International Urology and Nephrology

, Volume 50, Issue 9, pp 1653–1660 | Cite as

Discontinuation of antiviral prophylaxis increased the risk of hepatitis B virus reactivation in glomerulonephritis patients under immunotherapy: a real-life observation

  • Jing Fang
  • Wenge Li
  • Min Tan
  • Wen Chen
  • Cong Zhang
  • Wenbo Wang
  • Qianqian Xu
  • Xinzhen Guo
Nephrology - Original Paper



Antiviral prophylaxis is proved to be effective in reducing the risk of hepatitis B virus (HBV) reactivation in hepatitis B surface antigen (HBsAg)-positive patients under immunotherapy. But outcomes referring to discontinuation of antiviral prophylaxis in these patients are lacking.


We performed a retrospective study of 105 HBsAg-positive patients under immunotherapy for glomerulonephritis and evaluated the incidence and risk factors for HBV reactivation.


Among 105 patients, 55.24% completed antiviral prophylaxis, while 20.00% discontinued and 24.76% rejected antiviral prophylaxis. HBV reactivation was significantly different among completion, discontinuation, and rejection of antiviral prophylaxis: 5.17% versus 38.10% versus 15.38% in the incidence of HBV reactivation (P = 0.001), 3.45% versus 23.81% versus 11.54% in HBV DNA ≥ 5 Log copies/ml (P = 0.023), and 0 versus 14.29% versus 3.85% in hepatitis B e antigen seroconversion from negative to positive (P = 0.014). Survival curve showed the median occurrence time of HBV reactivation in discontinuation group was 32 months (95% CI 24–39 months), earlier than 69 months (95% CI 65–72 months) of completion group and 43 months (95% CI 37–49 months) of rejection group (χ2 = 13.780, P = 0.001). Univariate and multivariate analysis identified two independent risk factors for HBV reactivation: baseline HBV DNA detectable (OR 5.009, 95% CI 1.717–16.335, P = 0.012) and discontinuation of antiviral prophylaxis (OR 5.213, 95% CI 1.688–18.105, P = 0.011).


Discontinuation of antiviral prophylaxis increased the risk of HBV reactivation in HBsAg-positive patients under immunotherapy for glomerulonephritis.


HBV reactivation Immunotherapy Antiviral prophylaxis HBsAg-positive Glomerulonephritis 



The authors thank the many physicians who cared for the patients described in this report, including Drs. Yanfang Yang, Zhao Tan, Zhihong Xu, Li Zhuo, Gumin Zou, and the nursing staff of nephrology department.

Compliance with ethical standards

Conflict of interest

All authors declare that they have no financial support or relationships that may pose conflict of interest.


