Hepatitis B surface antigen (HBsAg) seroclearance has been recommended as an optimal endpoint of antiviral treatment by the latest chronic hepatitis B management guideline.1 However, few reports investigated the durability of response after HBsAg seroclearance, because of a lower HBsAg seroclearance rate and the difficulty of obtaining a sufficient number of samples for analysis. Our center has made a long-term commitment to investigate the personalized antiviral therapy for chronic hepatitis B. More than 300 patients achieved HBsAg seroclearance by interferon (IFN)-based antiviral treatment. In this study, the durability and the effects of hepatitis B virus (HBV) surface antibody (Anti-HBs) level on relapse after HBsAg seroclearance were investigated.

Hepatitis B surface antigen (HBsAg) seroclearance is regarded as the ideal endpoint for antiviral treatment. However, reports on the durability of and outcomes after HBsAg seroclearance are few, which has become a focus in clinical practice. This meta‐analysis was performed to evaluate the durability and hepatocellular carcinoma (HCC) incidence after HBsAg seroclearance after treatment cessation. We searched PubMed, Embase, Medline and Web of Science for studies that reported the durability and HCC incidence after HBsAg seroclearance published between 1 January 2000 and 31 January 2020. Data were analysed by a random‐effects model. Thirty‐eight studies and 43,924 patients were finally included. The results showed that HBsAg seroclearance was durable, with a pooled recurrence rate of 6.19% (95% CI: 4.10%–8.68%). There was no significant difference in recurrence rates after different seroclearance methods or among recurrence types and different regions. Anti‐HBs seroconversion resulted in a significantly reduced recurrence rate (RR = 0.25, p < .001). Patients who experienced HBsAg seroclearance had significantly lower HCC incidence than HBsAg‐positive (RR = 0.41, p < .001). The pooled HCC incidence after HBsAg seroclearance was 1.88%; this rate was reduced to 0.76% among patients without baseline cirrhosis. In conclusion, the analysis during an average follow‐up of 4.74 years suggested that in patients who experienced sustained HBsAg seroclearance and anti‐HBs seroconversion, this was associated with low HCC incidence. Patients without baseline cirrhosis benefited even more. We emphasize the importance of gaining HBsAg seroclearance while highlighting the benefits of achieving this as early as possible.

Hepatitis B surface antigen (HBsAg) clearance is regarded as the ideal endpoint for antiviral treatment in terms of drug withdrawal safety and improvements in prognosis. However, the overall rate of HBsAg clearance is low and differs based on treatment method and course. The recent application of combined and extended treatment strategies have improved the HBsAg clearance rate, and several patients achieved HBsAg clearance in clinical treatment. In addition, the durability of and clinical outcomes after HBsAg clearance have become the focus of both researchers and clinicians. This article reviews HBsAg clearance in terms of accessibility, durability, improvements in prognosis and relevant advances.

Background: Expanding antiviral therapy to benefit more populations and optimizing treatment to improve prognoses are two main objectives in current guidelines on antiviral therapy. However, the guidelines do not recommend antiviral therapy for inactive hepatitis B surface antigen (HBsAg) carriers (IHCs). Recent studies have shown that antiviral therapy is effective with good treatment outcomes in IHC populations. We conducted a systematic review and meta-analysis of HBsAg clearance and conversion in IHCs. Methods: We searched PubMed, Embase, Medline, and Web of Science to retrieve articles on HBsAg clearance in IHCs published between January 2000 and August 2021. Data were collected and analysed using the random-effects model for meta-analysis. Results: A total of 1029 IHCs from 11 studies were included in this analysis. The overall HBsAg clearance rate was 47% (95% confidence interval (CI): 31% - 64%), with a conversion rate of 26% (95% CI: 15% - 38%) after 48 weeks of Pegylated interferon (Peg-IFN) treatment. In the control group (including nucleos(t)ide analogue (NA) treatment or no treatment), the overall HBsAg clearance rate was only 1.54% (95% CI: 0.56% - 3.00%), which was markedly lower than that in the Peg-IFN group. Further analysis showed that a low baseline HBsAg level and long treatment duration contributed to a higher HBsAg clearance rate. Conclusion: This study showed that treatment of IHCs can be considered to achieve a clinical cure for chronic hepatitis B virus (HBV) infection. After Peg-IFN treatment, the HBsAg clearance rate was 47%, and the conversion rate was 26%, which are markedly higher than those reported by previous studies on Peg-IFN treatment in patients with chronic hepatitis B (CHB). A low baseline HBsAg level and long treatment duration were associated with HBsAg clearance in IHCs. Therefore, antiviral therapy is applicable for IHCs, a population who may be clinically cured. Systematic Review Registration: http://www.crd.york.ac.uk/PROSPERO, CRD): CRD42021259889.