Skip to main content

Advertisement

SpringerLink
Log in

Antiviral prophylaxis for preventing reactivation of hepatitis B virus in rheumatic patients: a systematic review and meta-analysis

  • Original Article
  • Published:
Clinical Rheumatology Aims and scope Submit manuscript

Abstract

To estimate the risk of reactivation of hepatitis B virus (HBV) and evaluate the effectiveness of antiviral prophylaxis (AVP) in patients with different status of HBV infection undergoing antirheumatic therapies. We searched Cochrane Library, Medline, and EMBASE for randomized controlled trials (RCTs), quasi-RCTs, non-RCTs, cohort studies, or case series studies examining reactivation of HBV in patients undergoing antirheumatic therapy with or without AVP. We estimated the HBV reactivation rate (HRR) and its 95% confidence interval (CI) among different patient groups (indirect comparison). We also calculated rate ratio (RR), rate difference (RD) with their 95% CIs, and the number needed to treat (NNT) of AVP (direct comparison). Fifty-three case series studies with 2162 patients were included. The RD of AVP was − 0.13 (95% CI − 0.21 to − 0.05) for all patients, − 0.16 (95% CI − 0.26 to − 0.06) for rheumatic patients with chronic HBV infection, but not statistically significant for patients with other status of HBV infection. Lamivudine (RD − 0.10, 95% CI − 0.25 to 0.05) was less effective than other prophylactic antiviral drugs (RD − 0.31, 95% CI − 0.52 to − 0.11). The HHR varied from 55 to 5% by HBV status and treatment. There is limited evidence that AVP was effective for preventing reactivation of HBV in patients undergoing antirheumatic therapy. The effectiveness varies by patient HBV status and antiviral regimens. Rheumatic HBV carriers may be more beneficial from AVP, and lamivudine may be inferior to other AVP regimens. Findings in this study warrant further investigation in rigorous RCTs.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Ott JJ, Stevens GA, Groeger J, Wiersma ST (2012) Global epidemiology of hepatitis B virus infection: new estimates of age-specific HBsAg seroprevalence and endemicity. Vaccine 30(12):2212–2219. https://doi.org/10.1016/j.vaccine.2011.12.116

    Article  CAS  PubMed  Google Scholar 

  2. Lavanchy D (2004) Hepatitis B virus epidemiology, disease burden, treatment, and current and emerging prevention and control measures. J Viral Hepat 11(2):97–107

    Article  CAS  Google Scholar 

  3. MacLachlan JH, Cowie BC (2015) Hepatitis B virus epidemiology. Cold Spring Harbor Perspect Med 5(5):a021410. https://doi.org/10.1101/cshperspect.a021410

    Article  CAS  Google Scholar 

  4. Liang X, Bi S, Yang W, Wang L, Cui G, Cui F, Zhang Y, Liu J, Gong X, Chen Y, Wang F, Zheng H, Wang F, Guo J, Jia Z, Ma J, Wang H, Luo H, Li L, Jin S, Hadler SC, Wang Y (2009) Epidemiological serosurvey of hepatitis B in China—declining HBV prevalence due to hepatitis B vaccination. Vaccine 27(47):6550–6557. https://doi.org/10.1016/j.vaccine.2009.08.048

    Article  PubMed  Google Scholar 

  5. Zou CJ, Zhu LJ, Li YH, Mo YQ, Zheng DH, Ma JD, Ou-Yang X, Pessler F, Dai L (2013) The association between hepatitis B virus infection and disease activity, synovitis, or joint destruction in rheumatoid arthritis. Clin Rheumatol 32(6):787–795. https://doi.org/10.1007/s10067-013-2170-1

    Article  PubMed  Google Scholar 

  6. Yeo W, Johnson PJ (2006) Diagnosis, prevention and management of hepatitis B virus reactivation during anticancer therapy. Hepatology 43(2):209–220. https://doi.org/10.1002/hep.21051

