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DOI: 10.1055/s-0033-1345722
Immunosuppression and HBV Reactivation
Publikationsverlauf
Publikationsdatum:
08. Juni 2013 (online)
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Abstract
Hepatitis B virus (HBV) reactivation following immunosuppression is defined by an abrupt rise in HBV replication followed by laboratory signs of hepatocellular injury in a “silent” hepatitis B surface antigen (HBsAg) carrier. Reactivation can also occur, albeit at a lower rate, in patients with occult HBV infection. The clinical presentation of reactivation is variable ranging from an asymptomatic course to severe hepatitis, liver failure, and death. It is most frequently observed in patients with lymphoma treated with rituximab and corticosteroids as well as in patients undergoing stem cell and bone marrow transplantation. Other risk groups include patients with solid tumors, subjects infected with human immunodeficiency virus, organ transplant recipients, and those with autoimmune diseases (i.e., inflammatory bowel disease, rheumatoid arthritis). In cancer patients, HBV reactivation can lead to interruption of chemotherapy with serious impact on prognosis. In HBsAg-positive patients who are candidates for chemotherapy or treatment with biologic agents, preemptive treatment with an antiviral agent such as lamivudine, and lately with the more potent tenofovir or entecavir, has become a standard of care, effectively preventing HBV reactivation. Patients with occult HBV should be monitored for alanine aminotransferase and HBV DNA during the course of immunosuppression. Prompt administration of a potent antiviral agent upon diagnosis of reactivation may be lifesaving in such patients.
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References
- 1 Ott JJ, Stevens GA, Groeger J, Wiersma ST. Global epidemiology of hepatitis B virus infection: new estimates of age-specific HBsAg seroprevalence and endemicity. Vaccine 2012; 30 (12) 2212-2219
- 2 Hepatitis B vaccines. Wkly Epidemiol Rec 2009; 84 (40) 405-419
- 3 Rossi C, Shrier I, Marshall L , et al. Seroprevalence of chronic hepatitis B virus infection and prior immunity in immigrants and refugees: a systematic review and meta-analysis. PLoS ONE 2012; 7 (9) e44611
- 4 Becker N, Schnitzler P, Boffetta P , et al. Hepatitis B virus infection and risk of lymphoma: results of a serological analysis within the European case-control study Epilymph. J Cancer Res Clin Oncol 2012; 138 (12) 1993-2001
- 5 Lok AS, Liang RH, Chiu EK, Wong KL, Chan TK, Todd D. Reactivation of hepatitis B virus replication in patients receiving cytotoxic therapy. Report of a prospective study. Gastroenterology 1991; 100 (1) 182-188
- 6 Lalazar G, Rund D, Shouval D. Screening, prevention and treatment of viral hepatitis B reactivation in patients with haematological malignancies. Br J Haematol 2007; 136 (5) 699-712
- 7 Hoofnagle JH. Reactivation of hepatitis B. Hepatology 2009; 49 (5, Suppl): S156-S165
- 8 Hwang JP, Vierling JM, Zelenetz AD, Lackey SC, Loomba R. Hepatitis B virus management to prevent reactivation after chemotherapy: a review. Support Care Cancer 2012; 20 (11) 2999-3008
- 9 McMahon BJ. Epidemiology and natural history of hepatitis B. Semin Liver Dis 2005; 25 (Suppl. 01) 3-8
- 10 Yim HJ, Lok AS. Natural history of chronic hepatitis B virus infection: what we knew in 1981 and what we know in 2005. Hepatology 2006; 43 (2) (Suppl. 01) S173-S181
