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托珠单抗治疗的类风湿关节炎患者乙型肝炎病毒再激活的风险。

Risk of Hepatitis B Virus Reactivation in Rheumatoid Arthritis Patients Undergoing Tocilizumab-Containing Treatment.

机构信息

Department of Pharmacy, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chia-Yi, Taiwan.

School of Medicine, Tzuchi University, Hualien, Taiwan.

出版信息

Dig Dis Sci. 2021 Nov;66(11):4026-4034. doi: 10.1007/s10620-020-06725-1. Epub 2021 Jan 2.

Abstract

BACKGROUND AND AIM

To investigate the risk of hepatitis B virus reactivation in patients undergoing long-term tocilizumab therapy for rheumatoid arthritis.

METHOD

From January 2011 through August 2019, a total of 97 patients were enrolled in this retrospective study. Clinical data, comedications, and the occurrence of HBV reactivation were recorded.

RESULTS

Seven patients were HBsAg+ (7.2%), 64 were HBsAg-/HBcAb+ (65.9%), and 26 were HBsAg-/HBcAb- (26.8%). The median disease follow-up time was 9 years. TCZ was administered for a median of 29 months. Four patients (4.1%) experienced HBV reactivation after tocilizumab therapy. Of the 7 HBsAg+ patients, 4 received antiviral prophylaxis and had no HBV reactivation; the remaining 3 patients did not receive antiviral prophylaxis, and all 3 (100%) experienced HBV reactivation and hepatitis flare-up. Hyperbilirubinemia occurred in 2 of these 3 patients, with mild prothrombin time prolongation in one. After salvage entecavir treatment, all patients had a favorable outcome. Of the 64 HBsAg-/HBcAb+ patients, only one became positive for serum HBV DNA (2.5 × 10 IU/mL) after 18 months of tocilizumab treatment (1.6%; 1/64). This patient was immediately treated with entecavir, which prevented hepatitis flare-up.

CONCLUSIONS

Tocilizumab is widely used in treating rheumatoid arthritis and has the potential to reduce the mortality rate among severe COVID-19 patients. However, HBV reactivation needs to be considered. HBsAg+ patients have a high risk of HBV reactivation, which could be prevented by antiviral prophylaxis. Although the risk of reactivation is low in HBsAg-/HBcAb+ patients, strict monitoring is necessary.

摘要

背景与目的

研究接受托珠单抗治疗类风湿关节炎的患者发生乙型肝炎病毒(HBV)再激活的风险。

方法

本回顾性研究共纳入 97 例患者,时间为 2011 年 1 月至 2019 年 8 月。记录患者的临床资料、合并用药情况和 HBV 再激活的发生情况。

结果

7 例患者 HBsAg+(7.2%),64 例患者 HBsAg-/HBcAb+(65.9%),26 例患者 HBsAg-/HBcAb-(26.8%)。中位疾病随访时间为 9 年,托珠单抗治疗中位时间为 29 个月。4 例(4.1%)患者在托珠单抗治疗后发生 HBV 再激活。7 例 HBsAg+患者中,4 例接受抗病毒预防治疗,均未发生 HBV 再激活;3 例未接受抗病毒预防治疗,均发生 HBV 再激活和肝炎发作(100%)。其中 2 例患者出现高胆红素血症,1 例患者出现轻微的凝血酶原时间延长。经恩替卡韦挽救治疗后,所有患者预后良好。64 例 HBsAg-/HBcAb+患者中,1 例患者在托珠单抗治疗 18 个月后乙型肝炎病毒脱氧核糖核酸(HBV DNA)转为阳性(2.5×10 IU/ml,1.6%;1/64),立即给予恩替卡韦治疗,预防了肝炎发作。

结论

托珠单抗广泛用于治疗类风湿关节炎,有降低重症 COVID-19 患者死亡率的潜力,但需要考虑 HBV 再激活的问题。HBsAg+患者 HBV 再激活风险高,可通过抗病毒预防治疗来预防。HBsAg-/HBcAb+患者的再激活风险虽低,但需要严格监测。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff02/7775841/0205a51167ce/10620_2020_6725_Fig1_HTML.jpg

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