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Athni TS, Barmettler S. Hypogammaglobulinemia, late-onset neutropenia, and infections following rituximab. Ann Allergy Asthma Immunol 2023; 130:699-712. [PMID: 36706910 PMCID: PMC10247428 DOI: 10.1016/j.anai.2023.01.018] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2022] [Revised: 12/23/2022] [Accepted: 01/16/2023] [Indexed: 01/26/2023]
Abstract
Rituximab is a chimeric anti-CD20 monoclonal antibody that targets CD20-expressing B lymphocytes, has a well-defined efficacy and safety profile, and is broadly used to treat a wide array of diseases. In this review, we cover the mechanism of action of rituximab and focus on hypogammaglobulinemia and late-onset neutropenia-2 immune effects secondary to rituximab-and subsequent infection. We review risk factors and highlight key considerations for immunologic monitoring and clinical management of rituximab-induced secondary immune deficiencies. In patients treated with rituximab, monitoring for hypogammaglobulinemia and infections may help to identify the subset of patients at high risk for developing poor B cell reconstitution, subsequent infections, and adverse complications. These patients may benefit from early interventions such as vaccination, antibacterial prophylaxis, and immunoglobulin replacement therapy. Systematic evaluation of immunoglobulin levels and peripheral B cell counts by flow cytometry, both at baseline and periodically after therapy, is recommended for monitoring. In addition, in those patients with prolonged hypogammaglobulinemia and increased infections after rituximab use, immunologic evaluation for inborn errors of immunity may be warranted to further risk stratification, increase monitoring, and assist in therapeutic decision-making. As the immunologic effects of rituximab are further elucidated, personalized approaches to minimize the risk of adverse reactions while maximizing benefit will allow for improved care of patients with decreased morbidity and mortality.
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Affiliation(s)
| | - Sara Barmettler
- Allergy and Clinical Immunology Unit, Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, Boston, Massachusetts.
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Xing F, Lo SKF, Lau SKP, Woo PCY. Listeriosis in a Metropolitan Hospital: Is Targeted Therapy a Risk Factor for Infection? Front Med (Lausanne) 2022; 9:888038. [PMID: 35572995 PMCID: PMC9100811 DOI: 10.3389/fmed.2022.888038] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2022] [Accepted: 04/13/2022] [Indexed: 01/26/2023] Open
Abstract
Targeted therapies are widely used for treatment of autoimmune diseases as well as solid organ and hematological malignancies. Various opportunistic infections have been described in patients on targeted therapies. Although case reports or a few case series of listeriosis have been reported to be associated with targeted therapy, most of the cases were related to anti-tumor necrosis factor-α monoclonal antibody. In this study, we describe the epidemiological and clinical profiles of listeriosis in a tertiary hospital in Shenzhen, a Southern Chinese metropolitan city in China. During the 9-year-and-6-month study period, a total of five cases of listeriosis were recorded and all of them had Listeria monocytogenes bacteremia. All five patients had predisposing factors, including corticosteroid (n = 3), targeted therapy (n = 2), pregnancy (n = 2) and anti-interferon gamma autoantibody (n = 1). The two patients who had targeted therapy during their course of cancer treatment received inhibitors of the epidermal growth factor receptor (EGFR)/human epidermal growth factor receptor 2 (HER2) pathway. The first one was a 52-year-old woman with metastatic adenocarcinoma of the lung. She was given gefitinib (EGFR tyrosine kinase inhibitor), osimertinib (third-generation EGFR tyrosine kinase inhibitor) and afatinib (tyrosine kinase inhibitor that can bind to EGFR, HER2 and HER4). The second one was a 40-year-old woman with carcinoma of the breast with brain metastasis. She was given trastuzumab (anti-HER2 monoclonal antibody) and lapatinib (dual tyrosine kinase inhibitor of the EGFR/HER2 pathway). These two patients represent the second and third reports of listeria infections associated with EGFR/HER2 pathway inhibitors in the literature. Targeted therapy is an important predisposing factor for listeriosis. Listeria infection is an important differential diagnosis in patients on targeted therapy who present with sepsis and/or central nervous system infection, and the use of antibiotic regimens that cover listeria is crucial for empirical treatment. Avoidance of high-risk food items in these patients is important for the prevention of listeriosis.
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Affiliation(s)
- Fanfan Xing
- Department of Clinical Microbiology and Infection Control, The University of Hong Kong - Shenzhen Hospital, Shenzhen, China
| | - Simon K. F. Lo
- Department of Clinical Microbiology and Infection Control, The University of Hong Kong - Shenzhen Hospital, Shenzhen, China
| | - Susanna K. P. Lau
- Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, Hong Kong SAR, China
| | - Patrick C. Y. Woo
- Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, Hong Kong SAR, China
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Infectious Challenges with Novel Antibody–Based Therapies. Curr Infect Dis Rep 2021. [DOI: 10.1007/s11908-021-00753-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
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Haberli N, Coban H, Padam C, Montezuma-Rusca JM, Creed MA, Imitola J. Babesia microti infection in a patient with multiple sclerosis treated with ocrelizumab. Mult Scler Relat Disord 2021; 48:102731. [PMID: 33450528 DOI: 10.1016/j.msard.2020.102731] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2020] [Revised: 11/17/2020] [Accepted: 12/30/2020] [Indexed: 01/24/2023]
Abstract
Ocrelizumab is a humanized monoclonal anti-CD20 antibody approved for treatment of relapsing-remitting and primary progressive multiple sclerosis (MS). Rare parasitic infections have been reported in patients with lymphoproliferative disorders using rituximab, a chimeric anti-CD20 antibody used off-label for the treatment of MS. Here, we report a patient with MS on ocrelizumab with B-cell depletion who developed severe Babesia microti (B. microti) infection with neutropenia, hemolytic anemia, and thrombocytopenia. He recovered after prompt diagnosis and treatment. This case represents the first published occurrence of babesiosis in a patient with MS on ocrelizumab. It also adds to the accumulating evidence from databases of emergent severe or relapsing B. microti infection in patients receiving anti-CD20 antibodies. This presentation stresses the diagnostic vigilance required by MS neurologists in endemic areas to identify cases of babesiosis in patients on anti-CD20 therapy and to better counsel these individuals on their risks of B. microti infection.
