Cytokine levels contribute to the pathogenesis of minimal hepatic encephalopathy in patients with hepatocellular carcinoma via STAT3 activation.
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ABSTRACT:
SUBMITTER: Wu H
PROVIDER: S-EPMC4725946 | biostudies-other | 2016 Jan
REPOSITORIES: biostudies-other
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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:IntroductionSerum biomarkers for the diagnosis of minimal hepatic encephalopathy (MHE) in patients with liver cirrhosis would be desirable. In this proof-of-concept study, we investigated the association between MHE and serum levels of neurofilament light chains (sNfL) in patients with liver cirrhosis.MethodssNfL were studied in patients with liver cirrhosis (with or without MHE) and controls (patients with ischemic stroke, transitory ischemic attack, and healthy individuals). MHE was diagnosed using the Psychometric Hepatic Encephalopathy Score.ResultsPatients with MHE showed higher sNfL than patients without MHE and controls. In multivariable analyses, higher sNfL were independently associated with the presence of MHE. sNfL had a reliable discriminative power for the detection of MHE with an area under the curve of 0.872.DiscussionMHE is associated with higher sNfL.
| S-EPMC8528231 | biostudies-literature
Project description:Tetraspanin CD63 has been widely implicated in tumour progression of human malignancies. However, its role in the tumorigenesis and metastasis of hepatocellular carcinoma (HCC) remains unclear yet. In the present study, we aimed to investigate the specific function and underlying mechanisms of CD63 in HCC progression. CD63 expression in HCC tissues was detected using immunohistochemistry and quantitative real-time PCR analyses; effects of CD63 on HCC cell proliferation and migration were investigated by CCK-8 assay, colony formation assay, transwell assay and a xenograft model of nude mice. RNA-sequencing, bioinformatics analysis, dual-luciferase reporter assay and Western blot analysis were performed to explore the underlying molecular mechanisms. Results of our experiments showed that CD63 expression was frequently reduced in HCC tissues compared with adjacent normal tissues, and decreased CD63 expression was significantly associated with larger tumour size, distant site metastasis and higher tumour stages of HCC. Overexpression of CD63 inhibited HCC cell proliferation and migration, whereas knockdown of CD63 promoted these phenotypes. IL-6, IL-27 and STAT3 activity was regulated by CD63, and blockade of STAT3 activation impaired the promotive effects of CD63 knockdown on HCC cell growth and migration. Our findings identified a novel CD63-IL-6/IL-27-STAT3 axis in the development of HCC and provided a potential target for the diagnosis and treatment of this disease.
| S-EPMC7812266 | 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:Oxidative stress plays a crucial role in the pathogenesis of hepatic encephalopathy (HE), but the mechanism remains unclear. GABAergic neurons in substantia nigra pars reticulata (SNr) contribute to the motor deficit of HE. The present study aims to investigate the effects of oxidative stress on HE in male mice. The results validate the existence of oxidative stress in both liver and SNr across two murine models of HE induced by thioacetamide (TAA) and bile duct ligation (BDL). Systemic mitochondria-targeted antioxidative drug mitoquinone (Mito-Q) rescues mitochondrial dysfunction and oxidative injury in SNr, so as to restore the locomotor impairment in TAA and BDL mice. Furthermore, the GAD2-expressing SNr population (SNrGAD2) is activated by HE. Both overexpression of mitochondrial uncoupling protein 2 (UCP2) targeted to SNrGAD2 and SNrGAD2-targeted chemogenetic inhibition targeted to SNrGAD2 rescue mitochondrial dysfunction in TAA-induced HE. These results define the key role of oxidative stress in the pathogenesis of HE.
| S-EPMC10366183 | 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
Project description: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 (vibration, cooling, and heat pain detection) by electromyography and quantitative sensory testing. The detection thresholds for cold and heat pain on the foot were higher in patients with, than those without MHE. This hyposensitivity was correlated with attention deficits. Reaction times in the foot were longer in patients with, than without MHE. Patients with normal sural nerve amplitude showed altered thermal sensitivity and autonomic function, with stronger alterations in patients with, than in those without MHE. MHE patients show a general decrease in cognitive and sensory abilities. Small fibers of the autonomic nervous system and thermal sensitivity are altered early on in MHE, before large sensory fibers. Quantitative sensory testing could be used as a marker of MHE.
| S-EPMC7826803 | biostudies-literature
Project description:The syndrome we refer to as Hepatic Encephalopathy (HE) was first characterized by a team of Nobel Prize winning physiologists led by Pavlov and Nencki at the Imperial Institute of Experimental Medicine in Russia in the 1890's. This focused upon the key observation that performing a portocaval shunt, which bypassed nitrogen-rich blood away from the liver, induced elevated blood and brain ammonia concentrations in association with profound neurobehavioral changes. There exists however a spectrum of metabolic encephalopathies attributable to a variety (or even absence) of liver hepatocellular dysfunctions and it is this spectrum rather than a single disease entity that has come to be defined as HE. Differences in the underlying pathophysiology, treatment responses and outcomes can therefore be highly variable between acute and chronic HE. The term also fails to articulate quite how systemic the syndrome of HE can be and how it can be influenced by the gastrointestinal, renal, nervous, or immune systems without any change in background liver function. The pathogenesis of HE therefore encapsulates a complex network of interdependent organ systems which as yet remain poorly characterized. There is nonetheless a growing recognition that there is a complex but influential synergistic relationship between ammonia, inflammation (sterile and non-sterile) and oxidative stress in the pathogenesis HE which develops in an environment of functional immunoparesis in patients with liver dysfunction. Therapeutic strategies are thus moving further away from the traditional specialty of hepatology and more towards novel immune and inflammatory targets which will be discussed in this review.
| S-EPMC4442852 | biostudies-other
Project description:BackgroundMinimal hepatic encephalopathy (MHE) reduces quality of life, increases the risk of road traffic incidents and predicts progression to overt hepatic encephalopathy and death. Current psychometry-based diagnostic methods are effective, but time-consuming and a universal 'gold standard' test has yet to be agreed upon. Critical Flicker Frequency (CFF) is a proposed language-independent diagnostic tool for MHE, but its accuracy has yet to be confirmed.AimTo assess the diagnostic accuracy of CFF for MHE by performing a systematic review and meta-analysis of all studies, which report on the diagnostic accuracy of this test.MethodsA systematic literature search was performed to locate all publications reporting on the diagnostic accuracy of CFF for MHE. Data were extracted from 2 × 2 tables or calculated from reported accuracy data. Collated data were meta-analysed for sensitivity, specificity, diagnostic odds ratio (DOR) and summary receiver operator curve (sROC) analysis. Prespecified subgroup analysis and meta-regression were also performed.ResultsNine studies with data for 622 patients were included. Summary sensitivity was 61% (95% CI: 55-67), specificity 79% (95% CI: 75-83) and DOR 10.9 (95% CI: 4.2-28.3). A symmetrical sROC gave an area under the receiver operator curve of 0.84 (SE = 0.06). The heterogeneity of the DOR was 74%.ConclusionsCritical Flicker Frequency has a high specificity and moderate sensitivity for diagnosing minimal hepatic encephalopathy. Given the advantages of language independence and being both simple to perform and interpret, we suggest the use of critical flicker frequency as an adjunct (but not replacement) to psychometric testing.
| S-EPMC3761188 | biostudies-literature