Risk Factors for Hepatitis B During Solid Cancer Treatment

Overview

Journal World J Clin Cases

Publisher Baishideng Publishing Group

Specialty General Medicine

Date 2021 Jan 4

PMID 33392307

Citations 1

Authors

Rie Sugimoto

Masayuki Furukawa

Takeshi Senju

Yoshihusa Aratake

Mototsugu Shimokawa

Yuki Tanaka

Hiroki Inada

Tatsuya Noguchi

Lingaku Lee

Masami Miki

Yuji Maruyama

Risa Hashimoto

Terumasa Hisano

Affiliations

Soon will be listed here.

Abstract

Background: Reactivation of hepatitis B virus (HBV) during anticancer treatment is a critical issue. When treating patients with solid tumors, it is unclear whether specific cancer types or treatments affect HBV reactivation in hepatitis B surface antigen (HBsAg)-negative and hepatitis B core antibody (HBcAb)-positive patients, so-called hepatitis B patients. The risk of hepatitis B may vary based on different background factors.

Aim: To determine the frequency and risk factors for hepatitis B during solid tumor treatment.

Methods: This retrospective cohort study comprised 1040 patients without HBsAgs and with HBcAbs and/or hepatitis B surface antibodies (HBsAbs). The patients were treated for solid cancer from 2008 to 2018 at the National Kyushu Cancer Center and underwent HBV DNA measurements. Patient characteristics and disease and treatment information were investigated. HBV DNA measurements were performed using TaqMan polymerase chain reaction (PCR). To identify the risk factors associated with HBV DNA expression, the age, sex, original disease, pathology, treatment method, presence or absence of hepatitis C virus (HCV), and HBsAb and/or HBcAb titers of all subjects were investigated. In patients with HBV DNA, the time of appearance, presence of HBsAgs and HBsAbs at the time of appearance, and course of the subsequent fluctuations in virus levels were also investigated.

Results: Among the 1040 patients, 938 were HBcAb positive, and 102 were HBcAb negative and HBsAb positive. HBV DNA expression was observed before the onset of treatment in nine patients (0.9%) and after treatment in 35 patients (3.7%), all of whom were HBcAb positive. The HBV reactivation group showed significantly higher median HBcAb values [9.00 (8.12-9.89) 7.22 (7.02-7.43), = 0.0001] and significantly lower HBsAb values (14 46, = 0.0342) than the group without reactivation. Notably, the reactivated group showed a significantly higher proportion of cancers in organs related to digestion and absorption (79.0% 58.7%, = 0.0051). A high HBcAb titer and cancers in organs involved in digestion and absorption were identified as independent factors for HBV reactivation (multivariate analysis, = 0.0002 and = 0.0095). The group without HBsAbs tended to have a shorter time to reactivation (day 43 day 193), and the frequency of reactivation within 6 mo was significantly higher in this group ( = 0.0459) than in the other group.

Conclusion: A high HBcAb titer and cancers in organs involved in digestion and absorption are independent factors that contribute to HBV reactivation during solid tumor treatment.

Citing Articles

De novo Hepatitis B Virus Reactivation during Treatment with an Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor in a Patient with Advanced Lung Cancer.

Horibe R, Yokota M, Uemura K, Hashimoto M, Kawagishi N, Nishiyama K Intern Med. 2023; 63(12):1797-1800.

PMID: 37926534 PMC: 11239268. DOI: 10.2169/internalmedicine.2731-23.

References

Matsubara T, Nishida T, Shimoda A, Shimakoshi H, Amano T, Sugimoto A . The combination of anti-HBc and anti-HBs levels is a useful predictor of the development of chemotherapy-induced reactivation in lymphoma patients with resolved HBV infection. Oncol Lett. 2017; 14(6):6543-6552. PMC: 5680641. DOI: 10.3892/ol.2017.7012. View

Reddy K, Beavers K, Hammond S, Lim J, Falck-Ytter Y . American Gastroenterological Association Institute guideline on the prevention and treatment of hepatitis B virus reactivation during immunosuppressive drug therapy. Gastroenterology. 2014; 148(1):215-9. DOI: 10.1053/j.gastro.2014.10.039. View

Yang H, Tsou H, Pei S, Chang C, Chen J, Yao M . Quantification of HBV core antibodies may help predict HBV reactivation in patients with lymphoma and resolved HBV infection. J Hepatol. 2018; 69(2):286-292. DOI: 10.1016/j.jhep.2018.02.033. View

Hoofnagle J, Dusheiko G, Schafer D, Jones E, Micetich K, Young R . Reactivation of chronic hepatitis B virus infection by cancer chemotherapy. Ann Intern Med. 1982; 96(4):447-9. DOI: 10.7326/0003-4819-96-4-447. View