  1. 1.
    López-Serrano Pilar, Pérez-Calle Jose Lázaro, Sánchez-Tembleque Maria Dolores (2013) Hepatitis B and inflammatory bowel disease: role of antiviral prophylaxis. World J Gastroenterol 19:1342–1348CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Fang Jing, Li Wenge, Tan Zhao, Li Duo (2014) Comparison of prednisolone and lamivudine combined therapy with prednisolone monotherapy on carriers of hepatitis B virus with IgA nephropathy: a prospective cohort study. Int Urol Nephrol 46:49–56CrossRefPubMedGoogle Scholar
  3. 3.
    Buti M, García-Samaniego J, Prieto M, Rodríguez M, Sánchez- Tapias JM, Suárez E et al (2012) Consensus document of the Spanish Association for the Study of the Liver on the treatment of hepatitis B infection. Gastroenterol Hepatol 35:512–528CrossRefPubMedGoogle Scholar
  4. 4.
    Mastroianni CM, Lichtner M, Citton R, Del Borgo C, Rago A, Martini H et al (2011) Current trends in management of hepatitis B virus reactivation in the biologic therapy era. World J Gastroenterol 17:3881–3887CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    European Association For The Study Of The Liver (2012) EASL clinical practice guidelines: management of chronic hepatitis B virus infection. J Hepatol 57:167–185CrossRefGoogle Scholar
  6. 6.
    Omuse G, Maina D, Mwangi J, Wambua C, Kanyua A, Kagotho E et al (2017) Comparison of equations for estimating glomerular filtration rate in screening for chronic kidney disease in asymptomatic black Africans: a cross sectional study. BMC Nephrol 18:369–377CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Yi Zhou, Jie Yuan Wei, Nan Zhu (2011) The efficacy of anti-viral therapy on hepatitis B virus-associated glomerulonephritis: a systematic review and meta-analysis. Ann Hepatol 10:165–173PubMedGoogle Scholar
  8. 8.
    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 30:2212–2219CrossRefPubMedGoogle Scholar
  9. 9.
    Franco E, Bagnato B, Marino MG, Meleleo C, Serino L, Zarat-ti L (2012) Hepatitis B: epidemiology and prevention in developing countries. World J Hepatol 4:74–80CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Fang Jing, Li Wenge, Peng Xiangxin, Tan Zhao, Tan Min, Zhang Cong et al (2017) Hepatitis B reactivation in HBsAg-negative/HBeAb-positive patients receiving immunosuppressive therapy for glomerulonephritis: a retrospective analysis. Int Urol Nephrol 49:475–482CrossRefPubMedGoogle Scholar
  11. 11.
    Cheng AL, Hsiung CA, Su IJ, Chen PJ, Chang MC, Tsao CJ et al (2003) Steroid-free chemotherapy decreases risk of hepatitis B virus (HBV) reactivation in HBV-carriers with lymphoma. Hepatology 37:1320–1328CrossRefPubMedGoogle Scholar
  12. 12.
    Lalazar G, Rund D, Shouval D (2007) Screening, prevention and treatment of viral hepatitis B reactivation in patients with haematological malignancies. Br J Haematol 136:699–712CrossRefPubMedGoogle Scholar
  13. 13.
    Viganò M, Vener C, Lampertico P et al (2011) Risk of hepatitis B surface antigen seroreversion after allogeneic hematopoietic SCT. Bone Marrow Transplant 46:125–131CrossRefPubMedGoogle Scholar
  14. 14.
    Lau GK, Yiu HH, Fong DY, Cheng HC, Au WY, Lai LS et al (2003) Early is superior to deferred preemptive lamivudine therapy for hepatitis B patients undergoing chemotherapy. Gastroenterology 125:1742–1749CrossRefPubMedGoogle Scholar
  15. 15.
    Loras C, Gisbert JP, Mínguez M, Merino O, Bujanda L, Saro C et al (2010) Liver dysfunction related to hepatitis B and C in patients with inflammatory bowel disease treated with immunosuppressive therapy. Gut 59:1340–1346CrossRefPubMedGoogle Scholar
  16. 16.
    López-Serrano P, de la Fuente Briongos E, Alonso EC, Pérez-Calle JL, Rodríguez CF (2015) Hepatitis B and immunosuppressive therapies for chronic inflammatory diseases: when and how to apply prophylaxis, with a special focus on corticosteroid therapy. World J Hepatol 27:539–547CrossRefGoogle Scholar
  17. 17.
    Loomba R, Rowley A, Wesley R, Liang TJ, Hoofnagle JH, Pucino F et al (2008) Systematic review: the effect of preventive lamivudine on hepatitis B reactivation during chemotherapy. Ann Int Med 148:519–528CrossRefPubMedGoogle Scholar
  18. 18.
    Kitrinos KM, Corsa A, Liu Y, Flaherty J, Snow-Lampart A, Marcellin P et al (2014) No detectable resistance to tenofovir disoproxil fumarate after 6 years of therapy in patients with chronic hepatitis B. Hepatology 59:434–442CrossRefPubMedGoogle Scholar
  19. 19.
    Huang H, Li X, Zhu J, Ye S, Zhang H, Wang W et al (2014) Entecavir vs lamivudine for prevention of hepatitis B virus reactivation among patients with untreated diffuse large B-cell lymphoma receiving R-CHOP chemotherapy: a randomized clinical trial. JAMA 312:2521–2530CrossRefPubMedGoogle Scholar
  20. 20.
    Ayoub WS, Keeffe EB (2011) current antiviral therapy of chronic hepatitis B. Aliment Pharmacol Ther 34:1145–1158CrossRefPubMedGoogle Scholar
  21. 21.
    Hatzakis A, Wait S, Bruix J, Buti M, Carballo M, Cavaleri M et al (2011) The state of hepatitis B and C in Europe: report from the hepatitis B and C summit conference. J Viral Hepat 18(Suppl 1):1–16CrossRefPubMedGoogle Scholar
  22. 22.
    Huang YH, Hsiao LT, Hong YC, Chiou TJ, Yu YB, Gau JP et al (2013) Randomized controlled trial of entecavir prophylaxis for rituximab-associated hepatitis B virus reactivation in patients with lymphoma and resolved hepatitis B. J Clin Oncol 31:2765–2772CrossRefPubMedGoogle Scholar
  23. 23.
    Ohishi W, Chayama K (2011) Prevention of hepatitis B virus reactivation in immunosuppressive therapy or chemotherapy. Clin Exp Nephrol 15:634–640CrossRefPubMedGoogle Scholar
  24. 24.
    Thomas HC (2007) Best practice in the treatment of chronic hepatitis B: a summary of the European Viral Hepatitis Educational Initiative (EVHEI). J Hepatol 47:588–597CrossRefPubMedGoogle Scholar
  25. 25.
    Yeo W, Zee B, Zhong S, Chan PK, Wong WL, Ho WM et al (2004) Comprehensive analysis of risk factors associating with Hepatitis B virus (HBV) reactivation in cancer patients undergoing cytotoxic chemotherapy. Br J Cancer 90:1306–1311CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Yeo W, Chan PK, Zhong S 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 62:299–307CrossRefPubMedGoogle Scholar
  27. 27.
    Du W, Zheng Z, Han S et al (2013) HBV reactivation in an occult HBV infection patient treated with prednisone for nephrotic syndrome: case report and literature review. BMC Infect Dis 13:394CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Moses SE, Lim Z, Zuckerman MA (2011) Hepatitis B virus infection: pathogenesis, reactivation and management in hematopoietic stem cell transplant recipients. Expert Rev Anti-Infect Ther 9:891–899CrossRefPubMedGoogle Scholar
  29. 29.
    Kusumoto S, Tanaka Y, Ueda R et al (2011) Reactivation of hepatitis B virus following rituximab-plus-steroid combination chemotherapy. J Gastroenterol 46:9–16CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media B.V., part of Springer Nature 2018

Authors and Affiliations

  • Jing Fang
    • 1
  • Wenge Li
    • 1
  • Min Tan
    • 1
  • Wen Chen
    • 1
  • Cong Zhang
    • 1
  • Wenbo Wang
    • 1
  • Qianqian Xu
    • 1
  • Xinzhen Guo
    • 2
  1. 1.Department of NephrologyChina-Japan Friendship HospitalBeijingChina
  2. 2.Department of HepatologyChina-Japan Friendship HospitalBeijingChina

Personalised recommendations