Risk of Hepatitis B Virus Reactivation in Patients With Inflammatory Arthritis Receiving Disease-Modifying Antirheumatic Drugs: A Systematic Review and Meta-Analysis

Overview

Journal Arthritis Care Res (Hoboken)

Specialty Rheumatology

Date 2017 Aug 24

PMID 28834412

Citations 14

Authors

Tzu-Chieh Lin

Kazuki Yoshida

Sara K Tedeschi

Mirhelen Mendes de Abreu

Nikroo Hashemi

Daniel H Solomon

Affiliations

Soon will be listed here.

Abstract

Objective: To assess hepatitis B virus (HBV) reactivation rates in patients with resolved or chronic HBV infection, receiving disease-modifying antirheumatic drugs (DMARDs) and with or without antiviral prophylaxis.

Methods: We conducted a systematic review and meta-analysis. Electronic searches were conducted in PubMed, Medline, and Embase using Ovid through December 31, 2015. A search strategy was developed for each database using the following inclusion criteria: for participants, rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, and resolved or chronic HBV infection; for intervention, tumor necrosis factor (TNF) inhibitors or non-TNF biologic or nonbiologic DMARDs; and for outcome, HBV reactivation. Four reviewers independently extracted study data and assessed study quality using the Newcastle-Ottawa Scale. To determine the pooled HBV reactivation rate, the variances of the raw proportions were stabilized using a Freeman-Tukey-type arcsine square root transformation, using a random-effects model.

Results: Twenty-five studies met the inclusion criteria. The overall pooled rate of HBV reactivation was 1.6% (95% confidence interval [95% CI] 0.8-2.6) in patients with resolved HBV. Similar rates were observed in resolved patients taking TNF inhibitors (1.4% [95% CI 0.5-2.6]), non-TNF biologics (6.1% [95% CI 0.0-16.6]), and nonbiologic DMARDs (1.7% [95% CI 0.2-4.2]). We also found that the reactivation rate was lower in patients with chronic HBV infection who received antiviral prophylaxis (9.0% [95% CI 4.1-15.5]) than in those who did not (14.6% [95% CI 4.3-29.0]).

Conclusion: We found that the HBV reactivation rate in inflammatory arthritis patients receiving DMARDs was low in resolved patients and moderate in patients with chronic HBV infection. Further, lower rates were observed in patients with chronic HBV infection who were using antiviral prophylaxis.

Citing Articles

Patient-Centric Approach for the Treatment of Rheumatoid Arthritis-Associated Interstitial Lung Disease in Older People.

Mueller K, Saavedra A, OKeeffe L, Sparks J Drugs Aging. 2025; 42(2):81-94.

PMID: 39800810 DOI: 10.1007/s40266-024-01175-0.

Pappa M, Koutsogianni A, Karamanakos A, Kyriazi N, Cheila M, Moschou D Rheumatol Int. 2025; 45(1):15.

PMID: 39751658 DOI: 10.1007/s00296-024-05771-6.

Hepatitis and Hepatitis B Virus Reactivation in Everolimus-Treated Solid Tumor Patients: A Focus on HBV-Endemic Areas.

Su C, Chen C, Liu C, Yang Y, Wu P Cancers (Basel). 2024; 16(23).

PMID: 39682184 PMC: 11640431. DOI: 10.3390/cancers16233997.

The Epidemiology, Transmission, Genotypes, Replication, Serologic and Nucleic Acid Testing, Immunotolerance, and Reactivation of Hepatitis B Virus.

Patel A, Dossaji Z, Gupta K, Roma K, Chandler T, Minacapelli C Gastro Hep Adv. 2024; 3(2):139-150.

PMID: 39129942 PMC: 11307719. DOI: 10.1016/j.gastha.2023.10.008.

HBV reactivation in patients with rheumatoid arthritis treated with anti-interleukin-6: a systematic review and meta-analysis.

Katelani S, Fragoulis G, Bakasis A, Pouliakis A, Nikiphorou E, Atzeni F Rheumatology (Oxford). 2023; 62(SI3):SI252-SI259.

PMID: 37871924 PMC: 10715785. DOI: 10.1093/rheumatology/kead243.

References

Urata Y, Uesato R, Tanaka D, Kowatari K, Nitobe T, Nakamura Y . Prevalence of reactivation of hepatitis B virus replication in rheumatoid arthritis patients. Mod Rheumatol. 2010; 21(1):16-23. DOI: 10.1007/s10165-010-0337-z. View

Perrillo R, Gish R, Falck-Ytter Y . American Gastroenterological Association Institute technical review on prevention and treatment of hepatitis B virus reactivation during immunosuppressive drug therapy. Gastroenterology. 2014; 148(1):221-244.e3. DOI: 10.1053/j.gastro.2014.10.038. View

Laurenti R, Giovannangeli F, Gubinelli E, Viviano M, Errico A, Leoni L . Long-term safety of anti-TNF adalimumab in HBc antibody-positive psoriatic arthritis patients: a retrospective case series of 8 patients. Clin Dev Immunol. 2013; 2013:410521. PMC: 3623386. DOI: 10.1155/2013/410521. View

