Tesis doctoral de Rita Garcia Martinez
Historically, hepatic encephalopathy has been considered a reversible neuropsychiatric syndrome with the astrocyte as the pathological target. Implementation of liver transplantation showed the ability to improve cognitive and neuroradiological abnormalities related to liver failure and on the other hand revealed persistence of neuropsychological deficits in some cases. In addition, neuroimaging studies performed in recent decades unfolded brain atrophy in patients with chronic hepatic encephalopathy. Thus, last years pointed that hepatic encephalopathy may cause structural brain injure and sequels. this research investigates the outcome of neuropsychological function and brain structure following successful liver transplant. Specifically, the effect of hepatic encephalopathy and its outcome have been analyzed. Other variables with suspected influence in the cognitive function were also evaluated. these objectives were assessed by a dual approach of neuropsychological tests and magnetic resonance in longitudinal studies. a heterogeneous cognitive outcome was found after one year of successful liver transplantation. Several pre-transplant conditions can impair the pos-transplant neurological function. Hepatic encephalopathy has been linked to a persistent damage (predominantly in psychomotor function) in addition to alcohol abuse and diabetes mellitus. Besides, hepatic encephalopathy was associated to a decreased brain volume evoking loss of brain tissue. Spectroscopic analyses suggested neuronal loss with the smaller brain volume. at long-term, cognitive function remained stable unless de novo neurological diseases cause cognitive decline. In fact, small vessel cerebrovascular disease was associated with loss of memory in those patients with accumulation of cardiovascular risk factors such as diabetes mellitus and arterial hypertension. some factors implicated in neurological injury may not be appropriately investigated due to methodological issues as immunosuppressive drug effects or perioperative ischemia. Additionally, the fact that other factors (e.G. Alcohol, diabetes) affect cognitive function make difficult to define the damage due to hepatic encephalopathy. Despite these limitations, the present research strongly suggests that hepatic encephalopathy is associated with permanent structural injury and loss of neurons. This concept is supported by other lines of evidence such as activation of mechanism of cell death (oxidative/nitrosative stress, energy impairment and inflammation) in hepatic encephalopathy. Besides, neuronal loss has been previously demonstrated in other neurological diseases associated with liver failure as cerebellar degeneration and acquired hepatocerebral degeneration (non-wilsonian). it is important to note that persistent damage is mild and on average, cognitive function after liver transplant remains within normal range. in order to establish a causal relationship further investigation is required. However, the results of this research can have important implications. from a pathogenic perspective, the classical consideration of hepatic encephalopathy as exclusively an astrocytic disease needs re-evaluation. from a clinical and prognostic point of view some considerations must be taken into consideration. Strategies focussed on avoiding or minimizing the occurrence of hepatic encephalopathy may prevent cognitive decline, especially in those patients with other neurological comorbidities and in those at risk of cognitive damage as liver transplant candidates.
Datos académicos de la tesis doctoral «Cognitive function and liver transplantation: implications of hepatic encephalopathy«
- Título de la tesis: Cognitive function and liver transplantation: implications of hepatic encephalopathy
- Autor: Rita Garcia Martinez
- Universidad: Autónoma de barcelona
- Fecha de lectura de la tesis: 18/04/2011
Dirección y tribunal
- Director de la tesis
- Juan Córdoba Cardona
- Tribunal
- Presidente del tribunal: María Buti ferret
- piero Amodio (vocal)
- (vocal)
- (vocal)