Yang H Y, Hao K Y, Liang X E, Liu Z H, Zhong C X, Yin J H, Xu Y, Wu L Y, Yu Y C, Hou J L, Fan R
Liver Disease Center and Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
Liver Disease Treatment Center, Department of Infectious Diseases, Qinhuai Medical District, Eastern Theater Command General Hospital, Nanjing 210002, China.
Zhonghua Gan Zang Bing Za Zhi. 2025 Jun 20;33(6):551-559. doi: 10.3760/cma.j.cn501113-20250506-00173.
To explore the predictive value of hepatitis B surface antibody (HBsAb) quantitative level for achieving hepatitis B surface antigen (HBsAg) seroclearance and serological conversion in patients with chronic hepatitis B (CHB) treated with nucleos(t)ide analogs (NAs) or interferon (IFN). A two-center prospective cohort study was conducted, including CHB patients from Nanfang Hospital Southern Medical University and Eastern Theater General Hospital treated with NAs and IFN. All patients were followed up once every three to six months. Basic clinical information and test results were collected at each follow-up. The presence or absence of HBsAg seroclearance and serological conversion rate was evaluated. HBsAg serological conversion was defined as HBsAg quantification continuously below the detection limit (<0.05 IU/mL) at two detection time points at least six months apart. HBsAg serological conversion was defined as HBsAb positivity (≥10 IU/L) at the same time as the first HBsAg seroclearance. The Kruskal-Wallis test was used to compare the quantitative data of multiple groups, and the Wilcoxon rank-sum test was used to compare the data between groups. The chi-square test was used for the count data, and the Fisher exact test was used when the chi-square test was not met. Univariate and multivariate Cox analysis was used to determine the predictors of the study endpoints, and stepwise regression was used for variable screening. A total of 2 266 CHB cases were included, of which 86.5% (1 959/2 266) were NA antiviral-received population. The median treatment duration before baseline was 10.5 (2.5, 37.6) months, and the baseline HBsAg quantification was 3.1 (2.6, 3.5) log IU/mL. A total of 68 cases (3.0%) had HBsAg seroclearance, and 44 cases (1.9%) achieved serological conversion after 85.0 (62.7, 97.3) months of prospective follow-up. The level and positivity rate of HBsAb showed a progressive increase 36 months before and significantly after HBsAg seroclearance. Cox regression analysis results showed that baseline HBsAb level was an independent predictor of HBsAg serological conversion (=2.26, =0.002) in the overall population, especially in the subgroup with HBsAg between 100 and 1 000 IU/mL, suggesting HBsAb level had important predictive value. In addition, the serological conversion development rate was significantly higher in the GOLDEN model favourable patients than in the unfavourable patients (11.5% vs. 0, <0.001). The baseline HBsAb quantitative level can predict HBsAg seroclearance and serological conversion for patients with CHB receiving antiviral treatment, which is of significant value in long-term treatment monitoring.
探讨慢性乙型肝炎（CHB）患者接受核苷（酸）类似物（NAs）或干扰素（IFN）治疗时，乙肝表面抗体（HBsAb）定量水平对实现乙肝表面抗原（HBsAg）血清学清除及血清学转换的预测价值。进行了一项两中心前瞻性队列研究，纳入南方医科大学南方医院和东部战区总医院接受NAs和IFN治疗的CHB患者。所有患者每三至六个月随访一次。每次随访时收集基本临床信息和检查结果。评估HBsAg血清学清除情况及血清学转换率。HBsAg血清学转换定义为在至少相隔六个月的两个检测时间点，HBsAg定量持续低于检测下限（<0.05 IU/mL）。HBsAg血清学转换同时定义为首次HBsAg血清学清除时HBsAb阳性（≥10 IU/L）。采用Kruskal-Wallis检验比较多组定量数据，采用Wilcoxon秩和检验比较组间数据。计数资料采用卡方检验，不满足卡方检验条件时采用Fisher确切概率法。采用单因素和多因素Cox分析确定研究终点的预测因素，并采用逐步回归进行变量筛选。共纳入2266例CHB病例，其中86.5%（1959/2266）为接受NA抗病毒治疗人群。基线前治疗中位疗程为10.5（2.5，37.6）个月，基线HBsAg定量为3.1（2.6，3.5）log IU/mL。经过85.0（62.7，97.3）个月的前瞻性随访，共有68例（3.0%）实现HBsAg血清学清除，44例（1.9%）实现血清学转换。HBsAg血清学清除前36个月及清除后，HBsAb水平及阳性率呈逐渐升高趋势。Cox回归分析结果显示，基线HBsAb水平是总体人群中HBsAg血清学转换的独立预测因素（=2.26，=0.002），尤其在HBsAg为100至1000 IU/mL的亚组中，提示HBsAb水平具有重要预测价值。此外，GOLDEN模型有利患者的血清学转换发生率显著高于不利患者（11.5%比0，<0.001）。基线HBsAb定量水平可预测接受抗病毒治疗的CHB患者的HBsAg血清学清除及血清学转换，对长期治疗监测具有重要价值。
