Retrospective Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. Dec 26, 2020; 8(24): 6264-6273
Published online Dec 26, 2020. doi: 10.12998/wjcc.v8.i24.6264
Risk factors for de novo hepatitis B during solid cancer treatment
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
Rie Sugimoto, Masayuki Furukawa, Takeshi Senju, Yoshihusa Aratake, Yuki Tanaka, Hiroki Inada, Tatsuya Noguchi, Lingaku Lee, Masami Miki, Yuji Maruyama, Risa Hashimoto, Terumasa Hisano, Department of Hepato-Biliary-Pancreatology, National Hospital Organization Kyushu Cancer Center, Fukuoka City 811-1395, Fukuoka Prefecture, Japan
Mototsugu Shimokawa, National Hospital Organization Kyushu Cancer Center, Clinical Research Institute, Fukuoka City 811-1395, Fukuoka Prefecture, Japan
Mototsugu Shimokawa, Department of Biostatistics, Yamaguchi University Graduate School of Medicine, Ube City 755-8505, Yamaguchi Prefecture, Japan
Author contributions: Sugimoto R designed the study, collected and analyzed the data, and drafted the first manuscript; Furukawa M prepared and reviewed the manuscript; Senju T and Aratake Y collected and analyzed the data; Shimokawa M analyzed and reviewed the data; Tanaka Y, Inada H and Noguchi T collected the data; Lee L and Miki M participated in the acquisition and interpretation of the data; Maruyama Y prepared and reviewed the manuscript; Hashimoto R and Hisano T analyzed the data.
Supported by Eisai Corporation, No. HHCS20181030011.
Institutional review board statement: This study was reviewed and approved by the Ethics Committee of the National Hospital Organization Kyushu Cancer Center (Approval No.2017-16).
Informed consent statement: Patients were not required to give informed consent to the study because the analysis used anonymous clinical data that were obtained after each patient agreed to participate in clinical research by written consent. For full disclosure, the details of the study are published on the home page of National Hospital Organization Kyushu Cancer Center and patients are asked to inform us if they disagree with the use of the clinical data.
Conflict-of-interest statement: This work was partly supported by funding from Eisai (Grant No. HHCS20181030011) (Tokyo, Japan); however, that did not result in potential conflicts for this study because it was designed and performed independently of this funding agency.
Data sharing statement: Technical appendix, statistical code, and dataset available from the corresponding author at sugirie5@yahoo.co.jp. Participants gave informed consent for data sharing.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Rie Sugimoto, MD, PhD, Chief Doctor, Department of Hepato-Biliary-Pancreatology, National Hospital Organization Kyushu Cancer Center, 3-1-1 Notame Minami-ku, Fukuoka City 811-1395, Fukuoka Prefecture, Japan. sugirie5@yahoo.co.jp
Received: August 31, 2020
Peer-review started: August 31, 2020
First decision: September 30, 2020
Revised: October 13, 2020
Accepted: November 2, 2020
Article in press: November 2, 2020
Published online: December 26, 2020
Processing time: 110 Days and 4.6 Hours
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 de novo hepatitis B patients. The risk of de novo hepatitis B may vary based on different background factors.

AIM

To determine the frequency and risk factors for de novo 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) vs 7.22 (7.02-7.43), P = 0.0001] and significantly lower HBsAb values (14 vs 46, P = 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% vs 58.7%, P = 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, P = 0.0002 and P = 0.0095). The group without HBsAbs tended to have a shorter time to reactivation (day 43 vs day 193), and the frequency of reactivation within 6 mo was significantly higher in this group (P = 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.

Keywords: Hepatitis B; Reactivation; Solid cancer treatment; Digestion and absorption organ; Hepatitis B surface antibody; Hepatitis B core antibody titer

Core Tip: Hepatitis B virus (HBV) reactivation in patients during cancer treatment is a critical issue. We retrospectively reviewed the expression of HBV DNA in 1040 patients undergoing anticancer treatment for various types of solid tumors at our institution and examined the patient and disease information. Among the 1040 patients, 938 had both hepatitis B core antibodies (HBcAbs) and hepatitis B surface antibodies (HBsAbs), while 102 had only HBsAbs. We confirmed HBV DNA expression in 44 patients (4.7%, 44/938), all of whom were HBcAb–positive patients. HBV DNA expression was detected before treatment in 9 patients and after treatment in 35 patients. A comparison of the treatments in patients with reactivation and those in patients without reactivation revealed no differences in treatment between groups. However, multivariate analysis identified both a high HBcAb titer and cancers in organs involved in digestion and absorption (such as the oral cavity, esophagus, stomach, colon, and others) as independent factors that contributed to HBV reactivation. Our findings may help identify a subset of cancer patients undergoing treatment that should be monitored for HBV reactivation.