HBsAg阴性/抗-HBc阳性患者抗肿瘤相关HBV再激活风险的前瞻性评估

肝脏 ›› 2024, Vol. 29 ›› Issue (12): 1464-1467.

HBsAg阴性/抗-HBc阳性患者抗肿瘤相关HBV再激活风险的前瞻性评估

郝坤艳, 张怡青, 王锋, 朱浩, 汪文洋, 沈敏, 陈晓慧, 李平, 于乐成

210002 江苏南京大学医学院附属金陵医院(东部战区总医院)感染病科与肝病中心(郝坤艳,汪文洋,沈敏,陈晓慧,李平,于乐成),检验科(张怡青),肿瘤科(王锋),药学科(朱浩)

收稿日期:2024-05-08 出版日期:2024-12-31 发布日期:2025-02-19
通讯作者: 于乐成,Email:gslsycy@ 163.com
基金资助:
南京大学医学院附属金陵医院(东部战区总医院)临床科研课题(22LCZLXJS14)

Risk of hepatitis B virus reactivation in HBsAg negative/anti-HBc positive patients with malignancies: a prospective study

HAO Kun-yan¹, ZHANG Yi-qing², WANG Feng³, ZHU Hao⁴, WANG Wen-yang¹, SHEN Min¹, CHEN Xiao-hui¹, LI Ping¹, YU Yue-cheng¹

1. Center of Hepatology and Department of Infectious Disease, Jinling Hospital (General Hospital of Eastern Theater Command) Affiliated to School of Medicine, Nanjing University, Jiangsu 210002, China;
2. Department of Clinical Laboratory, Jinling Hospital (General Hospital of Eastern Theater Command) Affiliated to School of Medicine, Nanjing University, Jiangsu 210002, China;
3. Department of Oncology, Jinling Hospital (General Hospital of Eastern Theater Command) Affiliated to School of Medicine, Nanjing University, Jiangsu 210002, China;
4. Department of Pharmacy, Jinling Hospital (General Hospital of Eastern Theater Command) Affiliated to School of Medicine, Nanjing University, Jiangsu 210002, China

Received:2024-05-08 Online:2024-12-31 Published:2025-02-19
Contact: YU Yue-cheng, Email:gslsycy@163.com

摘要/Abstract

摘要： 目的评估HBsAg阴性/抗-HBc阳性患者抗肿瘤治疗相关HBV再激活(HBV reactivation, HBVr)的发生率。方法以2021年6至7月在东部战区总医院肿瘤科住院的HBsAg-/抗-HBc+、并接受抗肿瘤治疗的恶性肿瘤患者为研究对象。收集人口学资料、肿瘤类型、抗肿瘤治疗方案、基线及抗癌治疗6个月时的HBV RNA、HBV DNA、HBsAg及HBeAg相关指标,其中任何一项指标转阳即判断为HBVr,统计并分析HBVr发生率。结果纳入HBsAg-/抗-HBc+恶性肿瘤患者36例。基线血清HBV DNA<10 IU/mL,HBV RNA<50拷贝/mL;HBsAg及HBeAg均阴性;抗-HBs阳性24例(66.67%),抗-HBs≥100 mIU/mL 9例(25.00%)。抗肿瘤方案高风险2例(5.56%)、中风险4例(11.11%)、低风险26例(72.22%)、不确定风险4例(11.11%)。治疗6个月时,HBVr的发生率为8.33%(3/36)。高、中、低和不确定风险组的HBVr分别为0%(0/2)、25%(1/4)、3.85%(1/26)和25%(1/4)。抗-HBs阳性组与阴性组(3/24比0/12,P=0.54)、抗-HBs≥100 mIU/mL组与<100 mIU/mL组(1/9比2/27, P=1.00)之间的HBVr率差异均无统计学意义。3例HBVr患者均表现为血清HBV DNA弱阳性(12.49、19.24及71.55 IU/mL),分别位于中、低、不确定风险组,基线抗-HBs分别为23.19、1.23和 145.58 mIU/mL。结论 HBsAg-/抗-HBc+且HBV RNA和HBV DNA均低于检测下限的恶性肿瘤患者,甚至是基线抗-HBs水平相对高、采用低风险或不确定风险抗肿瘤方案的患者,仍存在HBVr风险。