    Article  CAS  PubMed  Google Scholar 

  7. Loomba R, Rowley A, Wesley R, Liang TJ, Hoofnagle JH, Pucino F, Csako G (2008) Systematic review: the effect of preventive lamivudine on hepatitis B reactivation during chemotherapy. Ann Intern Med 148(7):519–528

    Article  Google Scholar 

  8. Rossi G, Pelizzari A, Motta M, Puoti M (2001) Primary prophylaxis with lamivudine of hepatitis B virus reactivation in chronic HbsAg carriers with lymphoid malignancies treated with chemotherapy. Br J Haematol 115(1):58–62

    Article  CAS  Google Scholar 

  9. Hsu C, Hsiung CA, Su IJ, Hwang WS, Wang MC, Lin SF, Lin TH, Hsiao HH, Young JH, Chang MC, Liao YM, Li CC, Wu HB, Tien HF, Chao TY, Liu TW, Cheng AL, Chen PJ (2008) A revisit of prophylactic lamivudine for chemotherapy-associated hepatitis B reactivation in non-Hodgkin’s lymphoma: a randomized trial. Hepatology 47(3):844–853. https://doi.org/10.1002/hep.22106

    Article  CAS  PubMed  Google Scholar 

  10. Lok AS, McMahon BJ (2009) Chronic hepatitis B: update 2009. Hepatology 50(3):661–662. https://doi.org/10.1002/hep.23190

    Article  PubMed  Google Scholar 

  11. Singh JA, Saag KG, Bridges SL Jr, Akl EA, Bannuru RR, Sullivan MC, Vaysbrot E, McNaughton C, Osani M, Shmerling RH, Curtis JR, Furst DE, Parks D, Kavanaugh A, O'Dell J, King C, Leong A, Matteson EL, Schousboe JT, Drevlow B, Ginsberg S, Grober J, St Clair EW, Tindall E, Miller AS, McAlindon T (2016) 2015 American College of Rheumatology guideline for the treatment of rheumatoid arthritis. Arthritis Rheumatol 68(1):1–26. https://doi.org/10.1002/art.39480

    Article  PubMed  Google Scholar 

  12. Reddy KR, Beavers KL, Hammond SP, Lim JK, Falck-Ytter YT, American Gastroenterological Association I (2015) American Gastroenterological Association Institute guideline on the prevention and treatment of hepatitis B virus reactivation during immunosuppressive drug therapy. Gastroenterology 148(1):215–219; quiz e216–217. https://doi.org/10.1053/j.gastro.2014.10.039

    Article  CAS  PubMed  Google Scholar 

  13. Mori S, Fujiyama S (2015) Hepatitis B virus reactivation associated with antirheumatic therapy: risk and prophylaxis recommendations. World J Gastroenterol 21(36):10274–10289. https://doi.org/10.3748/wjg.v21.i36.10274

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Pattullo V (2016) Prevention of hepatitis B reactivation in the setting of immunosuppression. Clin Mol Hepatol 22(2):219–237. https://doi.org/10.3350/cmh.2016.0024

    Article  PubMed  PubMed Central  Google Scholar 

  15. Vigano M, Serra G, Casella G, Grossi G, Lampertico P (2016) Reactivation of hepatitis B virus during targeted therapies for cancer and immune-mediated disorders. Expert Opin Biol Ther 16(7):917–926. https://doi.org/10.1080/14712598.2016.1177017

    Article  CAS  PubMed  Google Scholar 

  16. Loomba R, Liang TJ (2017) Hepatitis B reactivation associated with immune suppressive and biological modifier therapies: current concepts, management strategies, and future directions. Gastroenterology 152(6):1297–1309. https://doi.org/10.1053/j.gastro.2017.02.009

    Article  PubMed  PubMed Central  Google Scholar 

  17. Mo YQ, Liang AQ, Ma JD, Chen LF, Zheng DH, Schumacher HR, Dai L (2014) Discontinuation of antiviral prophylaxis correlates with high prevalence of hepatitis B virus (HBV) reactivation in rheumatoid arthritis patients with HBV carrier state: a real-world clinical practice. BMC Musculoskelet Disord 15:449. https://doi.org/10.1186/1471-2474-15-449