- 11 Bertoletti A, Gehring AJ. The immune response during hepatitis B virus infection. J Gen Virol 2006; 87 (Pt 6) 1439-1449
- 12 Locarnini S, Zoulim F. Molecular genetics of HBV infection. Antivir Ther 2010; 15 (Suppl. 03) 3-14
- 13 Levrero M, Pollicino T, Petersen J, Belloni L, Raimondo G, Dandri M. Control of cccDNA function in hepatitis B virus infection. J Hepatol 2009; 51 (3) 581-592
- 14 Raimondo G, Allain JP, Brunetto MR , et al. Statements from the Taormina expert meeting on occult hepatitis B virus infection. J Hepatol 2008; 49 (4) 652-657
- 15 Yeo W, Johnson PJ. Diagnosis, prevention and management of hepatitis B virus reactivation during anticancer therapy. Hepatology 2006; 43 (2) 209-220
- 16 Loomba R, Rowley A, Wesley R , et al. Systematic review: the effect of preventive lamivudine on hepatitis B reactivation during chemotherapy. Ann Intern Med 2008; 148 (7) 519-528
- 17 Torres HA, Davila M. Reactivation of hepatitis B virus and hepatitis C virus in patients with cancer. Nat Rev Clin Oncol 2012; 9 (3) 156-166
- 18 Lok AS, McMahon BJ. Chronic hepatitis B: update 2009. Hepatology 2009; 50 (3) 661-662
- 19 Lau GK. Hepatitis B reactivation after chemotherapy: two decades of clinical research. Hepatol Int 2008; 2 (2) 152-162
- 20 Niitsu N, Hagiwara Y, Tanae K, Kohri M, Takahashi N. Prospective analysis of hepatitis B virus reactivation in patients with diffuse large B-cell lymphoma after rituximab combination chemotherapy. J Clin Oncol 2010; 28 (34) 5097-5100
- 21 Marignani M, Marzano A. Surveillance and treatment protocols to detect and treat hepatitis B virus reactivation in hepatitis B surface antigen-negative/antibody to hepatitis B core antigen-positive patients receiving chemotherapy for onco-hematologic malignancies. J Clin Oncol 2011; 29 (8) e210 , author reply e211
- 22 Xunrong L, Yan AW, Liang R, Lau GK. Hepatitis B virus (HBV) reactivation after cytotoxic or immunosuppressive therapy—pathogenesis and management. Rev Med Virol 2001; 11 (5) 287-299
- 23 Yeo W, Chan PK, Hui P , et al. Hepatitis B virus reactivation in breast cancer patients receiving cytotoxic chemotherapy: a prospective study. J Med Virol 2003; 70 (4) 553-561
- 24 Hui CK, Cheung WW, Zhang HY , et al. Kinetics and risk of de novo hepatitis B infection in HBsAg-negative patients undergoing cytotoxic chemotherapy. Gastroenterology 2006; 131 (1) 59-68
- 25 Vallet-Pichard A, Fontaine H, Mallet V, Pol S. Viral hepatitis in solid organ transplantation other than liver. J Hepatol 2011; 55 (2) 474-482
- 26 Lau GK, Yiu HH, Fong DY , et al. Early is superior to deferred preemptive lamivudine therapy for hepatitis B patients undergoing chemotherapy. Gastroenterology 2003; 125 (6) 1742-1749
- 27 Alexopoulos CG, Vaslamatzis M, Hatzidimitriou G. Prevalence of hepatitis B virus marker positivity and evolution of hepatitis B virus profile, during chemotherapy, in patients with solid tumours. Br J Cancer 1999; 81 (1) 69-74
- 28 Kusumoto S, Tanaka Y, Mizokami M, Ueda R. Clinical significance of hepatitis B virus (HBV)-DNA monitoring to detect HBV reactivation after systemic chemotherapy. J Clin Oncol 2011; 29 (4) e100 , author reply e101
- 29 Kawsar HI, Shahnewaz J, Gopalakrishna KV, Spiro TP, Daw HA. Hepatitis B reactivation in cancer patients: role of prechemotherapy screening and antiviral prophylaxis. Clin Adv Hematol Oncol 2012; 10 (6) 370-378
- 30 Yeo W, Zee B, Zhong S , 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 (7) 1306-1311
- 31 Yeo W, Chan PK, Zhong S , et al. 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 2000; 62 (3) 299-307