关键词: 抗-HBc阳性, HBsAg阴性, HBV RNA, HBV DNA, 抗肿瘤治疗, HBV再激活

Abstract: Objective To prospectively evaluate the rate of hepatitis B virus reactivation (HBVr) in HBsAg negative/anti-HBc positive (HBsAg-/anti-HBc+) patients with malignancies, thus to assess the risk of HBVr more accurately and optimize the management in this special population.Methods HBsAg-/anti-HBc+ patients with malignant tumors admitted to the Department of Oncology in a tertiary hospital from June to July 2021 and received anti-tumor treatment were selected as the subjects. Demographic data, tumor type, anti-tumor regimen, HBV markers such as HBV RNA, HBV DNA, HBsAg and HBeAg were collected prospectively at baseline and 6 months of anti-tumor treatment. HBVr was confirmed if any of the HBV markers turned positive, and the incidence of HBVr was analyzed to evaluate the risk of HBVr in the HBsAg-/anti-HBc+ background.Results A total of 36 HBsAg-/anti-HBc+patients with malignancies were included, all of whom had baseline serum HBV DNA <10 IU/mL, HBV RNA <50 copies/mL, HBsAg and HBeAg negative. Anti-HBs was detectable in 24 cases (66.67%), with 9 patients (25.00%) had anti-HBs≥100 mIU/mL. There were 2 patients (5.56%) in high risk subgroup, 4 patients (11.11%) in moderate risk subgroup, 26 patients (72.22%) in low risk subgroup, and 4 patients (11.11%) in uncertain risk subgroup. After 6 months of anti-cancer treatment, the total incidence of HBVr was 8.33% (3/36). The rates of HBVr in the high, moderate, low and uncertain risk subgroups were 0% (0/2), 25% (1/4), 3.85% (1/26) and 25% (1/4), respectively. No significant difference in HBVr rates were seen between anti-HBs positive and negative subgroups (3/24 vs 0/12, P=0.54), or between anti-HBs≥100 mIU/mL and <100 mIU/mL subgroups (1/9 vs 2/27, P=1.00). The levels of HBV DNA by the end of 6 months in the three HBVr patients (with baseline anti-HBs and risk stratification of anti-tumor treatment) were 12.49 IU/mL (23.19 mIU/mL and moderate risk), 19.24 IU/mL (1.23 mIU/mL and low risk), and 71.55 IU/mL (145.58 mIU/mL and uncertain risk).Conclusion Tumor patients with baseline HBsAg-/anti-HBc+and both HBV RNA and HBV DNA below the lower limit of detection, even those with relatively higher baseline anti-HBs and low or uncertain risk of anti-tumor regimens, may be still at risk of HBV reactivation. The results strongly mean that careful assessment and prevention of HBVr should also be emphasized in these patients.

Key words: Anti-HBc positive, HBsAg negative, HBV DNA, HBV RNA, Malignant tumors, Hepatitis B virus reactivation

郝坤艳, 张怡青, 王锋, 朱浩, 汪文洋, 沈敏, 陈晓慧, 李平, 于乐成. HBsAg阴性/抗-HBc阳性患者抗肿瘤相关HBV再激活风险的前瞻性评估[J]. 肝脏, 2024, 29(12): 1464-1467.

HAO Kun-yan, ZHANG Yi-qing, WANG Feng, ZHU Hao, WANG Wen-yang, SHEN Min, CHEN Xiao-hui, LI Ping, YU Yue-cheng. Risk of hepatitis B virus reactivation in HBsAg negative/anti-HBc positive patients with malignancies: a prospective study[J]. Chinese Hepatolgy, 2024, 29(12): 1464-1467.

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参考文献

[1] Lau G, Yu ML, Wong G, et al. APASL clinical practice guideline on hepatitis B reactivation related to the use of immunosuppressive therapy[J]. Hepatol Int,2021,15(5):1031-1048.
[2] Kathleen NLY, Jian X, Philip RS. Trends in prevalence and characteristics of resolved and current hepatitis B among US-born persons: national health and nutrition examination survey, 2001-2018[J]. Infect Dis,2021,224(5):804-812.
[3] Wang J, Shen t, Huang XB, et al. Serum hepatitis B virus RNA is encapsidated pregenome RNA that may be associated with persistence of viral infection and rebound[J]. Hepatology,2016,65(4):700-710.
[4] Liu S, Zhou B, Valdes JD, et al. Serum hepatitis B virus RNA: a new potential biomarker for chronic hepatitis B virus infection[J]. Hepatology, 2019,69(4):1816-1827.
[5] Cerva C, Salpini R, Alkhatib M, et al. Highly sensitive HBsAg, snti-HBc and snti HBsAg titres in early diagnosis of HBV reactivation in anti-HBc-positive onco-haematological patients[J]. Biomedicines,2022,10(2):443.
[6] Liu H, He Z, Gui R, et al. Stratified management based on surface antibody for the prevention of hepatitis B virus reactivation in lymphoma patients[J]. Br J Haematol,2023,203(4):571-580.
[7] Clerico M, Dogliotti I, Ghione P, et al. HBV reactivation in patients with past infection affected by non-hodgkin lymphoma and treated with anti-CD20 antibody based immuno-chemotherapy: a multicenter experience[J]. Pers Med,2022,12(2):285.
[8] Michele S, Giacomo E, Laura D, et al. Safety of targeted prophylaxis strategy in patients with resolved hepatitis B virus infection receiving rituximab for immune-mediated diseases[J]. Eur J Gastroenterol Hepatol,2018,30(7):756-760.
[9] Blanca M, Angela VJ, Castilló J, et al. Hepatitis B reactivation is a rare event among patients with resolved infection undergoing anti-CD20 antibodies in monotherapy without antiviral prophylaxis: results from the HEBEM study[J]. Neurol,2024,271(1):134-140.
[10] Inoue T, Tanaka Y. The role of hepatitis B core-related antigen[J]. Genes,2019,10(5):357.
[11] Revill PA, Chisari FV, Block JM, et al. A global scientific strategy to cure hepatitis B[J].Lancet Gastroenterol Hepatol, 2019, 4(7):545-558.
[12] Gentile G, Antonelli G. HBV reactivation in patients undergoing hematopoietic stem cell transplantation: a narrative review[J].Viruses,2019,11(11):1049.
[13] Elsebaey MA,Elbedewy TA,Elashry H, et al. Resolved hepatitis B infection in patients receiving immunosuppressive therapy: monitor versus prophylaxis against viral reactivation[J].Medicine(Baltimore),2022,101(47):e31962.

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