Clinically detected hepatitis B virus reactivation in HBsAg-negative, anti-HBc-positive breast cancer patients receiving systemic therapy without antiviral prophylaxis: a two-centre descriptive cohort and nested case study

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Background: Hepatitis B virus (HBV) reactivation is a recognised complication in HBsAg-negative, anti-HBc-positive patients receiving cytotoxic cancer therapy. Guidelines place anti-HBc-positive patients exposed to anthracyclines in a moderate-risk band warranting on-treatment monitoring or selective prophylaxis, yet real-world data from non-prophylaxis breast cancer practice, where serial HBV DNA surveillance is often incomplete, remain scarce. Methods: We retrospectively studied HBsAg-negative, anti-HBc-positive breast cancer patients treated with systemic therapy between 2018 and 2024 at two centres in Turkey, none of whom received antiviral prophylaxis. We extracted demographic, oncological and virological data, including baseline anti-HBs titres and all available HBV DNA and alanine aminotransferase (ALT) results, and we quantified the completeness of virological surveillance. Because on-treatment HBV DNA was tested only when hepatitis was clinically suspected, the outcome captured was clinically detected reactivation; the study therefore describes surveillance quality rather than estimating true incidence. With a single event, analyses were kept descriptive. Results: Among 139 patients (mean age 60.1 years), 89.2% were anti-HBs-positive and 65.5% received anthracyclines. Baseline HBV DNA was documented in all patients, but serial on-treatment monitoring was not. One clinically overt reactivation occurred (0.7%; 95% CI 0.02%-3.94%) in an anti-HBs-negative woman receiving doxorubicin-cyclophosphamide, presenting as icteric hepatitis at month 4 and responding to entecavir. Since subclinical events would have escaped detection, this figure is best read as a lower bound rather than a true incidence. Conclusions: The single reactivation we detected arose in the patient profile that the guidelines flag as moderate-risk-absent anti-HBs together with anthracycline exposure. These observations are consistent with, but do not establish, a risk-adapted approach, given one event and incomplete surveillance. Prospective studies using standardised serial HBV DNA monitoring are needed to estimate true reactivation incidence in this population.

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