Diagnosis Of Covert Hepatic Encephalopathy Research Articles

Other causes of neurocognitive impairment than covert hepatic encephalopathy (CHE) are very frequent, either alone or associated with CHE, in cirrhotic patients with cognitive complaints.

Although it is well admitted that cirrhotic patients display various causes of neurocognitive impairment (NI) hampering the diagnosis of covert hepatic encephalopathy (CHE), those are almost never investigated per se. The aims of this study were, in cirrhotic patients displaying cognitive complaints explored by a complete multimodal work-up, to assess: (1) the prevalence of CHE and/or that of other causes of NI and (2) their outcomes, according to the cause of NI. Prospective cohort of cirrhotic patients referred in a dedicated clinic because of cognitive complaints. Work-up included a complete neuropsychological assessment, electroencephalogram (EEG) and brain magnetic resonance imaging with spectroscopy. The diagnosis of CHE was made by an adjudication committee involving the physicians/neuropsychologist. One hundred and twenty-three patients were included (alcohol/MASLD/virus in 63/53/14%, MELD = 11). Sixty-six per cent of them were diagnosed with CHE; among them, 73% exhibited also other causes of NI, mainly cerebrovascular diseases/psychiatric. Among patients without CHE, 48% and 59% displayed pathological Psychometric Hepatic Encephalopathy Score and animal naming test, respectively. Clinical improvement was observed in 77% of the patients re-evaluated after specific management. CHE, but not the other causes of NI, was independently associated with OHE occurrence. Other causes of NI than CHE are frequent in patients with cirrhosis, and not ruled-out by the classical tests dedicated to CHE. Prognosis was influenced by the cause of NI. The management of patients even without CHE led to clinical improvement, underlining the need for a multifaceted approach of cirrhotic patients with cognitive complaints.

Covert hepatic encephalopathy is associated with aggressive disease progression and poor survival in patients with cirrhosis.

Covert hepatic encephalopathy (CHE) negatively affects the health-related quality of life and increases the risk of overt HE (OHE) in patients with liver cirrhosis. However, the impact of CHE on long-term patient outcomes remains controversial. This study aimed to explore the association between CHE and disease progression and survival among cirrhotic patients. This was a single-center prospective study that enrolled 132 hospitalized patients with cirrhosis, with an average follow-up period of 45.02 ± 23.06 months. CHE was diagnosed using the validated Chinese standardized psychometric hepatic encephalopathy score. CHE was detected in 35.61% cirrhotic patients. During the follow-up, patients with CHE had a higher risk of developing OHE (log-rank 5.840, P = 0.016), exacerbation of ascites(log-rank 4.789, P = 0.029), and portal vein thrombosis (PVT) (log-rank 8.738, P = 0.003). Cox multivariate regression analyses revealed that CHE was independently associated with the occurrence of OHE, exacerbation of ascites, and PVT. Furthermore, patients with progression of cirrhosis were more likely to be diagnosed as CHE (log-rank 4.462, P = 0.035). At the end of the follow-up, patients with CHE had a lower survival rate compared to those without CHE (log-rank 8.151, P = 0.004). CHE diagnosis (hazard ratio 2.530, P = 0.008), together with elder age and higher Child-Pugh score, were risk factors for impaired survival in cirrhotic patients. CHE is associated with disease progression and poor survival in patients with cirrhosis, indicating that CHE may serve as an independent predictor of poor prognosis among these patients.

Elevated serum levels of glial fibrillary acidic protein are associated with covert hepatic encephalopathy in patients with cirrhosis

