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Research ArticleArticle

Low Risk of Hepatitis B Virus Reactivation in HBsAg-negative/Anti-HBc–positive Carriers Receiving Rituximab for Rheumatoid Arthritis: A Retrospective Multicenter Italian Study

Valentina Varisco, Mauro Viganò, Alberto Batticciotto, Pietro Lampertico, Antonio Marchesoni, Patrizia Gibertini, Raffaele Pellerito, Guido Rovera, Roberto Caporali, Monica Todoerti, Michele Covelli, Antonella Notarnicola, Fabiola Atzeni and Piercarlo Sarzi-Puttini
The Journal of Rheumatology May 2016, 43 (5) 869-874; DOI: https://doi.org/10.3899/jrheum.151105
Valentina Varisco
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.
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Mauro Viganò
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Alberto Batticciotto
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Pietro Lampertico
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Antonio Marchesoni
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Patrizia Gibertini
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Raffaele Pellerito
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Guido Rovera
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Roberto Caporali
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Monica Todoerti
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Michele Covelli
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Antonella Notarnicola
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Fabiola Atzeni
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Piercarlo Sarzi-Puttini
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  • For correspondence: sarzi.piercarlo@hsacco.it
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Abstract

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.

Key Indexing Words:
  • HEPATITIS B VIRUS REACTIVATION
  • HBsAg
  • HBV DNA
  • RITUXIMAB
  • RHEUMATOID ARTHRITIS
  • Accepted for publication January 9, 2016.
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1 May 2016
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Low Risk of Hepatitis B Virus Reactivation in HBsAg-negative/Anti-HBc–positive Carriers Receiving Rituximab for Rheumatoid Arthritis: A Retrospective Multicenter Italian Study
Valentina Varisco, Mauro Viganò, Alberto Batticciotto, Pietro Lampertico, Antonio Marchesoni, Patrizia Gibertini, Raffaele Pellerito, Guido Rovera, Roberto Caporali, Monica Todoerti, Michele Covelli, Antonella Notarnicola, Fabiola Atzeni, Piercarlo Sarzi-Puttini
The Journal of Rheumatology May 2016, 43 (5) 869-874; DOI: 10.3899/jrheum.151105

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Low Risk of Hepatitis B Virus Reactivation in HBsAg-negative/Anti-HBc–positive Carriers Receiving Rituximab for Rheumatoid Arthritis: A Retrospective Multicenter Italian Study
Valentina Varisco, Mauro Viganò, Alberto Batticciotto, Pietro Lampertico, Antonio Marchesoni, Patrizia Gibertini, Raffaele Pellerito, Guido Rovera, Roberto Caporali, Monica Todoerti, Michele Covelli, Antonella Notarnicola, Fabiola Atzeni, Piercarlo Sarzi-Puttini
The Journal of Rheumatology May 2016, 43 (5) 869-874; DOI: 10.3899/jrheum.151105
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Keywords

HEPATITIS B VIRUS REACTIVATION
HBsAg
HBV DNA
RITUXIMAB
RHEUMATOID ARTHRITIS

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Keywords

  • HEPATITIS B VIRUS REACTIVATION
  • HBsAg
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  • RITUXIMAB
  • rheumatoid arthritis

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