J Rheum Dis.  2015 Oct;22(5):282-287. 10.4078/jrd.2015.22.5.282.

Reactivation of Hepatitis B Virus in Patients with Rheumatologic Disease Treated with Biologic Disease Modifying Anti-rheumatic Drugs: Screening and Treatment

• Lee JI

• KMID: 2222839
• DOI: http://doi.org/10.4078/jrd.2015.22.5.282

Abstract

Reactivation of hepatitis B virus (HBV) is not infrequently reported in patients with rheumatologic diseases treated with biologic disease modify anti-rheumatic drugs (DMARDs) such as a tumor necrosis factor-alpha inhibitor or a B cell depleting molecule. HBV reactivation is reported not only in patients with chronic hepatitis B but also in cases with resolved HBV where HBsAg is negative and anti-HBc positive. Studies suggest that with treatment using biologic DMARDs, the risk of HBV reactivation increases when HBsAg is positive independent of HBV DNA replication status, and in those with anti-HBc positive and serum HBV DNA positive. Therefore, testing for HBsAg as well as anti-HBc is important before initiating treatment with a biologic DMARD. In addition, evaluation of serum HBV DNA may be required when either HBsAg or anti-HBc turns out to be positive. Although series of reports suggest that prophylactic antiviral therapy in patients with higher risk of HBV reactivation would diminish morbidity and mortality from hepatic cause, solid guidelines pertaining to when to initiate and terminate HBV antiviral therapy and which agent should be used should be provided in the future.

Keyword

Hepatitis B virus; Anti-rheumatic drugs; Reactivation; Prophylactic antiviral therapy

MeSH Terms

Antirheumatic Agents*
DNA
DNA Replication
Hepatitis B Surface Antigens
Hepatitis B virus*
Hepatitis B*
Hepatitis B, Chronic
Hepatitis*
Humans
Mass Screening*
Mortality
Tumor Necrosis Factor-alpha
Antirheumatic Agents
DNA
Hepatitis B Surface Antigens
Tumor Necrosis Factor-alpha

Reference

1. Jang JW. Hepatitis B virus reactivation in patients with hepatocellular carcinoma undergoing anticancer therapy. World J Gastroenterol. 2014; 20:7675–85.

2. Nard FD, Todoerti M, Grosso V, Monti S, Breda S, Rossi S, et al. Risk of hepatitis B virus reactivation in rheumatoid arthritis patients undergoing biologic treatment: Extending perspective from old to newer drugs. World J Hepatol. 2015; 7:344–61.

3. Ahn YO. A review study on descriptive epidemiology of HBs antigen positivity in Korea. Korean J Epidemiol. 1982; 4:35–45.

4. Sim JG, Seo JK, Suh SJ. Prevalence and its changes of hepatitis b viral markers from 1988 to 1993 in Korean children. J Korean Pediatr Soc. 1995; 38:1535–9.

5. Ministry of Health & Welfare. Korea health statistics 2011: Korea national health and nutrition examination survey (KNHANESV-2). Seoul: Ministry of Health & Welfare;2012.

6. Lok AS, McMahon BJ. Chronic hepatitis B. Hepatology. 2007; 45:507–39.

7. Hoofnagle JH, Doo E, Liang TJ, Fleischer R, Lok AS. Management of hepatitis B: summary of a clinical research workshop. Hepatology. 2007; 45:1056–75.

8. Tran TT. Immune tolerant hepatitis B: a clinical dilemma. Gastroenterol Hepatol (N Y). 2011; 7:511–6.

9. Lok AS, Lai CL. A longitudinal follow-up of asymptomatic hepatitis B surface antigen-positive Chinese children. Hepatology. 1988; 8:1130–3.

10. Chang MH, Hsu HY, Hsu HC, Ni YH, Chen JS, Chen DS. The significance of spontaneous hepatitis B e antigen seroconversion in childhood: with special emphasis on the clearance of hepatitis B e antigen before 3 years of age. Hepatology. 1995; 22:1387–92.

