Clinical Value Of Non-invasive Examination In Evaluating The Degree Of Steatosis Inflammation And Fibrosis In Non-alcoholic Fatty Liver Disease

Objective In this study,98 patients with non-alcoholic fatty liver disease(NAFLD)who were first diagnosed by B-ultrasound were studied to analyse the factors related to the progression of NAFLD steatosis,inflammation and hepatic fibrosis,and the clinical value of various noninvasive examinations in evaluating the degree of NAFLD steatosis,inflammation and hepatic fibrosis.Methods 98 patients with NAFLD who were first diagnosed by B-ultrasound were selected from Tianjin third Central Hospital,since July 2018 to March 2019.The demographic characteristics(gender,age,personal habits and personal history of diseases),physical examination(height,weight,BMI,waist circumference,blood pressure,grip strength),laboratory tests(blood count,liver function,renal function,fasting blood glucose,blood lipid),imaging examination(liver plain scan CT,Fibrotouch and body composition measurement)were collected and sorted out.The degrees of hepatic steatosis were divided according to CT and CAP,respectively;the degrees of hepatic inflammation were divided according to ALT level;the degrees of hepatic fibrosis were divided according to LSM value.The data were statistically analyzed by SPSS V25.0 software to explore the factors related to the progression of NAFLD steatosis,inflammation and hepatic fibrosis,and the clinical value of various noninvasive examinations in evaluating the degree of NAFLD steatosis,inflammation and hepatic fibrosis.Results 1.In 98 patients with NAFLD who were first diagnosed by B-ultrasound,there were 68 cases(70.4%),21 cases(21.4%)and 9 cases(9.2%)in mild,moderate and severe NAFLD steatosis diagnosed by CT;there were 4 cases(4.1%),13 cases(13.3%),25 cases(25.5%)and 56 cases(57.1%)in normal,mild,moderate and severe NAFLD steatosis diagnosed by CAP.The sensitivity and specificity of CAP for the diagnosis of mild,moderate,severe,moderate-severe steatosis were: 17.6% and 96.7%,14.3% and 71.4%,66.7% and 43.8%,96.7% and 23.5%,respectively,as CT was the “gold standard” for the diagnosis of NAFLD steatosis.There was a correlation between CAP and CT in the diagnosis of moderate-severe NAFLD steatosis(r=0.246,P =0.015).CAP can accurately diagnose moderate-severe steatosis(P<0.05),the cut-off value was 279.5 dB/m,sensitivity was 0.90,specificity was 0.41 and AUROC was 0.650.2.When CT was used to diagnose the steatosis degrees of NAFLD,the ALT,AST,GGT,CAP and LSM value were significantly different(P<0.05)and related(P<0.05)with the steatosis degrees of NAFLD.The ALT,AST,GGT,CAP and LSM value were positively correlated with the steatosis degrees of NAFLD,because theirs r>0.The diagnosis of mild NAFLD steatosis: there were no significant difference in ALT,AST,GGT,LSM value(AUROC<0.5);the diagnosis of moderate NAFLD steatosis: there were no significant difference in area under the curve of ALT,AST,GGT,LSM value(AUROC>0.5,P>0.05);the diagnosis of severe NAFLD steatosis: there was no significant difference in area under the curve of GGT(AUROC>0.5,P>0.05),there were significant difference in area under the curve of ALT,AST,LSM value(AUROC>0.5,P<0.05),the diagnostic accuracy of AST(AUROC=0.752)was the highest,followed by ALT(AUROC=0.745)and LSM value(AUROC=0.723).3.When CAP was used to diagnose the steatosis degrees of NAFLD,weight,BMI,waist circumference,MetS,ALT,AST,GGT,LDL,liver CT value / spleen CT value ratio,LSM value,VAT,FM and SMM were significantly different(P<0.05)and related(P<0.05)with the steatosis degrees of NAFLD.The weight,BMI,waist circumference,MetS,ALT,AST,GGT,LDL,LSM value,VAT,FM and SMM were positively correlated with the steatosis degrees of NAFLD because theirs r>0,while the