0000000000242042
AUTHOR
Amparo Urios
A New Score Unveils a High Prevalence of Mild Cognitive Impairment in Patients with Nonalcoholic Fatty Liver Disease
Patients with nonalcoholic fatty liver disease (NAFLD) may show mild cognitive impairment (MCI). The neurological functions affected remain unclear. The aims were to: (1) Characterize the neuropsychological alterations in NAFLD patients; (2) assess the prevalence of impairment of neurological functions evaluated; (3) develop a new score for sensitive and rapid MCI detection in NAFLD; (4) assess differences in MCI features between patients with nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH); and (5) compare neuropsychological alterations in NAFLD patients with cirrhotic patients with MCI. Fifty-nine NAFLD patients and 53 controls performed psychometric tests assessin…
The PHES battery does not detect all cirrhotic patients with early neurological deficits, which are different in different patients.
Background and aims The psychometric hepatic encephalopathy score (PHES) is the “gold standard” for minimal hepatic encephalopathy (MHE) diagnosis. Some reports suggest that some cirrhotic patients “without” MHE according to PHES show neurological deficits and other reports that neurological alterations are not homogeneous in all cirrhotic patients. This work aimed to assess whether: 1) a relevant proportion of cirrhotic patients show neurological deficits not detected by PHES; 2) cirrhotic patients with mild neurological deficits are a homogeneous population or may be classified in sub-groups according to specific deficits. Methods Cirrhotic patients “without” (n = 56) or “with” MHE (n = 4…
Minimal hepatic encephalopathy is associated with expansion and activation of CD4+CD28−, Th22 and Tfh and B lymphocytes
AbstractPeripheral inflammation acts synergistically with hyperammonemia in inducing neurological alterations in cirrhotic patients with minimal hepatic encephalopathy (MHE). We hypothesized that appearance of MHE would be associated to some specific qualitative change in peripheral inflammation. The aim of this work was to characterize the changes in peripheral inflammation associated to appearance of MHE. We analyzed it by immunophenotyping and cytokine profile analysis, in cirrhotic patients without or with MHE and controls. The main alterations associated specifically with MHE are: 1) increased activation of all subtypes of CD4+ T-lymphocytes, with the increased expression of CD69; 2) i…
Klotho urinario determinado por ELISA como biomarcador precoz de fracaso renal agudo en pacientes sometidos a cirugía cardiaca o angiografía coronaria
ResumenIntroducción y objetivos: El fracaso renal agudo (FRA) es una complicación frecuente tras la cirugía cardiaca y las intervenciones percutáneas coronarias cuya aparición empeora el pronóstico de manera marcada. En los últimos años se han identificado nuevos biomarcadores precoces de FRA, pero aún quedan muchos aspectos importantes por resolver. Klotho es una proteína pleiotrópica que actúa como un factor paracrino y endocrino en múltiples órganos. En diversos modelos animales de FRA se ha demostrado niveles disminuidos de Klotho renal. No se ha publicado ningún estudio en el que se haya probado Klotho como marcador precoz de FRA en humanos. El objetivo de este trabajo es investigar la…
Cirrhotic patients with minimal hepatic encephalopathy have increased capacity to eliminate superoxide and peroxynitrite in lymphocytes, associated with cognitive impairment
Patients with minimal hepatic encephalopathy (MHE) show increased oxidative stress in blood. We aimed to assess whether MHE patients show alterations in different types of blood cells in (a) basal reactive oxygen and nitrogen species levels; (b) capacity to metabolise these species. To assess the mechanisms involved in the altered capacity to metabolise these species we also analysed: (c) peroxynitrite formation and d) peroxynitrite reaction with biological molecules. Levels of reactive oxygen and nitrogen species were measured by flow cytometry in blood cell populations from cirrhotic patients with and without MHE and controls, under basal conditions and after adding generators of superoxi…
Focal cortical damage parallels cognitive impairment in minimal hepatic encephalopathy
Little attention has been paid to cortical integrity in patients with minimal hepatic encephalopathy (MHE), although cognitive functions affected in early stages of liver disease are mainly allocated in different neocortical structures. Here we used cortical surface-based analysis techniques to investigate if patterns of cortical thinning accompany the mildest form of HE. To aim this goal, cortical thickness obtained from high-resolution 31 magnetic resonance imaging (MRI) was measured in patients with no MHE (NMHE), MHE, and healthy controls. Further correlation analyses were performed to examine whether scores in the critical flicker frequency (CFF) test, and blood ammonia levels accounte…
