Studies On Clinical Diagnostic Methods For Minimal Hepatic Encephalopathy In Patients With Cirrhosis

Objectives:To investigate the prevalence and analyse the correlative factors of minimal hepatic encephalopathy(MHE) in cirrhosis patients without overt hepatic encephalopathy.To research the diagnostic value and the correlative factors of critical flicker frequency(CFF)in cirrhosis patients.To analyze the expression difference of S100 B 、 neuron specific enolase(NSE) of MHE patients.Methods:(1)According to the included and excluded criteria,a total of 86 cirrhosis patients were recruited in the study,and cirrhosis was diagnosed by liver function tests,imageology or biopsy.Included patients were screened for MHE using PHES,as number connection test A(NCT-A)and digit symbol test(DST).MHE was diagnosed when the results of both NCT-A and DST presented abnormal and analyse the relevant factors of MHE.(2) CFF was determined for all the patients as the blinding principle.Diagnostic fourfold table was build to calculate sensitivity、specificity、mistake diagnostic rate、omission diagnostic rate、Youden index、positive predictive value、positive likelihood ratio、total consistent rate and the ROC curve was drown.The clinical value of CFF and relevant factors were evaluated.(3)The S100 B and NSE,as well as,the biochemical indicators of liver function expression were detect by enzyme linked immunosorbent assay(ELISA) and their significance were analysed.Results:(1) The “gold standard” for MHE was both NCT-A(+) and DST(+). In 86 cirrhotic patients, 47 patients(47/86, 54.7%) were NCT-A(+),and 39 patients(39/86, 45.3%) wereDST(+).In total,32 patients(37.2%) were both NCT-A(+) and DST(+),and they were diagnosed with MHE.32 MHE patients compared with 54 non-MHE patients,the education level(c2=8.940,P=0.030)、cirrhotic duration(t=2.422,P=0.019)、Child-Pugh score(t=35.839,P=0.000)、model for endstage liver disease(MELD)(t=5.704,P=0.000)、ascites(c2=8.750,P=0.003)、hepatic encephalopathy(c2=5.247,P=0.022)of MHE were significantly different.(2) The diagnostic method was CFF,and it was abnormal when CFF<39.0Hz. In the total 86 cirrhosis patients, 31 patients(31/86, 36.05%) was CFF(+).Among 31 patients there were 26 patients(26/32, 81.25%) belonging to MHE group,and 5 patients(5/54,9.3%) belonging to non-MHE group.Sensitivity was 81.25%, and specificity was90.74%,and mistake diagnostic rate was 9.3%, and omission diagnostic rate was18.8%,and positive predictive value was 83.87%,and positive likelihood ratio was8.775,and diagnostic odd ratio was 42.47.The Kappa value was 0.725 between CFF and PHES.The area under the ROC curve was 0.849.(3) In the total 86 cirrhosis patients,there were 31 patients in CFF(+) group and 55 patients in CFF(-) group.The sex(male41.15±4.56 Hz,female39.64±3.26 Hz,t=1.566,P=0.124)、age(r=-0.191,P=0.078)、education(F=2.315,P=0.082)and course of cirrhosis(F=1.243,P=0.299)were not significance in MHE compared to the non-MHE group.(4) Compared to non-MHE patients,MHE patients had significant different of S100 B protein(t=-2.171,P=0.030)、NSE(t=2.270,P=0.028)、total bilirubin(t=-4.449,P=0.000)、albumin(t=-5.564,P=0.000)、Cholinesterase(t=-4.607,P=0.000)、Prothrombin time(t=4.619,P=0.000)、Prothrombin activity(t=-4.729,P=0.000)、International normalized ratio(t=4.622,P=0.000)、ammonia(t=2.842,P=0.007).Conclusions:(1) MHE patients have higher incidence when they get higher score of Child-Pugh and MELD, and were appeared ascites or hepatic encephalopathy.(2) CFF has certain diagnostic value with sensitivity of 81.25% and specificity of90.74%,as well as,the area under the ROC curve of 0.849.CFF is a simple and reliable parameter for quantification of MHE in cirrhotic patients.It is not influenced by gender,age,education and cirrhosis etiology.(3) It is feasible that S100 B protein and NSE would provide reference basis for early diagnosis of MHE,because they were high expression in MHE group compared with non-MHE group.