- 32 Long M, Jia W, Li S , et al. A single-center, prospective and randomized controlled study: can the prophylactic use of lamivudine prevent hepatitis B virus reactivation in hepatitis B s-antigen seropositive breast cancer patients during chemotherapy?. Breast Cancer Res Treat 2011; 127 (3) 705-712
- 33 Lee HJ, Kim DY, Keam B , et al. Lamivudine prophylaxis for hepatitis B virus carrier patients with breast cancer during adjuvant chemotherapy. Breast Cancer 2012;
- 34 Nagamatsu H, Kumashiro R, Itano S, Matsugaki S, Sata M. Investigation of associating factors in exacerbation of liver damage after chemotherapy in patients with HBV-related HCC. Hepatol Res 2003; 26 (4) 293-301
- 35 Jang JW, Choi JY, Bae SH , et al. Transarterial chemo-lipiodolization can reactivate hepatitis B virus replication in patients with hepatocellular carcinoma. J Hepatol 2004; 41 (3) 427-435
- 36 Yeo W, Lam KC, Zee B , et al. Hepatitis B reactivation in patients with hepatocellular carcinoma undergoing systemic chemotherapy. Ann Oncol 2004; 15 (11) 1661-1666
- 37 Lau GK, Leung YH, Fong DY , et al. High hepatitis B virus (HBV) DNA viral load as the most important risk factor for HBV reactivation in patients positive for HBV surface antigen undergoing autologous hematopoietic cell transplantation. Blood 2002; 99 (7) 2324-2330
- 38 Yu MW, Yeh SH, Chen PJ , et al. Hepatitis B virus genotype and DNA level and hepatocellular carcinoma: a prospective study in men. J Natl Cancer Inst 2005; 97 (4) 265-272
- 39 Chu CM, Liaw YF. Genotype C hepatitis B virus infection is associated with a higher risk of reactivation of hepatitis B and progression to cirrhosis than genotype B: a longitudinal study of hepatitis B e antigen-positive patients with normal aminotransferase levels at baseline. J Hepatol 2005; 43 (3) 411-417
- 40 Shibolet O, Ilan Y, Gillis S, Hubert A, Shouval D, Safadi R. Lamivudine therapy for prevention of immunosuppressive-induced hepatitis B virus reactivation in hepatitis B surface antigen carriers. Blood 2002; 100 (2) 391-396
- 41 Hu KQ. Occult hepatitis B virus infection and its clinical implications. J Viral Hepat 2002; 9 (4) 243-257
- 42 Aksoy S, Harputluoglu H, Kilickap S , et al. Rituximab-related viral infections in lymphoma patients. Leuk Lymphoma 2007; 48 (7) 1307-1312
- 43 Iannitto E, Minardi V, Calvaruso G , et al. Hepatitis B virus reactivation and alemtuzumab therapy. Eur J Haematol 2005; 74 (3) 254-258
- 44 Méndez-Navarro J, Corey KE, Zheng H , et al. Hepatitis B screening, prophylaxis and re-activation in the era of rituximab-based chemotherapy. Liver Int 2011; 31 (3) 330-339
- 45 Liang R, Lau GK, Kwong YL. Chemotherapy and bone marrow transplantation for cancer patients who are also chronic hepatitis B carriers: a review of the problem. J Clin Oncol 1999; 17 (1) 394-398
- 46 Targhetta C, Cabras MG, Mamusa AM, Mascia G, Angelucci E. Hepatitis B virus-related liver disease in isolated anti-hepatitis B-core positive lymphoma patients receiving chemo- or chemo-immune therapy. Haematologica 2008; 93 (6) 951-952
- 47 Perceau G, Diris N, Estines O, Derancourt C, Lévy S, Bernard P. Late lethal hepatitis B virus reactivation after rituximab treatment of low-grade cutaneous B-cell lymphoma. Br J Dermatol 2006; 155 (5) 1053-1056
- 48 Dai MS, Wu PF, Shyu RY, Lu JJ, Chao TY. Hepatitis B virus reactivation in breast cancer patients undergoing cytotoxic chemotherapy and the role of preemptive lamivudine administration. Liver Int 2004; 24 (6) 540-546