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Affiliation(s)
- Nicholas Haberli
- Division of Multiple Sclerosis and Neuroimmunology, Comprehensive MS Center, University of Connecticut School of Medicine
| | - Hamza Coban
- Division of Multiple Sclerosis and Neuroimmunology, Comprehensive MS Center, University of Connecticut School of Medicine
| | - Charanpreet Padam
- Division of Multiple Sclerosis and Neuroimmunology, Comprehensive MS Center, University of Connecticut School of Medicine
| | - Jairo M Montezuma-Rusca
- Division of Infectious Diseases, Department of Medicine, University of Connecticut School of Medicine; Department of Pediatrics, University of Connecticut School of Medicine
| | - Marina A Creed
- Division of Multiple Sclerosis and Neuroimmunology, Comprehensive MS Center, University of Connecticut School of Medicine
| | - Jaime Imitola
- Division of Multiple Sclerosis and Neuroimmunology, Comprehensive MS Center, University of Connecticut School of Medicine.
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Davis JS, Ferreira D, Paige E, Gedye C, Boyle M. Infectious Complications of Biological and Small Molecule Targeted Immunomodulatory Therapies. Clin Microbiol Rev 2020; 33:e00035-19. [PMID: 32522746 PMCID: PMC7289788 DOI: 10.1128/cmr.00035-19] [Citation(s) in RCA: 82] [Impact Index Per Article: 16.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
The past 2 decades have seen a revolution in our approach to therapeutic immunosuppression. We have moved from relying on broadly active traditional medications, such as prednisolone or methotrexate, toward more specific agents that often target a single receptor, cytokine, or cell type, using monoclonal antibodies, fusion proteins, or targeted small molecules. This change has transformed the treatment of many conditions, including rheumatoid arthritis, cancers, asthma, and inflammatory bowel disease, but along with the benefits have come risks. Contrary to the hope that these more specific agents would have minimal and predictable infectious sequelae, infectious complications have emerged as a major stumbling block for many of these agents. Furthermore, the growing number and complexity of available biologic agents makes it difficult for clinicians to maintain current knowledge, and most review articles focus on a particular target disease or class of agent. In this article, we review the current state of knowledge about infectious complications of biologic and small molecule immunomodulatory agents, aiming to create a single resource relevant to a broad range of clinicians and researchers. For each of 19 classes of agent, we discuss the mechanism of action, the risk and types of infectious complications, and recommendations for prevention of infection.
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Affiliation(s)
- Joshua S Davis
- Department of Infectious Diseases and Immunology, John Hunter Hospital, Newcastle, NSW, Australia
- Global and Tropical Health Division, Menzies School of Health Research and Charles Darwin University, Darwin, NT, Australia
- School of Medicine and Public Health, University of Newcastle, Newcastle, NSW, Australia
| | - David Ferreira
- School of Medicine, University of New South Wales, Sydney, NSW, Australia
| | - Emma Paige
- Department of Infectious Diseases, Alfred Hospital, Melbourne, VIC, Australia
| | - Craig Gedye
- School of Medicine, University of New South Wales, Sydney, NSW, Australia
- Department of Oncology, Calvary Mater Hospital, Newcastle, NSW, Australia
| | - Michael Boyle
- Department of Infectious Diseases and Immunology, John Hunter Hospital, Newcastle, NSW, Australia
- School of Medicine and Public Health, University of Newcastle, Newcastle, NSW, Australia
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Merli M, Rattotti S, Gotti M, Arcaini L. Antiviral therapies for managing viral hepatitis in lymphoma patients. Expert Opin Pharmacother 2017; 18:363-376. [PMID: 28140702 DOI: 10.1080/14656566.2017.1288718] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
INTRODUCTION In patients with lymphoma the detection of positive hepatitis B or C viruses (HBV and HCV) serology involves crucial therapeutic consequences. In HBV-infected patients the serological profile of active (HBsAg-positive) or resolved (HBsAg-negative/anti-HBcAb-positive) infection is associated to differential risk of viral reactivation during rituximab-based therapy and require appropriate strategies of monitoring and of antiviral prophylaxis. In HCV-associated NHL patients consolidated data demonstrated that interferon (IFN)-based antiviral therapy (AT) is able to induce lymphoma regression strictly related to viral eradication, while preliminary data of the new direct-acting antivirals (DAAs) are very promising. Areas covered: This review summarizes current evidences about HBV reactivation risk in patients undergoing rituximab-based treatments and appropriate options of antiviral prophylaxis with lamivudine, entecavir or tenofovir, as well as pre-emptive strategy in HBsAg-negative/HBcAb-positive patients. Moreover previous experiences with IFN-based AT as well as recent studies with DAAs in HCV-associated indolent lymphomas or diffuse large B-cell lymphoma (DLBCL) are reviewed. Expert opinion: Entecavir or tenofovir prophylaxis is recommended for HBsAg-positive patients, while universal prophilaxis with lamivudine may be preferred in HBsAg-negative/anti-HBc-positive patients. In asymptomatic patients with HCV-associated indolent lymphoma DAA-based AT should be used as first-line option, while in DLBCL its deliver after immunochemotherapy-induced complete remission is suggested.
