Abstract: Objective To explore the clinical value of the chitinase-3-like protein 1(CHI3L1), Golgi protein 73 (GP73) and four items of liver fibrosis- hyaluronicacid(HA),laminin(LN),type Ⅲ procollagen peptide (PⅢP) and collagen type Ⅳ(CⅣ) in diagnosing early liver fibrosis in patients with the chronic hepatitis B (CHB). Methods A total of 295 patients with CHB who underwent liver biopsy at Mengchao Hepatobiliary Hospital of Fujian Medical University from January 2018 to January 2024 were included in this study.Based on liver histopathological staging, the patients were divided into five stages: S0 (n=26), S1 (n=112), S2 (n=63), S3 (n=54), and S4 (n=40).The correlation between (CHI3L1 ,GP73) and (HA,LN,PⅢNP,CⅣ) was anlyzed. Receiver operating characteristic (ROC) curve of CHI3L1,GP73,HA,LN,PⅢNP and CⅣ and their combined detection value in the different fibrosis(S1/S0,S2/S1,S3/S2) were analyzed. Results The serum levels of CHI3L1,GP73,HA,LN,PⅢNP and CⅣ increased with their progress of liver fibrosis (Z=82.926,37.635,22.441,33.136,49.484,53.823,P<0.001),There was no significant difference between the groups of S1 and S0 stage on various indicators. There were significant differences between the groups of S1 and S2 stage on CHI3L1、GP73、HA and LN (Z=-4.278,-3.389,-3.114,-0.331,P<0.05). There were significant differences between the groups of S3 and S2 stage on CHI3L1,GP73,PⅢNP and CⅣ (Z=-2.856, -1.976, -2.365, -3.020,P<0.05). There was significant difference between the groups of S4 and S3 stage only on PⅢNP[39.60 (28.27,71.20) vs. 28.64(19.66,55.20),Z=-2.119,P<0.05].Pearson correlation analysis showed that the levels of CHI3L1 and GP73 were positively correlated with HA,LN,PⅢNP and CⅣ levels(r=0.289,0.372,0.326,0.341,P<0.01)and (r=0.365,0.400,0.510,0.543,P<0.01) respectively;CHI3L1 level was positively correlated with GP73 (r=0.39,P<0.01).The area under curve (AUC) of CH3L1,GP73,HA,LN,PⅢNP and CⅣ and their combined detection in the diagnosis of (S1/S0,S2/S1,S3/S2) stages were (0.478,0.508,0.441,0.570,0.544,0.410,0.689),(0.684,0.682,0.603,0.674,0.580,0.570,0.756)and(0.759,0.711,0.610,0.651,0.723,0.745,0.847) respectively.In S1 stage, AUC of all items were lower than 0.55 (0.478,0.508,0.441,0.570,0.544 ,0.410),which had no diagnostic value for S1. However, the combined detection yielded an AUC of 0.689, providing some reference value for predicting S1. In S2 stage,the size of AUC of these items were CHI3L1＞GP73＞LN＞HA＞PⅢNP＞CⅣ(0.684,0.682,0.674,0.603,0.580,0.570)and only the first 3 items were higher than 0.61,and AUC,sensitivity,specificity and Youden index of their combined items were 0.75,93.0%,46.7% and 0.397,which had good valuable for prediction of S2.In S3 stage,the size of AUC of these items were CHI3L1＞CⅣ＞PⅢNP＞GP73＞LN＞HA (0.759,0.745,0.723,0.711,0.651,0.610), and all items were higher than 0.6,and AUC,sensitivity,specificity and Youden index of their combined items were 0.847,92.5%,70.7% and 0.632,and both single and combined items were all valuable for prediction of S3. Conclusion With the progression of liver fibrosis, the serum levels of CHI3L1,GP73 and four items progressively increased.TAmong individual biomarkers, CHI3L1 exhibits the highest diagnostic efficacy for early liver fibrosis, followed by GP73 and the four liver fibrosis markers. Clinical diagnostic value of combined detection was superior to the single detection in the diagnosis of early liver fibrosis with CHB and can enhance the detection of early liver fibrosis up to the S1 stage.

Key words: Chronic hepatitis B, Chitinase-3-like protein 1, Golgi protein 73, Four items of liver fibrosis, Early liver fibrosis, Clinical diagnostic value