Dynamic changes of HBsAg and hepatitis B virus DNA in chronic hepatitis B patients with entecavir monotherapy for 5 years / 临床肝胆病杂志

ABSTRACT

ObjectiveTo investigate the dynamic changes of serum HBsAg and hepatitis B virus (HBV) DNA in chronic hepatitis B patients (CHB) with entecavir (ETV) monotherapy for 5 years. MethodsA retrospective analysis was performed for the clinical data of 918 CHB patients who attended the Second Affiliated Hospital of Xi’an Jiaotong University from January 2012 to August 2020 and received ETV monotherapy for ≥5 years, among whom 556 had positive HBeAg and 362 had negative HBeAg at initial treatment. Serum HBsAg level and HBV DNA load at baseline and at 1, 2, 3, 4, and 5 years of treatment were collected to analyze their dynamic changes. The t-test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups; log10 logarithmic transformation was performed for non-normally distributed repeated measurement data, and then a repeated-measures analysis of variance was used for comparison between groups or within each group; the chi-square test was used for comparison of categorical data between two groups. ResultsBoth HBeAg-positive and HBeAg-negative patients had a significant reduction in HBsAg level over the time of ETV treatment (F=174.168 and 49.845, both P＜0.001). The HBeAg-positive patients had a baseline HBsAg level of 18 043.1 (7868.9-26 342.4) IU/ml, which significantly decreased to 13976 (626.4-3419.4) IU/ml after 5 years of ETV treatment (P＜0.001); the HBeAg-positive patients had a baseline HBV DNA load of (67±1.7) log10 IU/ml and achieved an HBV DNA clearance rate of 100% after 5 years of ETV treatment. The HBeAg-negative patients had a baseline HBsAg level of 2420.0 (662.6-5621.2) IU/ml, which significantly decreased to 407.2 (56.7-1104.7) IU/ml after 5 years of ETV treatment (P＜0.001); the HBeAg-negative patients had a baseline HBV DNA load of 4.9±1.4 log10 IU/ml and achieved an HBV DNA clearance rate of 100% after 5 years of ETV treatment. The HBeAg-positive patients had a significantly higher median HBsAg level than the HBeAg-negative patients at each time point (all P＜0.001). Both HBeAg-positive and HBeAg-negative patients showed a changing trend of rapid reduction followed by slow reduction in HBsAg, and the mean annual rate of reduction in HBsAg in the first 2 years of ETV treatment was significantly higher than that in the last 3 years of ETV treatment (HBeAg-positive: Z=-13.605, P＜0001; HBeAg-negative: Z=-5.950, P＜0.001). The HBeAg-positive patients had a significantly lower HBV DNA clearance rate than the HBeAg-negative patients at 1 year of ETV treatment (χ2=71.013, P＜0.001), and both HBeAg-positive and HBeAg-negative patients achieved an HBV DNA clearance rate of 100% at 2, 3, 4, and 5 years of treatment. After 5 years of ETV treatment, the cumulative proportions of patients with HBsAg clearance, HBsAg ＜200 IU/ml, HBsAg ＜1000 IU/ml, and HBsAg＜1500 IU/ml were 3.6%, 23.9%, 57.0%, and 67.3%, respectively. ConclusionDuring the EVT treatment of CHB, the levels of HBsAg and HBV DNA gradually decrease, and the level of HBsAg shows a trend of rapid reduction followed by slow reduction. After 5 years of ETV monotherapy, 67.3% of the patients can achieve an HBsAg level of ＜1500 IU/ml.