liver CT value / spleen CT value ratio was negatively correlated with the steatosis degrees of NAFLD because theirs r<0.The diagnosis of mild and moderate NAFLD steatosis: there were no significant difference in weight,BMI,waist circumference,ALT,AST,GGT,LDL,LSM value,VAT,FM and SMM(AUROC<0.5);the diagnosis of severe NAFLD steatosis: there were significant difference in area under curve of weight,BMI,waist circumference,ALT,AST,GGT,LDL,LSM value,VAT,FM and SMM(AUROC>0.5,P<0.05),the diagnostic accuracy of BMI(AUROC=0.752)was the highest,followed by weight(AUROC=0.693),GGT(AUROC=0.691),waist circumference(AUROC=0.679),LSM value(AUROC=0.675),LDL(AUROC=0.667),SMM(AUROC=0.659),FM(AUROC=0.658),VAT(AUROC=0.651),ALT(AUROC=0.639),AST(AUROC=0.627).4.The average levels of ALT in normal ALT group and abnormal ALT group were 25.0(19.0,34.0)U/L and 80.0(54.5,105.9)U/L,respectively.The AST,GGT,FBG,liver CT value / spleen CT value,FM,FMI,AST/ALT,APRI score,BARD score and BAAT score were significantly different(P<0.05)and related(P<0.05)with whether ALT was abnormal or not.The AST,GGT,FBG,FM,FMI,APRI score and BAAT score were positively correlated with the abnormal of ALT because theirs r>0,while the liver CT value / spleen CT value ratio,AST/ALT and BARD score were negatively correlated with the abnormal of ALT because theirs r<0.The diagnosis of abnormal ALT: there were no significant difference in liver CT value / spleen CT value ratio,AST/ALT ratio,BARD score(AUROC<0.5);there were significant difference in area under curve of AST,GGT,FBG,LSM value,FM,FMI,APRI score and BAAT score(AUROC>0.5,P<0.05),the diagnostic accuracy of AST(AUROC=0.953)was the highest,followed by APRI score(AUROC=0.909),GGT(AUROC=0.815),LSM value(AUROC=0.699).FBG(AUROC=0.678),FMI(AUROC=0.647),BAAT score(AUROC=0.641)and FM(AUROC=0.635).5.In 98 patients with NAFLD who were first diagnosed by B-ultrasound,there were 58 cases(59.2%)in F0 fibrosis,19 cases(19.4%)in F1 fibrosis,15 cases(15.3%)in F2 fibrosis,5 cases(5.1%)in F3 fibrosis and 1 cases(1%)in F4 fibrosis.Among them,there were 40 cases(40.8%)of hepatic fibrosis(≥F1),21 cases(21.4%)of significant fibrosis(≥F2)and 6 cases(6.1%)of advanced fibrosis(≥F3).6.The BMI,waist circumference,diabetes mellitus,ALT,AST,GGT,DBIL,FBG,CAP,liver CT value/ spleen CT value ratio,VAT,FM,FMI,ALT/ULN ratio,AST/ULN ratio,GGT/ULN ratio,FIB-4 score,APRI score and BAAT score were significant difference between the patients with and without hepatic fibrosis(P<0 05).Except the liver CT value / spleen CT value ratio,the other indexes were correlated with NAFLD hepatic fibrosis(P<0.05),and all the correlation indexes were positively correlated with NAFLD hepatic fibrosis because theirs r>0.The diagnosis of NAFLD with hepatic fibrosis: there were significant difference in area under curve of BMI,waist circumference,ALT,AST,GGT,DBIL,FBG,CAP value,VAT,FM,FMI,ALT/ULN ratio,AST/ULN ratio,GGT/ULN ratio,FIB-4 score,APRI score and BAAT score(AUROC>0.5,P<0.05),the diagnostic accuracy of AST(AUROC=0.757)was the highest,followed by AST/ULN ratio(AUROC=0.752),APRI score(AUROC=0.717),GGT/ULN ratio(AUROC=0.708),ALT/ULN ratio(AUROC=0.706),ALT(AUROC=0.716),FM(AUROC=0.697),FMI(AUROC=0.694),BMI(AUROC=0.686),GGT(AUROC=0.684),BAAT score(AUROC=0.68),waist circumference(AUROC=0.677),FBG(AUROC=0.67),VAT(AUROC=0.662),DBIL(AUROC=0.656),FIB-4 score(AUROC=0.638),CAP value(AUROC=0.633).7.The sex,age,BMI,waist circumference,diabetes mellitus,ALT,AST,FBG,TC,CAP,liver CT value / spleen CT value ratio,FM,FMI,ALT/ULN ratio,AST/ULN ratio,GGT/ULN ratio,FIB-4 score,NFS score and APRI score were significant difference between the significant hepatic fibrosis and the non-significant hepatic fibrosis(P<0.05).Except the BMI,waist circumference and TC and CAP,the other indexes were