Blood biomarkers facilitating the diagnosis of covert hepatic encephalopathy (CHE) in patients with cirrhosis are lacking. Astrocyte swelling is a major component of hepatic encephalopathy. Thus, we hypothesised that glial fibrillary acidic protein (GFAP), the major intermediate filament of astrocytes, might facilitate early diagnosis and management. This study aimed to investigate the utility of serum GFAP (sGFAP) levels as a biomarker of CHE. In this bicentric study, 135 patients with cirrhosis, 21 patients with ongoing harmful alcohol use and cirrhosis, and 15 healthy controls were recruited. CHE was diagnosed using psychometric hepatic encephalopathy score. sGFAP levels were measured using a highly sensitive single-molecule array (SiMoA) immunoassay. In total, 50 (37%) people presented with CHE at study inclusion. Participants with CHE displayed significantly higher sGFAP levels than those without CHE (median sGFAP, 163pg/ml [IQR 136; 268] vs. 106pg/ml [IQR 75; 153]; p <0.001) or healthy controls (p <0.001). sGFAP correlated with results in psychometric hepatic encephalopathy score (Spearman's ρ=-0.326, p <0.001), model for end-stage liver disease score (Spearman's ρ= 0.253, p= 0.003), ammonia (Spearman's ρ= 0.453, p= 0.002), and IL-6 serum levels (Spearman's ρ= 0.323, p= 0.006). Additionally, sGFAP levels were independently associated with the presence of CHE in multivariable logistic regression analysis (odds ratio 1.009; 95% CI 1.004-1.015; p <0.001). sGFAP levels did not differ between patients with alcohol-related cirrhosis vs. patients with non-alcohol-related cirrhosis or between patients with ongoing alcohol use vs. patients with discontinued alcohol use.Conclusions: sGFAP levels are associated with CHE in patients with cirrhosis. These results suggest that astrocyte injury may already occur in patients with cirrhosis and subclinical cognitive deficits and that sGFAP could be explored as a novel biomarker. Blood biomarkers facilitating the diagnosis of covert hepatic encephalopathy (CHE) in patients with cirrhosis are lacking. In this study, we were able to demonstrate that sGFAP levels are associated with CHE in patients with cirrhosis. These results suggest that astrocyte injury may already occur in patients with cirrhosis and subclinical cognitive deficits and that sGFAP could be explored as a novel biomarker.

Psychometric tests, critical flicker frequency, and inflammatory indicators in covert hepatic encephalopathy diagnosis.

Hepatic encephalopathy (HE) is a frequent complication of liver diseases. Systemic inflammation is key for HE pathogenesis. The main goal of the study was to investigate the role of psychometric tests, critical flicker frequency (CFF), and comparative evaluation of inflammatory indicators for the diagnosis of covert HE (CHE). The study was a prospective, nonrandomized, case-control study with a total of 76 cirrhotic patients and 30 healthy volunteers. The West Haven criteria were used to determine the occurrence of CHE in cirrhotic patients. Psychometric tests were applied to healthy and cirrhotic groups. CFF, venous ammonia, serum endotoxin, IL-6, IL-18, tumor necrosis factor alpha (TNF-α) levels, and hemogram parameters were evaluated for cirrhotic patients. CFF values and psychometric tests were found to accurately discriminate CHE positives from CHE negatives (p<0.05). When the control group was excluded, the digit symbol test and the number connection A test failed, unlike CFF and other psychometric tests. Using CFF, a 45 Hz cutoff value had 74% specificity and 75% sensitivity. Basal albumin levels (p=0.063), lymphocyte-to-monocyte ratio (LMR) (p=0.086), and neutrophil-to-lymphocyte ratio (p 0.052) were significant, albeit slightly, among CHE groups. Basal albumin levels had 50% sensitivity and 71% specificity when 2.8 g/dL was used as a cutoff value to determine CHE. Both psychometric tests and CFF can be useful in diagnosing CHE. Using cytokine and endotoxin levels seems to be inadequate to diagnose CHE. Using LMR and albumin levels instead of psychometric tests for diagnosing CHE can be promising.

QuickStroop, a Shortened Version of EncephalApp, Detects Covert Hepatic Encephalopathy With Similar Accuracy Within One Minute

Covert hepatic encephalopathy (CHE) is associated with poor outcomes but is often not diagnosed because of the time requirement. Psychometric hepatic encephalopathy score (PHES) is the gold standard against which EncephalApp Stroop has been validated. However, EncephalApp (5 runs each in "Off" and "On" state) can take up to 10 minutes. This study sought to define the smallest number of EncephalApp runs needed for comparable accuracy to the total EncephalApp using CHE on PHES as gold standard. A derivation and a validation cohort of outpatients with cirrhosis who underwent PHES (gold standard) and total EncephalApp was recruited. Data were analyzed for individual runs versus total EncephalApp time versus PHES-CHE. The derivation cohort (n= 398) was split into training (n= 299) and test (n= 99) sets. From the training data set a regression model was created with age, gender, education, and various sums of the "Off" settings. After this, a K-fold cross-validation on the test dataset was performed for both total EncephalApp time and individual Off runs and for the validation cohort. In both cohorts, Off runs 1+ 2 had statistically similar area under the receiver operating curve and P value to the total EncephalApp for PHES-CHE prediction. The adjusted (age, gender, education) regression formula from the derivation cohort showed an accuracy of 84% to diagnose PHES-CHE in the validation cohort. Time for CHE diagnosis decreased from 203.7 (67.82) to 36.8 (11.25) seconds in the derivation and from 178.2 (46.19) to 32.9 (9.94) seconds in the validation cohort. QuickStroop, which is completed within 1 minute, gives an equivalent ability to predict CHE on the gold standard compared with the entire EncephalApp time.

