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면역억제제 혹은 항암 치료가 필요한 B형간염 환자의 치료

Management of Patients with Hepatitis B Virus Infection Who Receive Immunosuppressive Treatment or Chemotherapy

  • 장정원 (가톨릭대학교 의과대학 내과학교실)
  • Jang, Jeong-Won (Department of Internal Medicine, The Catholic University of Korea School of Medicine)
  • 발행 : 2012.02.01

초록

Reactivation of hepatitis B virus (HBV) has been well documented as a complication in HBV surface antigen (HBsAg) carriers who receive cytotoxic or immunosuppressive therapy. With the recent introduction of newer agents with a high level of immunosuppressive effect, this unfavorable event often occurs in patients with HBsAg-negative and/or occult HBV infection. The first step in HBV reactivation management is the identification of the patients at risk of viral reactivation by testing for HBV serology prior to commencing immunosuppressive treatment or chemotherapy. Multiple publications have consistently indicated the benefit of prophylactic or preemptive antiviral therapy in this setting, and justified such approach before the start of cytotoxic therapy. Unresolved issues concerning such prophylactic approach remain in the situations of HBsAg-negative/anti-HBc-positive or negative status, which presumably consists of a large number of occult HBV infection cases. This topic review will summarize clinical issues related to HBV reactivation, focusing clinical manifestations, risk factors associated with HBV reactivation, and a growing body of evidence supporting preventive antiviral therapy in high-risk patients.

