Safety of long-term biologic therapy in rheumatologic patients with a previously resolved hepatitis B viral infection
Safety of long-term biologic therapy in rheumatologic patients with a previously resolved hepatitis B viral infection
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DOI：
10.1002/hep.27716
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发表时间：
2015-07-01
期刊：
影响因子：
13.5
通讯作者：
Lapadula, Giovanni
中科院分区：
文献类型：
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作者：
Barone, Michele;Notarnicola, Antonella;Lapadula, Giovanni
欧洲和亚洲的研究报告了关于既往已消退的HBV（prHBV）感染的风湿病患者接受长期生物治疗后再激活B型肝炎病毒（HBV）风险的相互矛盾的数据。在这类患者中，评估了不同免疫抑制生物治疗（包括利妥昔单抗）的安全性。2001年至2012年期间，共有1218名白人风湿病患者连续门诊入院并接受生物治疗，每3个月进行一次抗HCV和HBV标志物以及肝脏氨基转移酶的评价。从2009年1月开始，在2009年之前和之后开始免疫抑制生物治疗的prHBV感染患者中进行HBV DNA监测。如果在随访期间至少有一次数值> 1倍正常上限，则认为患者的转氨酶水平升高。我们发现了179例prHBV感染患者（14例接受利妥昔单抗治疗，146例接受抗肿瘤坏死因子-α治疗，19例接受其他生物治疗）和959例无prHBV感染或其他肝病患者（对照组）。前者的平均年龄明显高于对照组。prHBV感染的患者从未显示出可检测的HBV DNA血清水平或B型肝炎表面抗原抗体/B型肝炎表面抗原血清逆转。然而，当将prHBV感染患者中氨基转移酶升高的患病率与对照组进行比较时，前者仅在转氨酶水平> 1倍正常上限时显著较高，而当转氨酶水平> 2倍正常上限时则不显著。结论：在具有prHBV感染和长期生物治疗的风湿病适应症的患者中，未观察到HBV再激活;这表明在这种临床环境中，普遍预防是不合理的，也不具有成本效益。（肝病学2015;62：40-46）
European and Asian studies report conflicting data on the risk of hepatitis B virus (HBV) reactivation in rheumatologic patients with a previously resolved HBV (prHBV) infection undergoing long-term biologic therapies. In this patient category, the safety of different immunosuppressive biologic therapies, including rituximab, was assessed. A total of 1218 Caucasian rheumatologic patients, admitted consecutively as outpatients between 2001 and 2012 and taking biologic therapies, underwent evaluation of anti-HCV and HBV markers as well as liver amino transferases every 3 months. Starting from January 2009, HBV DNA monitoring was performed in patients with a prHBV infection who had started immunosuppressive biologic therapy both before and after 2009. Patients were considered to have elevated aminotransferase levels if values were >1x upper normal limit at least once during follow-up. We found 179 patients with a prHBV infection (14 treated with rituximab, 146 with anti-tumor necrosis factor-alpha, and 19 with other biologic therapies) and 959 patients without a prHBV infection or other liver disease (controls). The mean age in the former group was significantly higher than the controls. Patients with a prHBV infection never showed detectable HBV DNA serum levels or antibody to hepatitis B surface antigen/hepatitis B surface antigen seroreversion. However, when the prevalence of elevated amino transferases in patients with prHBV infection was compared to controls, it was significantly higher in the former group only for aminotransferase levels >1x upper normal limit but not when aminotransferase levels >2x upper normal limit were considered. Conclusion: Among patients with a prHBV infection and rheumatologic indications for long-term biologic therapies, HBV reactivation was not seen; this suggests that universal prophylaxis is not justified and is not cost-effective in this clinical setting. (Hepatology 2015;62:40-46)