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Affiliation(s)
- Michele Merli
- a Division of Hematology , University Hospital Ospedale di Circolo & Fondazione Macchi, University of Insubria , Varese , Italy
| | - Sara Rattotti
- b Department of Hematology-Oncology , Fondazione IRCCS Policlinico San Matteo , Pavia , Italy
| | - Manuel Gotti
- b Department of Hematology-Oncology , Fondazione IRCCS Policlinico San Matteo , Pavia , Italy
| | - Luca Arcaini
- b Department of Hematology-Oncology , Fondazione IRCCS Policlinico San Matteo , Pavia , Italy.,c Department of Molecular Medicine , University of Pavia , Pavia , Italy
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Viganò M, Serra G, Casella G, Grossi G, Lampertico P. Reactivation of hepatitis B virus during targeted therapies for cancer and immune-mediated disorders. Expert Opin Biol Ther 2016; 16:917-26. [PMID: 27088278 DOI: 10.1080/14712598.2016.1177017] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
INTRODUCTION Targeted therapies have gained popularity in the treatment of several oncologic and immune-mediated diseases. Immunosuppression caused by these drugs has been associated to reactivation of hepatitis B virus (HBV) in both hepatitis B surface antigen (HBsAg) positive patients (overt infection) and HBsAg negative/anti-hepatitis B core antigen (anti-HBc) positive carriers (resolved infection), leading to premature discontinuation of therapy and potentially fatal hepatitis. AREAS COVERED This review summarizes the evidence of HBV reactivation in patients with overt or resolved HBV infection undergoing targeted therapies for cancer or immune-mediated disorders, providing recommendations for the management of these patients. EXPERT OPINION The risk of HBV reactivation relies on the immunosuppressive potency and duration of these therapies, the underlying disease and the virological patient's profile. However, HBV reactivation is preventable by screening for HBV markers in all patients scheduled to receive targeted therapies, assessing the virological profile and patient's clinical state, followed by appropriate antiviral treatment or prophylaxis in those patients at high risk of HBV reactivation. Close monitoring of HBV carriers at low risk of reactivation is warranted with the aim to start antiviral therapy as soon as HBV reactivates.
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Affiliation(s)
- Mauro Viganò
- a Hepatology Unit, Ospedale San Giuseppe , Università di Milano , Milan , Italy
| | | | | | - Glenda Grossi
- c A.M. and A. Migliavacca" Center for Liver Disease, Division of Gastroenterology and Hepatology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico , Università di Milano , Milan , Italy
| | - Pietro Lampertico
- c A.M. and A. Migliavacca" Center for Liver Disease, Division of Gastroenterology and Hepatology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico , Università di Milano , Milan , Italy
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Tsutsumi Y, Yamamoto Y, Ito S, Ohigashi H, Shiratori S, Naruse H, Teshima T. Hepatitis B virus reactivation with a rituximab-containing regimen. World J Hepatol 2015; 7:2344-2351. [PMID: 26413224 PMCID: PMC4577642 DOI: 10.4254/wjh.v7.i21.2344] [Citation(s) in RCA: 54] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/20/2015] [Revised: 07/27/2015] [Accepted: 09/08/2015] [Indexed: 02/06/2023] Open
Abstract
Rituximab is currently used not only in the treatment of B-cell lymphoma but also for various other diseases, including autoimmune diseases, post-transplant graft vs host disease, and rejection following kidney transplants. Due to rituximab’s widespread use, great progress has been made regarding research into complications that arise from its use, one of the most serious being the reactivation of hepatitis B virus (HBV), and efforts continue to establish guidelines for preventive treatment against this occurrence. This report discusses preventive measures against rituximab-induced HBV reactivation and future objectives.
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Hsiao LT, Chiou TJ, Gau JP, Yang CF, Yu YB, Liu CY, Liu JH, Chen PM, Tzeng CH, Chan YJ, Yang MH, Huang YH. Risk of Reverse Seroconversion of Hepatitis B Virus Surface Antigen in Rituximab-Treated Non-Hodgkin Lymphoma Patients: A Large Cohort Retrospective Study. Medicine (Baltimore) 2015; 94:e1321. [PMID: 26266374 PMCID: PMC4616669 DOI: 10.1097/md.0000000000001321] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
Rituximab causes hepatitis B virus (HBV) reactivation in HBV surface antigen (HBsAg)-seronegative patients with CD20-positive B-cell non-Hodgkin lymphoma (CD20 NHL), especially for those seropositive to the antibody of core antigen (anti-HBc). Clinical hepatitis usually develops after reverse seroconversion of HBsAg (HBV-RS), indicated by the reappearance of HBsAg in serum. Because of the relatively high prevalence of anti-HBc seropositivity in unvaccinated HBsAg-seronegative adults in an HBV hyperendemic area, we aimed to investigate additional factors influencing the development of rituximab-associated HBV-RS.Between January 2000 and December 2010, unvaccinated HBsAg-seronegative adults with CD20 NHL who had received rituximab-containing therapy but not anti-HBV agents were enrolled. Patients with and without HBV-RS were compared in terms of clinical factors and treatments including the number of cycles of rituximab therapy, and transplantation. Competing risk regression was used to identify the factors associated with HBV-RS.For the 482 patients enrolled, the serological status of anti-HBc was available in 75.9%, with a seropositivity rate of 86.6%. At the last follow-up, a total of 33 (6.85%) patients had HBV-RS, with 95.8% anti-HBc seropositive, 78.9% anti-HBs seropositive, and none anti-HCV seropositive. HBV-RS patients have received more cycles (≥6) and prolonged durations of rituximab therapy, and hematopoietic stem cell transplantation. The overall survival was not different between patients with and those without HBV-RS. At the time of HBV-RS, a total of 25 (78.1%) patients had hepatitis flare, especially when HBV-RS appeared during/after induction therapy (100%, 10 of 10). Three (9.1%) patients had fulminant hepatitis, resulting in death in 1 (3%) patient. A higher rituximab cycle intensity was associated with a higher rate of hepatitis flare at the time of HBV-RS. When death in the absence of HBV-RS was considered as the competing risk, the univariate and multivariate regression analyses showed that several factors were independently associated with the development of HBV-RS, including anti-HCV seronegativity, histological subtype of posttransplant lymphoproliferative disorders, ≥6 cycles of rituximab therapy, and succeeding hematopoietic stem cell transplantation.The findings of our study identify additional factors influencing the development of rituximab-associated HBV-RS in HBsAg-seronegative adults with CD20 NHL.