11. Hui CK, Leung N, Yuen ST, Zhang HY, Leung KW, Lu L, et al. Hong Kong Liver Fibrosis Study Group. Natural history and disease progression in Chinese chronic hepatitis B patients in immune-tolerant phase. Hepatology. 2007; 46:395–401.

12. Vierling JM. The immunology of hepatitis B. Clin Liver Dis. 2007; 11:727–59.

13. Lee PI, Chang MH, Lee CY, Hsu HY, Chen JS, Chen PJ, et al. Changes of serum hepatitis B virus DNA and aminotransferase levels during the course of chronic hepatitis B virus infection in children. Hepatology. 1990; 12:657–60.

14. Lok AS, Lai CL. Acute exacerbations in Chinese patients with chronic hepatitis B virus (HBV) infection. Incidence, predisposing factors and etiology. J Hepatol. 1990; 10:29–34.

15. McMahon BJ, Holck P, Bulkow L, Snowball M. Serologic and clinical outcomes of 1536 Alaska Natives chronically infected with hepatitis B virus. Ann Intern Med. 2001; 135:759–68.

16. Tsai SL, Chen PJ, Lai MY, Yang PM, Sung JL, Huang JH, et al. Acute exacerbations of chronic type B hepatitis are accompanied by increased T cell responses to hepatitis B core and e antigens. Implications for hepatitis B e antigen seroconversion. J Clin Invest. 1992; 89:87–96.

17. Martinot-Peignoux M, Boyer N, Colombat M, Akremi R, Pham BN, Ollivier S, et al. Serum hepatitis B virus DNA levels and liver histology in inactive HBsAg carriers. J Hepatol. 2002; 36:543–6.

18. Zacharakis GH, Koskinas J, Kotsiou S, Papoutselis M, Tzara F, Vafeiadis N, et al. Natural history of chronic HBV infection: a cohort study with up to 12 years follow-up in North Greece (part of the Interreg I-II/EC-project). J Med Virol. 2005; 77:173–9.

19. de Franchis R, Meucci G, Vecchi M, Tatarella M, Colombo M, Del Ninno E, et al. The natural history of asymptomatic hepatitis B surface antigen carriers. Ann Intern Med. 1993; 118:191–4.

20. Chen YC, Sheen IS, Chu CM, Liaw YF. Prognosis following spontaneous HBsAg seroclearance in chronic hepatitis B patients with or without concurrent infection. Gastroenterology. 2002; 123:1084–9.

21. Lok AS, McMahon BJ. Chronic hepatitis B: update 2009. Hepatology. 2009; 50:661–2.

22. Okamoto H, Tsuda F, Akahane Y, Sugai Y, Yoshiba M, Moriyama K, et al. Hepatitis B virus with mutations in the core promoter for an e antigen-negative phenotype in carriers with antibody to e antigen. J Virol. 1994; 68:8102–10.

23. Croagh CM, Bell SJ, Slavin J, Kong YX, Chen RY, Locarnini S, et al. Increasing hepatitis B viral load is associated with risk of significant liver fibrosis in HBeAg-negative but not HBeAg-positive chronic hepatitis B. Liver Int. 2010; 30:1115–22.

24. Yoo BC, Park JW, Kim HJ, Lee DH, Cha YJ, Park SM. Precore and core promoter mutations of hepatitis B virus and hepatitis B e antigen-negative chronic hepatitis B in Korea. J Hepatol. 2003; 38:98–103.

25. Gupta S, Govindarajan S, Fong TL, Redeker AG. Spontaneous reactivation in chronic hepatitis B: patterns and natural history. J Clin Gastroenterol. 1990; 12:562–8.

26. Yeo W, Johnson PJ. Diagnosis, prevention and management of hepatitis B virus reactivation during anticancer therapy. Hepatology. 2006; 43:209–20.

27. Yeo W, Zee B, Zhong S, Chan PK, Wong WL, Ho WM, et al. Comprehensive analysis of risk factors associating with Hepatitis B virus (HBV) reactivation in cancer patients undergoing cytotoxic chemotherapy. Br J Cancer. 2004; 90:1306–11.

