Avoid common mistakes on your manuscript.
Introduction
In chronic hepatitis B virus infection, immune suppression has been linked with potential activation and, in a number of cases, acute liver failure and fatal outcome; patients with haematologic or other malignancies under chemotherapy were mostly affected [1]. In the same cohort of patients the incidence of HBV reactivation rose significantly in the past decade, after the introduction of rituximab, a monoclonal antibody targeted against the CD20(+) lymphocytes [2, 3]. In this setting, reactivation was recorded even in HBsAb(+) patients [4]. In patients with rheumatic diseases, analogous cases are still mainly anecdotal. Taking into account the increasing application of rituximab in the treatment of autoimmune diseases, and the global prevalence of chronic hepatitis B virus infection, cases of treatment-induced reactivation need to be recorded, in order to formulate prophylaxis and treatment guidelines, and to safely establish the safety profile of these agents in analogous circumstances [5].
Case report
A 56-year-old female patient with a 21-year-history of severe rheumatoid arthritis (cervical fusion surgery, hip and knee arthroplasty) and arterial hypertension received the 1st cycle of rituximab in July 2008. The patient had received etanercept (monoclonal antibody targeted against the soluble TNFa receptor) in 2002 for 1 year with good response; treatment was discontinued after setting the diagnosis of chronic HBV infection (HBsAg+, HBeAg−, HBeAb+) and the patient was started on lamivudine, steroids and DMARDs (cyclosporine) with moderate response in terms of the primary disease until May 2007. In May 2007 infliximab, and adalimumab were initiated sequentially (HBV DNA PCR < 6 IU/ml). Both were discontinued shortly after initiation, due to failure of response. The patient developed an allergic reaction to abatacept and gave her informed consent to receive rituximab (at initiation DAS28 was 6.28, the biochemical profile was normal, and PCR for HBV DNA was 9.6 × 102 IU/ml).
One month after administration of rituximab (2 × 1,000 mg) the patient presented with fever (38°C) and elevated transaminases (SGOT 110, SGPT 150U/l). HBV DNA was >1.1 × 108 IU/ml and antibodies for HDV were negative. Tenofovir was added to the concomitant lamivudine. Transaminases normalised 1 month after initiation of tenofovir, and, 10 months later, HBV DNA was 46 IU/ml. The patient was in good clinical condition and liver morphology (by imaging studies) and function remain normal.
Discussion
An unrecognised HBV infection may lead to serious complications in patients receiving DMARDs and/or biologics (e.g. TNFa antagonists, rituximab). On the other hand, a diagnosed chronic HBV infection may cause delay to or undertreatment of patients with rheumatic diseases. Reactivation of chronic HBV infection has been reported with anti-TNF agents [6, 7]. However, under prophylactic antiviral treatment these agents seem, at least in a restricted number of patients and under short-term follow-up, to be relatively safe [8, 9]. Longer follow-up of the patients involved is needed to safely extrapolate this conclusion. Experience with rituximab in analogous patients is scarce [10]. Current guidelines suggest avoidance of this biologic in patients with chronic HBV infection (HBsAb−), based on experience from oncological patients and its interference with B-lymphocyte biology. In cases in which all other therapeutic options have been excluded and the patient consents to its use, treatment requires close monitoring of the patient (clinical and laboratory) under concomitant antiviral treatment, and prompt reevaluation of the latter with early signs of viral reactivation.
References
Yeo W, Chan PK, Zhong S, Ho WM et al (2000) Frequency of hepatitis B virus reactivation in cancer patients undergoing cytotoxic chemotherapy: a prospective study of 626 patients with identification of risk factors. J Med Virol 62:299–307
Tsutsumi Y, Kanamori H, Mori A et al (2005) Reactivation of hepatitis B virus with rituximab. Expert Opin Drug Saf 4:599–608
Yeo W, Chan TC, Leung NW et al (2009) Hepatitis B virus reactivation in lymphoma patients with prior resolved hepatitis B undergoing anticancer therapy with or without rituximab. J Clin Oncol 27:605–611
Sera T, Hiasa Y, Michitaka K et al (2006) Anti-HBs-positive liver failure due to hepatitis B virus reactivation induced by rituximab. Intern Med 45(11):721–724
Furst DE (2008) The risk of infections with biologic therapies for rheumatoid arthritis. Semin Arthritis Rheum (Epub ahead of print)
Zingarelli S, Ario P, Frassi M et al (2008) Prophylaxis and therapy of HBV infection in 20 patients treated with disease modifying antirheumatic drugs or with biological agents for rheumatic diseases. Reumatismo 60:22–27
Nathan DM, Angus PW, Gibson PR (2006) Hepatitis B and C virus infections and anti-tumor necrosis factor-alpha therapy: guidelines for clinical approach. J Gastroenterol Hepatol 21:1366–1371
Calabrese LH, Zein N, Vassilopoulos D (2004) Safety of antitumour necrosis factor (anti-TNF) therapy in patients with chronic viral infections: hepatitis C, hepatitis B, and HIV infection. Ann Rheum Dis 63(Suppl 2):ii18–ii24
Roux CH, Brocq O, Breuil V, Albert C, Euller-Ziegler L (2006) Safety of anti-TNF-alpha therapy in rheumatoid arthritis and spondyloarthropathies with concurrent B or C chronic hepatitis. Rheumatology 45(10):1294–1297
Salliot C, Dougados M, Gossec L (2009) Risk of serious infections during rituximab, abatacept and anakinra treatments for rheumatoid arthritis: meta-analyses of randomized placebo-controlled trials. Ann Rheum Dis 68:25–32
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Pyrpasopoulou, A., Douma, S., Vassiliadis, T. et al. Reactivation of chronic hepatitis B virus infection following rituximab administration for rheumatoid arthritis. Rheumatol Int 31, 403–404 (2011). https://doi.org/10.1007/s00296-009-1202-2
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00296-009-1202-2