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Affiliation(s)
- Liang-Tsai Hsiao
- From the Division of Hematology and Oncology, Department of Medicine, Taipei Veterans General Hospital (L-TH, J-PG, Y-BY, C-YL, J-HL, P-MC, C-HT, M-HY); Institute of Clinical Medicine, National Yang-Ming University School of Medicine (L-TH, T-JC, J-PG, C-FY, Y-BY, C-YL, J-HL, P-MC, C-HT, M-HY, Y-HH); Division of Transfusion Medicine, Department of Medicine (T-JC); Department of Pathology and Laboratory Medicine (C-FY); Division of Microbiology, Department of Pathology and Laboratory Medicine (Y-JC); Division of Infectious Diseases, Department of Medicine, Taipei Veterans General Hospital (Y-JC); Institute of Public Health, National Yang-Ming University (Y-JC); and Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital (Y-HH), Taipei, Taiwan
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Viganò M, Mangia G, Lampertico P. Management of patients with overt or resolved hepatitis B virus infection undergoing rituximab therapy. Expert Opin Biol Ther 2014; 14:1019-31. [DOI: 10.1517/14712598.2014.912273] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
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Tsutsumi Y, Yamamoto Y, Shimono J, Ohhigashi H, Teshima T. Hepatitis B virus reactivation with rituximab-containing regimen. World J Hepatol 2013; 5:612-620. [PMID: 24303089 PMCID: PMC3847944 DOI: 10.4254/wjh.v5.i11.612] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/06/2013] [Accepted: 11/05/2013] [Indexed: 02/06/2023] Open
Abstract
Rituximab is recognized as a useful drug for the treatment of B-cell non-Hodgkin’s lymphoma and its use has been extended to such diseases as idiopathic thrombocytopenic purpura, thrombotic thrombocytopenic purpura, chronic rheumatoid arthritis and ANCA-associated vasculitides. One serious complication associated with its use is the reactivation of hepatitis B virus and the search for methods to prevent this occurrence has resulted in the rapid accumulation of knowledge. In this review, we discuss case analyses from our department and other groups and outline the current knowledge on the topic and the remaining issues.
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Cholestatic liver disease after rituximab and adalimumab and the possible role of cross-reacting antibodies to Fab 2 fragments. PLoS One 2013; 8:e78856. [PMID: 24244376 PMCID: PMC3823999 DOI: 10.1371/journal.pone.0078856] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2013] [Accepted: 09/07/2013] [Indexed: 11/19/2022] Open
Abstract
BACKGROUND Millions of patients are treated with therapeutic monoclonal antibodies (Tmabs) for miscellaneous diseases. We investigated sera from six patients who received immune globulin, from one patient with refractory anti-neutrophil-cytoplasmic antibody (ANCA)-associated granulomatosis with polyangiitis (GPA) who developed two episodes of acute cholestatic liver disease, one after treatment with rituximab and a second after adalimumab and a healthy control group. METHODS Three sera from the patient and six sera from patients who received immune globulin were analyzed for antibodies to rituximab and adalimumab by ELISA. Additionally, sera from the patients and from nine healthy blood donors were coated with the Fab fragment of an unrelated humanized monoclonal antibody, with human Fc proteins as well as a mouse IgG globulin. RESULTS Viral serology for hepatitis A, B, C and autoantibodies specific for autoimmune liver disorders were negative. In all three sera from the patient antibodies to rituximab could be detected, but also antibodies to adalimumab were present even at time points when the patient had not yet received adalimumab, indicating cross reactivity between both substances. Testing against an unrelated human Fab fragment revealed positive results, indicating that the patient had antibodies against human Fab fragments in general. The Fc proteins were negative, and patients' sera did also not react with mouse IgG globulins. Remarkably, 2 out of 5 patients which were treated with immune globulin had antibodies against human Fab fragments in general whereas in none of the samples from healthy controls antibodies to Fab fragment could be detected. CONCLUSION This is the first study demonstrating cholestatic liver disease induced by two different Tmabs. Cross - reacting antibodies to Fab2 fragments in general are probably involved. Further studies must show if these Fab2 antibodies in general are related with drug-induced side effects and accelerated drug clearance in patients on Tmab therapy.
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Efficacy of prophylactic lamivudine to prevent hepatitis B virus reactivation in B-cell lymphoma treated with rituximab-containing chemotherapy. Support Care Cancer 2012; 21:1265-71. [PMID: 23151650 DOI: 10.1007/s00520-012-1656-8] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2012] [Accepted: 10/29/2012] [Indexed: 01/23/2023]
Abstract
PURPOSE Reactivation of hepatitis B virus (HBV) is a common complication in patients with HBV infection who receive cytotoxic chemotherapy. In rituximab-containing chemotherapy for B-cell lymphoma, severe hepatitis due to HBV reactivation occurred. The aim of this study is to estimate the effect of prophylactic lamivudine on the risk of HBV reactivation in patients with HBV infection who receive rituximab-containing chemotherapy. METHODS In this study, HBV markers and liver function tests were monitored in 268 consecutive patients with B-cell lymphoma, who received rituximab-containing chemotherapy between January 2008 and November 2011. Sixty-nine patients (25.7 %) with either chronic HBV infection or past HBV infection received prophylaxis with lamivudine 100 mg daily by oral intake. RESULTS In the HBsAg-positive group, six (6/38) patients developed hepatitis, only one of which was attributed to HBV reactivation. In the HBsAg-negative and HBcAb-positive group, two (2/31) patients developed hepatitis, none of which was attributed to HBV reactivation. CONCLUSIONS These results support that prophylactic lamivudine can prevent HBV reactivation for B-cell lymphoma with HBV infection who was receiving rituximab-containing chemotherapy.