Liver-Unrelated Comorbid Conditions Do Not Affect Cognitive Performance or Hepatic Encephalopathy Progression in Cirrhosis.

We aimed to determine the effect of comorbidities on covert hepatic encephalopathy (CHE) diagnosis and overt hepatic encephalopathy (OHE) development. Cirrhotic outpatients underwent CHE testing and 2-year follow-up. Cox regression was performed for time to OHE. In total, 700 patients (60 years, 84% men, model for end-stage liver disease 11) and 33% prior OHE underwent testing and follow-up. Major comorbidities were hypertension (54%), diabetes (35%), and depression (29%). Common medications were proton pump inhibitor (49%), beta-blockers (32%), and opioids (21%). Approximately 90 (40%) prior-OHE patients developed recurrence 93 (30,206) days post-testing predicted only by liverrelated variables. Demographics, cirrhosis characteristics, and opioid use, but not other comorbid conditions, were associated with CHE diagnosis and OHE progression.

Proposal of Stroop test cut-off values as screening for neuropsychological impairments in cirrhosis: A Japanese multicenter study.

Despite its relevant clinical impact and high prevalence, covert hepatic encephalopathy (HE) still remains underdiagnosed. As patients with liver cirrhosis tend to be older in Japan, more suitable tests for the elderly and cut-off values based on this attribute are needed. Recently, a Stroop test has been developed and validated for the screening and diagnosis of covert HE in the United States. The present study aims to establish the cut-off values of the Stroop test to screen covert HE. This study was a prospective multicenter cross-sectional endeavor. We undertook a survey of 311 cirrhotic patients, administering the number connection test (NCT)-A and -B and the Stroop-off and -on test. We determined the cut-off values of Stroop test results for cirrhotic patients in a variety of age ranges. The cut-off value of the Stroop test was strongly correlated with age. There was a significant correlation between the results of NCT-B and age, and Stroop-on test results showed a correlation with serum albumin (Alb) levels. Serum Alb ≤3.2g/dl could have the potential to be an objective biomarker of covert HE. In addition, stepwise logistic regression analysis revealed a relationship between the results of the Stroop-on test and plasma ammonia levels. We established the cut-off values of Stroop test results and confirmed the efficacy of the Stroop test as a simple tool for assessing cognitive alterations. The Stroop test could be suitable as a necessary minimum for the diagnosis of covert HE.

Radiomics-based classification models for HBV-related cirrhotic patients with covert hepatic encephalopathy.

IntroductionThe significant abnormalities of precuneus (PC), which are associated with brain dysfunction, have been identified in cirrhotic patients with covert hepatic encephalopathy (CHE). The present study aimed to apply radiomics analysis to identify the significant radiomic features in PC and their subregions, combine with clinical risk factors, then build and evaluate the classification models for CHE diagnosis.Methods106 HBV‐related cirrhotic patients (54 had current CHE and 52 had non‐CHE) underwent the three‐dimensional T1‐weighted imaging. For each participant, PC and their subregions were segmented and extracted a large number of radiomic features and then identified the features with significant discriminative power as the radiomics signature. The logistic regression analysis was employed to develop and evaluate the classification models, which are constructed using the radiomics signature and clinical risk factors.ResultsThe classification model (R‐C model) achieved best diagnostic performance, which incorporated radiomics signature (4 radiomic features from right PC), venous blood ammonia, and the Child‐Pugh stage. And the area under the receiver operating characteristic curve values (AUC), sensitivity, specificity, and accuracy values were 0.926, 1.000, 0.765, and 0.848, in the testing set. Application of the radiomics nomogram in the testing set still showed a good predictive accuracy.ConclusionsThis study presented the radiomic features of the right PC, as a potential image marker of CHE. The radiomics nomogram that incorporates the radiomics signature and clinical risk factors may facilitate the individualized prediction of CHE.