28. Hwang JP, Lok AS. Management of patients with hepatitis B who require immunosuppressive therapy. Nat Rev Gastroenterol Hepatol. 2014; 11:209–19.

29. Chung SJ, Kim JK, Park MC, Park YB, Lee SK. Reactivation of hepatitis B viral infection in inactive HBsAg carriers following anti-tumor necrosis factor-alpha therapy. J Rheumatol. 2009; 36:2416–20.

30. Kim YJ, Bae SC, Sung YK, Kim TH, Jun JB, Yoo DH, et al. Possible reactivation of potential hepatitis B virus occult infection by tumor necrosis factor-alpha blocker in the treatment of rheumatic diseases. J Rheumatol. 2010; 37:346–50.

31. Lee YH, Bae SC, Song GG. Hepatitis B virus reactivation in HBsAg-positive patients with rheumatic diseases undergoing anti-tumor necrosis factor therapy or DMARDs. Int J Rheum Dis. 2013; 16:527–31.

32. Pérez-Alvarez R, Díaz-Lagares C, García-Hernández F, Lopez-Roses L, Brito-Zerón P, Pérez-de-Lis M, et al. BIO-GEAS Study Group. Hepatitis B virus (HBV) reactivation in patients receiving tumor necrosis factor (TNF)-targeted therapy: analysis of 257 cases. Medicine (Baltimore). 2011; 90:359–71.

33. 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 Apr 4; [Epub].DOI: DOI: 10.1111/1756-185X.12359.

34. Liu HL, Zhao Z, Yang H, Liu FF, Liu Q, Luo Q, et al. The effects of nucleoside analogue prophylactic treatment on HBV activation in HBcAb+ patients undergoing immunosuppressive therapy. J Viral Hepat. 2013; 20:645–9.

35. Cheng AL, Hsiung CA, Su IJ, Chen PJ, Chang MC, Tsao CJ, et al. Lymphoma Committee of Taiwan Cooperative Oncology Group. Steroid-free chemotherapy decreases risk of hepatitis B virus (HBV) reactivation in HBV-carriers with lymphoma. Hepatology. 2003; 37:1320–8.

36. Yeo W, Chan TC, Leung NW, Lam WY, Mo FK, Chu MT, et al. Hepatitis B virus reactivation in lymphoma patients with prior resolved hepatitis B undergoing anticancer therapy with or without rituximab. J Clin Oncol. 2009; 27:605–11.

37. Kim SJ, Hsu C, Song YQ, Tay K, Hong XN, Cao J, et al. Hepatitis B virus reactivation in B-cell lymphoma patients treated with rituximab: analysis from the Asia Lymphoma Study Group. Eur J Cancer. 2013; 49:3486–96.

38. Hsu C, Tsou HH, Lin SJ, Wang MC, Yao M, Hwang WL, et al. Taiwan Cooperative Oncology Group. Chemotherapy-induced hepatitis B reactivation in lymphoma patients with resolved HBV infection: a prospective study. Hepatology. 2014; 59:2092–100.

39. Dong HJ, Ni LN, Sheng GF, Song HL, Xu JZ, Ling Y. Risk of hepatitis B virus (HBV) reactivation in non-Hodgkin lymphoma patients receiving rituximab-chemotherapy: a meta-analysis. J Clin Virol. 2013; 57:209–14.

40. Chen XQ, Peng JW, Lin GN, Li M, Xia ZJ. The effect of prophylactic lamivudine on hepatitis B virus reactivation in HBsAg-positive patients with diffuse large B-cell lymphoma undergoing prolonged rituximab therapy. Med Oncol. 2012; 29:1237–41.

41. Pyrpasopoulou A, Douma S, Vassiliadis T, Chatzimichaili-dou S, Triantafyllou A, Aslanidis S. Reactivation of chronic hepatitis B virus infection following rituximab administration for rheumatoid arthritis. Rheumatol Int. 2011; 31:403–4.

