Braun-Moscovici Yolanda, Braun Marius, Saadi Tarek, Markovits Doron, Nahir Menahem A, Balbir-Gurman Alexandra
From the *B. Shine Rheumatology Unit, Rambam Health Care Campus, B. Rappaport Faculty of Medicine, Technion-Israeli Institute of Technology, Haifa; †Liver Institute, Beilinson Hospital, Petah Tikva; and ‡Liver Unit, Rambam Health Care Campus, Haifa, Israel.
J Clin Rheumatol. 2016 Oct;22(7):364-8. doi: 10.1097/RHU.0000000000000434.
Immunosuppressive agents may induce hepatitis B flares. The minimal corticosteroid dose and duration of therapy leading to HBV reactivation is unknown.
To assess whether short-term corticosteroid therapy for rheumatologic diseases induces HBV reactivation.
The records of all HBsAg or HBcore antibodies positive, anti-HBs negative patients who were hospitalized in the rheumatology department during 2001-2014 and treated with corticosteroids were reviewed. Alanine aminotransferase (ALT), HBV serology, and serum HBV DNA at baseline and 1-3 months after discharge were recorded.
Complete data were found for 23 patients who were hospitalized 73 times for 7 days of treatment with IV corticosteroids. Eighteen patients were HBsAg positive. The mean methylprednisolone dose was 33.9 ± 24 mg/d. The concomitant therapy included DMARDs (15), low-dose corticosteroids (8), and biologicals (10). Serum HBV DNA was detected at baseline in seven patients. Three HBsAg-positive patients treated with cyclophosphamide had HBV hepatitis flare-up with elevated ALT. Two HBsAg-positive patients had reappearance of HBV DNA in serum after treatment with azathioprine and infliximab, respectively, but the ALT levels remained normal. Lamivudine therapy reduced the serum HBV DNA and improved ALT levels in all patients. Corticosteroid therapy by itself did not trigger exacerbation of HBV hepatitis. No HBV reactivation occurred in lamivudine-treated patients after recurrent exposure to biologicals or cyclophosphamide.
Short episodes of corticosteroids seem to be safe in HBV carriers, even in the presence of DMARDs, but lamivudine prophylaxis should be considered for patients exposed to biologicals or cyclophosphamide. Larger prospective trials are needed to establish guidelines.
免疫抑制剂可能诱发乙型肝炎复发。导致乙肝病毒再激活的最小糖皮质激素剂量和治疗持续时间尚不清楚。
评估用于治疗风湿性疾病的短期糖皮质激素疗法是否会诱发乙肝病毒再激活。
回顾了2001年至2014年期间在风湿科住院并接受糖皮质激素治疗的所有乙肝表面抗原（HBsAg）或乙肝核心抗体阳性、乙肝表面抗体阴性患者的病历。记录了基线时以及出院后1至3个月时的丙氨酸转氨酶（ALT）、乙肝血清学指标和血清乙肝病毒DNA。
发现23例患者的完整数据，这些患者因静脉注射糖皮质激素治疗7天而住院73次。18例患者乙肝表面抗原阳性。甲泼尼龙的平均剂量为33.9±24毫克/天。联合治疗包括改善病情抗风湿药（15例）、小剂量糖皮质激素（8例）和生物制剂（10例）。7例患者在基线时检测到血清乙肝病毒DNA。3例接受环磷酰胺治疗的乙肝表面抗原阳性患者出现乙肝病毒肝炎复发，ALT升高。2例乙肝表面抗原阳性患者分别在接受硫唑嘌呤和英夫利昔单抗治疗后血清中再次出现乙肝病毒DNA，但ALT水平仍正常。拉米夫定治疗降低了所有患者的血清乙肝病毒DNA水平并改善了ALT水平。糖皮质激素治疗本身并未引发乙肝病毒肝炎加重。在拉米夫定治疗的患者中，再次接触生物制剂或环磷酰胺后未发生乙肝病毒再激活。
短期使用糖皮质激素对乙肝病毒携带者似乎是安全的，即使同时使用改善病情抗风湿药，但对于接触生物制剂或环磷酰胺的患者应考虑预防性使用拉米夫定。需要进行更大规模的前瞻性试验以制定指南。