Lok A, McMahon B . Chronic hepatitis B. Hepatology. 2007; 45(2):507-39. DOI: 10.1002/hep.21513. View

NAGINGTON J . Reactivation of hepatitis b after transplantation operations. Lancet. 1977; 1(8011):558-60. DOI: 10.1016/s0140-6736(77)91995-x. View

Mori S . Past hepatitis B virus infection in rheumatoid arthritis patients receiving biological and/or nonbiological disease-modifying antirheumatic drugs. Mod Rheumatol. 2011; 21(6):621-7. PMC: 3236827. DOI: 10.1007/s10165-011-0458-z. View

Lee Y, Bae S, Song G . Hepatitis B virus reactivation in HBsAg-positive patients with rheumatic diseases undergoing anti-tumor necrosis factor therapy or DMARDs. Int J Rheum Dis. 2013; 16(5):527-31. DOI: 10.1111/1756-185X.12154. View

Jin D, Tie N, Liu J, Zhao L, Hao D, Zhao Y . [Investigation of the risk of hepatitis B virus reactivation in arthritis patients undergoing anti-tumour necrosis factor alpha therapy]. Zhonghua Nei Ke Za Zhi. 2015; 54(4):313-6. View

Ye H, Zhang X, Mu R, Fang L, Gu J, Lin J . Anti-TNF therapy in patients with HBV infection--analysis of 87 patients with inflammatory arthritis. Clin Rheumatol. 2013; 33(1):119-23. DOI: 10.1007/s10067-013-2385-1. View

10.

Lan J, Chen Y, Hsieh T, Chen Y, Hsieh C, Chen D . Kinetics of viral loads and risk of hepatitis B virus reactivation in hepatitis B core antibody-positive rheumatoid arthritis patients undergoing anti-tumour necrosis factor alpha therapy. Ann Rheum Dis. 2011; 70(10):1719-25. DOI: 10.1136/ard.2010.148783. View

11.

Schmajuk G, Solomon D, Yazdany J . Patterns of disease-modifying antirheumatic drug use in rheumatoid arthritis patients after 2002: a systematic review. Arthritis Care Res (Hoboken). 2013; 65(12):1927-35. PMC: 4204800. DOI: 10.1002/acr.22084. View

12.

Cho Y, Chen C, Chiu H, Tsai T . Use of anti-tumor necrosis factor-α therapy in hepatitis B virus carriers with psoriasis or psoriatic arthritis: a case series in Taiwan. J Dermatol. 2011; 39(3):269-73. DOI: 10.1111/j.1346-8138.2011.01434.x. View

13.

Ballanti E, Conigliaro P, Chimenti M, Kroegler B, Di Muzio G, Guarino M . Use of anti-tumor necrosis factor alpha therapy in patients with concurrent rheumatoid arthritis and hepatitis B or hepatitis C: a retrospective analysis of 32 patients. Drug Dev Res. 2014; 75 Suppl 1:S42-5. DOI: 10.1002/ddr.21193. View

14.

Charpin C, Guis S, Colson P, Borentain P, Mattei J, Alcaraz P . Safety of TNF-blocking agents in rheumatic patients with serology suggesting past hepatitis B state: results from a cohort of 21 patients. Arthritis Res Ther. 2009; 11(6):R179. PMC: 3003507. DOI: 10.1186/ar2868. View

15.

Galbraith R, Eddleston A, Williams R, Zuckerman A . Fulminant hepatic failure in leukaemia and choriocarcinoma related to withdrawal of cytotoxic drug therapy. Lancet. 1975; 2(7934):528-30. DOI: 10.1016/s0140-6736(75)90897-1. View

16.

Nakamura J, Nagashima T, Nagatani K, Yoshio T, Iwamoto M, Minota S . Reactivation of hepatitis B virus in rheumatoid arthritis patients treated with biological disease-modifying antirheumatic drugs. Int J Rheum Dis. 2014; 19(5):470-5. DOI: 10.1111/1756-185X.12359. View

17.

Tamori A, Koike T, Goto H, Wakitani S, Tada M, Morikawa H . Prospective study of reactivation of hepatitis B virus in patients with rheumatoid arthritis who received immunosuppressive therapy: evaluation of both HBsAg-positive and HBsAg-negative cohorts. J Gastroenterol. 2011; 46(4):556-64. DOI: 10.1007/s00535-010-0367-5. View

18.

Singh J, Saag K, Bridges Jr S, Akl E, Bannuru R, Sullivan M . 2015 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis. Arthritis Rheumatol. 2015; 68(1):1-26. DOI: 10.1002/art.39480. View

19.

Kim P, Ho G, Prete P, Furst D . Safety and efficacy of abatacept in eight rheumatoid arthritis patients with chronic hepatitis B. Arthritis Care Res (Hoboken). 2012; 64(8):1265-8. DOI: 10.1002/acr.21654. View

20.

Prignano F, Ricceri F, Pescitelli L, Zanieri F, Lotti T . Tumour necrosis factor-α antagonists in patients with concurrent psoriasis and hepatitis B or hepatitis C: a retrospective analysis of 17 patients. Br J Dermatol. 2011; 164(3):645-7. DOI: 10.1111/j.1365-2133.2010.10140.x. View