Hepatitis B virus reactivation during temozolomide administration for malignant glioma
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ORIGINAL ARTICLE
Hepatitis B virus reactivation during temozolomide administration for malignant glioma Takuhiro Shoji1 · Masayuki Kanamori1 · Jun Inoue2 · Ryuta Saito1 · Yoshinari Osada1 · Yoshiteru Shimoda1 · Masashi Chonan1 · Hiroshi Uenohara3 · Atsushi Masamune2 · Teiji Tominaga1 Received: 1 July 2020 / Accepted: 13 October 2020 © Japan Society of Clinical Oncology 2020
Abstract Introduction The purpose of this study is to clarify the clinical features of temozolomide (TMZ)-related hepatitis B virus (HBV) reactivation and to identify HBV reactivation predictive factors. Method We retrospectively reviewed the clinical course of 145 patients newly diagnosed or with recurrent malignant glioma treated with TMZ. Before treatment, we screened patients for HB surface antigen (HBsAg) positivity (HBV carrier) and HBsAg negativity. Patients were also screened for antibody for HB core antigen (anti-HBc) positivity and/or for HB surface antigen positivity (resolved HBV infection). The patients were monitored by HBV DNA, alanine, and aspartate aminotransaminase during and after the completion of TMZ. HBV carriers and those with resolved HBV infections with HBV reactivation received preemptive entecavir treatment. In those with resolved HBV infections, we analyzed clinical characters for the predictive factors for HBV reactivation. Results In one of two HBV carriers, HBV DNA turned positive 8 months after the completion of TMZ and entecavir. In four (16.7%) of 24 resolved HBV infections, HBV DNA turned detectable at completion of concomitant radiation and TMZ or during monthly TMZ. HBV DNA turned negative with entecavir in all patients without liver dysfunction. In resolved HBV infections, those with a high anti-HBc titer had significantly higher incidence of HBV reactivation than those with low anti-HBc titers (60% vs. 5.3%: p = 0.018). Conclusion Screenings, monitoring, and preemptive entecavir were important for preventing TMZ-related HBV reactivations. Anti-HBc titers could be the predictive markers for HBV reactivation in the those with resolved HBV infections. Keywords Hepatitis B virus reactivation · Temozolomide · Malignant glioma · Entecavir · Predictive factor
Introduction Hepatitis B virus (HBV) infections are characterized by a variety of clinical features, reflecting the interaction between HBV replication and a host immune response [1]. Infections begin as acute hepatitis, and progresses to an inactive HBV carrier status, then chronic hepatitis, and liver cirrhosis * Masayuki Kanamori [email protected] 1
Department of Neurosurgery, Tohoku University Graduate School of Medicine, 1‑1 Seiryo‑machi, Aoba‑ku, Sendai, Miyagi 980‑8574, Japan
2
Department of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan
3
Department of Neurosurgery, Sendai Medical Center, Sendai, Miyagi, Japan
in a small proportion of patients. Those recovering from acute hepatitis B and some patients with chronic hepatitis B will have hepatitis B surface antigen (HBsAg) negativity long a
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