Letter: Using Anti‐ <scp>HBs</scp> Titres to Tailor <scp>HBV</scp> Reactivation Monitoring in Patients With Solid Tumours

We read with interest the meta-analysis by Poola et al., “Meta-Analysis: High anti-HBs Titers Are Associated with Significantly Reduced Risk of Hepatitis B Virus Reactivation During Rituximab Treatment.” [1] The authors showed a titre-dependent reduction in HBV reactivation among HBsAg-negative/anti-HBc–positive patients (27.3% in anti-HBs–negative patients, 13.8% with titers of 10–100 IU/L, and 3.5% with titers > 100 IU/L) [1]. These findings suggest that patients with anti-HBs titers < 100 IU/L may warrant closer monitoring and consideration of antiviral therapy. Although HBV reactivation after resolved infection is well recognised with potent B–cell–depleting agents such as rituximab, it is uncommon during chemotherapy for solid tumours, and evidence specific to solid tumours is limited [2-5], including HBV-endemic regions [6]. In our integrated analysis (Table 1), reactivation-associated hepatitis occurred in 0.16% of patients, and HBV-related mortality was 0.08%, suggesting a low absolute risk; however, in an HCC cohort treated with immune checkpoint inhibitors or tyrosine kinase inhibitors, 12-month reactivation reached 9.2% in past infection [7]. A prospective study with scheduled HBV DNA monitoring reported higher virological reactivation rates but no reactivation-associated hepatitis, suggesting detection of transient, clinically silent events. Universal and prolonged HBV DNA monitoring for all patients can be difficult in routine practice because of cost and workflow burdens, including missed tests and uncertainty regarding the optimal duration of follow-up. Consistent with this concern, our outpatient data showed high HBsAg screening (95%); however, anti-HBs/anti-HBc testing and HBV DNA measurement were not consistently performed, and monitoring strategies varied among physicians [8]. In solid tumours, the rarity of reactivation may lower awareness and contribute to gaps in testing and poorly defined protocols. In this setting, anti-HBs titers may be more useful as a dynamic marker than as a single baseline cut-off. For example, in patients with stable high titers (e.g., ≥ 100 IU/L), periodic measurement of anti-HBs alongside routine blood tests could be used to trigger earlier HBV DNA testing when titers fall below 100 IU/L, decline rapidly, or coincide with increasing liver enzymes. This strategy is not intended to replace HBV DNA testing but to reduce unnecessary testing in low-risk patients while preserving the ability to respond promptly when the risk increases. Our previous study suggested that combining anti-HBs with anti-HBc may further refine risk stratification. We previously reported that baseline anti-HBs and anti-HBc titers predicted reactivation risk in patients with lymphoma and resolved HBV infection [9, 10]. As the authors noted, high anti-HBs titers do not completely exclude reactivation, and escape mutants remain a concern [1]. Therefore, even if antibody-guided stratification is adopted, HBV DNA surveillance should continue at least intermittently, with intervals adjusted according to the longitudinal trends in anti-HBs (and anti-HBc, when appropriate). We would appreciate the authors' perspectives on these two points. First, based on existing evidence, can a decline in anti-HBs titre levels be shown to precede HBV DNA positivity? Second, in the solid tumour setting, where reactivation is uncommon, do the authors consider a prospective study of personalised monitoring using anti-HBs titers (with anti-HBc as needed) to be feasible and informative? Tsutomu Nishida: conceptualization, writing – original draft, data curation, formal analysis. Satoru Okabe: writing – review and editing. Akira Doi: writing – review and editing. Kengo Matsumoto: writing – review and editing. The authors have nothing to report. This article is linked to Poola et al. papers. To view these articles, visit https://doi.org/10.1111/apt.70490 and https://doi.org/10.1111/apt.70541. The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.