Duration of the acute hepatic encephalopathy episode determines survival in cirrhotic patients.
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ABSTRACT:
SUBMITTER: Ventura-Cots M
PROVIDER: S-EPMC5784576 | biostudies-literature |
REPOSITORIES: biostudies-literature
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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 and Aim:Variceal bleeding is the second most important precipitating factor related to the development of episodic hepatic encephalopathy; but to date there are no recommendations to prevent this complication. The aim of this study was to compare if primary prophylaxis with lactulose or L-ornithine L-aspartate or rifaximin, in cirrhotic patients with variceal bleeding, is better than placebo for avoiding the development of hepatic encephalopathy. Methods:A randomized, double-blind, placebo-controlled clinical trial (ClinicalTrials.gov identifier: NCT02158182) which included cirrhotic patients with variceal bleeding, without minimal or clinical hepatic encephalopathy at admission. Findings:87 patients were randomized to one of four groups. The basal characteristics were similar between groups. Comparatively with placebo, the frequency with regard to the development of hepatic encephalopathy was as follows: lactulose (54.5% versus 27.3%; OR = 0.3, 95% CI 0.09-1.0; P = 0.06); L-ornithine L-aspartate (54.5% versus 22.7%, OR = 0.2, 95% CI 0.06-0.88; P = 0.03); rifaximin (54.5% versus 23.8%; OR = 0.3, 95% CI 0.07-0.9; P = 0.04). There was no significant difference between the three groups receiving any antiammonium drug (P = 0.94). In the group receiving lactulose, 59.1% had diarrhea, and 45.5% had abdominal discomfort, bloating, and flatulence. Two patients (10%) treated with lactulose and a patient (4.5%) in the placebo group developed spontaneous bacterial peritonitis due to E. coli; one of them died due to recurrent variceal bleeding. There were no other adverse effects. Conclusions:Antiammonium drugs, particularly L-ornithine L-aspartate and rifaximin, proved to be effective in preventing the development of hepatic encephalopathy in those cirrhotic patients with variceal bleeding.
| S-EPMC6069577 | 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:BackgroundThe occurrence of overt hepatic encephalopathy (OHE) is associated with increased mortality. HE is commonly precipitated by infection, but whether HE predisposes to new infection is unclear. This study aimed to test if OHE predisposes to de novo infection during hospitalisation and its association with short-term mortality.Aims and methodsSeven hundred and fifty-nine consecutive patients were identified at two institutions from prospectively maintained clinical databases of cirrhotic patients admitted with acute decompensation (AD). Infection and HE data were collected on the day of admission, and the occurrence of de novo infections was assessed for 28 days after admission. EASL-CLIF organ failure criteria were used to determine the presence of organ failures. Multivariable analysis using the logistic regression model was used to assess predictors of 28-day mortality and de novo infection.ResultsPatients were divided into four groups; no baseline OHE or infection (n = 352); OHE with no baseline Infection (n = 221); no OHE but baseline infection (n = 100) and OHE with baseline infection (n = 86). On multivariate analyses, OHE (OR, 1.532 [95% CI, 1.061-2.300, P = 0.024]), and admission to ITU (OR, 2.303 [95% CI, 1.508-3.517, P < 0.001]) were independent risk factors for de novo infection. 28-day mortality was 25.3%, 60.2%, 55.0% and 72.1% in the 4-groups respectively. Age, INR and creatinine were independently predictive of mortality. The presence of overt HE, infection, coagulation, kidney, circulatory, respiratory and liver failures were significantly associated with higher mortality.ConclusionOHE is an independent risk factor for de novo infection in cirrhotic patients with AD.
| S-EPMC9303427 | biostudies-literature
Project description:Minimal hepatic encephalopathy (MHE) is associated with changes in functional connectivity. To investigate the patterns of modular changes of the functional connectivity in the progression of MHE, resting-state functional magnetic resonance imaging was acquired in 24 MHE patients, 31 cirrhotic patients without minimal hepatic encephalopathy (non-HE), and 38 healthy controls. Newman's metric, the modularity Q value, was maximized and compared in three groups. Topological roles with the progression of MHE were illustrated by intra- and intermodular connectivity changes. Results showed that the Q value of MHE patients was significantly lower than that of controls (P < 0.01) rather than that of non-HE patients (P > 0.05), which was correlated with neuropsychological test scores rather than the ammonia level and Child-Pugh score. Less intrasubcortical connections and more isolated subcortical modules were found with the progression of MHE. The non-HE patients had the same numbers of connect nodes as controls and had more hubs compared with MHE patients and healthy controls. Our findings supported that both intra- and intermodular connectivity, especially those related to subcortical regions, were continuously impaired in cirrhotic patients. The adjustments of hubs and connector nodes in non-HE patients could be a compensation for the decreased modularity in their functional connectivity networks.
