Diagnostic Value Of Stroop Test In Covert Hepatic Encephalopathy Among Cirrhotic Patients

BackgroundCovert hepatic encephalopathy(CHE)is a common complication of liver cirrhosis.The CHE patients manifest as cognitive deficit.The Stroop test,a neurophysiological task based on the Stroop effect,was used to estimate the cognitive function in human.This test has been well-documented as an available screening tool for CHE with high sensitivity among cirrhotic patients in the USA,while its specificity remains unsatisfied.Recently,EncephalApp in Chinese,a streamlined mobile application based the Stroop test was developed.However,the researches focused on Stroop test were scarcity in China,and the normative data in the native persons and the diagnostic value of EncephalApp in cirrhotic patients in China need to be ascertained.Aims1.To build up the normative data of Stroop test based on Chinese healthy individuals and investigate its influencing factors.2.To explore the value of EncephalApp test in the diagnosis of CHE among cirrhotic patients in China.3.To establish a novel diagnostic strategy for CHE by means of combination of EncephalApp and a subtest of PHES,and further validate the utility of the new method in multicenter in cirrhotic patients.Methods1.Normative data of Stroop test and its influencing factors: A total of 620 healthy individuals were recruited according to the inclusion and the exclusion criteria from nine communities from January 2017 to November 2017.The basic information including age,gender and education levels were recorded.All the healthy individuals underwent EncephalApp.The multiple linear regression was performed to investigate the influencing factors of EncephalApp outcomes and the regression equations were established to predict EncephalApp outcomes preliminary.According to equation of 90% upper=mean+1.28×standard deviation(SD),the normative data of Stroop test were built up stratified by age,education levels and gender.2.Diagnostic value of Stroop test in CHE among cirrhotic patients: Totally,144 cirrhotic patients were prospectively enrolled from Shanghai Changzheng hospital and Peking university people’s hospital from March 2016 to July 2017.The basic informations were collected,including gender,age,education levels,etiology of liver cirrhosis,classification of Child-pugh and so on.All the cirrhotic patients were instructed to complete EncephalApp and PHES by trained professionals.The correlation between outcomes of EncephalApp and PHES were analyzed by Pearson correlation.The receiver operating characteristics(ROC)curves analysis was carried out to evaluate the value of EncephalApp in CHE diagnosing among cirrhotic patients.3.The establishment and validation of a new diagnostic strategy for CHE: We tried to develop a novel and efficient strategy for the diagnosis of CHE by means of combination of Stroop test with a single subtest of PHES.Furthermore,we validated the value of the new strategy in a sperate group involving 111 cirrhotic patients.Results1.Normative data of Stroop test and its influencing factors1)The multiple linear regression models showed age,education levels and gender were the main influence factors on the outcomes of EncephalApp.Among these factors,age contributed the greatest impact and was positively correlated with outcomes of Stoop test(β=0.464,P<0.0001).Education levels was negatively correlated with the results(β=-0.364,P<0.0001).Gender reached statistical significance as well(β=0.133,P<0.0001)and females manifested better performance of EncephalApp outcomes than males.2)Based on the multiple linear regression models,the regression equations were established to predict outcomes of Stroop test: OffTime+OnTime(s)=127.397+1.566×age-3.923×education years+(10.589×gender).Furthermore,according to the equation of 90% upper=mean+1.28×standard deviation(SD),the normative data of Stroop test were built up stratified by age,education levels and gender.2.Diagnostic value of Stroop test in CHE among cirrhotic patients1)The cirrhotic patients did poorer performance in each state of Stroop test than the healthy individuals(P<0.05),the CHE patients spent more time to complete Stroop test than patients without CHE(P<0.0001).2)Outcomes of EncephalApp had moderate correlations(r 0.238-0.733,p<0.01)with PHES and it spent less time to complete EncephalApp than PHES.Therefore,EncephalApp was a more accessible,convenient and acceptable than PHES.3)With the cutoff of OffTime+OnTime>186.63 seconds,the area under curve(AUC),sensitivity,specificity,accuracy,positive predict value(PPV)and negative PV(NPV)of Stroop test in the diagnosis of CHE among cirrhotic patients were 0.771,86.2%,59.3%,69.44%,59.00% and 86.00%,respectively(P < 0.0001).4)Age and alcoholic hepatitis(OR=1.05 and 3.12,both P<0.05)were positively correlated with the risk of CHE.The experience with electronic devices and education levels were negatively correlated(OR=0.21 and 0.92,both P<0.05).3.The establishment and validation of a new diagnostic strategy for CHE1)EncephalApp followed with connection test-B(NCT-B)was an efficient strategy in the diagnosis of CHE,and the sensitivity,specificity,accuracy,PPV and NPV were 60.34%,100%,84.02%,100% and 78.89%,respectively.2)The sensitivity,specificity,accuracy,PPV and NPV of the new strategy in the valiation cohort were 60.78%,93.33%,78.37%,88.57% and 73.68%,respectively,which were similar to the result in the initial cohort.Conclusions1.Age,education levels and gender were the main influencing factors of Stroop test in Chinese healthy individuals.According to these demographic variables,we established regression equation to predict Stroop test outcomes: OffTime+OnTime(seconds)=127.397+1.566×age-3.923×education levels+(10.589×gender).2.Cirrhotic patients and CHE patients exhibited worse performance in EncephalApp.The Stroop test was a good screening tool for CHE among cirrhotic patients.3.NCT-B followed by EncephalApp was a novel efficient and rapid strategy which should be recommended in diagnosis of CHE among cirrhotic patients.