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
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.
J Rheumatol. 2016 May;43(5):869-74. doi: 10.3899/jrheum.151105. Epub 2016 Feb 15.
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.
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.
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.
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.
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。
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。
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。
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。
