类风湿关节炎患者接受利妥昔单抗治疗时HBsAg阴性/抗-HBc阳性携带者的乙肝病毒再激活风险低：一项意大利多中心回顾性研究
Low Risk of Hepatitis B Virus Reactivation in HBsAg-negative/Anti-HBc-positive Carriers Receiving Rituximab for Rheumatoid Arthritis: A Retrospective Multicenter Italian Study.
作者信息
Varisco Valentina, Viganò Mauro, Batticciotto Alberto, Lampertico Pietro, Marchesoni Antonio, Gibertini Patrizia, Pellerito Raffaele, Rovera Guido, Caporali Roberto, Todoerti Monica, Covelli Michele, Notarnicola Antonella, Atzeni Fabiola, Sarzi-Puttini Piercarlo
机构信息
From the Rheumatology Unit, Ospedale L. Sacco; Hepatology Unit, Ospedale San Giuseppe, University of Milan; A.M. and A. Migliavacca Center for Liver Disease, Division of Gastroenterology and Hepatology, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ca' Granda Ospedale Maggiore Policlinico, University of Milan; Rheumatology Day Hospital, Istituto Ortopedico G. Pini, Milan; Rheumatology Unit, Ospedale Mauriziano, Turin; Rheumatology Division, IRCCS Fondazione San Matteo, Università di Pavia, Pavia; University Rheumatology Department, Azienda Ospedaliero Universitaria (AOU) Policlinico, Bari, Italy.V. Varisco*, MD, Rheumatology Unit, Ospedale L. Sacco; M. Viganò*, MD, Hepatology Unit, Ospedale San Giuseppe, University of Milan; A. Batticciotto, MD, PhD, Rheumatology Unit, Ospedale L. Sacco; P. Lampertico, MD, PhD, Professor, A.M. and A. Migliavacca Center for Liver Disease, Division of Gastroenterology and Hepatology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Milan; A. Marchesoni, MD, Rheumatology Day Hospital, Istituto Ortopedico G. Pini; P. Gibertini, MD, Rheumatology Day Hospital, Istituto Ortopedico G. Pini; R. Pellerito, MD, Rheumatology Unit, Ospedale Mauriziano; G. Rovera, MD, Rheumatology Unit, Ospedale Mauriziano; R. Caporali, MD, Professor, Rheumatology Division, IRCCS Fondazione San Matteo, Università di Pavia; M. Todoerti, MD, Rheumatology Division, IRCCS Fondazione San Matteo, Università di Pavia; M. Covelli, MD, University Rheumatology Department, AOU Policlinico; A. Notarnicola, MD, University Rheumatology Department, AOU Policlinico; F. Atzeni, MD, PhD, Rheumatology Unit, Ospedale L. Sacco; P. Sarzi-Puttini, MD, Rheumatology Unit, Ospedale L. Sacco.
出版信息
J Rheumatol. 2016 May;43(5):869-74. doi: 10.3899/jrheum.151105. Epub 2016 Feb 15.
OBJECTIVE
Patients with resolved hepatitis B virus (HBV) infection, i.e., hepatitis B surface antigen (HBsAg)-negative/antihepatitis B core antigen (anti-HBc)-positive, undergoing rituximab (RTX)-based chemotherapy for hematological malignancies without anti-HBV prophylaxis are at risk of HBV reactivation, but the risk in such patients receiving RTX for rheumatological disorders is not clear. We evaluated this risk in HBsAg-negative/anti-HBc-positive patients with rheumatoid arthritis (RA) undergoing RTX without prophylaxis.
METHODS
Thirty-three HBsAg-negative/anti-HBc-positive outpatients with RA with undetectable HBV DNA by sensitive PCR assay [73% women, median age 60 years, 85% with HBsAg antibodies (anti-HBs), 37% with antihepatitis B envelope antigen] received a median of 3 cycles of RTX (range 1-8) over 34 months (range 0-80) combined with disease-modifying antirheumatic drugs (DMARD) without prophylaxis. All underwent clinical and laboratory monitoring during and after RTX administration, including serum HBsAg and HBV DNA measurements every 6 months or whenever clinically indicated.
RESULTS
None of the patients seroreverted to HBsAg during RTX treatment, but 6/28 (21%) showed a > 50% decrease in protective anti-HBs levels, including 2 who became anti-HBs-negative. One patient (3%) who became HBV DNA-positive (44 IU/ml) after 6 months of RTX treatment was effectively rescued with lamivudine before any hepatitis flare occurred. Among the 14 patients monitored for 18 months (range 0-70) after RTX discontinuation, no HBV reactivation was observed.
CONCLUSION
The administration of RTX + DMARD in patients with RA with resolved HBV infection leads to a negligible risk of HBV reactivation, thus suggesting that serum HBsAg and/or HBV DNA monitoring but not universal anti-HBV prophylaxis is justified.
目的
已解决乙型肝炎病毒（HBV）感染的患者，即乙型肝炎表面抗原（HBsAg）阴性/抗乙型肝炎核心抗原（抗-HBc）阳性，在未进行抗HBV预防的情况下接受基于利妥昔单抗（RTX）的化疗治疗血液系统恶性肿瘤时存在HBV再激活风险，但此类患者接受RTX治疗风湿性疾病的风险尚不清楚。我们评估了未进行预防的HBsAg阴性/抗-HBc阳性类风湿关节炎（RA）患者的这种风险。
方法
33例HBsAg阴性/抗-HBc阳性的RA门诊患者，通过灵敏PCR检测未检测到HBV DNA[女性占73%，中位年龄60岁，85%有HBsAg抗体（抗-HBs），37%有抗乙型肝炎e抗原]，在34个月（范围0 - 80）内接受了中位3个周期（范围1 - 8）的RTX联合改善病情抗风湿药（DMARD）治疗，未进行预防。所有患者在RTX给药期间及之后均接受临床和实验室监测，包括每6个月或临床指征时检测血清HBsAg和HBV DNA。
结果
在RTX治疗期间，无患者血清学转化为HBsAg阳性，但6/28（21%）患者的保护性抗-HBs水平下降超过50%，其中2例抗-HBs转阴。1例患者（3%）在RTX治疗6个月后HBV DNA转为阳性（44 IU/ml），在任何肝炎发作前用拉米夫定有效挽救。在RTX停药后监测18个月（范围0 - 70）的14例患者中，未观察到HBV再激活。
结论
在已解决HBV感染的RA患者中给予RTX + DMARD导致HBV再激活的风险可忽略不计，因此表明监测血清HBsAg和/或HBV DNA而非普遍进行抗HBV预防是合理的。
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