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实体癌治疗期间乙型肝炎的危险因素。

Risk factors for hepatitis B during solid cancer treatment.

作者信息

Sugimoto Rie, Furukawa Masayuki, Senju Takeshi, Aratake Yoshihusa, Shimokawa Mototsugu, Tanaka Yuki, Inada Hiroki, Noguchi Tatsuya, Lee Lingaku, Miki Masami, Maruyama Yuji, Hashimoto Risa, Hisano Terumasa

机构信息

Department of Hepato-Biliary-Pancreatology, National Hospital Organization Kyushu Cancer Center, Fukuoka City 811-1395, Fukuoka Prefecture, Japan.

National Hospital Organization Kyushu Cancer Center, Clinical Research Institute, Fukuoka City 811-1395, Fukuoka Prefecture, Japan.

出版信息

World J Clin Cases. 2020 Dec 26;8(24):6264-6273. doi: 10.12998/wjcc.v8.i24.6264.

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.

摘要

背景

抗癌治疗期间乙型肝炎病毒(HBV)再激活是一个关键问题。在治疗实体瘤患者时,尚不清楚特定的癌症类型或治疗方法是否会影响乙肝表面抗原(HBsAg)阴性和乙肝核心抗体(HBcAb)阳性患者(即所谓的乙肝患者)的HBV再激活。乙肝风险可能因不同的背景因素而有所不同。

目的

确定实体瘤治疗期间乙肝的发生频率和危险因素。

方法

这项回顾性队列研究纳入了1040例无HBsAg且有HBcAb和/或乙肝表面抗体(HBsAbs)的患者。这些患者于2008年至2018年在国立九州癌症中心接受实体癌治疗,并进行了HBV DNA检测。调查了患者的特征、疾病及治疗信息。使用TaqMan聚合酶链反应(PCR)进行HBV DNA检测。为确定与HBV DNA表达相关的危险因素,调查了所有受试者的年龄、性别、原发疾病、病理、治疗方法、丙型肝炎病毒(HCV)的有无以及HBsAb和/或HBcAb滴度。对于HBV DNA阳性的患者,还调查了其出现时间、出现时HBsAg和HBsAbs的存在情况以及随后病毒水平波动的过程。

结果

在1040例患者中,938例HBcAb阳性,102例HBcAb阴性且HBsAb阳性。9例患者(0.9%)在治疗开始前出现HBV DNA表达,35例患者(3.7%)在治疗后出现,所有这些患者均为HBcAb阳性。HBV再激活组的HBcAb中位数显著高于未再激活组[9.00(8.12 - 9.89)对7.22(7.02 - 7.43),P = 0.0001],而HBsAb值显著低于未再激活组(14对46,P = 0.0342)。值得注意的是,再激活组中与消化吸收相关器官的癌症比例显著更高(79.0%对58.7%,P = 0.0051)。高HBcAb滴度和消化吸收相关器官的癌症被确定为HBV再激活的独立因素(多变量分析,P = 0.0002和P = 0.0095)。无HBsAbs的组再激活时间往往较短(43天对193天),该组在6个月内的再激活频率显著高于另一组(P = 0.0459)。

结论

高HBcAb滴度和消化吸收相关器官的癌症是实体瘤治疗期间导致HBV再激活的独立因素。

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