S1180 Low Impact of Co-Morbid Conditions on the Diagnosis of Covert Hepatic Encephalopathy in a Cohort of 690 Patients With Cirrhosis

S1180 Low Impact of Co-Morbid Conditions on the Diagnosis of Covert Hepatic Encephalopathy in a Cohort of 690 Patients With Cirrhosis

Combined Scores from the EncephalApp Stroop Test, Number Connection Test B, and Serial Dotting Test Accurately Identify Patients With Covert Hepatic Encephalopathy

The EncephalApp Stroop test is a high-sensitivity but low-specificity test that has been used to identify patients with covert hepatic encephalopathy (CHE). We aimed to develop a new strategy to detect CHE, combining EncephalApp Stroop test score with scores from subtests of the psychometric hepatic encephalopathy scoring system (PHES). We performed a survey of 569 adult volunteers (229 men) in 9 communities in Shanghai, China, administering the EncephalApp Stroop test to determine the range of scores in the general population. Data from the standard PHES, including the number connection test-A, number connection test-B (NCT-B), line tracing test, serial dotting test (SDT), and digit symbol test, were used as the reference standard for diagnosis of CHE. A combination of the EncephalApp Stroop with subtests of the PHES was used to establish a new strategy for CHE diagnosis. We validated our findings using data from 160 patients with cirrhosis from 5 centers China. We determined the range of EncephalApp Stroop test scores for the volunteers of different decades of age, education levels, and sexes. Age, education level, and sex were independently associated with EncephalApp Stroop test scores. A combination of scores from the EncephalApp Stroop test, the NCT-B, and the SDT identified patients with CHE with the highest level of accuracy, when the standard PHES was used as the reference standard. A combination of scores of 187 sec for the EncephalApp Stroop test and below -1 for the NCT-B or below -1 for the SDT identified patients with CHE with an area under the curve (AUC) of 0.86, 81.0% sensitivity, and 91.9% specificity, and 87.5% accuracy. In the validation cohort, these cutoff scores identified patients with CHE with an AUC of 0.88, 97.1% sensitivity, 79.3% specificity, and 86.9% accuracy. The average time to calculate this score was 374±140 sec, compared 424±115 sec for the entire PHES. Scores from the EncephalApp Stroop test, NCT-B, and SDT identify patients with CHE with approximately 87% accuracy, and in a much shorter time than the standard PHES. This score combination could be a valid and convenient method for identifying patients with CHE. chictr.org.cn number, ChiCTR-EDC-17012007, ChiCTR1800019954.

P: 54 Diagnosis of Covert Hepatic Encephalopathy Is Influenced by Multiple Non-cognitive Variables That Varies by Testing Strategy

BACKGROUND: Covert hepatic encephalopathy (CHE) is a serious complication on cirrhosis that manifests as an amnestic cognitive dysfunction. Diagnosis is based on examining cognitive functions, but results are influenced by multiple non-cognitive factors such as sleep and medications but data regarding the influence of other non-cognitive covariates is limited. We aimed to examine the potential non-cognitive variables that could influence testing on the psychometric hepatic encephalopathy score (PHES) and the encephalapp stroop. METHODS: Patients between ages 20-75 years were enrolled from clinic between 2012–2018. Those with severe uncontrolled psychiatric comorbidities were excluded as were those actively abusing alcohol or drugs. All patients underwent testing for CHE based on 2 testing strategy as recommended by the AASLD/EASL guidelines. Demographics and details of comorbidities were collected. CHE was diagnosed based on published norms. Appropriate t tests and logistic regression were done. Dependent variable was CHE on PHES and Stroop. RESULTS: We enrolled a total of 257 patients with mean age 61.1 ± 8.3, 72% were males, HCV was he predominant etiology 96 (37.3%). Median BMI was 29 (26, 34). Median education was 13 (12, 16) years. Median MELD was 11 (7.25, 15) with median childs score of 6 (5, 8). Charlson comorbidity score (CCI) was 5 (4, 6). Eighty five (33%) had a history of prior OHE and were on lactulose (13), rifaximin (9) or both (63), 95 (37%) had ascites with 58 (61%) controlled on diuretics and 17 (18%) had a h/o SBP. 41 (16%) had a h/o variceal bleeding. In terms of comorbidities 34.2% had Diabetes Mellitus, 58% had Hypertension, 11% had Coronary artery disease, 14% had hypothyroidism, 2% had CHF, 2.3% had COPD, 30% had depression and 87% were controlled on medications. 2.3% had post traumatic stress disorder (PTSD) and were on medications. 14% were on chronic narcotic medications. On cognitive testing 109 (42.4%) had CHE with a median PHES score of −3 (−7, 0) whereas 206 (80%) tested positive on encephalapp stroop. On univariable analysis hypertension was found to be significant only for stroop. On multivariable analysis age and prior OHE were predictive for both tests but for the Encephalapp stroop hypertension was found to be independently predictive (Table 1). CONCLUSION: The diagnosis of CHE can be influenced by other non-cognitive variables and these vary between individual testing strategies probably due to the differential effects that these systemic conditions have on cerebral/subcortical functions. Physicians must take into consideration these covariates while interpreting CHE testing based on these 2 tests.

