目的：藉由病歷回顧評估免疫抑制劑對於B 型肝炎病毒表面抗原 (hepatitis B surface antigen, HBsAg [+]) 類風濕性關節炎 (rheumatoid arthritis, RA) 病人之B 型肝炎病毒再活化 (hepatitis B virus reactivation, HBVr) 的影響。
方法：回顧分析2002 年1 月至2017 年6 月間在某醫學中心檢測HBsAg 的RA病人。藥品暴露：指接受類固醇 (glucocorticoid, GC)、單一合成疾病調節抗風濕藥品 (synthetic disease-modifying antirheumatic drugs, sDMARDs) 或生物性疾病調節抗風濕藥品 (biological disease-modifying antirheumatic drugs, bDMARDs) ≥ 4 週。HBVr 之定義：(1) HBV DNA 增加 ≥ 10 倍；(2) 無藥品使用前HBV 病毒量者，血清丙胺酸轉胺酶 (alanine aminotransferase, ALT) 增加3 倍，伴隨HBV DNA > 100,000 copies/mL（20,000 IU/mL）。
結果：開始使用免疫抑制劑至發生HBVr 的中位時間為24.3 個月。男性在HBVr組有18 位，明顯高於非HBVr 組 (p = 0.002)。葉酸拮抗劑 (methotrexate, MTX) 使用者，在HBVr 組明顯高於非HBVr 組（78% 和44.7%, p = 0.000）。使用Kaplan–Meier 方法分析病人使用MTX 發生HBVr 累積風險，Log-rank test 檢測具統計學意義 (p = 0.026)。
結論：我們研究結果顯示MTX 可能增加HBsAg (+) RA 病人HBVr 風險，但是，不同類型bDMARD 導致RA 病人HBVr 風險程度，仍有待更多研究證實。

Objective: This study aimed to evaluate the impact of immunosuppressive agents on hepatitis B virus reactivation (HBVr) in the hepatitis B surface antigen-positive (HBsAg [+]) cases through medical record review of rheumatoid arthritis (RA) patients.
Methods: We retrospectively reviewed medical records of RA patients who had available HBsAg data in the medical center between January 2002 and June 2017. A drug exposure meant a patient took glucocorticoid (GC), synthetic disease-modifying antirheumatic drugs (sDMARDs), or biological disease-modifying antirheumatic drugs (bDMARDs) for more than 4 weeks. HBVr was defined as either an increase in HBV DNA ≥ 10 times compared with baseline or 3-fold increase in serum alanine aminotransferase (ALT) level accompanied with HBV DNA > 100,000 copies/mL (20,000 IU/mL) in cases without baseline HBV load.
Results: The median time of HBVr was 24.3 months after immunosuppressants. There were 18 males in the HBVr group, which was significantly higher than without the HBVr group (p = 0.02). The frequency of the methotrexate (MTX) use in patients with HBVr versus was significantly higher than those without HBVr (78% vs. 44.7%, p = 0.000). Kaplan–Meier method was used to analyze the cumulative risk of HBVr in RA patients using the MTX and Log-rank test showed statistically significant (p = 0.026).
Conclusions: Our study result showed that MTX may increase the risk of HBVr in HBsAg-positive RA patients. Therefore, more research is needed to confirm the risk of HBVr in RA patients caused by a different type of bDMARD.


Summited for publication: 2019.9.20; Accepted for publication: 2020.3.17