Serum nitrotyrosine and psychometric tests as indicators of impaired fitness to drive in cirrhotic patients with minimal hepatic encephalopathy
BACKGROUND & AIMS: Cirrhotic patients with minimal hepatic encephalopathy (MHE) show impaired driving ability and increased vehicle accidents. The neurological deficits contributing to impair driving and the underlying mechanisms are poorly understood. Early detection of driving impairment would help to reduce traffic accidents in MHE patients. It would be therefore useful to have psychometric or biochemical parameters reflecting driving impairment. The aims of this work were as follows: (i) to shed light on the neurological deficits contributing to impair driving; (ii) to assess whether some psychometric test or biochemical parameter is a good indicator of driving impairment. METHODS: We a…
Non invasive blood flow measurement in cerebellum detects minimal hepatic encephalopathy earlier than psychometric tests
AIM: To assess whether non invasive blood flow measurement by arterial spin labeling in several brain regions detects minimal hepatic encephalopathy. METHODS: Blood flow (BF) was analyzed by arterial spin labeling (ASL) in different brain areas of 14 controls, 24 cirrhotic patients without and 16 cirrhotic patients with minimal hepatic encephalopathy (MHE). Images were collected using a 3 Tesla MR scanner (Achieva 3T-TX, Philips, Netherlands). Pulsed ASL was performed. Patients showing MHE were detected using the battery Psychometric Hepatic Encephalopathy Score (PHES) consisting of five tests. Different cognitive and motor functions were also assessed: alterations in selective attention we…
Nitic oxide promotes strong cytotoxicity of phenolic compounds against escherichia coli. The influence of antioxidant defenses
[EN] The induction of mutagenic and cytotoxic effects by simple phenolics, including catechol (CAT), 3,4dihydroxyphenylacetic acid (DOPAC), hydroquinone (HQ), and 2,5-dihydroxyphenylacetic (homogentisic) acid (HGA), appears to occur through an oxidative mechanism based on the ability of these compounds to undergo autoxidation, leading to quinone formation with the production of reactive oxygen species. This is supported by the detection of such adverse effects in plate assays using Escherichia coli tester strains deficient in the OxyR function, but not in OxyR(+) strains. The OxyR protein is a redox-sensitive regulator of genes encoding antioxidant enzymes including catalase and alkyl hydro…
Histological Features of Cerebellar Neuropathology in Patients With Alcoholic and Nonalcoholic Steatohepatitis
Alcoholic steatohepatitis (ASH) and nonalcoholic steatohepatitis (NASH) affect 29 million people in the European Union. Patients with ASH and NASH may exhibit cognitive impairment, reducing their quality of life. Steatohepatitis induces cerebral alterations. It is not known if histological analysis could allow distinguishing ASH, NASH, and/or cirrhosis neuropathology and other entities. The aim of this work was to analyze a set of histopathological features characterizing the brain lesions due to ASH, NASH, and cirrhosis. We performed a histological study using hematoxylin and eosin staining and immunohistochemical techniques in cerebellum of 31 subjects who died with healthy liver (n = 6),…
Patients with minimal hepatic encephalopathy show impaired mismatch negativity correlating with reduced performance in attention tests
Attention deficit is an early event in the cognitive impairment of patients with minimal hepatic encephalopathy (MHE). The underlying mechanisms remain unclear. Mismatch negativity (MMN) is an auditory event-related potential that reflects an attentional trigger. Patients with schizophrenia show impaired attention and cognitive function, which are reflected in altered MMN. We hypothesized that patients with MHE, similarly to those with schizophrenia, should show MMN alterations related with attention deficits. The aims of this work were to assess whether (1) MMN is altered in cirrhotic patients with MHE, compared to those without MHE, (2) MMN changes in parallel with performance in attentio…
Detection of oxidative mutagenesis by isoniazid and other hydrazine derivatives in Escherichia coli WP2 tester strain IC203, deficient in OxyR: strong protective effects of rat liver S9
Abstract Strain IC203, deficient in the OxyR function, was sensitive to both cytotoxic and mutagenic effects of isoniazid (INH) whereas its parent, WP2 uvrA /pKM101, was resistant to these effects. Four other hydrazine compounds, hydrazine hydrate (HZH), phenylhydrazine (PHZ), hydralazine (HLZ) and nialamide (NLD), were mutagenic in WP2 uvrA /pKM101. Increases in mutagenicity were observed in IC203 for HZH and PHZ but not for HLZ and NLD. Growth inhibition zones by HZH, PHZ and NLD were larger in IC203 than in WP2 uvrA /pKM101. The enhancements in the effects of INH, HZH and PHZ in IC203 with respect to its oxyR + parent are considered to be caused by the production of reactive oxygen speci…