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Ruggenenti P, Cravedi P, Chianca A, Perna A, Ruggiero B, Gaspari F, Rambaldi A, Marasà M, Remuzzi G. Rituximab in idiopathic membranous nephropathy. J Am Soc Nephrol 2012; 23:1416-25. [PMID: 22822077 DOI: 10.1681/asn.2012020181] [Citation(s) in RCA: 218] [Impact Index Per Article: 16.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
Selective depletion of B cells with the mAb rituximab may benefit the autoimmune glomerular disease idiopathic membranous nephropathy (IMN). Here, we describe our experience treating 100 consecutive IMN patients with persistent nephrotic syndrome with rituximab. We defined complete remission as persistent proteinuria <0.3 g/24 h and partial remission as persistent proteinuria <3 g/24 h, each also having >50% reduction in proteinuria from baseline. During a median follow-up of 29 months after rituximab administration, 65 patients achieved complete or partial remission. The median time to remission was 7.1 months. All 24 patients who had at least 4 years of follow-up achieved complete or partial remission. Rates of remission were similar between patients with or without previous immunosuppressive treatment. Four patients died and four progressed to ESRD. Measured GFR increased by a mean 13.2 (SD 19.6) ml/min per 1.73 m(2) among those who achieved complete remission. Serum albumin significantly increased and albumin fractional clearance decreased among those achieving complete or partial remission. Proteinuria at baseline and the follow-up duration each independently predicted the decline of proteinuria. Furthermore, the magnitude of proteinuria reduction significantly correlated with slower GFR decline (P=0.0001). No treatment-related serious adverse events occurred. In summary, rituximab achieved disease remission and stabilized or improved renal function in a large cohort of high-risk patients with IMN.
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Affiliation(s)
- Piero Ruggenenti
- Mario Negri Institute for Pharmacological Research, Clinical Research Center for Rare Diseases, Aldo e Cele Daccò, Villa Camozzi, Ranica, Italy
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Tani Y, Aso H, Matsukura H, Tadokoro K, Tamori A, Nishiguchi S, Yoshizawa H, Shibata H. Significant background rates of HBV and HCV infections in patients and risks of blood transfusion from donors with low anti-HBc titres or high anti-HBc titres with high anti-HBs titres in Japan: a prospective, individual NAT study of transfusion-transmitted HBV, HCV and HIV infections. Vox Sang 2012; 102:285-293. [PMID: 22082342 DOI: 10.1111/j.1423-0410.2011.01561.x] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
BACKGROUND The Japanese Red Cross (JRC) conducted a prospective study to evaluate the frequency of transfusion-transmitted HBV, HCV and HIV infections to assess the risk of transfusion of blood components routinely supplied to hospitals. STUDY DESIGN AND METHODS Post-transfusion specimens from patients at eight medical institutes were examined for evidence of infection with HBV (2139 cases), HCV (2091) and HIV (2040) using individual nucleic acid amplification testing (NAT). If these specimens were reactive, pre-transfusion specimens were also examined for the virus concerned by individual NAT. In the event that the pre-transfusion specimen was non-reactive, then all repository specimens from implicated donors were tested for the viruses by individual donation NAT. In addition, a further study was carried out to evaluate the risk of transfusion of components from donors with low anti-HBc titres or high anti-HBc with high anti-HBs titres. RESULTS Transfusion-transmitted HCV and HIV infections were not observed. One case of post-transfusion HBV infection was identified (rate, 0·0004675; 95% CI for the risk of transmission, 1 in 451-41,841). The background rates of HBV, HCV and HIV infections in patients prior to transfusion were 3·4% (72/2139), 7·2% (150/2091) and 0% (0/2040), respectively. Sixty-four anti-HBc- and/or anti-HBs-reactive blood components were transfused to 52 patients non-reactive for anti-HBc or anti-HBs before and after transfusion (rate, 0; 95% CI for the risk of transmission, <1 in 22). CONCLUSION This study demonstrated that the current criteria employed by JRC have a low risk, but the background rates of HBV and HCV infections in Japanese patients are significant.
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Affiliation(s)
- Y Tani
- Japanese Red Cross Osaka Blood Center, Osaka, Japan.
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Pei SN, Ma MC, Wang MC, Kuo CY, Rau KM, Su CY, Chen CH. Analysis of hepatitis B surface antibody titers in B cell lymphoma patients after rituximab therapy. Ann Hematol 2012; 91:1007-12. [PMID: 22273839 DOI: 10.1007/s00277-012-1405-6] [Citation(s) in RCA: 63] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2011] [Accepted: 01/03/2012] [Indexed: 12/14/2022]
Abstract
Hepatitis B virus (HBV) reactivation is a well-known complication after rituximab therapy in patients with B cell lymphoma. Traditionally, hepatitis B surface antibody (anti-HBs) is a protective antibody, but the effect of rituximab on these antibodies has not been well studied. In 29 B cell lymphoma patients who were positive for anti-HBs before rituximab therapy, anti-HBs serologies before and after rituximab therapy were compared. Anti-HBs titers after rituximab treatment were significantly lower (P < 0.001) than those before treatment. None of the ten cases with pre-treatment anti-HBs titers above 100 mIU/mL became negative for anti-HBs after rituximab therapy. In contrast, 8 of the 19 patients with pre-treatment anti-HBs titers below 100 mIU/mL lost their anti-HBs (P = 0.027). Of these, one patient developed HBsAg seroreversion and HBV reactivation after rituximab therapy. Regarding patients with loss of anti-HBs or not, there was no significant difference in pre- and post-treatment immunoglobulin G levels between both groups. The rate of anti-HBs loss increased with advanced lymphoma stage and international prognostic index (P = 0.002 and <0.001, respectively). Multiple logistic regression analysis showed that pre-treatment anti-HBs titer is the only independent factor influencing the loss of anti-HBs (per one log mIU/mL, odds ratio, 0.003; 95% confidence interval, 0.000-0.302; P = 0.014). In conclusion, we found that anti-HBs titers decreased significantly (P < 0.001) after rituximab treatment. B cell lymphoma patients with low pre-treatment anti-HBs titers (<100 mIU/mL) were more likely to lose anti-HBs antibodies and were at risk of HBV reactivation after rituximab immunochemotherapy.