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Malespin M, Wong S, Siqueira F, Luc B, Ravaee B, Vainder C, Cotler SJ (2012) Barriers to treatment of hepatitis B in an urban Chinatown community. J Clin Gastroenterol 46(8):e66–e70. https://doi.org/10.1097/MCG.0b013e31824e159c

    Article  CAS  PubMed  Google Scholar 

  19. National Health Institute. Quality assessment tool for case series studies. https://www.nhlbi.nih.gov/health-pro/guidelines/in-develop/cardiovascular-risk-reduction/tools/case_series. Accessed 20th May 2017

  20. Liu Z, Jiang L, Liang G, Song E, Jiang W, Zheng Y, Gong C (2017) Hepatitis B virus reactivation in breast cancer patients undergoing chemotherapy: a review and meta-analysis of prophylaxis management. J Viral Hepat 24(7):561–572. https://doi.org/10.1111/jvh.12672

    Article  CAS  PubMed  Google Scholar 

  21. Wu YT, Li X, Liu ZL, Xu Z, Dai W, Zhang K, Wu JS, Arshad B, Wu KN, Kong LQ (2017) Hepatitis B virus reactivation and antiviral prophylaxis during lung cancer chemotherapy: a systematic review and meta-analysis. PLoS One 12(6):e0179680. https://doi.org/10.1371/journal.pone.0179680

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Zhang MY, Zhu GQ, Zheng JN, Cheng Z, Van Poucke S, Shi KQ, Huang HH, Chen FY, Zheng MH (2017) Nucleos(t)ide analogues for preventing HBV reactivation in immunosuppressed patients with hematological malignancies: a network meta-analysis. Expert Rev Anti-Infect Ther 15(5):503–513. https://doi.org/10.1080/14787210.2017.1309291

    Article  CAS  PubMed  Google Scholar 

  23. Paul S, Saxena A, Terrin N, Viveiros K, Balk EM, Wong JB (2016) Hepatitis B virus reactivation and prophylaxis during solid tumor chemotherapy: a systematic review and meta-analysis. Ann Intern Med 164(1):30–40. https://doi.org/10.7326/M15-1121

    Article  PubMed  Google Scholar 

  24. Tang W, Chen L, Zheng R, Pan L, Gao J, Ye X, Zhang X, Zheng W (2015) Prophylactic effect of lamivudine for chemotherapy-induced hepatitis B reactivation in breast cancer: a meta-analysis. PLoS One 10(6):e0128673. https://doi.org/10.1371/journal.pone.0128673

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Liu JY, Sheng YJ, Ding XC, Tang H, Tong SW, Zhang DZ, Zhou Z, Hu P, Liao Y, Ren H, Hu HD (2015) The efficacy of lamivudine prophylaxis against hepatitis B reactivation in breast cancer patients undergoing chemotherapy: a meta-analysis. J Formosan Med Assoc Taiwan yi zhi 114(2):164–173. https://doi.org/10.1016/j.jfma.2012.10.007

    Article  CAS  PubMed  Google Scholar 

  26. Li H, Zhang HM, Chen LF, Chen YQ, Chen L, Ren H, Hu HD (2015) Prophylactic lamivudine to improve the outcome of HBsAg-positive lymphoma patients during chemotherapy: a systematic review and meta-analysis. Clin Res Hepatol Gastroenterol 39(1):80–92. https://doi.org/10.1016/j.clinre.2014.07.010

    Article  CAS  PubMed  Google Scholar 

  27. Paul S, Dickstein A, Saxena A, Terrin N, Viveiros K, Balk EM, Wong JB (2017) Role of surface antibody in hepatitis B reactivation in patients with resolved infection and hematologic malignancy: a meta-analysis. Hepatology 66(2):379–388. https://doi.org/10.1002/hep.29082