Real-time cytometric assay of nitric oxide and superoxide interaction in peripheral blood monocytes: A no-wash, no-lyse kinetic method
Background Nitric oxide (NO) and its related reactive nitrogen species (RNS) and reactive oxygen species (ROS) are crucial in monocyte responses against pathogens and also in inflammatory conditions. Central to both processes is the generation of the strong oxidant peroxynitrite (ONOO) by a fast reaction between NO and superoxide anion. ONOO is a biochemical junction for ROS- and RNS cytotoxicity and causes protein nitrosylation. Circulating by-products of protein nitrosylation are early biomarkers of inflammation-based conditions, including minimal hepatic encephalopathy in cirrhotic patients (Montoliu et al., Am J Gastroenterol 2011; 106:1629–1637). In this context, we have designed a nov…
Patients with Minimal Hepatic Encephalopathy Show Altered Thermal Sensitivity and Autonomic Function
Cirrhotic patients may experience alterations in the peripheral nervous system and in somatosensory perception. Impairment of the somatosensory system could contribute to cognitive and motor alterations characteristic of minimal hepatic encephalopathy (MHE), which affects up to 40% of cirrhotic patients. We assessed the relationship between MHE and alterations in thermal, vibration, and/or heat pain sensitivity in 58 cirrhotic patients (38 without and 20 with MHE according to Psychometric Hepatic Encephalopathy Score) and 39 controls. All participants underwent attention and coordination tests, a nerve conduction study, autonomic function testing, and evaluation of sensory thresholds (vibra…
The Erythrocytic Hypothesis of Brain Energy Crisis in Sporadic Alzheimer Disease: Possible Consequences and Supporting Evidence
Alzheimer’s disease (AD) is a fatal form of dementia of unknown etiology. Although amyloid plaque accumulation in the brain has been the subject of intensive research in disease pathogenesis and anti-amyloid drug development; the continued failures of the clinical trials suggest that amyloids are not a key cause of AD and new approaches to AD investigation and treatment are needed. We propose a new hypothesis of AD development based on metabolic abnormalities in circulating red blood cells (RBCs) that slow down oxygen release from RBCs into brain tissue which in turn leads to hypoxia-induced brain energy crisis; loss of neurons; and progressive atrophy preceding cognitive dysfunction. This …
Motor and Cognitive Performance in Patients with Liver Cirrhosis with Minimal Hepatic Encephalopathy
Minimal hepatic encephalopathy (MHE) is associated with mild cognitive impairment and frailty. This study aims to identify cognitive and motor differences in cirrhotic patients with and without MHE, and the correlations between motor signs and cognitive performance. Gait, balance, hand strength and motor speed performance were evaluated in 66 cirrhotic patients (38 without and 28 with MHE, according to the Psychometric Hepatic Encephalopathy Score (PHES). Cognitive performance was measured with the Mini-Mental State Examination, Verbal Fluency Test, Aprendizaje Verbal España-Complutense Test (TAVEC), Wechsler Adult Intelligence Scale III, Hamilton Depression and Anxiety Rating Scale and Fun…
P1296 : Blocking NMDA receptors prolongs survival in rats with acute liver failure by dual protective mechanisms in kidney and brain
were 1094.67±239.37mIU/ml. The difference in values between these groups was statistically significant (p = 0.004). There was a statistically significant difference in total leucocyte count, serum creatinine, INR and cleaved CK18 M30 levels among those that survived vs expired. Multivariate analysis found that all these independently predict mortality. A receiver operating characteristic curve was drawn for the new score. The score found was compared with the King’s College criteria and the MELD score, the new scoring system was found to have higher sensitivity and specificity for mortality compared with other standard prognostic markers in ALF, and has a better diagnostic accuracy (Table 1…
Altered postural control and stability in cirrhotic patients with minimal hepatic encephalopathy correlate with cognitive deficits
Background & Aims: Cognitive dysfunction in cirrhotic patients with minimal hepatic encephalopathy (MHE) is associated with falls. Alterations in postural control and stability could contribute to increase falls risk in these patients. We aimed to assess whether postural control and direction-specific limits of stability are altered in cirrhotic patients with MHE compared to patients without MHE and controls. We also assessed if alterations in postural control correlate with neurological impairment and/or blood biomarkers. Methods: Posturography analysis, attention Stroop test and bimanual and visuo-motor coordination tests were performed in 18 controls, 19 patients with cirrhosis without M…