz University |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational [Patient Registry]
|
Clinical Trial Summary
Several neurological problems which include both central nervous system and peripheral
nervous system can occur as a result of acute liver failure or severe chronic liver failure.
The main reason of cerebral damage in liver failure is cellular metabolic changes, long term
neuro-inflammation status, activation of brain microglia, accumulation of manganese and
ammonia besides acute and severe hyperammoniemia that triggers systemic inflammation.
Examples of neurological complications of serious hepatocellular failure are hepatic
encephalopathy, diffuse brain edema, Wilson disease, hepatic myelopathy, acquired
hepatocerebral degeneration; Parkinsonism induced cirrhosis and osmatic demyelinization.
Attentive neurological evaluation is of high importance in order to define seriousness level
and distribution of neurologic disorders besides current treatable anomalies and potentially
prescribe postoperative prognosis.
S100β is released by astrocytes in brain damage. S100β increases in the beginning of brain
damage so it can be used to diagnose early stage brain damage. Neuron specific enolase (NSE)
acts as intracytoplasmic enzyme and increases serum levels in neuron damage.
The aim of the study is to evaluate neurological damage and analyze its effect on prognosis
by considering S100β and NSE levels in liver transplantation.
Description:
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.
