類風濕性關節炎病人接受免疫抑制治療對B型肝炎病毒再活化之影響

Influence of HBVr on Rheumatoid Arthritis Patients With Immunosuppressive Therapy

王嘉珍(Chia-Chen Wang) ； 蘇建豪(Hien-Hao Su) ； 戴慶玲(Ching-Lin Tai) ； 賴漢明(Han-Ming Lai) ； 陳英州(Ying-Chou Chen)

《臺灣臨床藥學雜誌》 28卷3期 (2020/07) Pp. 219-230

https://doi.org/10.6168/FJCP.202007_28(3).0007

摘要

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）HBVDNA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HBVDNA＞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。

關鍵字

B型肝炎 ； 類風濕性關節炎 ； 生物製劑

並列摘要

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.

並列關鍵字

Hepatitis B ； Rheumatoid Arthritis ； Biological Therapy