| S-EPMC4066720 | biostudies-literature
Project description:PurposeHepatic encephalopathy (HE) is a potential complication of cirrhosis. Magnetic resonance imaging (MRI) may demonstrate hyperintense T1 signal in the globi pallidi. The purpose of this study was to evaluate the performance of MRI-based radiomic features for diagnosing and grading chronic HE in adult patients affected by cirrhosis.MethodsAdult patients with and without cirrhosis underwent brain MRI with identical imaging protocol on a 3T scanner. Patients without history of chronic liver disease were the control population. HE grading was based on underlying liver disease, severity of clinical manifestation, and number of encephalopathic episodes. Texture analysis was performed on axial T1-weighted images on bilateral lentiform nuclei at the level of the foramina of Monro. Diagnostic performance of texture analysis for the diagnosis and grading of HE was assessed by calculating the area under the receiver operating characteristics (AUROC) with 95% confidence interval (CI).ResultsThe final study population consisted of 124 patients, 70 cirrhotic patients, and 54 non-cirrhotic controls. Thirty-eight patients had history of HE with 22 having an HE grade > 1. The radiomic features predicted the presence of HE with an AUROC of 0.82 (95% CI: 0.73, 0.90; P < .0001; 82% sensitivity, 66% specificity). Radiomic features predicted grade 1 HE (AUROC 0.75; 95% CI: 0.61, 0.89; P < .0001; 94% sensitivity, 60% specificity) and grade ≥ 2 HE (AUROC 0.82; 95% CI: 0.71, 0.93; P < .0001, 95% sensitivity, 57% specificity).ConclusionIn cirrhotic patients, MR radiomic is effective in predicting the presence of chronic HE and in grading its severity.
| S-EPMC9474333 | biostudies-literature
Project description:ObjectivePatients with cirrhosis often exhibit cognitive deficits, particularly executive dysfunction, which is considered a predictor of overt hepatic encephalopathy (OHE). We examined brain intrinsic networks associated with executive function to investigate the neural basis of this cognitive deficiency in cirrhosis.MethodsResting-state functional MRI data were acquired from 20 cirrhotic patients and 18 healthy controls. Seed-based correlation analysis was used to identify the three well-known networks associated with executive function, including executive control (ECN), default mode (DMN), and salience (SN) networks. Functional connectivity (FC) within each network was compared between groups and correlated with patient executive performance (assessed by the Stroop task).ResultsPatients showed decreased FC between the ECN seed (right dorsolateral prefrontal cortex) and several regions (including right middle/inferior frontal gyrus, left inferior frontal gyrus, bilateral inferior/superior parietal lobules, bilateral middle/inferior temporal gyrus, and right medial frontal gyrus), between the DMN seed [posterior cingulate cortex (PCC)] and several regions (including bilateral medial frontal gyrus, bilateral anterior cingulate cortex, bilateral superior frontal gyrus, bilateral precuneus/PCC, left supramarginal gyrus, and left middle temporal gyrus), and between the SN seed (right anterior insula) and right supramarginal gyrus. FC strength in the ECN and SN was negatively correlated with patient performance during the Stroop task.ConclusionDisrupted functional integration in the core brain cognitive networks, which is reflected by reductions in FC, occurs before OHE bouts and may play an important role in the neural mechanism of executive dysfunction associated with cirrhosis.