Use of Psycometric tests, Critical flicker frequency test and comparative evaluation of inflammation indicators in the diagnosis of covert hepatic encephalopathy

Use of Psycometric tests, Critical flicker frequency test and comparative evaluation of inflammation indicators in the diagnosis of covert hepatic encephalopathy

Development and Validation of a Prognostic Score to Predict Covert Hepatic Encephalopathy in Patients With Cirrhosis.

Diagnosis of covert hepatic encephalopathy (CHE) is challenging and often neglected in clinical practice. The aim of this study was to develop an easy-to-perform score to predict CHE in patients with cirrhosis. For the development or validation cohort of the proposed clinical CHE score, 142 or 96 consecutive patients with cirrhosis were prospectively enrolled. The Psychometric Hepatic Encephalopathy Score was used to detect minimal hepatic encephalopathy. All patients were examined with the simplified animal naming test and were asked to complete the Chronic Liver Disease Questionnaire. We followed the TRIPOD guideline for development, validation, and reporting of the proposed score. The clinical covert hepatic encephalopathy score containing the variables-clinically detectable ascites, history of overt hepatic encephalopathy (OHE), albumin serum level, activity subdomain of the Chronic Liver Disease Questionnaire, and simplified animal naming test-discriminated best between patients with and without CHE. We generated 2 cutoff values for the identification of the high-, intermediate- (with need for additional specialized testing), and low-risk groups for CHE. By applying these cutoffs, the sensitivity, specificity, positive predictive value, and negative predictive value were 90%, 91%, 85%, and 94%, respectively. The AUC was 0.908 or 0.872 for the development or the validation cohort, respectively. Higher scores were further associated with poorer quality of life, and the high-risk group was predictive for first-time OHE within 180 days. We developed an easy-to-perform score to identify patients with cirrhosis at risk of CHE, which correlates with quality of life and risk of first-time OHE.

Diagnosis of covert hepatic encephalopathy: a multi-center study testing the utility of single versus combined testing.

Covert hepatic encephalopathy (CHE) affects cognition in a multidimensional fashion. Current guidelines recommend performing Psychometric Hepatic Encephalopathy Score (PHES) and a second test to diagnose CHE for multi-center trials. We aimed to determine if a two-test combination strategy improved CHE diagnosis agreement, and accuracy to predict overt hepatic encephalopathy (OHE), compared to single testing. Cirrhotic outpatients without baseline OHE performed PHES, Inhibitory Control Test (ICT), and Stroop EncephAlapp (StE) at three centers. Patients were followed for OHE development. Areas under the receiver operation characteristic curve (AUROC) were calculated. We included 437 patients (399 with follow-up data). CHE prevalence varied with testing strategy: PHES+ICT 18%, ICT + StE 25%, PHES+StE 29%, ICT 35%, PHES 37%, and StE 54%. Combination with best test agreement was PHES+StE (k = 0.34). Sixty patients (15%) developed OHE. Although CHE by StE showed the highest sensitivity to predict OHE, PHES and PHES+StE were more accurate at the expense of a lower sensitivity (55%, AUROC: 0.587; 36%, AUROC: 0.629; and 29%, AUROC: 0.623; respectively). PHES+ICT was the most specific (85%) but all strategies including ICT showed sensitivities in the 33-45% range. CHE diagnosis by PHES (HR = 1.79, p= 0.04), StE (HR = 1.69, p= 0.04), and PHES+StE (HR = 1.72, p= 0.04), were significant OHE predictors even when adjusted for prior OHE and MELD. Our results demonstrate that combined testing decreases CHE prevalence without improving the accuracy of OHE prediction. Testing with PHES or StE alone, or a PHES+StE combination, is equivalent to diagnose CHE and predict OHE development in a multi-center setting.

