Clinical Application Of Serological Examination In The Diagnosis Of HBV-related Liver Fibrosis

Objective:Study 1:To evaluate the value of APRI、FIB-4、GPR and S index in the diagnosis of HBV-related liver fibrosis by collecting and collating the clinical data of chronic HBV-infected patients who underwent liver biopsy in the infection department of our hospital.Study 2:To detect CHI3L1 and to analyze the ability of CHI3L1 and FIB-4 in the diagnosis of liver fibrosis by collecting patients’ clinical data and serum.The purpose of both studies is to find serological indicators that can replace the role of liver biopsy and elastography in HBV-related liver fibrosis.Methods:A total of 125 patients with chronic HBV infection were included in the study 1 and the subjects were from the Department of Infectious Disease,the first affiliated Hospital of Kunming Medical University,who were hospitalized with biopsy from January 2017 to December 2019.The sex,age,hepatitis B surface antigen,surface antibody,e antigen,e antibody,HBVDNA,albumin,alanine aminotransferase,aspartate aminotransferase,γ-gamma glutamyl transpeptidase,total bilirubin,direct bilirubin,PT,INR,platelet were counted.Pearson correlation analysis was used to analyze the relationship between routine serological indexes and non-invasive diagnostic model,and Spearman correlation analysis was used to analyze the relationship between serological indexes,non-invasive diagnostic model and the degree of inflammation and fibrosis of liver tissue.The working curve of the subjects was drawn,and the corresponding sensitivity,specificity,PPV and NPV were calculated to evaluate the application value of APRI、FIB-4、GPR and S index in HBV-related liver fibrosis.In study 2,there were 44 patients with chronic hepatitis B and 92 patients with liver cirrhosis.The clinical data,such as sex,age,ALB,AST,ALT and so on were collected,and the serum of the patients was retained.The content of CHI3L1 was determined by ELISA test,the working curve of the subjects was drawn,and the value of CHI3L1 in the diagnosis of liver cirrhosis was analyzed.Results:Study 1:1.125 patients with chronic HBV infection,including 77 males(61.60%)and 48 females(38.40%),with an average age of(35.64±8.97)years,including 107 cases of S0-S1 and cases of S2-S4.2.In the correlation analysis,ALT,AST,GGT,PT are positively correlated with APRI,FIB-4,GPR,S index(P<0.05),PLT is negatively correlated with APRI,FIB-4,GPR,S index(P<0.05);ALT,AST,APRI are positively correlated with the degree of liver inflammation(P<0.05);ALB and PLT are negatively correlated with the degree of hepatic fibrosis(P<0.05),while age,ALT,GGT,PT,INR,APRI,FIB-4,GPR,S index are positively correlated with the degree of liver fibrosis(P<0.05).3.When APRI,FIB-4,GPR and S index are used to diagnose liver fibrosis,the AUROC are 0.769,0.789,0.849 and 0.883 respectively.When the area under the curve is compared,the predictive value of S index is higher than that of the other three(P<0.05).4.In pairwise diagnosis of non-invasive diagnostic model,the comprehensive effect of GPR+S index is the best,and its AUROC,sensitivity,specificity,PPV,NPV and accuracy are 0.919,0.944,0.794,0.821,0.934 and 0.869,respectively.5.When multiple non-invasive indexes are combined,the diagnostic effect of FIB-4+GPR+S index is the best,and its AUROC,sensitivity,specificity,PPV,NPV and accuracy are 0.912,0.944,0.785,0.814,0.933 and 0.865 respectively.When APRI,FIB-4,GPR and S index are used together,the AUROC,sensitivity,specificity,PPV,NPV and accuracy are 0.914,1.000,0.673,0.754,1.000 and 0.837 respectively.Study 2:1.There are 44 patients with chronic hepatitis B,with an average age of(38.18±10.87)years and 29 males(65.90%).There are 92 patients with liver cirrhosis,with an average age of(52.74±10.75)years and 68 males(73.90%).There is no significant difference in gender between the two groups(P>0.05),but significant difference in age(P<0.05).2.In the correlation analysis,CHI3L1 has no correlation with ALT and PLT(P>0.05),but has correlation with age,AST,TBIL,DBIL and ALB,with correlation coefficients of 0.397,0.331,0.367,0.386 and-0.356 respectively.ALT,AST and APRI have no correlation with liver cirrhosis(P>0.05),while age,TBIL,DBIL,CHI3L1 and FIB-4 are positively correlated with liver cirrhosis(P<0.05),while ALB and PLT are negatively correlated with liver cirrhosis(P<0.05).3.CHI3L1,FIB-4,CHI3L1+FIB-4 in the diagnosis of liver metastases,CHI3L1 is the most effective.Its AUROC,sensitivity,specificity,PPV,NPV and accuracy are 0.797,0.848,0.705,0.742,0.823,0.777,respectively.4.When AST<2ULN,CHI3L1 has the best diagnostic efficiency,and its AUROC,sensitivity,specificity,PPV,NPV and accuracy are 0.811,0.884,0.727,0.764,0.862 and 0.806 respectively.AST≥ 2ULN,CHI3L1+FIB-4 have the best diagnostic efficiency,and their AUROC,sensitivity,specificity,PPV,NPV and accuracy are 0.822,0.687,0.957,0.727,0.778,0.994 and 0.842 respectively.Conclusions:1.In a single noninvasive serological diagnostic model,S index has the best diagnostic efficiency,GPR is the next;2.When the non-invasive serological diagnosis model is combined,the predictive efficiency of GPR+S index is the best,followed by APRI+S index and FIB-4+S index;3.When multiple non-invasive serum diagnostic models are combined,FIB-4+GPR+S index have the best diagnostic efficiency,while when four non-invasive diagnostic models of APRI+FIB-4+GPR+S index are combined,the sensitivity and negative predictive value could reach 100%;4.CHI3L1 has a strong diagnostic ability in the diagnosis of cirrhosis;5.AST is a confounding factor of CHI3L1 in the diagnosis of cirrhosis.When AST<2ULN,CHI3L1 still has the best diagnostic ability,and when AST≥2ULN,CHI3L1+FIB-4 has the best diagnostic ability.