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Affiliation(s)
- Sung-Nan Pei
- Division of Hema-Oncology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
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Izadi M, Taheri S. Hepatitis B virus infection has no significant role on lymphoproliferative disorders post liver transplantation: PTLD. int survey. Ann Hepatol 2011; 10:315-320. [PMID: 21677333 DOI: 10.1016/s1665-2681(19)31543-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2025]
Abstract
INTRODUCTION Based on very limited data, it has been recently suggested that hepatitis B virus infection can play significant roles in post transplantation lymphoproliferative disorders. In the current study pooling data of PTLD in HBV positive liver recipients gathered from the existing literature, we sought to analyze and compare characteristics, behavior and prognosis of PTLD arising in HBV positive liver graft recipients. METHODS A comprehensive search for the available data though PubMed and Google Scholar for reports of PTLD and HBV infection in liver recipients was conducted. Data of 18 different studies were pooled and analyzed. RESULTS Liver recipients with HBV positive-PTLD were comparable to their HBV negative counterparts in gender, age at transplantation, time from transplantation to PTLD development, lymphoma cell type, histopathology of lesions, remission episodes, mortality rate, multi-organ involvement, and disseminated PTLD (p > 0.1 for all). HBV positive PTLD patients were significantly less likely to complicate spleen (0 vs. 23%, respectively; p = 0.015). Survival of the two patient groups were comparable (p = 0.8). CONCLUSION HBV infection has no significant impact on inducing some distinct types of PTLD and represents no survival effect in PTLD setting. Future prospective studies are needed for confirming our findings.
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Affiliation(s)
- Morteza Izadi
- Health Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran
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Nath A, Agarwal R, Malhotra P, Varma S. Prevalence of hepatitis B virus infection in non-Hodgkin lymphoma: a systematic review and meta-analysis. Intern Med J 2011; 40:633-41. [PMID: 19811561 DOI: 10.1111/j.1445-5994.2009.02060.x] [Citation(s) in RCA: 80] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND AND AIM A recent meta-analysis has demonstrated an association between hepatitis C virus and non-Hodgkin lymphoma (NHL). There is also evidence on the association between hepatitis B virus (HBV) and NHL. The aim of this study was to evaluate this evidence using a meta-analytic approach. METHODS We searched the MEDLINE database from 1962 to 2008 for case-control studies that have reported the association of HBV with NHL. We calculated the odds ratio (OR) and 95% confidence intervals (CI) to assess the prevalence of HBV infection and pooled the results using three different statistical models. RESULTS Our search yielded 12 studies with 11 studies (3262 NHL patients, 1,523,205 controls) evaluating HBV infection in NHL and one study (3888 HBV-infected individuals, 205,203 controls) that had investigated for NHL in HBV infection. The OR of detecting HBV infection in NHL when compared with the control population was 2.56 (95% CI, 2.24-2.92) by the fixed effects model; 2.61 (95% CI, 2.29-2.98) by the exact method and 2.67 (95% CI, 2.04-3.49) by the random effects model suggesting a high prevalence of HBV carrier state in lymphoma. There was evidence of statistical heterogeneity which disappeared after exclusion of retrospective studies on sensitivity analysis. CONCLUSIONS The results of this study suggest a possible causal relation between HBV infection and NHL which needs to be confirmed by experimental and epidemiological studies. In countries where prevalence of HBV infection is 1% or more, it may be prudent to screen patients with NHL for occult HBV infection.
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Affiliation(s)
- A Nath
- Postgraduate Institute of Medical Education and Research, Chandigarh, India
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19
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Huang SL, Chou YT, Hsieh YC, Huang YC, Lin TY, Chiu CH. Epidemiology and clinical characteristics of Listeria monocytogenes bacteremia in a Taiwanese medical center. JOURNAL OF MICROBIOLOGY, IMMUNOLOGY, AND INFECTION = WEI MIAN YU GAN RAN ZA ZHI 2011; 43:485-90. [PMID: 21195975 DOI: 10.1016/s1684-1182(10)60075-8] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/30/2009] [Revised: 06/14/2009] [Accepted: 08/20/2009] [Indexed: 01/22/2023]
Abstract
BACKGROUND/PURPOSE There have been many reported cases of Listeria monocytogenes bacteremia in Europe and the United States, but only a few from Taiwan. The present study was undertaken to analyze the clinical characteristics of patients with L. monocytogenes bacteremia in Taiwan. METHODS Patients with culture-confirmed L. monocytogenes bacteremia were identified at Chang Gung Memorial Hospital between January 2001 and December 2008. The clinical features and outcomes of the patients and the antimicrobial susceptibilities of the clinical isolates were analyzed. RESULTS Forty-three patients, including two newborn babies (4.7%) and 41 adults (95.3%), with at least one episode of Listeria bacteremia were identified. Forty-two (97.7%) of these patients had underlying diseases. Thirty-three patients (76.7%) had fever, 14 (32.6%) had experienced respiratory distress, and 11 (25.6%) had reported changes in consciousness. Twelve patients died within 14 days of infection, corresponding to a case-fatality rate of 27.9%. All the clinical isolates tested were susceptible to ampicillin, penicillin and vancomycin. CONCLUSION Most cases of L. monocytogenes infection occurred in adults with underlying diseases, especially malignancy, and only two cases of neonatal L. monocytogenes bacteremia were identified over the 8-year period. Penicillin, ampicillin and vancomycin could be used for the treatment of L. monocytogenes bacteremia, with the case-fatality rate lower for patients who received appropriate treatment.