Validation of the simplified Animal Naming Test as primary screening tool for the diagnosis of covert hepatic encephalopathy

BackgroundDiagnosis of covert hepatic encephalopathy (CHE) is time consuming in clinical practice. Recently, a new diagnostic tool - the simplified Animal Naming Test (S-ANT1) - was presented with promising results in an Italian cohort. The aim of the present study was to validate S-ANT1 in a cohort of cirrhotic patients from a German tertiary referral centre. Methods143 cirrhotic patients and 37 healthy controls were enrolled. Hepatic encephalopathy (HE) grade 1 (HE1) was clinically diagnosed according to the West-Haven Criteria. Critical flicker frequency and Psychometric Hepatic Encephalopathy Score were used to detect minimal HE (MHE). All participants were additionally examined by S-ANT1. Results58 (40.6%) patients presented with CHE (40 MHE, 18 HE1). S-ANT1 was lowest in patients with HE1, followed by patients with MHE, patients without CHE, and healthy controls, respectively (each p < 0.05). Naming <20 animals discriminated best between patients with and without CHE in ROC analysis (with Youden's index). With a cut-off value of ≥23 mentioned animal names further testing for CHE could be avoided in 38.5% of patients with a negative predictive value of 84%. ConclusionsS-ANT1 may become an important first screening tool for the assessment of CHE in clinical practice.

Effect of Post-Traumatic Stress Disorder on Cognitive Function and Covert Hepatic Encephalopathy Diagnosis in Cirrhotic Veterans.

In veterans, post-traumatic stress disorder (PTSD) is often associated with substance abuse, which in turn can lead to cirrhosis. Cirrhotic patients are prone to cognitive impairment, which is typically due to covert hepatic encephalopathy (CHE), but can also be affected by PTSD. The aim was to define the impact of PTSD on cognitive performance and the diagnosis of CHE in cirrhotic patients. Outpatient veterans with cirrhosis underwent two separate modalities for CHE cognitive testing [Psychometric Hepatic Encephalopathy Scale (PHES) and Inhibitory Control Test (ICT)]. ICT tests for inhibitory control and response inhibition, while PHES tests for attention and psychomotor speed. Comparisons were made between patients with/without PTSD. Multivariable logistic regression with CHE on PHES and CHE on ICT as dependent variables including prior OHE, demographics, PTSD and psychotropic medications was performed. Of 402 patients with cirrhosis, 88 had evidence of PTSD. Fifty-five of these were on psychoactive medications, 15 were undergoing psychotherapy, while no specific PTSD-related therapy was found in 28 patients. Cirrhotic patients with/without PTSD were statistically similar on demographics and cirrhosis severity, but cirrhotic subjects with PTSD had a higher frequency of alcoholic cirrhosis etiology and psychotropic drug use. PTSD cirrhosis had higher ICT lure and switching errors (NCT-B response), but on regression, there was no significant impact of PTSD on CHE diagnosis using either the ICT or PHES. Veterans with cirrhosis and PTSD have a higher frequency of psychotropic drug use and alcoholic cirrhosis etiology. CHE diagnosis using PHES or ICT is not affected by concomitant PTSD.

Su1464 - Validation of Thai Encephalapp in Smartphone for the Diagnosis of Covert Hepatic Encephalopathy

Su1464 - Validation of Thai Encephalapp in Smartphone for the Diagnosis of Covert Hepatic Encephalopathy

Does Diagnosis of Covert Hepatic Encephalopathy (CHE) With Two Testing Strategy Improving Prediction of Overt HE When Compared To Single Testing?

Does Diagnosis of Covert Hepatic Encephalopathy (CHE) With Two Testing Strategy Improving Prediction of Overt HE When Compared To Single Testing?

