Quantification of HBV core antibodies may help predict HBV reactivation in patients with lymphoma and resolved HBV infection
Journal
Journal of Hepatology
Journal Volume
69
Journal Issue
2
Pages
286-292
Date Issued
2018
Author(s)
Tsou H.-H
Pei S.-N
Chang C.-S
Chen J.-H
Lin S.-J
Lin J
Yuan Q
Xia N
Liu T.-W
Taiwan Cooperative Oncology Group
Abstract
Background & Aims: Absence or low anti-HBV surface antibody (anti-HBs) is associated with an increased risk of HBV reactivation in patients with lymphoma and resolved HBV infection receiving rituximab-containing chemotherapy. Quantification of anti-HBV core antibody (anti-HBc) is a new marker associated with the natural history and treatment response of chronic HBV infection. This study investigated whether baseline anti-HBc and anti-HBs levels may better predict HBV reactivation. Methods: We prospectively measured the HBV DNA levels of patients with lymphoma and resolved HBV infection receiving rituximab–cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisolone-based chemotherapy and started an antiviral therapy upon HBV reactivation, defined as a greater than 10-fold increase in HBV DNA compared with previous nadir levels. Anti-HBs and anti-HBc were quantified by a double-sandwich assay. Receiver-operating-characteristic-curve analysis was used to determine the optimal baseline anti-HBc/anti-HBs levels for predicting HBV reactivation. Results: HBV reactivation occurred in 24 of the 197 patients enrolled, with an incidence of 11.6/100 person-years. For the 192 patients with enough serum samples for analysis, low anti-HBs (<56.48 mIU/ml) and high anti-HBc (?6.41 IU/ml) at baseline were significantly associated with high risk of HBV reactivation (hazard ratio [HR] 8.48 and 4.52, respectively; p <0.01). The multivariate analysis indicated that (1) patients with both high anti-HBc and low anti-HBs at baseline (36 of 192 patients) had an HR of 17.29 for HBV reactivation (95% CI 3.92–76.30; p <0.001), and (2) HBV reactivation may be associated with inferior overall survival (HR 2.41; 95% CI 1.15–5.05; p = 0.02). Conclusions: Baseline anti-HBc/anti-HBs levels may predict HBV reactivation in these patients with lymphoma and help optimize prophylactic antiviral therapy for high-risk patients. Lay summary: In this study, we identified a subgroup of patients with lymphoma and resolved hepatitis B virus infection that had a high risk of hepatitis B virus reactivation after receiving rituximab-containing chemotherapy. These findings will help optimize a preventive strategy, especially in hepatitis B virus endemic regions with limited healthcare resources. Clinical trial number: NCT 00931229. ? 2018 European Association for the Study of the Liver
SDGs
Other Subjects
cyclophosphamide plus doxorubicin plus prednisolone plus rituximab plus vincristine; entecavir; hepatitis B core antibody; hepatitis B surface antibody; hepatitis B surface antigen; virus DNA; antineoplastic agent; antivirus agent; biological marker; hepatitis B antibody; hepatitis B surface antigen; rituximab; virus DNA; adult; aged; antibody blood level; antiviral therapy; Article; cancer combination chemotherapy; cancer survival; chronic hepatitis B; clinical outcome; cohort analysis; diffuse large B cell lymphoma; disease exacerbation; female; follicular lymphoma; Hepatitis B virus; high risk patient; human; incidence; lymphoma; major clinical study; male; nonhuman; overall survival; priority journal; progression free survival; prospective study; quantitative analysis; treatment response; virus reactivation; blood; complication; hepatitis B; Hepatitis B virus; immunology; middle aged; nonhodgkin lymphoma; physiology; predictive value; procedures; risk assessment; Taiwan; virus activation; Adult; Antineoplastic Combined Chemotherapy Protocols; Antiviral Agents; Biomarkers; DNA, Viral; Female; Hepatitis B; Hepatitis B Antibodies; Hepatitis B Surface Antigens; Hepatitis B virus; Humans; Lymphoma, Non-Hodgkin; Male; Middle Aged; Predictive Value of Tests; Risk Assessment; Rituximab; Taiwan; Virus Activation
Publisher
Elsevier B.V.
Type
journal article