JOURNAL OF CLINICAL AND EXPERIMENTAL HEPATOLOGY
43 THE PHES SCORE DOES NOT CORRELATE WITH BLOOD AMMONIA LEVELS, CIRCULATING ENDOTOXINS OR MARKERS OF SYSTEMIC INFLAMMATION Nina Kimer, Lise L. Gluud, Julie S. Pedersen, Juliette Tavenier, Søren Møller, Flemming Bendtsen, Marsha Y. Morgan
Figure 1 Representative images from electron microscope, indicating the lack of swelling of astrocytes in the control group (C) and after vivomorpholino technique with saline (C-VM) but the occurrence of swelling in AOM mice (AOM) and after knockdown SN1 tra.
microscopic observations of the pertinent brain regions. In the prtefrontal cortex of AOM mice we observed decreased expression at the mRNA level of not only SN1 (by 30%), but also one other N system glutamine transporter SN2 (by 60%). However, at the protein level, only SN1 was reduced (by 30%), while SN2 protein remained unaffected. Analysis of the electron micrographs allowed to determine that 38% of blood vessels had altered morphology of endothelial cells, with visible cracks between the cells indicating damage of tight junction, which suggested the presence of vasogenic edema. Additionally, approximately 44% of vessels were found to contact swollen astrocytes and swelling affected precapillary vessels indicating occurrence of cytotoxic edema. Local knockdown of SN1 in prefrontal cortex of control mice reproduced the effects of AOM treatment: a 55% decrease of SN1 protein level and the occurrence of astrocytic endfeet with the features of edema in the vicinity of 48% of blood vessels as well as substantial swelling of precapillary vessels. Collectively, the results support the hypothesis implicating SN1 protein deﬁciency as a causative factor in local cytotoxic brain edema in acute HE (Figure 1). Disclosures: Supported by the National Centre for Research and Development (Program ‘‘Core’’) grant no. Pol-Nor/196190/26/2013 and the Leading National Research Centre (KNOW).
CONFLICTS OF INTEREST The authors have none to declare. Corresponding author: Magdalena Zielinska. E-mail: [email protected]
Background and Aims: The pathogenesis of hepatic encephalopathy (HE) remains unclear but impaired hepatic clearance of gut-derived neurotoxins and activation of systemic inﬂammatory responses are thought to play key roles. The diagnosis is based on detection of neurocognitive/neurophysiological abnormalities but the patterns of abnormalities even in individuals displaying equivalent degrees of neuropsychiatric impairment vary considerably. Interleukin 6, C-reactive protein (CRP) and tumour necrosis factor-a (TNFa) have been show to be independent predictors of abnormal PHES (Montagnese et al., 2011) but these ﬁnding have not been conﬁrmed. In this study the associations between the PHES score and circulating arterial blood ammonia, markers of systemic infection and endotoxins were explored using the baseline data from a RCT involving patients with cirrhosis and ascites but no clinical evidence of HE (NCT01769040). Methods: Patients underwent detailed neurological examination and assessment of their cognitive function using the Psychometric Hepatic Encephalopathy Score (PHES) with a cut off of