Mochida S, Nakao M, Nakayama N, Uchida Y, Nagoshi S, Ido A . Nationwide prospective and retrospective surveys for hepatitis B virus reactivation during immunosuppressive therapies. J Gastroenterol. 2016; 51(10):999-1010. DOI: 10.1007/s00535-016-1168-2. View

Kotake T, Satake H, Okita Y, Hatachi Y, Hamada M, Omiya M . Prevalence and risk factors of hepatitis B virus reactivation in patients with solid tumors with resolved HBV infection. Asia Pac J Clin Oncol. 2018; 15(1):63-68. PMC: 7379615. DOI: 10.1111/ajco.13050. View

Taira R, Satake M, Momose S, Hino S, Suzuki Y, Murokawa H . Residual risk of transfusion-transmitted hepatitis B virus (HBV) infection caused by blood components derived from donors with occult HBV infection in Japan. Transfusion. 2012; 53(7):1393-404. DOI: 10.1111/j.1537-2995.2012.03909.x. View

Chou H, Chien W, Wu L, Cheng C, Chung C, Horng J . Age-related immune clearance of hepatitis B virus infection requires the establishment of gut microbiota. Proc Natl Acad Sci U S A. 2015; 112(7):2175-80. PMC: 4343154. DOI: 10.1073/pnas.1424775112. View

Tanaka J, Kumagai J, Katayama K, Komiya Y, Mizui M, Yamanaka R . Sex- and age-specific carriers of hepatitis B and C viruses in Japan estimated by the prevalence in the 3,485,648 first-time blood donors during 1995-2000. Intervirology. 2004; 47(1):32-40. DOI: 10.1159/000076640. View

10.

Paul S, Dickstein A, Saxena A, Terrin N, Viveiros K, Balk E . Role of surface antibody in hepatitis B reactivation in patients with resolved infection and hematologic malignancy: A meta-analysis. Hepatology. 2017; 66(2):379-388. PMC: 6485929. DOI: 10.1002/hep.29082. View

11.

Kusumoto S, Tanaka Y, Suzuki R, Watanabe T, Nakata M, Takasaki H . Monitoring of Hepatitis B Virus (HBV) DNA and Risk of HBV Reactivation in B-Cell Lymphoma: A Prospective Observational Study. Clin Infect Dis. 2015; 61(5):719-29. DOI: 10.1093/cid/civ344. View

12.

Loomba R, Liang T . Hepatitis B Reactivation Associated With Immune Suppressive and Biological Modifier Therapies: Current Concepts, Management Strategies, and Future Directions. Gastroenterology. 2017; 152(6):1297-1309. PMC: 5501983. DOI: 10.1053/j.gastro.2017.02.009. View

13.

Lok A, Liang R, Chiu E, Wong K, Chan T, Todd D . Reactivation of hepatitis B virus replication in patients receiving cytotoxic therapy. Report of a prospective study. Gastroenterology. 1991; 100(1):182-8. DOI: 10.1016/0016-5085(91)90599-g. View

14.

. JSH Guidelines for the Management of Hepatitis B Virus Infection. Hepatol Res. 2014; 44 Suppl S1:1-58. DOI: 10.1111/hepr.12269. View

15.

Jang J, Kim Y, Lee S, Kwon J, Nam S, Bae S . Reactivation of hepatitis B virus in HBsAg-negative patients with hepatocellular carcinoma. PLoS One. 2015; 10(3):e0122041. PMC: 4403914. DOI: 10.1371/journal.pone.0122041. View

16.

Liu J, Yang H, Lee M, Lu S, Jen C, Wang L . Incidence and determinants of spontaneous hepatitis B surface antigen seroclearance: a community-based follow-up study. Gastroenterology. 2010; 139(2):474-82. DOI: 10.1053/j.gastro.2010.04.048. View

17.

Sugimoto R, Enjoji M, Kotoh K, Noguchi K, Tsuruta S, Nakamuta M . [Effect of lamivudine for hepatitis B virus reactivation in blood cancer patients undergoing immunosuppressive chemotherapy]. Fukuoka Igaku Zasshi. 2005; 95(10):274-9. View

18.

Ling W, Soe P, Pang A, Lee S . Hepatitis B virus reactivation risk varies with different chemotherapy regimens commonly used in solid tumours. Br J Cancer. 2013; 108(10):1931-5. PMC: 3670504. DOI: 10.1038/bjc.2013.225. View

19.

Liaw Y, Sheen I, Chen T, Chu C, PAO C . Incidence, determinants and significance of delayed clearance of serum HBsAg in chronic hepatitis B virus infection: a prospective study. Hepatology. 1991; 13(4):627-31. View

20.

Seto W, Chan T, Hwang Y, Wong D, Fung J, Liu K . Hepatitis B reactivation in patients with previous hepatitis B virus exposure undergoing rituximab-containing chemotherapy for lymphoma: a prospective study. J Clin Oncol. 2014; 32(33):3736-43. DOI: 10.1200/JCO.2014.56.7081. View