- 49 Cholongitas E, Papatheodoridis GV, Burroughs AK. Liver grafts from anti-hepatitis B core positive donors: a systematic review. J Hepatol 2010; 52 (2) 272-279
- 50 Blaich A, Manz M, Dumoulin A , et al. Reactivation of hepatitis B virus with mutated hepatitis B surface antigen in a liver transplant recipient receiving a graft from an antibody to hepatitis B surface antigen- and antibody to hepatitis B core antigen-positive donor. Transfusion 2012; 52 (9) 1999-2006
- 51 Michel M, Duvoux C, Hezode C, Cherqui D. Fulminant hepatitis after infliximab in a patient with hepatitis B virus treated for an adult onset still's disease. J Rheumatol 2003; 30 (7) 1624-1625
- 52 Ostuni P, Botsios C, Punzi L, Sfriso P, Todesco S. Hepatitis B reactivation in a chronic hepatitis B surface antigen carrier with rheumatoid arthritis treated with infliximab and low dose methotrexate. Ann Rheum Dis 2003; 62 (7) 686-687
- 53 Vassilopoulos D, Calabrese LH. Viral hepatitis: review of arthritic complications and therapy for arthritis in the presence of active HBV/HCV. Curr Rheumatol Rep 2013; 15 (4) 319
- 54 Pérez-Alvarez R, Díaz-Lagares C, García-Hernández F , et al; BIOGEAS Study Group. Hepatitis B virus (HBV) reactivation in patients receiving tumor necrosis factor (TNF)-targeted therapy: analysis of 257 cases. Medicine (Baltimore) 2011; 90 (6) 359-371
- 55 Vassilopoulos D, Calabrese LH. Management of rheumatic disease with comorbid HBV or HCV infection. Nat Rev Rheumatol 2012; 8 (6) 348-357
- 56 Carroll MB. The impact of biologic response modifiers on hepatitis B virus infection. Expert Opin Biol Ther 2011; 11 (4) 533-544
- 57 Lee YH, Bae SC, Song GG. Hepatitis B virus (HBV) reactivation in rheumatic patients with hepatitis core antigen (HBV occult carriers) undergoing anti-tumor necrosis factor therapy. Clin Exp Rheumatol 2013; 31 (1) 118-121
- 58 Morisco F, Castiglione F, Rispo A , et al. Hepatitis B virus infection and immunosuppressive therapy in patients with inflammatory bowel disease. Dig Liver Dis 2011; 43 (Suppl. 01) S40-S48
- 59 Urata Y, Uesato R, Tanaka D , et al. Prevalence of reactivation of hepatitis B virus replication in rheumatoid arthritis patients. Mod Rheumatol 2011; 21 (1) 16-23
- 60 Tamori A, Koike T, Goto H , et al. 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) 556-564
- 61 Alter MJ. Epidemiology of viral hepatitis and HIV co-infection. J Hepatol 2006; 44 (1, Suppl): S6-S9
- 62 Wursthorn K, Wedemeyer H, Manns MP. Republished paper: managing HBV in patients with impaired immunity. Postgrad Med J 2011; 87 (1025) 223-238
- 63 Thio CL, Seaberg EC, Skolasky Jr R , et al; Multicenter AIDS Cohort Study. HIV-1, hepatitis B virus, and risk of liver-related mortality in the Multicenter Cohort Study (MACS). Lancet 2002; 360 (9349) 1921-1926
- 64 Biggar RJ, Goedert JJ, Hoofnagle J. Accelerated loss of antibody to hepatitis B surface antigen among immunodeficient homosexual men infected with HIV. N Engl J Med 1987; 316 (10) 630-631
- 65 Vento S, Di Perri G, Garofano T, Concia E, Bassetti D. Reactivation of hepatitis B in AIDS. Lancet 1989; 2 (8654) 108-109
- 66 Altfeld M, Rockstroh JK, Addo M , et al. Reactivation of hepatitis B in a long-term anti-HBs-positive patient with AIDS following lamivudine withdrawal. J Hepatol 1998; 29 (2) 306-309
- 67 Mallet V, Vallet-Pichard A, Pol S. The impact of human immunodeficiency virus on viral hepatitis. Liver Int 2011; 31 (Suppl. 01) 135-139