키워드

참고문헌

  1. Wands JR, Chura CM, Roll FJ, Maddrey WC. Serial studies of hepatitis-associated antigen and antibody in patients receiving antitumor chemotherapy for myeloproliferative and lymphoproliferative disorders. Gastroenterology 1975; 68:105-112.
  2. Yeo W, Johnson PJ. Diagnosis, prevention and management of hepatitis B virus reactivation during anticancer therapy. Hepatology 2006;43:209-220. https://doi.org/10.1002/hep.21051
  3. 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;70:553-561. https://doi.org/10.1002/jmv.10430
  4. Mindikoglu AL, Regev A, Schiff ER. Hepatitis B virus reactivation after cytotoxic chemotherapy: the disease and its prevention. Clin Gastroenterol Hepatol 2006;4:1076-1081. https://doi.org/10.1016/j.cgh.2006.05.027
  5. Rossi G. Prophylaxis with lamivudine of hepatitis B virus reactivation in chronic HbsAg carriers with hematooncological neoplasias treated with chemotherapy. Leuk Lymphoma 2003;44:759-766. https://doi.org/10.1080/104281903100006351
  6. Lau GK. Hepatitis B reactivation after chemotherapy: two decades of clinical research. Hepatol Int 2008;2:152-162. https://doi.org/10.1007/s12072-008-9056-3
  7. Lau GK, Yiu HH, Fong DY, et al. Early is superior to deferred preemptive lamivudine therapy for hepatitis B patients undergoing chemotherapy. Gastroenterology 2003; 125:1742-1749. https://doi.org/10.1053/j.gastro.2003.09.026
  8. Jang JW, Choi JY, Bae SH, et al. A randomized controlled study of preemptive lamivudine in patients receiving transarterial chemo-lipiodolization. Hepatology 2006;43: 233-240. https://doi.org/10.1002/hep.21024
  9. 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;100:182-188. https://doi.org/10.1016/0016-5085(91)90599-G
  10. Kusumoto S, Tanaka Y, Ueda R, Mizokami M. Reactivation of hepatitis B virus following rituximab-plus-steroid combination chemotherapy. J Gastroenterol 2011;46:9-16. https://doi.org/10.1007/s00535-010-0331-4
  11. Park JW, Park KW, Cho SH, et al. Risk of hepatitis B exacerbation is low after transcatheter arterial chemoembolization therapy for patients with HBV-related hepatocellular carcinoma: report of a prospective study. Am J Gastroenterol 2005;100:2194-2200. https://doi.org/10.1111/j.1572-0241.2005.00232.x
  12. Kusumoto S, Tanaka Y, Mizokami M, Ueda R. Reactivation of hepatitis B virus following systemic chemotherapy for malignant lymphoma. Int J Hematol 2009;90:13-23. https://doi.org/10.1007/s12185-009-0359-5
  13. Tur-Kaspa R, Burk RD, Shaul Y, Shafritz DA. Hepatitis B virus DNA contains a glucocorticoid-responsive element. Proc Natl Acad Sci U S A 1986;83:1627-1631. https://doi.org/10.1073/pnas.83.6.1627
  14. Hsu CH, Hsu HC, Chen HL, et al. Doxorubicin activates hepatitis B virus (HBV) replication in HBV-harboring hepatoblastoma cells: a possible novel mechanism of HBV reactivation in HBV carriers receiving systemic chemotherapy. Anticancer Res 2004;24:3035-3040.
  15. Chou CH, Chen PJ, Lee PH, Cheng AL, Hsu HC, Cheng JC. Radiation-induced hepatitis B virus reactivation in liver mediated by the bystander effect from irradiated endothelial cells. Clin Cancer Res 2007;13:851-857. https://doi.org/10.1158/1078-0432.CCR-06-2459
  16. Burpee SE, Kurian M, Murakame Y, Benevides S, Gagner M. The metabolic and immune response to laparoscopic versus open liver resection. Surg Endosc 2002;16:899-904. https://doi.org/10.1007/s00464-001-8122-x
  17. Lubel JS, Angus PW. Hepatitis B reactivation in patients receiving cytotoxic chemotherapy: diagnosis and management. J Gastroenterol Hepatol 2010;25:864-871. https://doi.org/10.1111/j.1440-1746.2010.06243.x
  18. Kim JH, Park JW, Kim TH, Koh DW, Lee WJ, Kim CM. Hepatitis B virus reactivation after three-dimensional conformal radiotherapy in patients with hepatitis B virus-related hepatocellular carcinoma. Int J Radiat Oncol Biol Phys 2007;69:813-819. https://doi.org/10.1016/j.ijrobp.2007.04.005
  19. Jang JW, Kwon JH, You CR, et al. Risk of HBV reactivation according to viral status and treatment intensity in patients with hepatocellular carcinoma. Antivir Ther 2011;16:969-977. https://doi.org/10.3851/IMP1840
  20. 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;41:427-435. https://doi.org/10.1016/j.jhep.2004.05.014
  21. Nagamatsu H, Itano S, Nagaoka S, et al. Prophylactic lamivudine administration prevents exacerbation of liver damage in HBe antigen positive patients with hepatocellular carcinoma undergoing transhepatic arterial infusion chemotherapy. Am J Gastroenterol 2004;99:2369-2375. https://doi.org/10.1111/j.1572-0241.2004.40069.x
  22. Yeo W, Lam KC, Zee B, et al. Hepatitis B reactivation in patients with hepatocellular carcinoma undergoing systemic chemotherapy. Ann Oncol 2004;15:1661-1666. https://doi.org/10.1093/annonc/mdh430
  23. 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;26:293-301 https://doi.org/10.1016/S1386-6346(03)00158-X
  24. Lao XM, Wang D, Shi M, et al. Changes in hepatitis B virus DNA levels and liver function after transcatheter arterial chemoembolization of hepatocellular carcinoma. Hepatol Res 2011;41:553-563. https://doi.org/10.1111/j.1872-034X.2011.00796.x
