Division of Allergy, Immunology, & Rheumatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
Faculty of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
Ann Rheum Dis. 2021 Nov;80(11):1393-1399. doi: 10.1136/annrheumdis-2021-220774. Epub 2021 Jun 29.
Hepatitis B surface antigen (HBsAg) reverse seroconversion (RS) can happen in patients with rheumatoid arthritis (RA) with resolved hepatitis B (RHB) undergoing biological disease-modifying antirheumatic drugs (bDMARDs). But the incidence and risk factors need to be delineated.
From 2003 to 2019, 1937 patients with RA with available HBsAg and antibody to hepatitis B virus (HBV) core antigen data were retrospectively reviewed, and 489 patients with RHB undergoing bDMARDs treatment were identified. Factors associated with HBsAg RS were analysed.
During 67 828 person-months of follow-up, 27 (5.5%) patients developed HBsAg RS after bDMARD treatment. As compared with those without HBsAg RS, patients with HBsAg RS were older, had lower frequency of antibody to HBsAg (anti-HBs), and lower baseline anti-HBs levels. In multivariate analysis, rituximab, abatacept and baseline negative for anti-HBs were the independent risk factors for HBsAg RS (adjusted HR: 87.76, 95% CI: 11.50 to 669.73, p<0.001; adjusted HR: 60.57, 95% CI: 6.99 to 525.15, p<0.001; adjusted HR: 5.15, 95% CI: 2.21 to 12.02, p<0.001, respectively). The risk of HBsAg RS was inversely related to the level of anti-HBs. Both rituximab and abatacept might result in anti-HBs loss, and abatacept had a cumulative incidence of HBsAg RS of 35.4%-62.5% in patients with low titers or negative of anti-HBs.
Not only rituximab, but also abatacept has a high risk of HBV reactivation in patient with RA with RHB. Anti-HBs positivity cannot confer HBV reactivation-free status if the anti-HBs levels are not high enough for patients with RHB on rituximab and abatacept treatment.
乙型肝炎表面抗原（HBsAg）逆转血清转换（RS）可发生于接受生物改善病情抗风湿药物（bDMARDs）治疗的乙型肝炎已恢复（RHB）的类风湿关节炎（RA）患者中。但需要明确其发生率和危险因素。
2003 年至 2019 年，回顾性分析了 1937 例 RA 患者的 HBsAg 和乙型肝炎病毒核心抗原抗体数据，其中 489 例 RHB 患者接受了 bDMARDs 治疗。分析了与 HBsAg RS 相关的因素。
在 67828 人年的随访中，27 例（5.5%）患者在 bDMARD 治疗后发生 HBsAg RS。与未发生 HBsAg RS 的患者相比，发生 HBsAg RS 的患者年龄更大，HBsAg 抗体（抗-HBs）频率更低，基线抗-HBs 水平更低。多因素分析显示，利妥昔单抗、阿巴西普和基线抗-HBs 阴性是 HBsAg RS 的独立危险因素（调整后的 HR：87.76，95%CI：11.50 至 669.73，p<0.001；调整后的 HR：60.57，95%CI：6.99 至 525.15，p<0.001；调整后的 HR：5.15，95%CI：2.21 至 12.02，p<0.001）。HBsAg RS 的风险与抗-HBs 水平呈负相关。利妥昔单抗和阿巴西普均可导致抗-HBs 丢失，在低滴度或抗-HBs 阴性的 RHB 患者中，阿巴西普的 HBsAg RS 累积发生率为 35.4%-62.5%。
不仅利妥昔单抗，阿巴西普也会使 RHB 患者发生乙型肝炎病毒再激活的风险增加。对于接受利妥昔单抗和阿巴西普治疗的 RHB 患者，如果抗-HBs 水平不足以高到足以避免乙型肝炎病毒再激活，则抗-HBs 阳性并不能保证无乙型肝炎病毒再激活状态。