- 68 Soriano V, Puoti M, Bonacini M , et al. Care of patients with chronic hepatitis B and HIV co-infection: recommendations from an HIV-HBV International Panel. AIDS 2005; 19 (3) 221-240
- 69 Colin JF, Cazals-Hatem D, Loriot MA , et al. Influence of human immunodeficiency virus infection on chronic hepatitis B in homosexual men. Hepatology 1999; 29 (4) 1306-1310
- 70 Konopnicki D, Mocroft A, de Wit S , et al; EuroSIDA Group. Hepatitis B and HIV: prevalence, AIDS progression, response to highly active antiretroviral therapy and increased mortality in the EuroSIDA cohort. AIDS 2005; 19 (6) 593-601
- 71 Rodríguez-Rosado R, García-Samaniego J, Soriano V. Hepatotoxicity after introduction of highly active antiretroviral therapy. AIDS 1998; 12 (10) 1256
- 72 Wit FW, Weverling GJ, Weel J, Jurriaans S, Lange JM. Incidence of and risk factors for severe hepatotoxicity associated with antiretroviral combination therapy. J Infect Dis 2002; 186 (1) 23-31
- 73 Benhamou Y. Hepatitis B in the HIV-coinfected patient. J Acquir Immune Defic Syndr 2007; 45 (Suppl. 02) S57-S65 , discussion S66–S67
- 74 Hammer SM, Eron Jr JJ, Reiss P , et al; International AIDS Society-USA. Antiretroviral treatment of adult HIV infection: 2008 recommendations of the International AIDS Society-USA panel. JAMA 2008; 300 (5) 555-570
- 75 Zacharakis G, Koskinas J, Kotsiou S , et al. The role of serial measurement of serum HBV DNA levels in patients with chronic HBeAg(-) hepatitis B infection: association with liver disease progression. A prospective cohort study. J Hepatol 2008; 49 (6) 884-891
- 76 Chemin I, Guillaud O, Queyron PC, Trépo C. Close monitoring of serum HBV DNA levels and liver enzymes levels is most useful in the management of patients with occult HBV infection. J Hepatol 2009; 51 (4) 824-825
- 77 European Association For The Study Of The Liver. EASL clinical practice guidelines: management of chronic hepatitis B virus infection. J Hepatol 2012; 57 (1) 167-185
- 78 Lok ASF, McMahon BJ. Chronic hepatitis B: Update 2009. AASLD Practice Guidelines. Hepatology 2009; 50: 1-36
- 79 Weinbaum CM, Williams I, Mast EE , et al; Centers for Disease Control and Prevention (CDC). Recommendations for identification and public health management of persons with chronic hepatitis B virus infection. MMWR Recomm Rep 2008; 57 (RR-8) 1-20
- 80 Day FL, Link E, Thursky K, Rischin D. Current hepatitis B screening practices and clinical experience of reactivation in patients undergoing chemotherapy for solid tumors: a nationwide survey of medical oncologists. J Oncol Pract 2011; 7 (3) 141-147
- 81 Hwang JP, Fisch MJ, Zhang H , et al. Low rates of hepatitis B virus screening at the onset of chemotherapy. J Oncol Pract 2012; 8 (4) e32-e39
- 82 Artz AS, Somerfield MR, Feld JJ , et al. American Society of Clinical Oncology provisional clinical opinion: chronic hepatitis B virus infection screening in patients receiving cytotoxic chemotherapy for treatment of malignant diseases. J Clin Oncol 2010; 28 (19) 3199-3202
- 83 Lok AS, Ward JW, Perrillo RP, McMahon BJ, Liang TJ. Reactivation of hepatitis B during immunosuppressive therapy: potentially fatal yet preventable. Ann Intern Med 2012; 156 (10) 743-745
- 84 Yu AS, Cheung RC, Keeffe EB. Hepatitis B vaccines. Infect Dis Clin North Am 2006; 20 (1) 27-45
- 85 Dhédin N, Douvin C, Kuentz M , et al. Reverse seroconversion of hepatitis B after allogeneic bone marrow transplantation: a retrospective study of 37 patients with pretransplant anti-HBs and anti-HBc. Transplantation 1998; 66 (5) 616-619
