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肿瘤坏死因子-α 阻断剂在乙肝病毒阳性患者中的应用:3例报告及文献复习

Use of tumor necrosis factor-alpha-blocking agents in hepatitis B virus-positive patients: reports of 3 cases and review of the literature.

作者信息

Zingarelli Stefania, Frassi Micol, Bazzani Chiara, Scarsi Mirko, Puoti Massimo, Airò Paolo

机构信息

Rheumatology and Clinical Immunology Service, Infectious and Tropical Diseases Department, Spedali Civili and University of Brescia, Brescia, Italy.

出版信息

J Rheumatol. 2009 Jun;36(6):1188-94. doi: 10.3899/jrheum.081246. Epub 2009 May 15.

Abstract

OBJECTIVE

To evaluate the development of hepatitis B virus (HBV) infection in patients receiving tumor necrosis factor-alpha-blocking agents (TNFBA), and to evaluate whether lamivudine (LAM) prophylaxis can reduce the risk of viral reactivation in inactive HBsAg carriers.

METHODS

Local experience and published reports were reviewed. Patients with HBV infection were classified as having chronic HBV hepatitis, or being inactive HBsAg carriers or occult carriers.

RESULTS

Three patients in our series and 24 patients in the literature were identified: 2 had active HBV-associated disease, 23 were inactive HBsAg carriers, and 2 occult carriers. When exposed to TNFBA, HBsAg-inactive carriers pretreated with LAM had lower risk of having detectable HBV-DNA (p=0.02) or viral reactivation (p=0.046) than those without LAM prophylaxis. In 3 patients who discontinued TNFBA, LAM prophylaxis was also discontinued 10-12 months thereafter without hepatitis flares. Two cases of reactivation in occult carriers (HBsAg-negative, anti-HBs+, anti-HBc+) were described in the literature.

CONCLUSION

TNFBA should be avoided in patients with active HBV replication and should be used with caution in inactive HBsAg carriers. In these patients, the risk of viral reactivation seems to be high, but it might be reduced by prophylactic LAM, which should probably be given for a long time when TNFBA are discontinued (e.g., 12 mo). Potential occult carriers might carry a low, but not negligible, risk of viral reactivation. They should therefore be monitored with particular care.

摘要

目的

评估接受肿瘤坏死因子-α阻断剂(TNFBA)治疗的患者中乙型肝炎病毒(HBV)感染的发展情况,并评估拉米夫定(LAM)预防是否可降低HBsAg阴性携带者病毒再激活的风险。

方法

回顾了当地经验及已发表的报告。将HBV感染患者分为慢性HBV肝炎患者、HBsAg阴性携带者或隐匿性携带者。

结果

本研究系列中有3例患者,文献中报道了24例患者:2例患有活动性HBV相关疾病,23例为HBsAg阴性携带者,2例为隐匿性携带者。在接触TNFBA时,接受LAM预处理的HBsAg阴性携带者与未接受LAM预防的携带者相比,HBV-DNA可检测到的风险较低(p=0.02)或病毒再激活的风险较低(p=0.046)。在3例停用TNFBA的患者中,LAM预防在10-12个月后也停用,未出现肝炎发作。文献中描述了2例隐匿性携带者(HBsAg阴性、抗-HBs阳性、抗-HBc阳性)的再激活病例。

结论

活动性HBV复制患者应避免使用TNFBA,HBsAg阴性携带者应谨慎使用。在这些患者中,病毒再激活的风险似乎很高,但预防性使用LAM可能会降低该风险,在停用TNFBA时(如12个月)可能需要长期使用LAM。潜在隐匿性携带者可能具有较低但不可忽视的病毒再激活风险。因此,应对其进行特别密切的监测。

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