| Objective: In the natural course of chronic hepatitis B(CHB)and under different treatment regimens,hepatitis B surface antigen(HBs Ag)exhibits different kinetics,and the relationship between different HBs Ag kinetics and clinical prognosis of hepatitis B-related diseases is not currently.There are insufficient clinical data on the relationship between different HBs Ag kinetics and clinical prognosis of hepatitis B-related diseases.It is known that patients with Low-Level Viremia(LLV)have a higher risk of end-stage liver diseases and LLV is the independent risk factor for the development of end-stage liver diseases,and it remains to be studied whether different HBs Ag kinetics of LLV have different probabilities of occurrence and risk factors for the development of LLV.The aim of this study was to analyze the factors influencing HBs Ag kinetics and compare the clinical outcomes of patients with different HBs Ag kinetics,and to analyze the correlation between LLV and HBs Ag kinetics and the factors associated with the occurrence of LLV.Methods: This study is a retrospective longitudinal study,and a total of 409 patients with CHB with a definite diagnosis and >12 months of treatment who were seen between 2013 and 2022 in two centers were collected,and the included patients were on regular medication and had regular outpatient follow-up,and the primary endpoint event was defined as the occurrence of end-stage liver diseases(including decompensated cirrhosis and hepatocellular liver cancer(HCC)in patients after 3 years of antiviral therapy.Patients were divided into HBs Ag rising group,HBs Ag fluctuating group,and HBs Ag declining group according to the HBs Ag kinetics at 12 months of treatment in each patient,and the HBs Ag rising group and HBs Ag fluctuating group were defined as HBs Ag non-declining group according to the purpose of the study.And the clinical indexes were collected and the clinical outcomes after 3 years were counted,and the influencing factors of HBs Ag kinetics were analyzed by χ2 test and K-W test,and the correlation between HBs Ag kinetics and clinical prognosis was analyzed by χ2 test,while the patients were divided into LLV group and maintained virological response(MVR)group according to HBV DNA level.The analysis of clinical indexes between the two groups by Mann-Whitney rank sum test,the risk factors for the occurrence of LLV by logistic regression analysis,and the correlation between LLV and HBs Ag kinetics by χ2 test.Results.1.the 3-year cumulative incidence of end-stage liver diseases was higher in the HBs Ag rising group(63.9%)than in the HBs Ag fluctuating group(34.9%)and HBs Ag declining group(13.8%),and the differences were statistically significant(all P < 0.01).2.The rate of NAs use in the HBs Ag non-declining group(86.3%)was higher than that in the HBs Ag declining group(70.1%),and the difference was statistically significant(P<0.01),and the rate of combination drug use in the HBs Ag declining group(25.3%)was higher than that in the HBs Ag non-declining group(10.2%),and the difference was statistically significant(P<0.01).The rate of combined medication in the HBs Ag fluctuating group(12.6%)was higher than that in the HBs Ag rising group(0%),and the difference was statistically significant(P<0.01).And the rate of drug change in the HBs Ag declining group(42.5%)was higher than that in the HBs Ag fluctuating group(26.8%)and HBs Ag rising group(6.6%),and the difference was statistically significant(both P<0.01).3.The proportion of patients with other diseases combined in the HBs Ag non-declining group(97.2%)was higher than that in the HBs Ag declining group(90.9%),and the difference was statistically significant(P=0.015).The mean age of patients in the HBs Ag fluctuating group(51 years)was significantly higher than that in the HBs Ag rising group(44 years)and the HBs Ag declining group(43 years),and the difference was statistically significant(P<0.01).However,the difference in age distribution between the HBs Ag rising group and HBs Ag falling group was not statistically significant(P=0.886).4.The incidence of LLV in the HBs Ag rising group(42.3%)was significantly higher than that in the HBs Ag non-rising group(20.1%)The difference was statistically significant(P<0.01).5.HBs Ag quantification,ALT,Aspartate aminotransferase(AST),Alkaline phosphatase(ALP),Glutamyl transpeptidase(GGT)and HBV DNA was significantly higher in the MVR group(P<0.05),while serum albumin(ALb)was significantly lower than in the MVR group(P<0.05).Multifactorial regression analysis revealed that patients with low ALP levels(<100 U/l)and low HBV DNA levels(<6log10IU/ml)at baseline were less likely to develop LLV(OR=0.467,95% CI=0.248-0.877,P=0.018;OR=0.158,95% CI=0.074-0.319,P=0.000).It indicates that high ALP levels(≥100 U/l)and high HBV DNA levels(≥6log10IU/ml)are independent risk factors for the development of LLV.Conclusion.1.HBs Ag in patients with combined other underlying diseases and high age are not easy to achieve a decrease after antiviral therapy.Combination of drugs,timely adjustment of interferon or NAs application according to changes in disease are more likely to achieve HBs Ag decline.2.Patients with an increasing trend in HBs Ag kinetics are more likely to have LLV,which is likely to occur in patients with high baseline ALP levels and HBV DNA levels,suggesting that we should pay sufficient attention to this group of patients in clinical work,closely monitor changes in their condition and adjust treatment regimens when necessary.3.HBs Ag kinetics are related to the clinical prognosis of hepatitis B patients,and an increasing trend of HBs Ag predicts a higher likelihood of end-stage liver diseases and a poorer prognosis. |
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