Kinetics and risk of de novo hepatitis B infection in HBsAg-negative patients undergoing cytotoxic chemotherapy.

BACKGROUND & AIMS De novo hepatitis B virus (HBV)-related hepatitis after chemotherapy results in high morbidity and mortality. We evaluate the clinical course of de novo HBV-related hepatitis after chemotherapy. METHODS Two hundred forty-four consecutive hepatitis B surface antigen (HBsAg)-negative lymphoma patients treated with chemotherapy were followed up for a median of 12.4 (range, 0.1-65.0) months. Serially collected serum samples were analyzed for hepatitis, serum HBV DNA, and HBsAg seroreversion. RESULTS Eight of the 244 patients (3.3%) developed de novo HBV-related hepatitis. A 100-fold increase in serum HBV DNA preceded de novo HBV-related hepatitis by a median of 18.5 (range, 12-28) weeks. All 8 patients had normal serum alanine aminotransaminase level when the 100-fold increase in serum HBV DNA occurred. Patients with de novo HBV-related hepatitis were more likely to have occult HBV infection before chemotherapy. Direct sequencing results showed that these 8 patients had de novo HBV-related hepatitis from reactivation of occult HBV infection. Three of the 8 patients with de novo HBV-related hepatitis compared with 6 of the 236 patients without de novo HBV-related hepatitis developed fulminant hepatic failure (37.5% vs 2.5%, respectively, P < .001). On multivariate Cox analysis, de novo HBV-related hepatitis was independently associated with a higher risk of fulminant hepatic failure (relative risk, 29.854; 95% confidence interval: 4.844-183.980; P < .001). CONCLUSIONS Close surveillance for a 100-fold increase in HBV DNA is recommended for HBsAg-negative patients treated with chemotherapy so that early commencement of antiviral therapy can be initiated before the occurrence of de novo HBV-related hepatitis.

[1]  G. Raimondo,et al.  Occult hepatitis B virus infection. , 2007, Journal of hepatology.

[2]  I. Bernstein,et al.  Childhood Leukemias: Antibody-targeted therapy , 2006 .

[3]  W. Au,et al.  A long-term follow-up study on hepatitis B surface antigen-positive patients undergoing allogeneic hematopoietic stem cell transplantation. , 2005, Blood.

[4]  W. Au,et al.  Occult hepatitis B virus infection in hematopoietic stem cell donors in a hepatitis B virus endemic area. , 2005, Journal of hepatology.

[5]  P. Mouncey,et al.  Trials in advanced Hodgkin's disease: more than 30 years experience of the British National Lymphoma Investigation. , 2004, Clinical lymphoma.

[6]  G. Ossenkoppele,et al.  Antibody-targeted therapy: a paradigm of innovative treatment strategies in indolent and aggressive B-cell non-Hodgkin lymphoma , 2004, Current opinion in hematology.

[7]  T. Chao,et al.  Delayed hepatitis B virus reactivation after cessation of preemptive lamivudine in lymphoma patients treated with rituximab plus CHOP , 2004, Annals of Hematology.

[8]  A. González-Quintela,et al.  Truly de novo Hepatitis B After Liver Transplantation , 2004, American Journal of Gastroenterology.

[9]  E. Schiff,et al.  A treatment algorithm for the management of chronic hepatitis B virus infection in the United States. , 2004, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[10]  J. Marrero,et al.  Occult hepatitis B virus infection in patients with hepatocellular carcinoma: Innocent bystander, cofactor, or culprit? , 2004, Gastroenterology.

[11]  D. Fong,et al.  Early is superior to deferred preemptive lamivudine therapy for hepatitis B patients undergoing chemotherapy. , 2003, Gastroenterology.

[12]  B. E. C. Oiffier,et al.  CHOP Chemotherapy plus Rituximab Compared with CHOP Alone in Elderly Patients with Diffuse Large-B-Cell Lymphoma , 2002 .

[13]  V. Ribrag,et al.  Fatal reactivation of cytomegalovirus infection after use of rituximab for a post-transplantation lymphoproliferative disorder. , 2001, The New England journal of medicine.

