Seto Wai-Kay, Wong Danny Ka-Ho, Chan Thomas Sau-Yan, Hwang Yu-Yan, Fung James, Liu Kevin Sze-Hang, Gill Harinder, Lam Yuk-Fai, Cheung Ka-Shing, Lie Albert K W, Lai Ching-Lung, Kwong Yok-Lam, Yuen Man-Fung
Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, Hong Kong.
State Key Laboratory for Liver Research, The University of Hong Kong, Queen Mary Hospital, Hong Kong, Hong Kong.
Am J Gastroenterol. 2016 Dec;111(12):1788-1795. doi: 10.1038/ajg.2016.436. Epub 2016 Sep 20.
Hepatitis B core-related antigen (HBcrAg) is a novel serum marker that correlates with intrahepatic hepatitis B virus (HBV) activity. Its association with HBV reactivation in hepatitis B surface antigen (HBsAg)-negative antibody to hepatitis B core antigen (anti-HBc)-positive patients undergoing high-risk immunosuppressive therapy is undefined.
HBcrAg was measured in HBsAg-negative, anti-HBc-positive Asian patients with undetectable HBV DNA, who participated in two prospective studies investigating HBV reactivation during rituximab-containing chemotherapy and allogeneic hematopoietic stem cell transplantation (HSCT). Patients were monitored every 4 weeks for up to 2 years, with entecavir started when HBV reactivation, defined as HBV DNA ≥10 IU ml, developed.
One hundred and twenty-four HBsAg-negative, anti-HBc-positive patients (rituximab, N=62; allogeneic HSCT, N=62) with a median follow-up of 64 weeks (range: 4-104 weeks) were studied. HBV reactivation occurred in 31 patients, with a 2-year cumulative reactivation rate of 40.4%. Serum HBcrAg was detected in 43 (34.7%) patients. Baseline HBcrAg positivity was significantly associated with HBV reactivation (P=0.004, hazard ratio (HR): 2.94, 95% confidence interval (95% CI): 1.43-6.07). HBcrAg-positive patients had a significantly higher 2-year HBV reactivation rate than HBcrAg-negative patients (71.8 vs. 31%, P=0.002). In the rituximab cohort, the HRs for positive HBcrAg and negative antibody to HBsAg for HBV reactivation were 3.65 and 2.84, respectively (P=0.011, 95% CI: 1.35-9.86 and P=0.032, 95% CI: 1.10-7.37, respectively).
Serum HBcrAg positivity is a significant risk factor of HBV reactivation in HBsAg-negative, anti-HBc-positive patients undergoing high-risk immunosuppressive therapy and can potentially have a role in identifying patients who will best benefit from prophylactic nucleoside analogue treatment.
乙型肝炎核心相关抗原（HBcrAg）是一种新型血清标志物，与肝内乙型肝炎病毒（HBV）活性相关。在接受高风险免疫抑制治疗的乙型肝炎表面抗原（HBsAg）阴性、乙型肝炎核心抗体（抗-HBc）阳性患者中，其与HBV再激活的关联尚不清楚。
在HBsAg阴性、抗-HBc阳性且HBV DNA检测不到的亚洲患者中检测HBcrAg，这些患者参与了两项前瞻性研究，调查含利妥昔单抗化疗和异基因造血干细胞移植（HSCT）期间的HBV再激活情况。每4周对患者进行监测，最长监测2年，当出现HBV再激活（定义为HBV DNA≥10 IU ml）时开始使用恩替卡韦。
研究了124例HBsAg阴性、抗-HBc阳性患者（利妥昔单抗组，N = 62；异基因HSCT组，N = 62），中位随访时间为64周（范围：4 - 104周）。31例患者发生了HBV再激活，2年累积再激活率为40.4%。43例（34.7%）患者检测到血清HBcrAg。基线HBcrAg阳性与HBV再激活显著相关（P = 0.004，风险比（HR）：2.94，95%置信区间（95%CI）：1.43 - 6.07）。HBcrAg阳性患者的2年HBV再激活率显著高于HBcrAg阴性患者（71.8%对31%，P = 0.002）。在利妥昔单抗队列中，HBcrAg阳性和HBsAg阴性抗体对于HBV再激活的HR分别为3.65和2.84（P = 0.011，95%CI：1.35 - 9.86和P = 0.032，95%CI：1.10 - 7.37）。
血清HBcrAg阳性是接受高风险免疫抑制治疗的HBsAg阴性、抗-HBc阳性患者发生HBV再激活的重要危险因素，并且可能在识别最能从预防性核苷类似物治疗中获益的患者方面发挥作用。
