Letter: Using Anti‐ <scp>HBs</scp> Titers to Tailor <scp>HBV</scp> Reactivation Monitoring in Patients With Solid Tumours—Authors' Reply

We thank Dr. Nashida and colleagues for their kind interest in our work on HBV reactivation. Our Meta-Analysis focused on Rituximab-associated HBV reactivation risk [1], which is not used for solid tumours. Still, their letter raises several important aspects [2]. First, they indicate that a patient with anti-HBs titre < 100 iU/L may require more intense observation; thus, a patient with anti-HBs > 100 iU/L may not require as intense observation. This could be an option for low-risk HBV reactivation regimens. However, for patients undergoing therapy with rituximab, intense observation is likely always required. Furthermore, the current standard for anti-HBc positive patients on Rituximab is universal antiviral therapy. The aim of our study was to highlight that while antiviral therapy is likely appropriate for all anti-HBc positive, HBV DNA and HBsAg negative patients with no or low anti-HBs titre, patients with high anti-HBs titre (> 100 iU/L) could be selected for anti-HBs and HBV DNA surveillance vs. immediate antiviral therapy. This is now supported by EASL and AGA guidelines [3, 4]. Second, we concur to highlight that anti-HBs is a dynamic marker, where decline < 100 iU/L may indicate risk for reactivation [5]. In case of anti-HBs decline below 100 iU/L, antiviral therapy should be initiated and the patient should be considered for vaccination aiming to boost anti-HBs above 100 iU/L. Third, the HBV reactivation risk is lower for patients with solid tumours compared to hematologic malignancies, as reviewed in recent Meta-Analysis [6]. Hematologic malignancies likely have more aggravated reduction in immune competence. Among patients being treated for hematologic malignancy, those treated with B-cell depleting agents seem to be at further increased risk of reactivation. This may make it difficult to generalise to patients being treated for solid tumours. Fourth, among all solid tumours the risk of reactivation is highest for hepatocellular carcinoma (HCC) [7]. While unrelated to our study, it highlights an interesting observation, where definite reasons remain to be confirmed. Potentially, the appearance of HCC is partially related to reduced competence in immune surveillance, allowing a liver cancer to evade immunological detection and control, where the same mechanism then may result in reduced HBV immune surveillance and subsequent reactivation. Fifth, they further highlight a potential emerging marker: quantitative anti-HBc, where higher anti-HBc is associated with increased risk compared to higher anti-HBs being associated with reduced risk of HBV Reactivation. Data are currently limited to two studies which used different cohort-specific derived cut-offs (Table 1) [8, 9]. This picture is further complicated by the point that “high anti-HBc” was associated with low anti-HBs and vice versa. The role of baseline quantification and monitoring of anti-HBc titre remains to be confirmed. A third study, showing increased risk of reactivation associated with higher anti-HBc values, derived a 1.6 lg iU/L value equivalent to 39.8 iU/L, which differed from the other two studies and did not report on quantitative anti-HBs [10]. Finally, we believe that surveillance for quantitative anti-HBs and HBV-DNA should be performed at least every 3 months in the initial treatment phase, and the need for antiviral prophylaxis should be adapted accordingly. Hans L. Tillmann: conceptualization, writing – original draft, writing – review and editing. Shiva Poola: writing – original draft, writing – review and editing. MaryKate Kratzer: writing – review and editing, writing – original draft. 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.70522. The data that support the findings of this study are available in PubMed at https://pubmed.ncbi.nlm.nih.gov/. These data were derived from the following resources available in the public domain: PubMed, https://pubmed.ncbi.nlm.nih.gov/.