The Predictive Value Of CHI3L1 Combined With Th17/Treg For The Degree Of HBV-related Liver Fibrosis

BackgroundChronic hepatitis B（CHB）is a contagious viral hepatitis caused by persistent infection with the hepatitis B virus（HBV）.HBV infection is a dynamic process in which HBV interacts with the body’s adaptive immune response.The natural course of most CHB patients can be divided into the immune tolerance stage,immune clearance stage,immune control stage,and reactivation stage^[1,2].There are about 20to 30 million patients with CHB in China^[3].CHB is prone to develop into liver fibrosis,which is histologically reversible to a certain extent.However,if not detected and controlled promptly,it can further develop into liver cirrhosis or even hepatocellular carcinoma（HCC）,seriously threatening the lives and health of patients,and causing an economic burden to the country.Therefore,early diagnosis of HBV-related liver fibrosis is of great significance.ObjectiveTo determine the predictive value of Chitinase 3-like protein 1（CHI3L1）combined with Th17/Treg and compare the efficacy of the existing testing methods for the diagnosis of HBV-related liver fibrosis.Method246 patients with CHB who were treated at the second affiliated hospital of Nanchang university from November 2021 to February 2023 were collected.The liver stiffness（LSM）of CHB patients was divided into groups based on the Fibro Scan Pro.117 patients were in the non or mild liver fibrosis group（LSM<7.3k Pa;Group A）,57 patients were in the significant liver fibrosis group（7.3 k Pa≤LSM<12.4 k Pa;Group B）,25 patients were in the progressive liver fibrosis group（12.4 k Pa≤LSM<17.5 k Pa;Group C）and 47 patients were in the liver cirrhosis group（LSM≥17.5k Pa;Group D）.The level of CHI3L1 in CHB patients in each group was detected by the immunochemiluminescence method.In 39 patients with CHB,we simultaneously used flow cytometry to detect the percentage of peripheral blood Th17 cells and regulatory T cells（Treg）in peripheral blood CD4⁺T cells（Th17%and Treg%,respectively）,and the ratio of the two（Th17/Treg）.This part included 14 patients with no or mild liver fibrosis（LSM<7.3 k Pa;CHB-L）,and 25patients with moderate to severe liver fibrosis（7.3 k Pa≤LSM<17.5 k Pa;CHB-MS）.Statistical analysis was conducted on general clinical data,biochemical indicators,serum CHI3L1 level,Th17%,Treg%,and Th17/Treg in each group.The predictive value of various liver fibrosis indicators for the degree of HBV-related liver fibrosis was evaluated by ROC curves.Result1.The serum CHI3L1 level of patients in Group A was 40.33（29.95,57.52）ng/m L,Group B was 52.96（38.26,80.35）ng/m L,Group C was 92.28（47.89,163.67）ng/m L,and Group D was 153.63（92.39,224.86）ng/m L.There were significant differences between Group A and Group B（P=0.040）,Group C（P<0.0001）,and Group D（P<0.0001）;there was a significant difference between Group B and Group D（P<0.0001）.2.The peripheral blood Th17%of patients in the CHB-L group was 8.28（5.43,9.88）,and that in the CHB-MS group was 9.55（6.97,10.28）,with no statistical difference（P=0.286）;Treg%was 0.67（0.57,0.97）in the CHB-L group while that was 0.26（0.01,0.88）in the CHB-MS group,with a statistically significant difference（P=0.039）;Th17/Treg was 10.00（7.43,20.50）in the CHB-L group and that was61.26（9.777,88.50）in the CHB-MS group,with a statistically significant difference（P=0.010）.3.The AUC value of CHI3L1 for predicting significant and above HBV-related liver fibrosis was 0.774,with sensitivity and specificity of 67.69%and 77.32%,respectively;the AUC value of Th17/Treg was 0.750,with sensitivity and specificity of 60.00%and 94.12%,respectively;the AUC value of liver fibrosis combination（HA+LN+PCIII+CIV）+CG was 0.736,with sensitivity and specificity of 85.60%and 58.10%,respectively;the AUC value of CHI3L1 combined with Th17/Treg was0.814,with sensitivity and specificity of 100%and 92.90%,respectively.ConclusionWith the increase in the degree of HBV-related liver fibrosis,the level of serum CHI3L1 gradually increased;Peripheral blood Treg%decreased and Th17/Treg increased.CHI3L1 combined with Th17/Treg has a good predictive value for significant and above HBV-related liver fibrosis.