Carroll Matthew B, Bond Michael I
San Antonio Uniformed Services Health Education Consortium (SAUSHEC), Wilford Hall Medical Center, Lackland Air Force Base, Lackland, Texas, USA.
Semin Arthritis Rheum. 2008 Dec;38(3):208-17. doi: 10.1016/j.semarthrit.2007.10.011. Epub 2008 Jan 25.
Tumor necrosis factor-alpha (TNF-alpha) inhibitors have emerged as a potent treatment for rheumatoid arthritis (RA), but not without significant risks. In chronic hepatitis B viral infection TNF-alpha is readily produced, and viral clearance is dependent on the amount bioavailable. Limited data suggest that TNF-alpha inhibitors may facilitate uncontrolled hepatitis B viral replication. The purpose of this article was to provide a detailed review of the role of TNF-alpha in controlling hepatitis B viral infection and the clinical impact blockade might have on viral control.
We describe a patient with chronic hepatitis B viral infection and RA treated with etanercept. We then review case reports, expert opinion, and manufacturer recommendations regarding hepatitis B viral infection, TNF-alpha, and TNF-alpha inhibitors.
To date, 13 patients with chronic hepatitis B infection treated with TNF-alpha inhibitors have been reported: 11 with infliximab and 2 with etanercept. Some patients received antiviral therapy for hepatitis B (specifically lamivudine) before, during, or after TNF-alpha inhibitors were started. Clinically apparent reactivation of hepatitis B virus typically occurred 1 month after the 3rd dose of infliximab. Etanercept was not associated with a similar reactivation. The difference between infliximab and etanercept in viral reactivation may be linked to the pharmacologic difference of each medication.
TNF-alpha inhibitors in general should be used cautiously in chronic hepatitis B viral infection. But if necessary, when deciding which agent to use, the clinician should consider the mechanism by which the body clears TNF-alpha.
肿瘤坏死因子-α(TNF-α)抑制剂已成为类风湿关节炎(RA)的一种有效治疗方法,但并非没有显著风险。在慢性乙型肝炎病毒感染中,TNF-α很容易产生,且病毒清除取决于生物可利用量。有限的数据表明,TNF-α抑制剂可能会促进乙型肝炎病毒的不受控制复制。本文的目的是详细综述TNF-α在控制乙型肝炎病毒感染中的作用以及阻断TNF-α对病毒控制可能产生的临床影响。
我们描述了一名接受依那西普治疗的慢性乙型肝炎病毒感染合并RA患者。然后我们回顾了关于乙型肝炎病毒感染、TNF-α和TNF-α抑制剂的病例报告、专家意见及制造商建议。
迄今为止,已报道13例接受TNF-α抑制剂治疗的慢性乙型肝炎感染患者:11例使用英夫利昔单抗,2例使用依那西普。一些患者在开始使用TNF-α抑制剂之前、期间或之后接受了乙型肝炎抗病毒治疗(特别是拉米夫定)。乙型肝炎病毒的临床明显再激活通常发生在第3剂英夫利昔单抗后1个月。依那西普未出现类似的再激活情况。英夫利昔单抗和依那西普在病毒再激活方面的差异可能与每种药物的药理差异有关。
一般而言,TNF-α抑制剂在慢性乙型肝炎病毒感染中应谨慎使用。但如有必要,在决定使用哪种药物时,临床医生应考虑机体清除TNF-α的机制。