Gastroenterology Unit, Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy.
Rheumatology Unit, Medical School, University of Bari, Bari, Italy.
Hepatology. 2015 Jul;62(1):40-6. doi: 10.1002/hep.27716. Epub 2015 Feb 24.
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 >1× 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 >1× upper normal limit but not when aminotransferase levels >2× upper normal limit were considered.
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.
在有既往乙型肝炎病毒（HBV）感染已解决（prHBV）的接受长期生物治疗的风湿性疾病患者中，欧洲和亚洲的研究报告了关于 HBV 再激活风险的数据相互矛盾。在此患者人群中，评估了不同免疫抑制性生物疗法的安全性，包括利妥昔单抗。
2001 年至 2012 年间连续收治的 1218 名接受生物治疗的白种人风湿性疾病患者，接受了抗 HCV 和 HBV 标志物以及肝氨基转移酶检查，每 3 个月检查一次。自 2009 年 1 月起，对 2009 年之前和之后开始接受免疫抑制性生物治疗的 prHBV 感染患者进行 HBV DNA 监测。如果在随访期间至少有一次值>1×正常值上限，则认为患者的氨基转移酶水平升高。
我们发现有 179 名 prHBV 感染患者（14 名接受利妥昔单抗治疗，146 名接受抗肿瘤坏死因子-α治疗，19 名接受其他生物治疗）和 959 名无 prHBV 感染或其他肝病的患者（对照组）。前者的平均年龄明显高于对照组。prHBV 感染患者从未出现可检测的 HBV DNA 血清水平或乙型肝炎表面抗原/乙型肝炎表面抗原血清学转换抗体。但是，当比较 prHBV 感染患者和对照组中氨基转移酶升高的发生率时，仅在前者中当氨基转移酶水平>1×正常值上限而非>2×正常值上限时，升高的发生率明显更高。
在有 prHBV 感染和长期生物治疗风湿学适应证的患者中，未观察到 HBV 再激活；这表明在这种临床情况下，普遍预防不合理，也不具有成本效益。