  25. Zhong S, Yeo W, Schroder C, et al. High hepatitis B virus (HBV) DNA viral load is an important risk factor for HBV reactivation in breast cancer patients undergoing cytotoxic chemotherapy. J Viral Hepat 2004;11:55-59. https://doi.org/10.1046/j.1352-0504.2003.00467.x
  26. 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;99:2324-2330. https://doi.org/10.1182/blood.V99.7.2324
  27. Sugauchi F, Tanaka Y, Kusumoto S, et al. Virological and clinical characteristics on reactivation of occult hepatitis B in patients with hematological malignancy. J Med Virol 2011;83:412-418. https://doi.org/10.1002/jmv.21995
  28. Alexopoulou A, Theodorou M, Dourakis SP, et al. Hepatitis B virus reactivation in patients receiving chemotherapy for malignancies: role of precore stop-codon and basic core promoter mutations. J Viral Hepat 2006;13:591-596. https://doi.org/10.1111/j.1365-2893.2006.00728.x
  29. Borentain P, Colson P, Coso D, et al. Clinical and virological factors associated with hepatitis B virus reactivation in HBsAg-negative and anti-HBc antibodies-positive patients undergoing chemotherapy and/or autologous stem cell transplantation for cancer. J Viral Hepat 2010;17:807-815. https://doi.org/10.1111/j.1365-2893.2009.01239.x
  30. de novo hepatitis B infection in HBsAg-negative patients undergoing cytotoxic chemotherapy. Gastroenterology 2006;131:59-68. https://doi.org/10.1053/j.gastro.2006.04.015
  31. Yeo W, Chan TC, Leung NW, 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;27:605-611. https://doi.org/10.1200/JCO.2008.18.0182
  32. Pei SN, Chen CH, Lee CM, et al. Reactivation of hepatitis B virus following rituximab-based regimens: a serious complication in both HBsAg-positive and HBsAg-negative patients. Ann Hematol 2010;89:255-262. https://doi.org/10.1007/s00277-009-0806-7
  33. Manzano-Alonso ML, Castellano-Tortajada G. Reactivation of hepatitis B virus infection after cytotoxic chemotherapy or immunosuppressive therapy. World J Gastroenterol 2011; 17:1531-1537. https://doi.org/10.3748/wjg.v17.i12.1531
  34. 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;148:519-528. https://doi.org/10.7326/0003-4819-148-7-200804010-00008
  35. Yeo W, Hui EP, Chan AT, et al. Prevention of hepatitis B virus reactivation in patients with nasopharyngeal carcinoma with lamivudine. Am J Clin Oncol 2005;28:379-384. https://doi.org/10.1097/01.coc.0000159554.97885.88
  36. Idilman R, Arat M, Soydan E, et al. Lamivudine prophylaxis for prevention of chemotherapy-induced hepatitis B virus reactivation in hepatitis B virus carriers with malignancies. J Viral Hepat 2004;11:141-147. https://doi.org/10.1046/j.1365-2893.2003.00479.x
  37. Shibolet O, Ilan Y, Gillis S, Hubert A, Shouval D, Safadi R. Lamivudine therapy for prevention of immunosuppressiveinduced hepatitis B virus reactivation in hepatitis B surface antigen carriers. Blood 2002;100:391-396. https://doi.org/10.1182/blood.V100.2.391
  38. 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;24:540-546. https://doi.org/10.1111/j.1478-3231.2004.0964.x
  39. Yeo W, Chan PK, Ho WM, 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;22:927-934. https://doi.org/10.1200/JCO.2004.05.161
  40. Hsu C, Sur IJ, Hwang WS, et al. A prospective comparative study of prophylactic or therapeutic use of lamivudine for chemotherapy-associated hepatitis B (HBV) reactivation in non-Hodgkin's lymphoma patients [Abstract]. Hepatology 2006;131:S297.
  41. Lok AS, McMahon BJ. Chronic hepatitis B: update 2009. Hepatology 2009;50:661-662. https://doi.org/10.1002/hep.23190
  42. European Association For The Study Of The Liver. EASL Clinical Practice Guidelines: management of chronic hepatitis B. J Hepatol 2009;50:227-242. https://doi.org/10.1016/j.jhep.2008.10.001
  43. Liaw YF, Leung N, Guan R, et al. Asian-Pacific consensus statement on the management of chronic hepatitis B: a 2005 update. Liver Int 2005;25:472-489. https://doi.org/10.1111/j.1478-3231.2005.01134.x
  44. Pollard AJ, Perrett KP, Beverley PC. Maintaining protection against invasive bacteria with protein-polysaccharide conjugate vaccines. Nat Rev Immunol 2009;9:213-220. https://doi.org/10.1038/nri2494
  45. Ek T, Mellander L, Andersson B, Abrahamsson J. Immune reconstitution after childhood acute lymphoblastic leukemia is most severely affected in the high risk group. Pediatr Blood Cancer 2005;44:461-468. https://doi.org/10.1002/pbc.20255
  46. Hui CK, Cheung WW, Au WY, et al. Hepatitis B reactivation after withdrawal of pre-emptive lamivudine in patients with haematological malignancy on completion of cytotoxic chemotherapy. Gut 2005;54:1597-1603. https://doi.org/10.1136/gut.2005.070763

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  2. Reactivation of Hepatitis B Virus Following Systemic Chemotherapy for Malignant Lymphoma vol.85, pp.6, 2012, https://doi.org/10.3904/kjm.2013.85.6.598
  3. A Case of Reactivation of Hepatitis B and Fulminant Hepatitis which developed 3 months following Chemotherapy Including Rituximab in a Patient with Lymphoma vol.29, pp.2, 2012, https://doi.org/10.7180/kmj.2014.29.2.161