Clinical characteristics and molecular analysis of hepatitis B virus reactivation in hepatitis B surface antigen-negative patients during or after immunosuppressive or cytotoxic chemotherapy
Clinical characteristics and molecular analysis of hepatitis B virus reactivation in hepatitis B surface antigen-negative patients during or after immunosuppressive or cytotoxic chemotherapy
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DOI：
10.1007/s00535-016-1187-z
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发表时间：
2016-11-01
影响因子：
6.3
通讯作者：
Hirooka, Yoshiki
中科院分区：
文献类型：
--
作者：
Hayashi, Kazuhiko;Ishigami, Masatoshi;Hirooka, Yoshiki
在接受免疫抑制或细胞毒性化疗的乙肝表面抗原（HBsAg）阳性患者中乙肝病毒（HBV）的再激活是众所周知的，并已成为一个重要的临床问题。风险较低，但hbsag阴性患者在HBV感染消退后也会发生HBV再激活；然而，临床和病毒学特征仍不清楚。我们调查了在免疫抑制或细胞毒性化疗期间或之后发生HBV再激活的hbsag阴性患者，以阐明临床和病毒学特征。研究了30例先前感染的hbsag阴性患者在免疫抑制或细胞毒性化疗期间或之后的HBV再激活情况。再激活时的直接测序用于评估11例患者。大多数患者弥漫性大B细胞淋巴瘤采用利妥昔单抗联合环磷酰胺、阿霉素、长春新碱和强的松龙治疗。3例患者发生暴发性肝功能衰竭，没有存活。检测到HBV亚型A2/Ae （n = 1）、B1/Bj （n = 2）和C2/Ce （n = 8）。HBV再激活组和急性自限性肝炎患者之间BCP/PC变异的患病率无显著差异。BCP和PC变异与HBV再激活引起的暴发性肝衰竭的发展无关。HBV S区变异（包括免疫逃逸突变）在再激活患者中的流行率明显高于急性自限性肝炎患者。再激活的危险因素包括男性、高龄和血液恶性肿瘤。在免疫抑制或细胞毒性化疗期间或之后的hbsag阴性再激活患者中经常发现HBV S基因免疫逃逸突变体。
Reactivation of hepatitis B virus (HBV) in hepatitis B surface antigen (HBsAg)-positive patients treated with immunosuppressive or cytotoxic chemotherapy is well known and has emerged as an important clinical issue. The risk is low, but reactivation of HBV in HBsAg-negative patients after resolution of HBV infection also occurs; however, the clinical and virological characteristics remain somewhat unclear. We investigated HBsAg-negative patients who developed HBV reactivation during or after immunosuppressive or cytotoxic chemotherapy to clarify the clinical and virological features.Reactivation of HBV in 30 previously infected that is HBsAg-negative patients during or after immunosuppressive or cytotoxic chemotherapy was examined. Direct sequencing at the time of reactivation was used to evaluate 11 patients.The majority of patients had diffuse large B cell lymphoma treated by rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisolone. Fulminant hepatic failure developed in three patients, who did not survive. HBV subgenotypes A2/Ae (n = 1), B1/Bj (n = 2), and C2/Ce (n = 8) were detected. There were no significant differences in the prevalence of BCP/PC variants between HBV reactivation and acute self-limited hepatitis patient groups. BCP and PC variants were not associated with development of fulminant hepatic failure from HBV reactivation. The prevalence of HBV S region variants, including immune-escape mutants, among reactivation patients was significantly higher than that in acute self-limited hepatitis patients.Reactivation risk factors included male sex, advanced age, and hematological malignancy. HBV S gene immune-escape mutants were frequently found in the HBsAg-negative reactivation patients during or after immunosuppressive or cytotoxic chemotherapy.