Jang Jeong Won, Kim Young Woon, Lee Sung Won, Kwon Jung Hyun, Nam Soon Woo, Bae Si Hyun, Choi Jong Young, Yoon Seung Kew, Chung Kyu Won
Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
Department of Internal Medicine, The Catholic University of Korea Incheon St. Mary's Hospital, Incheon, Korea.
PLoS One. 2015 Apr 20;10(3):e0122041. doi: 10.1371/journal.pone.0122041. eCollection 2015.
BACKGROUND & AIMS: Despite increasing attention to hepatitis B virus (HBV) reactivation in hematologic settings, information on reactivation in hepatitis B surface (HBsAg)-negative patients with hepatocellular carcinoma (HCC) remains unknown. This study aimed to determine the incidence and risk factors of HBV reactivation in HBsAg-negative patients undergoing transarterial chemoembolization (TACE).
A total of 109 HBsAg-negative patients with HCC were consecutively recruited for this study and treated with either mono- (n = 75), combination-drug TACE (n = 20), or combination-drug TACE plus radiotherapy (n = 14). With serial monitoring of virological markers every 2-3 months, patients were observed for HBV reactivation (defined as the reappearance of HBV DNA or sero-reversion of HBsAg) in comparison with control subjects with HBsAg-negative cirrhosis (n = 16) or HBsAg loss (n = 46).
During the study period, HBV reactivation occurred in 12 (11.0%) and 1 (1.6%) patients in the TACE and control groups, respectively. The median level of HBV DNA at reactivation was 5,174 copies/ml (range: 216-116,058). Of the 12 patients with HBV reactivation, four (33.3%) developed clinical hepatitis, including one patient who suffered from decompensation. All antiviral-treated patients achieved undetectable HBV DNA or HBsAg loss after commencement of antiviral drugs. TACE was significantly correlated with a high incidence of HBV reactivation, with increasing risk of reactivation with intensive treatment. On multivariate analysis, treatment intensity and a prior history of chronic hepatitis B remained independently predictive of reactivation.
TACE can reactivate HBV replication in HBsAg-negative patients, with a dose-risk relationship between treatment intensity and reactivation. Patients with prior chronic HBV infection who are to undergo intensive TACE should be closely monitored, with an alternative approach of antiviral prophylaxis against HBV reactivation.
尽管血液学领域对乙型肝炎病毒（HBV）再激活的关注日益增加，但关于乙型肝炎表面抗原（HBsAg）阴性的肝细胞癌（HCC）患者再激活的信息仍不明确。本研究旨在确定接受经动脉化疗栓塞术（TACE）的HBsAg阴性患者中HBV再激活的发生率及危险因素。
本研究连续纳入了109例HBsAg阴性的HCC患者，分别接受单纯TACE治疗（n = 75）、联合药物TACE治疗（n = 20）或联合药物TACE加放疗（n = 14）。每2 - 3个月对病毒学标志物进行连续监测，观察患者的HBV再激活情况（定义为HBV DNA重新出现或HBsAg血清学逆转），并与HBsAg阴性肝硬化患者（n = 16）或HBsAg消失患者（n = 46）作为对照。
在研究期间，TACE组和对照组分别有12例（11.0%）和1例（1.6%）患者发生HBV再激活。再激活时HBV DNA的中位水平为5174拷贝/ml（范围：216 - 116,058）。在12例HBV再激活患者中，4例（33.3%）发生了临床肝炎，其中1例出现失代偿。所有接受抗病毒治疗的患者在开始使用抗病毒药物后均实现了HBV DNA检测不到或HBsAg消失。TACE与HBV再激活的高发生率显著相关，强化治疗会增加再激活风险。多因素分析显示，治疗强度和既往慢性乙型肝炎病史仍然是再激活的独立预测因素。
TACE可使HBsAg阴性患者的HBV复制再激活，治疗强度与再激活之间存在剂量 - 风险关系。既往有慢性HBV感染且即将接受强化TACE治疗的患者应密切监测，可采用抗病毒预防措施以防止HBV再激活。