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Affiliation(s)
- Sun-Lin Huang
- Division of Pediatric Infectious Diseases, Department of Pediatrics, Chang Gung Children's Hospital, Taoyuan, Taiwan
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Tsutsumi Y, Yamamoto Y, Tanaka J, Asaka M, Imamura M, Masauzi N. Prevention of hepatitis B virus reactivation under rituximab therapy. Immunotherapy 2011; 1:1053-61. [PMID: 20635919 DOI: 10.2217/imt.09.59] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Rituximab is a useful drug for the treatment of B-cell non-Hodgkin's lymphoma, and its use has been extended to other diseases such as idiopathic thrombocytopenic purpura and chronic rheumatoid arthritis. One serious complication associated with rituximab use is reactivation of hepatitis B virus, and the search for methods to prevent this occurrence has resulted in a rapid accumulation of knowledge in recent years. In this review, we will discuss case studies from our group, as well as other groups, and outline current knowledge on the topic together with issues that remain to be resolved.
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Affiliation(s)
- Yutaka Tsutsumi
- Department of Internal Medicine, Hakodate Municipal Hospital 1-10-1, Minato-cho, Hakodate 041-8680, Japan.
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Keyser FD. Choice of Biologic Therapy for Patients with Rheumatoid Arthritis: The Infection Perspective. Curr Rheumatol Rev 2011; 7:77-87. [PMID: 22081766 PMCID: PMC3182090 DOI: 10.2174/157339711794474620] [Citation(s) in RCA: 72] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2010] [Revised: 07/30/2010] [Accepted: 11/10/2010] [Indexed: 12/27/2022]
Abstract
Biologicals revolutionized the treatment of Rheumatoid Arthritis (RA). The targeted suppression of key inflammatory pathways involved in joint inflammation and destruction allows better disease control, which, however, comes at the price of an elevated infection risk due to relative immunosuppression. The disease-related infection risk and the infection risk associated with the use of TNF-α inhibitors (infliximab, adalimumab, etanercept, golimumab and certolizumab pegol), rituximab, abatacept and tocilizumab are discussed. Risk factors clinicians need to take into account when selecting the most appropriate biologic therapy for RA patients, as well as precautions and screening concerning a number of specific infections, such as tuberculosis, intracellular bacterial infections, reactivation of chronic viral infections and HIV are reviewed.
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Hepatitis B Reactivation in a HBsAg-Negative, HBcAb-Positive Patient Receiving Fludarabine for the Treatment of Chronic Lymphocytic Leukaemia. Case Reports Hepatol 2011; 2011:258791. [PMID: 25954538 PMCID: PMC4411891 DOI: 10.1155/2011/258791] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/18/2011] [Accepted: 05/17/2011] [Indexed: 11/17/2022] Open
Abstract
Hepatitis B virus (HBV) reactivation is an increasingly recognized cause of morbidity and mortality in patients undergoing chemotherapy. In haematology, the risk of reactivation of B hepatitis among HBsAg-positive patients has been documented; therefore, use of lamivudine prophylaxis is recommended before starting chemotherapy. Differently, for HBsAg-negative patients with markers of previous HBV infection (i.e., presence of isolated anti-HBc positivity) (anticore patients) management strategies are not univocal. We describe a rare case of HBV reactivation in an anticore patient after fludarabine therapy for chronic lymphocytic leukaemia. The patient fully recovered after a 6-month course of lamivudine with persistent HBV-DNA clearance and loss of HBsAg. The most important feature of this case is that fludarabine alone infrequently determines HBV reactivation, especially in anticore patients. Therefore, we suggest that patients candidates to receive fludarabine therapy should be considered for lamivudine prophylaxis, not only if HBsAg-positive, but even if anticore-positive only.
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Rituximab administration and reactivation of HBV. HEPATITIS RESEARCH AND TREATMENT 2010; 2010:182067. [PMID: 21188195 PMCID: PMC3003947 DOI: 10.1155/2010/182067] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 06/02/2010] [Revised: 09/03/2010] [Accepted: 09/29/2010] [Indexed: 12/11/2022]
Abstract
Rituximab is a drug used for the treatment of B-cell non-Hodgkin's lymphoma, and its range of use has expanded to the treatment of collagen diseases such as idiopathic thrombocytopenic purpura and rheumatoid arthritis. One serious complication of rituximab use is the reactivation of dormant hepatitis B virus, and prevention of this phenomenon has become an urgent issue. This paper provides a general outline of the problem through an analysis of patient cases that we and other groups have experienced to date.
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Kelesidis T, Daikos G, Boumpas D, Tsiodras S. Does rituximab increase the incidence of infectious complications? A narrative review. Int J Infect Dis 2010; 15:e2-16. [PMID: 21074471 DOI: 10.1016/j.ijid.2010.03.025] [Citation(s) in RCA: 146] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2009] [Revised: 03/23/2010] [Accepted: 03/30/2010] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Rituximab has increasingly been used for the treatment of hematological malignancies and autoimmune diseases, and its efficacy and safety are well established. Although clinical trials have shown conflicting results regarding the association of rituximab with infections, an increased incidence of infections has recently been reported in patients with lymphomas being treated with rituximab. However, clinical experience regarding the association of rituximab with different types of infection is lacking and this association has not been established in patients with rheumatoid arthritis. METHODS All previous studies included in our literature review were found using a PubMed, EMBASE, and Cochrane database search of the English-language medical literature applying the terms 'rituximab', 'monoclonal antibodies', 'infections', 'infectious complications', and combinations of these terms. In addition, the references cited in these articles were examined to identify additional reports. RESULTS We performed separate analyses of data regarding the association of rituximab with infection in (1) patients with hematological malignancies, (2) patients with autoimmune disorders, and (3) transplant patients. Recent data show that rituximab maintenance therapy significantly increases the risk of both infection and neutropenia in patients with lymphoma or other hematological malignancies. On the other hand, data available to date do not indicate an increased risk of infections when using rituximab compared with concurrent control treatments in patients with rheumatoid arthritis. However, there is a lack of sufficient long-term data to allow such a statement to be definitively made, and caution regarding infections should continue to be exercised, especially in patients who have received repeated courses of rituximab, are receiving other immunosuppressants concurrently, and in those whose immunoglobulin levels have fallen below the normal range. Few data are available concerning the risk of organ transplant recipients developing infections following rituximab therapy. Data from case reports, case series, and retrospective studies correlate rituximab use with the development of a variety of infections in transplant patients. CONCLUSIONS Further studies are needed to clarify the association of rituximab with infection. Physicians and patients should be educated about the association of rituximab with infectious complications. Monitoring of absolute neutrophil count and immunoglobulin levels and the identification of high-risk groups for the development of infectious complications, with timely vaccination of these groups, are clearly needed.
