Systemic inflammatory response exacerbates the neuropsychological effects of induced hyperammonemia in cirrhosis☆
Section snippets
Background
Hepatic encephalopathy (HE) is a neuropsychiatric syndrome which incorporates a spectrum of manifestations, which include psychomotor dysfunction, impaired memory, increased reaction time, sensory abnormalities and poor concentration. This occurs on the background of severe liver dysfunction and has the potential for full reversibility [1]. Ammonia is thought to be central in the pathogenesis of HE [2]. It is detoxified in the brain by the synthesis of glutamine in astrocytes from amidation of
Ethical considerations
Studies were undertaken with full approval of the local research ethics committee and the written informed consent from each patient in accordance with the Declaration of Helsinki (1989) of the World Medical Association. The safety of administering an aa solution to patients with cirrhosis has been extensively studied [8], [11], [12] without any complication such as development of overt HE. Similar studies have used aa [13] and glutamine challenge [14], [15], [16] which produces ammoniagenesis
Patients
Twelve patients with cirrhosis were recruited, of these 10 completed the study and are the subject of this report. Two patients were excluded because of worsening in clinical condition with progression to renal dysfunction in one and development of ‘overt’ HE in the other. Each patient had end-stage biopsy-proven cirrhosis, was on the waiting list for an orthotopic liver transplant and had been admitted to the hospital with clinical evidence of mild SIRS [9], [10], [25]. The SIRS was due to
Discussion
The results of this study show that hyperammonemia induced by administration of an aa solution to cirrhotic patients, results in a deterioration in neuropsychological function in the presence of a systemic inflammatory response. Following resolution of SIRS, there was no deterioration in neuropsychological function despite equivalent severity of induced hyperammonemia. We believe that these data provide direct evidence suggesting that inflammation plays a crucial role in the neuropsychological
Acknowledgements
We are grateful to Dr SWM Olde Damink for helpful discussions and to the generous support of The Sir Siegmund Warburg Voluntary Settlement.
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This paper was presented in part as an abstract at the British Society of Gastroenterology Annual Meeting in Birmingham, UK, 23–26 March 2003.