Abstract: Objective To investigate the changes of serum tissue matrix metalloproteinase inhibitor-1 (TIMP-1) and macrophage colony stimulating factor (M-CSF) levels in patients with chronic hepatitis B (CHB) treated with long-term antiviral therapy.Methods Between April 2017 and February 2019, 148 patients with CHB admitted to our hospital were the subjects of study and received continuous antiviral therapy for 2 years. The changes of serum TIMP-1 and M-CSF levels before and after treatment were observed. The occurrence of liver cirrhosis in CHB patients was counted and divided into an occurrence group and a non-occurring group according to whether or not liver cirrhosis occurred. The clinical data of patients in the occurrence group and the non-occurrence group were compared. Logistic multivariate regression analysis of factors affecting the occurrence of liver cirrhosis in patients with CHB. A receiver operating characteristic curve (ROC) was made, and the area under the curve (AUC) was used to evaluate the predictive power of changes in serum TIMP-1 and M-CSF on the occurrence of liver cirrhosis in patients with CHB.Results Compared with 1 day before treatment, serum TIMP-1 and M-CSF of CHB patients were reduced after 6 months after treatment (P<0.05), and ΔTIMP-1 and ΔM-CSF were (56.6± 8.3) μg/L, (62.5±9.2) ng/L. The incidence of liver cirrhosis after 2 years of treatment was 24.32%. The occurrence group alanine aminotransferase (ALT), hepatic portal vein diameter, liver elasticity value (LSM), TIMP-1, TIMP-1 after 6 months of treatment, and M-CSF after 6 months of treatment were all higher than those of the non-occurring group (P<0.05), ΔTIMP-1 and ΔM-CSF were lower than those in the non-occurring group (P<0.05). Logistic regression analysis showed that LSM, ΔTIMP-1 and ΔM-CSF were all risk factors affecting liver cirrhosis in patients with CHB (OR=2.732, 3.040, 3.330, P<0.05). ROC analysis showed that the best cut-off points of serum ΔTIMP-1 and ΔM-CSF for predicting the occurrence of liver cirrhosis in CHB patients were 50.9 μg/L and 61.4 ng/L, respectively, the sensitivity was 80.6%, 72.2%, and the specificity was 75.9%, 80.4%, and the AUC were 0.848 and 0.809, respectively.Conclusion Serum ΔTIMP-1 and ΔM-CSF have higher predictive power in predicting the occurrence of liver cirrhosis in CHB patients, and can be used as important reference indexes of whether CHB patients have liver cirrhosis. .

Key words: Chronic hepatitis B, Antiviral therapy, Tissue matrix metalloproteinase inhibitor-1, Macrophage colony stimulating factor