42. Ghrénassia E, Mékinian A, Rouaghe S, Ganne N, Fain O. Reactivation of resolved hepatitis B during rituximab therapy for rheumatoid arthritis. Joint Bone Spine. 2012; 79:100–1.

43. Gigi E, Georgiou T, Mougiou D, Boura P, Raptopoulou-Gigi M. Hepatitis B reactivation in a patient with rheumatoid arthritis with antibodies to hepatitis B surface antigen treated with rituximab. Hippokratia. 2013; 17:91–3.

44. Droz N, Gilardin L, Cacoub P, Berenbaum F, Wendling D, Godeau B, et al. Kinetic profiles and management of hepatitis B virus reactivation in patients with immunemediated inflammatory diseases. Arthritis Care Res (Hoboken). 2013; 65:1504–14.

45. Mitroulis I, Hatzara C, Kandili A, Hadziyannis E, Vassilopoulos D. Long-term safety of rituximab in patients with rheumatic diseases and chronic or resolved hepatitis B virus infection. Ann Rheum Dis. 2013; 72:308–10.

46. Germanidis G, Hytiroglou P, Zakalka M, Settas L. Reactivation of occult hepatitis B virus infection, following treatment of refractory rheumatoid arthritis with abatacept. J Hepatol. 2012; 56:1420–1.

47. Kim PS, Ho GY, Prete PE, Furst DE. Safety and efficacy of abatacept in eight rheumatoid arthritis patients with chronic hepatitis B. Arthritis Care Res (Hoboken). 2012; 64:1265–8.

48. Kishida D, Okuda Y, Onishi M, Takebayashi M, Matoba K, Jouyama K, et al. Successful tocilizumab treatment in a patient with adult-onset Still's disease complicated by chronic active hepatitis B and amyloid A amyloidosis. Mod Rheumatol. 2011; 21:215–8.

49. Yeo W, Chan PK, Ho WM, Zee B, Lam KC, Lei KI, et al. Lamivudine for the prevention of hepatitis B virus reactivation in hepatitis B s-antigen seropositive cancer patients undergoing cytotoxic chemotherapy. J Clin Oncol. 2004; 22:927–34.

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

51. Lau GK, He ML, Fong DY, Bartholomeusz A, Au WY, Lie AK, et al. Preemptive use of lamivudine reduces hepatitis B exacerbation after allogeneic hematopoietic cell transplantation. Hepatology. 2002; 36:702–9.

52. Lau GK, Yiu HH, Fong DY, Cheng HC, Au WY, Lai LS, et al. Early is superior to deferred preemptive lamivudine therapy for hepatitis B patients undergoing chemotherapy. Gastroenterology. 2003; 125:1742–9.

53. Hsu C, Hsiung CA, Su IJ, Hwang WS, Wang MC, Lin SF, et al. A revisit of prophylactic lamivudine for chemotherapy-associated hepatitis B reactivation in non-Hodgkin's lymphoma: a randomized trial. Hepatology. 2008; 47:844–53.

54. Lan JL, Chen YM, Hsieh TY, Chen YH, Hsieh CW, Chen DY, et al. 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; 70:1719–25.

55. Saab S, Dong MH, Joseph TA, Tong MJ. Hepatitis B prophylaxis in patients undergoing chemotherapy for lymphoma: a decision analysis model. Hepatology. 2007; 46:1049–56.

56. Hui CK, Cheung WW, Au WY, Lie AK, Zhang HY, Yueng YH, et al. Hepatitis B reactivation after withdrawal of preemptive lamivudine in patients with haematological malignancy on completion of cytotoxic chemotherapy. Gut. 2005; 54:1597–603.

57. Li HR, Huang JJ, Guo HQ, Zhang X, Xie Y, Zhu HL, et al. Comparison of entecavir and lamivudine in preventing hepatitis B reactivation in lymphoma patients during chemotherapy. J Viral Hepat. 2011; 18:877–83.