Comparative study on common diagnostic methods for covert hepatic encephalopathy

Objective To evaluate clinical application value of critical flicker frequency (CFF), psychometric hepatic encephalopathy score (PHES) and Stroop test in the diagnosis of covert hepatic encephalopathy (CHE). Methods A total of 110 patients with decompensated liver cirrhosis and 54 individuals without liver diseases were enrolled as control group. According to PHES<-4 points as reference threshold for CHE, the threshold of CFF and time of Stroop test for CHE diagnosis was caculated. Positive results of at least two of PHES, CFF and Stroop tests was considered as the gold standard for CHE diagnosis, and then the value of these three methods in CHE diagnosis was evaluated. Student′s t test and receiver operating characteristic curve (ROC) were used for statistical analysis. Results Among the 110 patients with liver cirrhosis, 40 patients had no hepatic encephalopathy (HE0), 52 patients had CHE, and 18 patients had grade 2 hepatic encephalopathy (HE2). The CFF value and total time of Stroop test of control group were (43.70±1.92) Hz and (201.17±20.65) s, respectively. The CFF value of HE0 group was (41.40±1.85) Hz, which was higher than that of CHE group ((38.33±2.32) Hz), and the difference was statistically significant (t=-7.116, P<0.01). The total time of Stroop test of HE0 group was (197.91±26.68) s, which was shorter than that of CHE group ((253.24±33.33) s), and the difference was statistically significant (t=8.936, P<0.01). When PHES<-4 points was considered as a reference threshold of CHE, the threshold of CFF for CHE diagnosis was 39 Hz, the sensitivity was 94.9% and the specificity was 73.1%, the area under the curve (AUC) was 0.879. The threshold of the total time of Stroop test for CHE diagnosis was 233.80 s, the sensitivity was 83.3% and the specificity was 71.1%, the AUC was 0.803.The completion time of the number connection test (NCT)-A, NCT-B and digit symbol test (DST), which were there of five subtests of PHES, of CHE group were (80.27±36.05) s, (124.18±55.96) s and (25.03±8.23) s, respectively, compared with those of HE0 patients ((56.68±18.82) s, (80.00±25.58) s and (34.68±8.75) s, respectively), the differences were statistically significant (t=3.691, 4.108 and -4.780; all P<0.01). Compared with the results of combined PHES and Stroop test in the diagnosis of HE0, CHE and HE2, the consistency rates of CFF<39 Hz as threshold for diagnosis were 95.0%, 61.5% and 100.0%, respectively. Conclusions NCT-A, NCT-B and DST three subtests of PHES have higher efficiency in CHE diagnosis. CFF and Stroop test are also reliable screening methods for CHE, with advantage of objectivity and high specificity. Key words: Liver cirrhosis; Hepatic encephalopathy; Critical flicker frequency; Psychometric hepatic encephalopathy score; Stroop test

Stepwise diagnosis in covert hepatic encephalopathy: critical flicker frequency and MELD-score as a first-step approach.

The diagnosis of covert hepatic encephalopathy (CHE) by means of portosystemic encephalopathy syndrome (PSE) test is costly and therefore infrequently performed. To determine the ability of critical flicker frequency (CFF) alone or in combination with laboratory findings, as an initial test to pre-select which patients should undergo further testing for the diagnosis of covert hepatic encephalopathy. This single-centre study included all patients with cirrhosis who underwent PSE and CFF in 2011. CHE was defined by abnormal PSE test. Logistic regression analysis was performed to identify predictors of CHE. ROC curves were used to identify cut-offs of these independent predictors. One hundred and seventeen patients were included. Seventy (60%) had CHE with a higher MELD [16 (IQR 13-21); P=0.001] and lower CFF [38Hz (IQR 36-41) P=0.0011]. On multivariate analyses, CFF [OR 0.83 (95% CI 0.74-0.94)] and MELD [OR 1.13 (95% CI 1.04-1.22)] were identified as independent predictors of CHE. Sensitivity and specificity of a CFF cut-off of 43Hz was 93.5% and 42.9%, and for a MELD cut-off of 24, it was 97.5% and 32.8% respectively. Most patients with a MELD-Score <24 and a CFF >43Hz did not have CHE (78%) and with a MELD-Score >24 and CFF <43Hz most patients had CHE (85%). Therefore, 27% of patients could avoid further testing with a diagnostic accuracy of 81%. The combination of MELD-score and critical flicker frequency may be used as a first diagnostic step to filter patients, in whom further covert hepatic encephalopathy testing could be avoided.