Dopamine Burden Induced the Inactivation of Sonic Hedgehog Signaling to Cognitive Decline in Minimal Hepatic Encephalopathy.
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ABSTRACT:
SUBMITTER: Ding S
PROVIDER: S-EPMC5524807 | biostudies-other | 2017 Jul
REPOSITORIES: biostudies-other
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Project description: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 Functioning Assessment Short Test (FAST). MHE patients performed worse than patients without MHE in cognitive and autonomous functioning, learning and long-term memory, and verbal fluency. The same pattern was found in gait, center of pressure movement, variability of hand strength performance and hand motor speed. In MHE patients, high correlations were found between balance and FAST test, gait velocity and verbal skills, hand strength variability and anxiety and depression, and motor speed and FAST and TAVEC. MHE patients showed worse motor and cognitive performance than patients without MHE. MHE patients could have impaired movement control expressed as bradykinesia, and this reduced motor performance could correlate with cognitive performance.
| S-EPMC7408738 | biostudies-literature
Project description:Minimal hepatic encephalopathy (MHE) adversely affects the clinical outcomes of patients with liver cirrhosis. This prospective study aimed to evaluate the utility of the Stroop test in the diagnosis of MHE and prediction of overt hepatic encephalopathy (OHE) in Japanese patients with cirrhosis. We enrolled 152 patients who underwent the Stroop test between November 2018 and February 2020. MHE was diagnosed using a combination of neuropsychological tests as the gold standard. The enrolled patients were followed up prospectively until the occurrence of OHE or August 2020. The optimal cutoff value of the Stroop test measurements was determined by receiver operating characteristic (ROC) curve analysis, and its predictive ability was assessed using the area under the ROC curve (AUC). Among the 139 eligible patients, 50 (36%) were diagnosed with MHE. The OffTime+OnTime cutoff value of 218.3 seconds had the best discriminative ability for MHE diagnosis, with an AUC of 0.77, a sensitivity of 74%, and a specificity of 75%. During a median follow-up of 10.8 months, 6 (4%) patients developed OHE. The OffTime+OnTime cutoff value of 305.6 seconds had the highest predictive ability for OHE, with an AUC of 0.79, a sensitivity of 67%, and a specificity of 92%. This value predicted OHE occurrence independent of liver functional reserve and prior OHE (hazard ratio, 19.8; P = 0.003). These two cutoff values remained statistically significant even when patients with prior OHE were excluded from the analysis. Conclusion: The Stroop test was useful for diagnosing patients with MHE and predicting OHE in Japanese patients with cirrhosis.
| S-EPMC8435282 | biostudies-literature
Project description:The psychometric hepatic encephalopathy score (PHES) is the gold standard for diagnosing minimal hepatic encephalopathy (MHE). Screening for MHE is frequently overlooked in clinical practice due to time constraints. Furthermore, the simplified animal naming test (S-ANT1) is a new simple tool for evaluating MHE in cirrhotic patients. The purpose of this study was to standardize the PHES in a healthy Thai population, assess the prevalence of MHE, and validate the S-ANT1 in detecting MHE in patients with cirrhosis. The study included 194 healthy controls and 203 cirrhotic patients without overt HE. Psychometric tests and the S-ANT1 were administered to all participants. Multiple linear regression was used to analyze factors related to PHES results, and formulas were developed to predict the results for each PHES subtest. In healthy controls, age and education were predictors of all five subtests. The PHES of the control group was -0.26 ± 2.28 points, and the threshold for detecting MHE was set at ≤ -5 points. The cirrhotic group had PHES values of -2.6 ± 3.1 points. Moreover, MHE was found to be present in 26.6% of cirrhotic patients. S-ANT1 had a moderate positive correlation with PHES (r = 0.44, p < 0.001). S-ANT1 < 22 named animals detected MHE with a sensitivity of 71.2%, specificity of 65%, and area under the receiver operating curve of 0.68 (p < 0.001). In conclusion, Thai PHES normative data have been developed to detect MHE in cirrhotic patients who do not have overt HE. The optimal cutoff for detecting MHE in Thai cirrhotic patients was PHES ≤ -5 points and S-ANT1 < 22 named.