    Article  CAS  PubMed  Google Scholar 

  28. Yu S, Luo H, Pan M, Luis AP, Xiong Z, Shuai P, Zhang Z (2016) Comparison of entecavir and lamivudine in preventing HBV reactivation in lymphoma patients undergoing chemotherapy: a meta-analysis. Int J Clin Pharm 38(5):1035–1043. https://doi.org/10.1007/s11096-016-0358-6

    Article  CAS  PubMed  Google Scholar 

  29. Yang C, Qin B, Yuan Z, Chen L, Zhou HY (2016) Meta-analysis of prophylactic entecavir or lamivudine against hepatitis B virus reactivation. Ann Hepatol 15(4):501–511

    CAS  PubMed  Google Scholar 

  30. Calica Utku A, Karabay O (2016) Treatment of chronic hepatitis B patients with tyrosine-methionine-aspartate-aspartate mutations. World J Gastroenterol 22(4):1727–1728. https://doi.org/10.3748/wjg.v22.i4.1727

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Cheng AL, Hsiung CA, Su IJ, Chen PJ, Chang MC, Tsao CJ, Kao WY, Uen WC, Hsu CH, Tien HF, Chao TY, Chen LT, Whang-Peng J, Lymphoma Committee of Taiwan Cooperative Oncology G (2003) Steroid-free chemotherapy decreases risk of hepatitis B virus (HBV) reactivation in HBV-carriers with lymphoma. Hepatology 37(6):1320–1328. https://doi.org/10.1053/jhep.2003.50220

    Article  CAS  PubMed  Google Scholar 

  32. Cantini F, Boccia S, Goletti D, Iannone F, Leoncini E, Panic N, Prignano F, Gaeta GB (2014) HBV reactivation in patients treated with antitumor necrosis factor-alpha (TNF-α) agents for rheumatic and dermatologic conditions: a systematic review and meta-analysis. Int J Rheumatol 2014:1–9

    Article  Google Scholar 

  33. Scullard GH, Smith CI, Merigan TC, Robinson WS, Gregory PB (1981) Effects of immunosuppressive therapy on viral markers in chronic active hepatitis B. Gastroenterology 81(6):987–991

    CAS  PubMed  Google Scholar 

  34. Hoofnagle JH, Davis GL, Pappas SC, Hanson RG, Peters M, Avigan MI, Waggoner JG, Jones EA, Seeff LB (1986) A short course of prednisolone in chronic type B hepatitis. Report of a randomized, double-blind, placebo-controlled trial. Ann Intern Med 104(1):12–17

    Article  CAS  Google Scholar 

  35. Sheen IS, Liaw YF, Lin SM, Chu CM (1996) Severe clinical rebound upon withdrawal of corticosteroid before interferon therapy: incidence and risk factors. J Gastroenterol Hepatol 11(2):143–147

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The authors would like to acknowledge Dr. Jing Zhu, who kindly answered questions of the authors, Dr. Yan Jiang (Chongqing, China), who helped perform the systemic literature search, and Mrs. Yang Xiao (Chengdu, China), who helped perform the statistical analysis.

Funding

This work was not supported by any funding.

Author information

Authors and Affiliations

  1. Department of Rheumatology and Immunology, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, Affiliated Hospital of the University of Electronic Science and Technology, Chengdu, China

    Jiang Su & Li Long

  2. Department of Medical Records and Statistics, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, Affiliated Hospital of the University of Electronic Science and Technology, No. 32, West Second Section, First Ring Road, Chengdu, China

    Kun Zou

Authors
  1. Jiang Su
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Li Long
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kun Zou
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kun Zou.

Ethics declarations

Disclosures

None.

Electronic supplementary material

ESM 1

(DOCX 136 kb).

ESM 2

(DOCX 25 kb).

ESM 3

(DOC 344 kb).

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Su, J., Long, L. & Zou, K. Antiviral prophylaxis for preventing reactivation of hepatitis B virus in rheumatic patients: a systematic review and meta-analysis. Clin Rheumatol 37, 3201–3214 (2018). https://doi.org/10.1007/s10067-018-4096-0

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10067-018-4096-0

Keywords

Search

Navigation