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摘要：
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摘要：目的 探讨非活动性乙型肝炎病毒表面抗原（hepatitis B virus surface antigen，
HBsAg）携带者乙型肝炎病毒（hepatitis B virus，HBV）再激活的发生率及临床特征。
方法 以2014年1月至2019年12月于深圳市第三人民医院随访的64例非活动性HBsAg携
带者为研究对象，6～12个月随访1次，收集HBV再激活发生情况、肝功能 [包括丙氨
酸氨基转移酶（alanine aminotransferase，ALT）、天门冬氨酸氨基转移酶（aspartate
aminotransferase，AST）、总胆红素（total bilirubin，TBil）和γ-谷氨酰转移酶（gammaglutamyltransferase，GGT）] 及肝组织病理学结果、HBV再激活发生后的临床结局等。
采用Kaplan-Meier法估计累积HBV再激活率；采用单因素和多因素Cox比例风险模型进
行HBV再激活的影响因素分析。结果 与基线相比，发现HBV再激活时研究对象的ALT
[7.69%（2/26）vs 0%（0/26）]、AST [0%（0/26）vs 0%（0/26）]、TBil [19.23%（5/26）
vs 19.23%（5/26）]和GGT [3.85%（1/26）vs 0%（0/26）] 异常率差异均无统计学意义（P
均 ＞ 0.05）。基线和发现HBV再激活时研究对象HBV DNA ≥ 2000 IU/ml比例分别为0%
（0/26）、46.15%（12/26），差异有统计学意义（χ
2
= 15.600，P ＜ 0.001）；HBV
再激活者基线HBeAg均为阴性，发现HBV再激活时有1例HBeAg复阳（P = 1.000）。
HBV再激活后共6例进行了肝脏穿刺病理检查，4例为G1S1，1例为G1-2S2，1例为
G1S2。多因素Cox比例风险模型分析表明基线HBV DNA ≥ 100 IU/ml者发生HBV
再激活的风险是基线HBV DNA ＜ 100 IU/ml者的2.62倍（HR = 2.62，95%CI：
1.04～6.58，P = 0.041）。随访12个月时累积HBV再激活率为37.1%（26/64，95%CI：
21.4%～49.6%）。基线HBV DNA ≥ 100 IU/ml者随访12个月时累积HBV再激活率
（43.8%，95%CI：22.4%～59.3%）显著高于基线HBV DNA ＜ 100 IU/ml者（24.3%，
95%CI：2.9%～40.9%），差异有统计学意义（Log-rank χ2 = 4.50，P = 0.03）。HBV再
激活后的2次随访发现，累积3例未经抗病毒治疗实现病毒学抑制，5例启动抗病毒治疗
后实现了病毒学抑制，1例实现HBsAg自发清除；随访患者ALT均在正常范围内。结论
非活动性HBsAg携带者可出现HBV再激活，基线较高的HBV DNA水平（≥ 100 IU/ml）
是非活动性HBsAg携带者HBV再激活的独立危险因素。提示对于非活动性HBsAg携带
者应加强随访，及时发现HBV再激活，并对HBV再激活者采取更积极的组织学检查和
抗病毒治疗策略。
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Abstract: Objective To investigate the incidence and clinical characteristics of hepatitis
B virus (HBV) reactivation in inactive hepatitis B virus surface antigen (HBsAg) carriers.
Methods A total of 64 inactive HBsAg carriers in Shenzhen Third People’s Hospital from
January 2014 to December 2019 were enrolled and followed up every 6～12 months.
Information including HBV reactivation, liver biochemistry [alanine aminotransferase (ALT),
aspartate aminotransferase (AST), total bilirubin (TBil) and gamma-glutamyltransferase
(GGT)], pathological characteristics of liver injury and outcomes of HBV reactivation were
collected during the following-up. Kaplan-Meier method was used to estimate cumulative
probabilities of HBV reactivation and multivariable Cox proportional hazards model was
used to explore the risk factors of HBV reactivation. Results Compared with baseline, there
were no significant differences on the abnormal rate of ALT [7.69% (2/26) vs 0% (0/26)], AST
[0% (0/26) vs 0% (0/26)], TBil [19.23% (5/26) vs 19.23% (5/26)] and GGT [3.85% (1/26)
vs 0% (0/26)] of objects when HBV reactivation was found. The ratio of objects with HBV DNA ≥
2000 IU/ml were 0% (0/26) and 46.15% (12/26) on baseline and when HBV reactivation
was found, respectively, and the difference was statistically significant (χ
2
= 15.600, P ＜
0.001). HBeAg of objects with HBV reactivation was negative on baseline, and there was one
case whose HBeAg converted from negative to positive when HBV reactivation was found
(P = 1.000). A total of six cases underwent liver puncture pathology after HBV reactivation,
among whom four patients presented G1S1, one presented G1-2S2 and one presented G1S2,
respectively. Multivariable Cox proportional hazards model showed that patients with baseline
HBV DNA ≥ 100 IU/ml had a 2.62-fold risk of HBV reactivation than those with baseline
HBV DNA ＜ 100 IU/ml (HR = 2.62, 95%CI: 1.04～6.58, P = 0.041). The cumulative
probabilities of HBV reactivation was 37.1% (26/64, 95%CI: 21.4%～49.6%) at 12 months
of follow-up. The cumulative probabilities of HBV reactivation in patients with baseline
HBV DNA ≥ 100 IU/ml (43.8%, 95%CI: 22.4%～59.3%) was significantly higher than that
in patients with baseline HBV DNA ＜ 100 IU/ml (24.3%, 95%CI: 2.9%～40.9%), and the
difference was statistically significant (Log-rank χ2 = 4.50, P = 0.03). During the follow-up
after HBV reactivation, a total of 3 cases achieved HBV DNA suppression, without antiviral
therapy, 5 cases achieved HBV DNA suppression after antiviral therapy, one case achieved HBsAg
clearance, and all the patients presented normal ALT levels. Conclusions HBV reactivation
can occur in inactive HBsAg carriers. Higher baseline HBV DNA level (≥ 100 IU/ml) was an
independent risk factor of HBV reactivation. Surveillance should be strengthened in inactive
HBsAg carriers to detect HBV reactivation timely. Histology examination and aggressive antiviral
strategy are necessary for HBsAg carriers with HBV reactivation.
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