| S-EPMC9864758 | biostudies-literature
Project description:Background & aimsPatients with cirrhosis are growing older. The overlap between minimal hepatic encephalopathy (MHE) and predementia mild cognitive impairment (MCI) could affect quality of life (QOL). We investigated the performance of elderly patients with cirrhosis on tests for MHE and MCI and their effects on QOL.MethodsWe recruited outpatients with cirrhosis (n = 109) and without cirrhosis (controls, n = 100), 65 years or older, at 4 centers (derivation cohort). All study participants were assessed for psychometric hepatic encephalopathy score (PHES), EncephalApp score, and QOL. MCI was tested in patients with cirrhosis using the repeatable battery for assessment of neuropsychological status and assigned to the following groups: unimpaired, MCI only, MHE only, and MCI+MHE. We created adjusted norms to detect MHE using PHES and EncephalApp scores from the controls. Findings were validated using data from a separate cohort of 77 patients with cirrhosis (mean age, 69.49 ± 4.36 y; 72% men) at the same study sites.ResultsControls were older but were more educated, performed better cognitively, and had better QOL. Among patients with cirrhosis, age, education, model for end-stage liver disease score, EncephalApp score, and QOL were similar, but PHES and repeatable battery for assessment of neuropsychological status differed among sites. In the derivation cohort, the presence of MHE, with or without MCI, was associated with poor QOL, which was lowest in the MCI+MHE group. When we adjusted for age, sex, and education, 49% of patients with cirrhosis had MHE based on the EncephalApp and 8% had MHE based on the PHES. A similar pattern (49% MHE based on EncephalApp and 6% MHE based on PHES) was found in a validation cohort.ConclusionsIn a multicenter study of patients with cirrhosis (>65 y) and controls, the presence of MHE, regardless of MCI, was associated with poor cognition and QOL. We created adjusted norms that defined the high sensitivity of EncephalApp for the detection of MHE in older individuals and validated it in a separate cohort.
| S-EPMC7502426 | biostudies-literature
Project description:Minimal hepatic encephalopathy (MHE) is associated with cognitive alterations and changes in connectivity. We assessed the relationship of the abnormalities of resting-state functional connectivity (rs-FC) and gray matter (GM) volume with different cognitive alterations and biochemical parameters associated to MHE.Thirty-nine cirrhotic patients (26 without and 13 with MHE) and 24 controls were widely cognitive assessed with a battery of psychometric tests. Atrophy was determined using Voxel-Based Morphometry and rs-FC was assessed by independent component analysis. Receiver operating characteristic (ROC) curves was performed to assess the diagnostic utility of rs-FC and GM reduction for the discrimination of patients with and without MHE. Blood ammonia, cGMP, and levels of pro-inflammatory interleukins were measured.MHE patients showed significant decrease of GM volume and lesser degree of rs-FC in different networks related to attention and executive functions as compared to controls and patients without MHE. There is a progressive reduction in rs-FC in the default mode network with the progression of cognitive impairment. MHE patients showed GM reduction in the right frontal lobe, right insula and right cerebellum compared to patients without MHE. Alterations in GM volume and rs-FC correlated with the scores of different cognitive tests.Decreased cognitive performance is associated by reduced rs-FC and GM atrophy in MHE patients. These changes could have predictive value for detecting MHE.
| S-EPMC5638549 | biostudies-other
Project description:OBJECTIVES:Minimal hepatic encephalopathy (MHE) is epidemic in cirrhosis, but testing strategies often have poor concordance. Altered gut/salivary microbiota occur in cirrhosis and could be related to MHE. Our aim was to determine microbial signatures of individual cognitive tests and define the role of microbiota in the diagnosis of MHE. METHODS:Outpatients with cirrhosis underwent stool collection and MHE testing with psychometric hepatic encephalopathy score (PHES), inhibitory control test, and EncephalApp Stroop. A subset provided saliva samples. Minimal hepatic encephalopathy diagnosis/concordance between tests was compared. Stool/salivary microbiota were analyzed using 16srRNA sequencing. Microbial profiles were compared between patients with/without MHE on individual tests. Logistic regression was used to evaluate clinical and microbial predictors of MHE diagnosis. RESULTS:Two hundred forty-seven patients with cirrhosis (123 prior overt HE, MELD 13) underwent stool collection and PHES testing; 175 underwent inhibitory control test and 125 underwent Stroop testing. One hundred twelve patients also provided saliva samples. Depending on the modality, 59%-82% of patients had MHE. Intertest Kappa for MHE was 0.15-0.35. Stool and salivary microbiota profiles with MHE were different from those without MHE. Individual microbiota signatures were associated with MHE in specific modalities. However, the relative abundance of Lactobacillaceae in the stool and saliva samples was higher in MHE, regardless of the modality used, whereas autochthonous Lachnospiraceae were higher in those without MHE, especially on PHES. On logistic regression, stool and salivary Lachnospiraceae genera (Ruminococcus and Clostridium XIVb) were associated with good cognition independent of clinical variables. DISCUSSION:Specific stool and salivary microbial signatures exist for individual cognitive testing strategies in MHE. The presence of specific taxa associated with good cognitive function regardless of modality could potentially be used to circumvent MHE testing.