- 86 Shouval D, Ilan Y. Immunization against hepatitis B through adoptive transfer of immunity. Intervirology 1995; 38 (1-2) 41-46
- 87 Rendi-Wagner P, Shouval D, Genton B , et al. Comparative immunogenicity of a PreS/S hepatitis B vaccine in non- and low responders to conventional vaccine. Vaccine 2006; 24 (15) 2781-2789
- 88 Wilson JN, Nokes DJ, Medley GF, Shouval D. Mathematical model of the antibody response to hepatitis B vaccines: implications for reduced schedules. Vaccine 2007; 25 (18) 3705-3712
- 89 Hourvitz A, Mosseri R, Solomon A , et al. Reactogenicity and immunogenicity of a new recombinant hepatitis B vaccine containing Pre S antigens: a preliminary report. J Viral Hepat 1996; 3 (1) 37-42
- 90 Hsu C, Hsiung CA, Su IJ , et al. A revisit of prophylactic lamivudine for chemotherapy-associated hepatitis B reactivation in non-Hodgkin's lymphoma: a randomized trial. Hepatology 2008; 47 (3) 844-853
- 91 Katz LH, Fraser A, Gafter-Gvili A, Leibovici L, Tur-Kaspa R. Lamivudine prevents reactivation of hepatitis B and reduces mortality in immunosuppressed patients: systematic review and meta-analysis. J Viral Hepat 2008; 15 (2) 89-102
- 92 Papamichalis P, Alexiou A, Boulbou M, Dalekos GN, Rigopoulou EI. Reactivation of resolved hepatitis B virus infection after immunosuppression: is it time to adopt pre-emptive therapy?. Clin Res Hepatol Gastroenterol 2012; 36 (1) 84-93
- 93 Sanchez MJ, Buti M, Homs M, Palacios A, Rodriguez-Frias F, Esteban R. Successful use of entecavir for a severe case of reactivation of hepatitis B virus following polychemotherapy containing rituximab. J Hepatol 2009; 51 (6) 1091-1096
- 94 Watanabe M, Shibuya A, Takada J , et al. Entecavir is an optional agent to prevent hepatitis B virus (HBV) reactivation: a review of 16 patients. Eur J Intern Med 2010; 21 (4) 333-337
- 95 Ryu HH, Lee EY, Shin K , et al. Hepatitis B virus reactivation in rheumatoid arthritis and ankylosing spondylitis patients treated with anti-TNFα agents: a retrospective analysis of 49 cases. Clin Rheumatol 2012; 31 (6) 931-936
- 96 Brost S, Schnitzler P, Stremmel W, Eisenbach C. Entecavir as treatment for reactivation of hepatitis B in immunosuppressed patients. World J Gastroenterol 2010; 16 (43) 5447-5451
- 97 Montineri A, Nigro L, La Rosa R , et al. Treatment induced seroconversion to HBsAb following HBV reactivation in the immunosuppressed haematology and oncology patient: a clinical survey of 5 cases in Catania, Italy. J Clin Virol 2011; 52 (4) 284-287
- 98 Li HR, Huang JJ, Guo HQ , et al. Comparison of entecavir and lamivudine in preventing hepatitis B reactivation in lymphoma patients during chemotherapy. J Viral Hepat 2011; 18 (12) 877-883
- 99 Lock G, Helmich F, Bertram M. [Impending liver failure after chemoimmunotherapy-induced reactivation of hepatitis B - successful treatment with entecavir]. Dtsch Med Wochenschr 2012; 137 (23) 1248-1250
- 100 Garg H, Sarin SK, Kumar M, Garg V, Sharma BC, Kumar A. Tenofovir improves the outcome in patients with spontaneous reactivation of hepatitis B presenting as acute-on-chronic liver failure. Hepatology 2011; 53 (3) 774-780
- 101 Dai MS, Chao TY, Kao WY, Shyu RY, Liu TM. Delayed hepatitis B virus reactivation after cessation of preemptive lamivudine in lymphoma patients treated with rituximab plus CHOP. Ann Hematol 2004; 83 (12) 769-774
- 102 Idilman R. Duration of lamivudine prophylaxis in inactive hepatitis B virus carriers with haemato/oncological malignancies who receive chemotherapy. Gut 2006; 55 (8) 1208-1209