Comparative Study On Common Diagnostic Methods For Covert Hepatic Encephalopathy

BackgroundHepatic encephalopathy is one of the major,unsolved complications of cirrhosis.Even its subtle form,termed minimal hepatic encephalopathy(MHE)or covert hepatic encephalopathy(CHE),is associated with increased mortality,risk of hospitalization,health realted quality of life impairment,and caregiver burden.Detection of MHE or CHE may guide treatment,which has the potential to improve outcomes and quality of life.However,testing of patients with cirrhosis for MHE or CHE remains uncommon in clinical practice.A primary obstacle to early diagnosis and treatment of HE is the lack of a well-validated,standardized method for detecting and characterizing HE.The absence of an bjective and sensitive HE grading method also has contributed to our limited understanding of the epidemiology and pathogenesis of HE and the difficulty in evaluating the efficacy of HE-targeted treatments.Therefore,the recent AASLD/EASL(American Association for the Study of Liver Diseases;European Association for the Study of the Liver)guidelines recommend use of two or more complementary strategies to diagnose covert HE in the research setting.These strategies include paper-pencil tests such as the PHES neurophysiological tests such as CFF or computerized tests such as the Encephal App Stroop test.Mini-Mental State Examination(MMSE)is one of the most commonly used methods in the assessment of cognitive mental status,has good reliability and validity in the screening of cognitive impairment.MMSE has been used in hepatology,also usedin the assessment of the severity and in monitoring of HE in several foreign studies.However,Chinese researchers have not conducted similar studies.ObjectiveOn the basis of the recent AASLD/EASLguidelines recommend use of two or more complementary strategies to diagnose CHE,to evaluate the diagnostic value of mini-mental state examination,MMSE),critical flicker frequency(CFF),psychometric hepatic encephalopathy score(PHES)and the Stroop test in detection of HE in patients with cirrhosis.MethodsA total of 110 inpatients with decompensated liver cirrhosis and 81 healthy controls without liver disease were enrolled,all completed PHES,CFF and Stroop tests orderly.The normal range and abnormal threshold of critical flicker frequency and Stroop test were established on the basis of PHES <-4 points.Within PHES,CFF and Stroop at least two out of three test abnormal as the gold standard in the diagnosis of covert hepatic encephalopathy,evaluation the application value of the three methods for the diagnosis of covert hepatic encephalopathy.Meanwhile,the mini-mental state examination was divided into several items according to the different functions of the test,the preliminary screening and predictive value of these compounds for hepatic encephalopathy were analyzed,respectively.T test,one-way ANOVA and receiver operating characteristic curve(ROC)were used to statistical analysis.Results Among the 110 patients with cirrhosis,52 patients were diagnosed to be CHE,40 patients without hepatic encephalopathy(HE0),and 18 patients were diagnosed to be the grade 2 of hepatic encephalopathy(HE2).(1)The mean of the CFF and total time of Stroop test of health control were(43.70±1.92)Hz and(201.17±20.65)s,respectively.The value of CFF were(41.40±1.85)Hz without HE group higher than the patients with covert hepatic encephalopathy group(38.33±2.32)Hz,has statistically significant between the two group(t=-7.116,P <0.01).(2)When using the PHES <-4 points as areference threshold of CHE,the threshold of CFF were 39 Hz,sensitivity were 94.9%and the specificity were 73.1%,the area under the curve(AUC)were 0.879;the threshold of the total time of Stroop test were 233.80 s,sensitivity were 83.3% and the specificity were 71.1%,the AUC were 0.803.(3)The results of the number connection test A(NCT-A),number connection test B(NCT–B)and digit symbol test(DST)were(80.27±36.05)s,(124.18±55.96)s,(25.03±8.23)s of the CHE patients,respectively,by contrast with HE0 patients(56.68±18.82)s,(80.00±25.58)s,(34.68±8.75)respectively),all has statistically significant(t=3.691,4.108,-4.780;all P<0.01).Compared with the results ofcombination of PHES with Stroop for diagnosis of HE0,CHE and HE2,the consistency percentage of the results with CFF borderlines(<39 Hz)were 95.0%,61.5% and 100%,respectively.(4)The pearson correlation coefficient between Child-pugh score and MMSE score,time orientation,space orientation,attention and computing power,memory,and write a sentence,draw pentagon were-0.352,-0.417,-0.342,-0.243,-0.275,-0.303,-0.278,respectively,All p value<0.01).Between the patients of HE0,CHE and OHE groups of the total score of MMSE was significantly different(p<0.001),especially in patients with OHE MMSE score compared with CHE and HE0 were significantly lower,(18.50±4.17),(24.93±4.23),(27.88±2.70),respectively.HE0 and CHE of the two groups found that there was no significant difference of time orientation and spatial orientation(p>0.05),and OHE group no matter compared with HE0 group or CHE group,time orientation and spatial orientation were significantly different(p<0.001).ConclusionsNCT-A,NCT-B and DST tests can be used as effective diagnostic methods for covert hepatic encephalopathy.The critical flicker frequency and Stroop test were reliable detection methods for covert hepatic encephalopathy,with the advantage of objective and strong specificity of detection.MMSE total score,time orientation and spatial orientation have certain predictive value for OHE,but the diagnosis of CHE still need to combine a variety of diagnostic methods to improve the screening rate.