Clinical outcomes of treatment-naïve HBeAg-negative patients with chronic hepatitis B virus infection with low serum HBsAg and undetectable HBV DNA

ABSTRACT

Serum hepatitis B surface antigen (HBsAg) level < 100 IU/ml and undetectable hepatitis B virus (HBV) DNA have been recently proposed as an alternate endpoint of “partial cure” in chronic hepatitis B (CHB). We investigated clinical outcomes of hepatitis B e antigen (HBeAg)-negative CHB patients with HBsAg <100 IU/ml and undetectable HBV DNA. Treatment-naïve HBeAg-negative CHB patients with undetectable HBV DNA and normal alanine aminotransferase were retrospectively included from three institutions. Patients were classified into the low HBsAg group (<100 IU/ml) and the high HBsAg group (≥100 IU/ml). Liver fibrosis was evaluated by noninvasive tests (NITs). A total of 1218 patients were included and the median age was 41.5 years. Patients with low HBsAg were older (45.0 vs. 40.0 years, P < 0.001) than those in the high HBsAg group, while the NIT parameters were comparable between groups. During a median follow-up of 25.7 months, patients with low HBsAg achieved a higher HBsAg clearance rate (13.0% vs. 0%, P < 0.001) and a lower rate of significant fibrosis development (2.2% vs. 7.0%, P = 0.049) compared to patients with high HBsAg. No patient developed HCC in either group. HBsAg level was negatively associated with HBsAg clearance (HR 0.213, P < 0.001) and patients with HBsAg < 100 IU/ml had a low risk of significant fibrosis development (HR 0.010, P = 0.002). The optimal cutoff value of HBsAg for predicting HBsAg clearance was 1.1 Log₁₀ IU/ml. Treatment-naïve HBeAg-negative CHB patients with HBsAg <100 IU/ml and undetectable HBV DNA had favourable outcomes with a high rate of HBsAg clearance and a low risk of fibrosis progression.

KEYWORDS:

• Chronic hepatitis B
• hepatitis B surface antigen
• liver fibrosis
• HBsAg clearance

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The data that support the study findings are available upon reasonable request from the corresponding authors (Rui Huang and Chao Wu).

Author contributions

All authors contributed to this study at different levels. Study concept and design (Rui Huang, Chao Wu, Chuanwu Zhu, Jian Wang); acquisition of data (Li Zhu, Shaoqiu Zhang, Zhiyi Zhang, Tao Fan, Ye Xiong, Fei Cao, Yifan Pan, Yuanyuan Li, Chao Jiang, Shengxia Yin, Xin Tong, Yali Xiong, Juan Xia, Yuxin Chen, Xiaomin Yan, Yong Liu, Xingxiang Liu, Jie Li, Chuanwu Zhu); statistical analysis and interpretation of data (Jian Wang, Shaoqiu Zhang); drafting of the manuscript (Jian Wang, Li Zhu, Rui Huang); critical revision of the manuscript for important intellectual content (Chao Wu, Rui Huang).

Additional information

Funding

Dr. Rui Huang acknowledges the support from the Nanjing Medical Science and Technique Development Foundation (JQX21002 and QRX17121), Natural Science Foundation of Jiangsu Province (BK20211004) and the Clinical Trials from the Affiliated Drum Tower Hospital, Medical School of Nanjing University (2022-LCYJ-MS-07). Dr. Jian Wang acknowledges the support from the National Natural Science Foundation of China (82300719), Clinical Trials from the Affiliated Drum Tower Hospital, Medical School of Nanjing University (2021-LCYJ-PY-43) and Nanjing Medical Science and Technique Development Foundation (YKK21067). Dr. Li Zhu acknowledges the support from the Clinical Disease Diagnosis and Treatment Technology Foundation of Suzhou (LCZX202117).