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Project description:Cognitive dysfunction due to minimal hepatic encephalopathy (MHE) adversely impacts patients with cirrhosis and more precise therapies are needed. Gut-brain axis changes are therapeutic targets, but prior studies have largely focused on bacterial changes. Our aim was to determine linkages between individual cognitive testing results and bacteria with the virome using a cross-sectional and longitudinal approach. We included cross-sectional (n = 138) and longitudinal analyses (n = 36) of patients with cirrhosis tested using three cognitive modalities, which were psychometric hepatic encephalopathy score (PHES), inhibitory control test (ICT), Stroop, and all three. Stool metagenomics with virome and bacteriome were analyzed studied cross-sectionally and in a subset followed for development/reversal of MHE repeated at 6 months (longitudinally only using PHES). Cross-sectional: We found no significant changes in α/β diversity in viruses or bacteria regardless of cognitive testing. Cognitively impaired patients were more likely to have higher relative abundance of bacteriophages linked with Streptococcus, Faecalibacterium, and Lactobacillus, which were distinct based on modality. These were also linked with cognition on correlation networks. Longitudinally, 27 patients remained stable while 9 changed their MHE status. Similar changes in phages that are linked with Streptococcus, Faecalibacterium, and Lactobacillus were seen. These phages can influence ammonia, lactate, and short-chain fatty acid generation, which are neuro-active. In conclusion, we found linkages between bacteriophages and cognitive function likely due to impact on bacteria that produce neuroactive metabolites cross-sectionally and longitudinally. These findings could help explore bacteriophages as options to influence treatment for MHE in cirrhosis.
| S-EPMC10730154 | biostudies-literature
Project description:ObjectivesHepatic encephalopathy (HE) is common in advanced cirrhosis and is characterized by marked neuropsychiatric abnormalities. However, despite its severity and effects on brain function, the impact of HE on psychological status of patients has not been adequately assessed. The aim of this study was to evaluate the effect of HE on psychological status of patients and their informal caregivers.MethodsFifteen patients with cirrhosis and episodic or persistent HE and their corresponding informal caregivers were included. Semistructured interviews were performed in patients and caregivers. Quality of life (QoL) was assessed by the short-form 36 in both patients and caregivers, and the Zarit burden score was measured in caregivers. The analysis of interviews was performed using qualitative methodology.ResultsHE causes a major psychological impact on patients with HE. The first episode of HE caused a very significant impact that was reported with deep feelings, mainly of fear, anger, misery, anxiety, and sorrow, which persisted with time. Symptoms causing more psychological impact on patients were impaired ability to walk and speak. All effects were associated with a marked impairment in QoL. The psychological impact was also marked in caregivers who had a major burden, as assessed by the Zarit score. Moreover, QoL, particularly the mental component score, was markedly impaired in caregivers in intensity similar to that of patients.DiscussionHE has a profound psychological impact on patients and their informal caregivers, associated with a marked negative influence on QoL. The psychological effects of HE on patients and caregivers should be evaluated and treated.
| S-EPMC7263656 | biostudies-literature
Project description:ObjectiveTo construct an MR-radiomics nomogram to predict minimal hepatic encephalopathy (MHE) in patients with chronic hepatic schistosomiasis (CHS).MethodsFrom July 2017 to July 2020, 236 CHS patients with non-HE (n = 140) and MHE (n = 96) were retrospective collected and randomly divided into training group and testing group. Radiomics features were extracted from substantia nigra-striatum system of a brain diffusion weighted images (DWI) and combined with clinical predictors to build a radiomics nomogram for predicting MHE in CHS patients. The ROC curve was used to evaluate the predicting performance in training group and testing group. The clinical decisive curve (CDC) was used to assess the clinical net benefit of using radiomics nomogram in predicting MHE.ResultsLow seralbumin (P < 0.05), low platelet count (P < 0.05) and high plasma ammonia (P < 0.05) was the significant clinical predictors for MHE in CHS patients. The AUC, specificity and sensitivity of the radiomics nomogram were 0.89, 0.90 and 0.86 in the training group, and were 0.83, 0.85 and 0.75 in the training group. The CDC analysis showed clinical net benefits for the radiomics nomogram in predicting MHE.ConclusionsThe radiomics nomogram combining DWI radiomics features and clinical predictors could be useful tool to predict MHE in CHS patients.
| S-EPMC8550421 | biostudies-literature
Project description:AIM:To evaluate the reversibility of minimal hepatic encephalopathy (MHE) following liver transplantation (LT) in Egyptian cirrhotic patients. METHODS:This prospective study included twenty patients with biopsy-proven liver cirrhosis listed for LT and twenty age- and sex-matched healthy control subjects. All underwent neuro-psychiatric examination, laboratory investigations, radiological studies and psychometric tests including trail making test A (TMT A), TMT B, digit symbol test and serial dotting test. The psychometric hepatic encephalopathy score (PHES) was calculated for patients to diagnose MHE. Psychometric tests were repeated six months following LT in the cirrhotic patient group. RESULTS:Before LT, psychometric tests showed highly significant deficits in cirrhotic patients in comparison to controls (P < 0.001). There was a statistically significant improvement in test values in the patient group after LT; however, their values were still significantly worse than those of the controls (P < 0.001). The PHES detected MHE in 16 patients (80%) before LT with a median value of -7 ± 3.5. The median PHES value was significantly improved following LT, reaching -4.5 ± 5 (P < 0.001), and the number of patients with MHE decreased to 11 (55%). The pre-transplant model for end-stage liver disease (MELD) score ? 15 was significantly related to the presence of post-transplant MHE (P = 0.005). More patients in whom reversal of MHE was observed had a pre-transplant MELD score < 15. CONCLUSION:Reversal of MHE in cirrhotic patients could be achieved by LT, especially in those with a MELD score < 15.
| S-EPMC5084057 | biostudies-literature