[14]  H. Kawasaki,et al.  Incidence of hepatitis virus infection and severe liver dysfunction in patients receiving chemotherapy for hematologic malignancies , 2001, European journal of haematology.

[15]  C. Bréchot,et al.  Persistent hepatitis B virus infection in subjects without hepatitis B surface antigen: Clinically significant or purely “occult”? , 2001, Hepatology.

[16]  H. Conjeevaram,et al.  Occult hepatitis B virus infection: A hidden menace? , 2001, Hepatology.

[17]  L. Grande,et al.  Evidence of serious graft damage induced by de novo hepatitis B virus infection after liver transplantation , 2001, Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society.

[18]  I. Dervite,et al.  Acute hepatitis B in a patient with antibodies to hepatitis B surface antigen who was receiving rituximab. , 2001, The New England journal of medicine.

[19]  J. Córdoba,et al.  De novo hepatitis B after liver transplantation from hepatitis B core antibody—Positive donors in an area with high prevalence of anti‐HBc positivity in the donor population , 2001, Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society.

[20]  S. Johnson,et al.  Therapeutic potential of purine analogue combinations in the treatment of lymphoid malignancies , 2000 .

[21]  T. Miller,et al.  Combined chemotherapy plus radiotherapy for treatment of earlystage intermediate- and high-grade non-Hodgkin’s lymphoma , 2000, Current oncology reports.

[22]  E. Conde,et al.  Fatal visceral varicella-zoster infection following rituximab and chemotherapy treatment in a patient with follicular lymphoma. , 2000, Haematologica.

[23]  D. Fleming,et al.  Pure red cell aplasia due to parvovirus B19 in a patient treated with rituximab. , 2000, Blood.

[24]  J. Crespo,et al.  Severe clinical course of de novo hepatitis B infection after liver transplantation. , 1999, Liver transplantation and surgery : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society.

[25]  L. Gordon,et al.  Treatment of patients with low-grade B-cell lymphoma with the combination of chimeric anti-CD20 monoclonal antibody and CHOP chemotherapy. , 1999, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[26]  C. Rieux,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. , 1998, Transplantation.

[27]  M. Altfeld,et al.  Reactivation of hepatitis B in a long-term anti-HBs-positive patient with AIDS following lamivudine withdrawal. , 1998, Journal of hepatology.

[28]  J. Fung,et al.  Infectivity of hepatic allografts with antibodies to hepatitis B virus. , 1997, Transplantation.

[29]  R. Wiesner,et al.  Transmission of hepatitis B by transplantation of livers from donors positive for antibody to hepatitis B core antigen. The National Institute of Diabetes and Digestive and Kidney Diseases Liver Transplantation Database. , 1997, Gastroenterology.

[30]  D. Samuel,et al.  De novo and apparent de novo hepatitis B virus infection after liver transplantation. , 1997, Journal of hepatology.

[31]  R. Wiesner,et al.  The clinical course of transplantation-associated de novo hepatitis B infection in the liver transplant recipient. , 1997, Liver transplantation and surgery : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society.

[32]  F. Chisari,et al.  The hepatitis B virus persists for decades after patients' recovery from acute viral hepatitis despite active maintenance of a cytotoxic T–lymphocyte response , 1996, Nature Medicine.

[33]  J. Emond,et al.  The Risk Of Transmission Of Hepatitis B From Hbsag(-), Hbcab(+), Hbigm(-) Organ Donors , 1995, Transplantation.

[34]  L. Ferrell,et al.  "Occult" hepatitis B virus as source of infection in liver transplant recipients , 1994, The Lancet.

[35]  C. Chi,et al.  Glucocorticoid stimulates hepatitis B viral gene expression in cultured human hepatoma cells , 1992, Hepatology.

[36]  H. Prentice,et al.  Fatal hepatitis B reactivation after autologous bone marrow transplantation. , 1989, Bone marrow transplantation.

[37]  R. Burk,et al.  Hepatitis B virus DNA contains a glucocorticoid-responsive element. , 1986, Proceedings of the National Academy of Sciences of the United States of America.