| S-EPMC5788959 | biostudies-literature
Project description:No therapies have been proven to increase survival after a hepatic encephalopathy (HE) episode. We hypothesize that two doses of albumin could improve 90-day survival rates after a HE episode.Methods(1) A randomized double-blind, placebo-controlled trial (BETA) was conducted in 12 hospitals. The effect of albumin (1.5 g/kg at baseline and 1 g/kg on day 3) on 90-day survival rates after a HE episode grade II or higher was evaluated. (2) A meta-analysis of individual patient's data for survival including two clinical trials (BETA and ALFAE) was performed.ResultsIn total, 82 patients were included. Albumin failed to increase the 90-day transplant-free survival (91.9% vs. 80.5%, p = 0.3). A competing risk analysis was performed, observing a 90-day cumulative incidence of death of 9% in the albumin group vs. 20% in the placebo (p = 0.1). The meta-analysis showed a benefit in the albumin group, with a lower rate of clinical events (death or liver transplant) than patients in the placebo (HR, 0.44; 95% CI, 0.21-0.82), when analyzed by a competing risk analysis (90-days mortality rate of 11% in the albumin group vs. 30% in the placebo, p = 0.02).ConclusionsRepeated doses of albumin might be beneficial for patient's survival as an add-on therapy after an HE episode, but an adequately powered trial is needed.
| S-EPMC8584661 | biostudies-literature
Project description:Background & aimsHepatic encephalopathy (HE) is a serious neurologic complication in patients with liver cirrhosis. Very little is known about the role of the meningeal lymphatic system in HE. We tested our hypothesis that enhancement of meningeal lymphatic drainage could decrease neuroinflammation and ameliorate HE.MethodsA 4-week bile duct ligation model was used to develop cirrhosis with HE in rats. Brain inflammation in patients with HE was evaluated by using archived GSE41919. The motor function of rats was assessed by the rotarod test. Adeno-associated virus 8-vascular endothelial growth factor C (AAV8-VEGF-C) was injected into the cisterna magna of HE rats 1 day after surgery to induce meningeal lymphangiogenesis.ResultsCirrhotic rats with HE showed significantly increased microglia activation in the middle region of the cortex (P < .001) as well as increased neuroinflammation, as indicated by significant increases in interleukin 1β, interferon γ, tumor necrosis factor α, and ionized calcium binding adaptor molecule 1 (Iba1) expression levels in at least 1 of the 3 regions of the cortex. Motor function was also impaired in rats with HE (P < .05). Human brains of patients with cirrhosis with HE also exhibited up-regulation of proinflammatory genes (NFKB1, IbA1, TNF-α, and IL1β) (n = 6). AAV8-VEGF-C injection significantly increased meningeal lymphangiogenesis (P = .035) and tracer dye uptake in the anterior and middle regions of the cortex (P = .006 and .003, respectively), their corresponding meninges (P = .086 and .006, respectively), and the draining lymph nodes (P = .02). Furthermore, AAV8-VEGF-C decreased microglia activation (P < .001) and neuroinflammation and ameliorated motor dysfunction (P = .024).ConclusionsPromoting meningeal lymphatic drainage and enhancing waste clearance improves HE. Manipulation of meningeal lymphangiogenesis could be a new therapeutic strategy for the treatment of HE.
| S-EPMC7956141 | biostudies-literature
Project description:Hepatic encephalopathy (HE) is one of the most important complications of patients with liver cirrhosis. In addition, HE is associated with a dismal prognosis and has detrimental effects on patients' quality of life. Thus, it is of pivotal importance to identify patients at high risk for overt HE (OHE) in whom primary prophylaxis may be justified. In this narrative review, we aim to provide insight into predictors and prediction tools for a first-time episode of OHE and to scrutinize the current level of evidence of primary prophylaxis. In recent decades, several cognitive tests, composite scores, and blood-based biomarkers have been demonstrated to be predictive of a first-time episode of OHE. Among the best validated are the established tests for minimal HE, such as the Psychometric Hepatic Encephalopathy Score, determination of the critical flicker frequency, Stroop EncephalApp, or the Animal Naming Test. Individualized risk stratification using blood-based biomarkers and cross-sectional imaging (sarcopenia and spontaneous portosystemic shunts) is coming to the fore, but validation in larger multicenter cohorts is often lacking. On the basis of current evidence, a recommendation for primary prophylaxis of a first episode of OHE cannot be made in general. Only 2 studies have investigated the prevention of a first-time OHE episode as the primary endpoint. In this narrative review, we provide a concise overview of the current evidence levels on prediction tools and pharmacological prevention of a first episode of OHE. In addition, we give an outlook on future research targets to improve knowledge on this important topic.
| S-EPMC10027066 | biostudies-literature