correlated with NAFLD significant hepatic fibrosis(P<0 05),the liver CT value / spleen CT value ratio was negatively correlated with NAFLD significant hepatic fibrosis because theirs r<0,while the other correlation indexes were positively correlated with NAFLD significant hepatic fibrosis because theirs r>0.The diagnosis of NAFLD significant hepatic fibrosis: the liver CT value / spleen CT value ratio was not significant(AUROC<0.5);there were no significant difference in area under the curve of BMI,waist circumference,TC,CAP value(AUROC>0.5,P>0.05),but there were significant difference in area under the curve of age,ALT,AST,FBG,FM,FMI,FIB-4 score,NFS score and APRI score(AUROC>0.5,P<0.05),the diagnostic accuracy of AST/ULN ratio(AUROC=0.851)was the highest,followed by AST(AUROC=0.842),APRI score(AUROC=0.816),ALT/ULN ratio(AUROC=0.796),ALT(AUROC=0.791),FIB-4 score(AUROC=0.742),FMI(AUROC=0.719),FBG(AUROC=0.717),age(AUROC=0.701),FM(AUROC=0.688),NFS score(AUROC=0.680),GGT/ULN ratio(AUROC=0.656).8.The sex,age,waist circumference,MetS,ALT,AST,TBIL,FM,FMI,FIB-4 score,NFS score,APRI score and BAAT score were significant differences between advanced hepatic fibrosis and non-advanced hepatic fibrosis(P<0.05).All the other indexes except waist circumference were correlated with NAFLD advanced hepatic fibrosis(P<0.05),all the correlation indexes were positively correlated with NAFLD advanced hepatic fibrosis because theirs r>0.The diagnosis of NAFLD advanced liver fibrosis: there were no significant difference in area under the curve of waist circumference,GGT/ULN ratio,BAAT score(AUROC>0.5,P>0.05);there were significant difference in area under the curve of age,ALT,AST,TBIL,FM,FMI,ALT/ULN ratio,AST/ULN ratio,FIB-4 score NFS score and APRI score(AUROC>0.5,P<0.05),the diagnostic accuracy of AST/ULN ratio(AUROC=0.901)was the highest,followed by AST(AUROC=0.896),APRI score(AUROC=0.892).FIB-4 score(AUROC=0.884),ALT/ULN ratio(AUROC=0.874),ALT(AUROC=0.842),TBIL(AUROC=0.811),NFS score(AUROC=0.807),age(AUROC=0.796),FMI(AUROC=0.788),FM(AUROC=0.763).Conclusions 1.CAP overestimates the degrees of NAFLD steatosis,with the aggravation of NAFLD steatosis,the sensitivity increases,but the specificity decreases when CAP is used to diagnose the degrees of NAFLD steatosis.CAP is consistent with CT in the diagnosis of moderate-severe NAFLD steatosis.With the aggravation of NAFLD steatosis,the level of hepatic inflammation and the degree of hepatic fibrosis may increase.when CT is used to diagnose the degrees of NAFLD steatosis,ALT,AST and LSM value are helpful in the diagnosis of severe NAFLD steatosis;when CAP is used to diagnose the degrees of NAFLD steatosis,weight,BMI,waist circumference,ALT,AST,GGT,LDL,LSM value,VAT,FM,SMM are helpful in the diagnosis of severe NAFLD steatosis.2.With the aggravation of liver inflammation in NAFLD,the degree of hepatic fibrosis may increase.When ALT is used to diagnose the degree of NAFLD inflammation,AST,GGT,FBG,LSM value,FM,FMI,APRI score and BAAT score are helpful in the diagnosis of NAFLD inflammation.3.Age,female,the increased inflammatory levels and metabolic disorder(combined with obesity,diabetes and MetS)may be risk factors for the progression of NAFLD hepatic fibrosis.When LSM value is used to diagnose the degree of NAFLD hepatic fibrosis,BMI,waist circumference,ALT,AST,GGT,DBIL,FBG,CAP,VAT,FM,FMI,ALT/ULN ratio,AST/ULN ratio,GGT/ULN ratio,FIB-4 score,APRI score and BAAT score are helpful in the diagnosis of NAFLD hepatic fibrosis;age,ALT,AST,FBG,FM,FMI,FIB-4 score.NFS score and APRI score are helpful in the diagnosis of NAFLD significant hepatic fibrosis;age,ALT,AST,TBIL,FM,FMI,ALT/ULN ratio,AST/ULN ratio,FIB-4 score,NFS score and APRI score are helpful in the diagnosis of NAFLD advanced hepatic fibrosis.