Altered intestinal microbiota are associated with sleep disturbances in patients with minimal hepatic encephalopathy caused by hepatitis B-related liver cirrhosis

Objective Minimal hepatic encephalopathy (MHE) caused by liver cirrhosis is quite prevalent, and approximately one-half of MHE patients have experience sleep disturbances. This study systematically evaluated the association between sleep disturbances and altered intestinal microbiota in patients with MHE caused by hepatitis B-related liver cirrhosis. Methods Ninety-eight and 45 MHE patients were respectively included in the exploration and validation cohorts. The Chinese version of the Pittsburgh Sleep Quality Index (PSQI) questionnaire was used to evaluate sleep disturbances. The intestinal microbiota of self-collected fecal samples was analyzed using the amplicon sequencing of bacterial 16S ribosomal RNA gene. Results MHE patients with sleep disturbances were characterized by lower bacterial diversities and distinct microbial composition in comparison to those without sleep disturbances. The relative abundances of Salivarius, Veillonella, Klebsiella, and Eubacterium were independent predictors of sleep disturbances in MHE patients. In MHE patients with sleep disturbances, the relative abundances of Salivarius and Veillonella were positively correlated with PSQI scores, respectively. Functional modules involved in lipopolysaccharide biosynthesis, as well as protein digestion and absorption, were increased in the microbiome of MHE patients with sleep disturbances. Conclusion Salivarius and Veillonella may be potential diagnostic biomarkers and therapeutic targets for sleep disturbances in MHE patients.

Amino Acid Profile in Malnourished Patients with Liver Cirrhosis and Its Modification with Oral Nutritional Supplements: Implications on Minimal Hepatic Encephalopathy

Low plasma levels of branched chain amino acids (BCAA) in liver cirrhosis are associated with hepatic encephalopathy (HE). We aimed to identify a metabolic signature of minimal hepatic encephalopathy (MHE) in malnourished cirrhotic patients and evaluate its modification with oral nutritional supplements (ONS) enriched with ß-Hydroxy-ß-methylbutyrate (HMB), a derivative of the BCAA leucine. Post hoc analysis was conducted on a double-blind placebo-controlled trial of 43 individuals with cirrhosis and malnutrition, who were randomized to receive, for 12 weeks, oral supplementation twice a day with either 220 mL of Ensure® Plus Advance (HMB group, n = 22) or with 220 mL of Ensure® Plus High Protein (HP group, n = 21). MHE evaluation was by psychometric hepatic encephalopathy score (PHES). Compared to the HP group, an HMB-specific treatment effect led to a larger increase in Val, Leu, Phe, Trp and BCAA fasting plasma levels. Both treatments increased Fischer’s ratio and urea without an increase in Gln or ammonia fasting plasma levels. MHE was associated with a reduced total plasma amino acid concentration, a reduced BCAA and Fischer´s ratio, and an increased Gln/Glu ratio. HMB-enriched ONS increased Fischer´s ratio without varying Gln or ammonia plasma levels in liver cirrhosis and malnutrition, a protective amino acid profile that can help prevent MHE.

Critical Flicker Fusion Frequency: A Narrative Review

This review presents the current knowledge of the usage of critical flicker fusion frequency (CFF) in human and animal model studies. CFF has a wide application in different fields, especially as an indicator of cortical arousal and visual processing. In medicine, CFF may be helpful for diagnostic purposes, for example in epilepsy or minimal hepatic encephalopathy. Given the environmental studies and a limited number of other methods, it is applicable in diving and hyperbaric medicine. Current research also shows the relationship between CFF and other electrophysiological methods, such as electroencephalography. The human eye can detect flicker at 50–90 Hz but reports are showing the possibility to distinguish between steady and modulated light up to 500 Hz. Future research with the use of CFF is needed to better understand its utility and application.

The Role of Helicobacter Pylori Eradication on the Pathogenesis of Minimal Hepatic Encephalopathy in Egyptian Patients with Liver Cirrhosis

Background Hepatic Encephalopathy (HE) is defined as alteration of mental state in the absence of other causes of encephalopathy due to liver failure and/or abnormal shunting of blood from portal to systemic circulation often accompanied by elevated blood ammonia. Objectives The aim of this study was to determine the relation between the Helicobacter pylori infectionand minimal hepatic encephalopathy (MHE) in cirrhotic patients and to assess the outcome after treatment of H. pylori. Patients and Methods This study was can•ied out at Egyptian Railway Medical Centre at the in-patients section at Gastroenterology and Hepatology Medicine Department with chronic liver disease who agreed to participate in the study. After performing the psychometric tests the patients were allocated in one of the two groups according to test results: Group I: consisted of 30 consecutive patients who have chronic liver disease and presented with evidence of Minimal hepatic encephalopathy (MHE), as recognized by positive psychometric tests, Group Il: included 30 consecutive patients who presented with chronic liver disease and did not have Minimal hepatic encephalopathy, as confirmed by negative psychometric test. Results In this study a significant reduction was found in blood ammonia levels in MHE and non- MHE after triple-drug anti-H. pylori treatment (p < 0.001). This reduction was more marked in patients with MHE group compared to non-MHE group with % improvement in ammonia level 26.1 ± 8.36 umol/L and 17.79 ± 7.308 for MHE and non-MHE respectively. This finding indicates that H. pylori may contribute to the development of hyperammonemia in patients with liver disease and MHE. The role of H. pylori in the pathogenesis of hyperammonemia has been shown in previous studies which showed a reduction in blood ammonia levels after eradication of H.pylori infection. Conclusion Helicobacter Pylori infection was more prevalent in patients with MHE than without MHE. Serum arnrnonia levels were significantly higher in MHE patients than without MHE and even higher in H.pylori positive patients than without H.pylori infection. Helicobacter Pylori eradication treatment significantly improves ammonia levels, results of psychometric tests and improves manifestations of MHE.

Standardization of the psychometric hepatic encephalopathy score in a French population

The Psychometric Hepatic Encephalopathy Score (PHES) has previously been standardized in thirteen countries on three continents, confirming its status of gold standard test to detect minimal hepatic encephalopathy (MHE). In the meantime, performance has also been shown to vary with variables such as age, education, and barely sex. The present study aimed at standardizing the PHES in a French population. One hundred and ninety-six French healthy participants completed a French version of the paper-and-pencil PHES, involving five tests and six measures. Importantly, the balance was perfect between all levels of the three controlled factors, which were sex, age (seven decade-levels from 20–29 to 80–89 years), and education (two levels below or above 12 years of education). Raw measures were transformed to fit the normal distribution. ANOVAs on transformed variables showed no effect of sex, but an effect of age on all measures, and of education on five measures. Multiple or simple regressions were completed to build up normograms. Thorough analysis of variability within each test failed to find outliers that may bias the results. Comparison between French and seminal German data showed that they highly fitted though cultural and cognitive style specificities could be observed. This is the first study to standardize the PHES in a French population and to extensively explore the effects of sex, age and education using perfectly balanced samples. Subtle differences between countries of the same continent emphasize the need to build up normative data in each country to get accurate PHES in patients.