Hung-Chih Yang1, Hsiao-Hui Tsou2, Sung-Nan Pei3, Cheng-Shyong Chang4, Jia-Hong Chen5, Ming Yao1, Shyh-Jer Lin6, Johnson Lin7, Quan Yuan8, Ningshao Xia8, Tsang-Wu Liu9, Pei-Jer Chen10, Ann-Lii Cheng11, Chiun Hsu12. 1. Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan. 2. Division of Biostatistics and Bioinformatics, Institute of Population Health Sciences, National Health Research Institutes, Miaoli, Taiwan; Graduate Institute of Biostatistics, College of Public Health, China Medical University, Taichung, Taiwan. 3. Department of Internal Medicine, Kaohsiung Chang-Gung Memorial Hospital, Kaohsiung, Taiwan. 4. Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan. 5. Department of Internal Medicine, Tri-Service General Hospital, Taipei, Taiwan. 6. Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan. 7. Department of Internal Medicine, Mackay Memorial Hospital, Taipei, Taiwan. 8. National Institute of Diagnostics and Vaccine Development in Infectious Diseases, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen, China. 9. National Institute of Cancer Research, National Health Research Institutes, Miaoli, Taiwan. 10. Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan. 11. Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan; Graduate Institute of Oncology, National Taiwan University College of Medicine, Taipei, Taiwan; National Taiwan University Cancer Center, Taipei, Taiwan. 12. Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan; Graduate Institute of Oncology, National Taiwan University College of Medicine, Taipei, Taiwan; National Taiwan University Cancer Center, Taipei, Taiwan. Electronic address: chsu1967@ntu.edu.tw.
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.
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.
Authors: Anna Kramvis; Kyong-Mi Chang; Maura Dandri; Patrizia Farci; Dieter Glebe; Jianming Hu; Harry L A Janssen; Daryl T Y Lau; Capucine Penicaud; Teresa Pollicino; Barbara Testoni; Florian Van Bömmel; Ourania Andrisani; Maria Beumont-Mauviel; Timothy M Block; Henry L Y Chan; Gavin A Cloherty; William E Delaney; Anna Maria Geretti; Adam Gehring; Kathy Jackson; Oliver Lenz; Mala K Maini; Veronica Miller; Ulrike Protzer; Jenny C Yang; Man-Fung Yuen; Fabien Zoulim; Peter A Revill Journal: Nat Rev Gastroenterol Hepatol Date: 2022-07-20 Impact factor: 73.082
Authors: Grécia C Pessoni; Tássia A Marinho; Megmar M Santos Carneiro; Regina M Martins; Caroline C Soares; Leandro N Silva; Marcia A Matos; Adriano M Arantes; Juliana A Teles; Nathalia C Santos; Sheila Araujo Teles Journal: Hematol Transfus Cell Ther Date: 2019-03-28