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Affiliation(s)
- Theodoros Kelesidis
- Department of Medicine, Division of Infectious Diseases, David Geffen School of Medicine at UCLA, 10833 Le Conte Ave., CHS 37-121, Los Angeles, CA 90095, USA.
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25
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Abstract
After more than 10 years of use, rituximab has proven to be remarkably safe. However, accumulated evidence now suggests that under some circumstances it may significantly increase the risk of infections. This risk is difficult to quantify because of confounding factors (namely, concomitant use of immunosuppressive or chemotherapeutic agents and underlying conditions), as well as under-reporting. Increased number of infections has been documented in patients treated with maintenance rituximab for low-grade lymphoma and in patients with concomitant severe immunodeficiency, whether caused by human immunodeficiency virus (HIV) infection or immunosuppressive agents like fludarabine. From the practical standpoint, the most important infection is hepatitis B reactivation, which may be delayed and result in fulminant liver failure and death. Special care should be placed on screening for hepatitis B virus (HBV) and preemptive antiviral treatment. Some investigators have reported an increase in Pneumocystis pneumonia. Finally, there is increasing evidence of a possible association with progressive multifocal leukoencephalopathy (PML), a lethal encephalitis caused by the polyomavirus JC. This review enumerates the described infectious complications, summarizes the possible underlying mechanisms of the increased risk, and makes recommendations regarding prevention, diagnosis and management.
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Affiliation(s)
- Juan C Gea-Banacloche
- Experimental Transplantation and Immunology Branch, National Cancer Institute, Bethesda, MD 20892, USA.
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26
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[Requirements for hygiene in the medical care of immunocompromised patients. Recommendations from the Committee for Hospital Hygiene and Infection Prevention at the Robert Koch Institute (RKI)]. Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz 2010; 53:357-88. [PMID: 20300719 PMCID: PMC7095954 DOI: 10.1007/s00103-010-1028-9] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
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Bennion JR, Sorvillo F, Wise ME, Krishna S, Mascola L. Decreasing listeriosis mortality in the United States, 1990-2005. Clin Infect Dis 2009; 47:867-74. [PMID: 18752441 DOI: 10.1086/591131] [Citation(s) in RCA: 52] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022] Open
Abstract
BACKGROUND Listeria monocytogenes is among the most virulent foodborne pathogens, with 20% of clinical infections resulting in death. To explore listeriosis-associated mortality in the United States and to evaluate prevention efforts, we reviewed vital records over a 16-year period to assess demographic, temporal, and seasonal trends. METHODS Nonperinatal listeriosis-associated deaths from 1990 through 2005 were identified from multiple-cause-coded death records and were combined with US census data to calculate mortality rates. Poisson regression was used to model time trends, and logistic regression was used to identify comorbid conditions associated with listeriosis on the death record. RESULTS Of the 37,267,946 deaths occurring in the United States during the 16-year study period, 1178 included listeriosis on the death record. Listeriosis-related mortality rates decreased annually by 10.74% from 1990 through 1996 and by 4.26% from 1996 through 2005. Seasonal trends show a distinct peak in mortality from July through October. After adjustment for age, sex, and race/ethnicity, listeriosis was positively associated with human immunodeficiency virus (HIV) infection (odds ratio, 4.19; 95% confidence interval, 3.06-5.73), lymphoid and hematopoietic cancers (odds ratio, 5.27; 95% confidence interval, 4.47-6.22), and liver disease (odds ratio, 2.05; 95% confidence interval, 1.54-2.73) on the death record. CONCLUSIONS Nonperinatal listeriosis-associated deaths in the United States have decreased, paralleling a decreasing trend in incidence. Strict monitoring of food manufacturing processes, as well as improved treatment for HIV infection, may have played influential roles in preventing human infections. Health care providers should be aware of seasonal listeriosis patterns, as well as conditions predisposing individuals to severe infection and death due to L. monocytogenes infection, to guide strategies for disease management and prevention.
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Affiliation(s)
- Jonathan R Bennion
- Los Angeles County Department of Public Health, University of California at Los Angeles, Los Angeles, California, USA
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28
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Pei SN, Chen CH, Lee CM, Wang MC, Ma MC, Hu TH, Kuo CY. Reactivation of hepatitis B virus following rituximab-based regimens: a serious complication in both HBsAg-positive and HBsAg-negative patients. Ann Hematol 2009; 89:255-62. [DOI: 10.1007/s00277-009-0806-7] [Citation(s) in RCA: 163] [Impact Index Per Article: 10.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2009] [Accepted: 07/31/2009] [Indexed: 12/13/2022]
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Kusakabe A, Tanaka Y, Mochida S, Nakayama N, Inoue K, Sata M, Isoda N, Kang JH, Sumino Y, Yatsuhashi H, Takikawa Y, Kaneko S, Yamada G, Karino Y, Tanaka E, Kato J, Sakaida I, Izumi N, Sugauchi F, Nojiri S, Joh T, Miyakawa Y, Mizokami M. Case-control study for the identification of virological factors associated with fulminant hepatitis B. Hepatol Res 2009; 39:648-656. [PMID: 19456899 DOI: 10.1111/j.1872-034x.2009.00519.x] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
BACKGROUND Host and viral factors can promote the development of fulminant hepatitis B (FHB), but there have been no case-control studies for figuring out virological parameters that can distinguish FHB. METHODS In a case-control study, virological factors associated with the development of FHB were sought in 50 patients with FH developed by transient hepatitis B virus (HBV) infection (FH-T) and 50 with acute self-limited hepatitis B (AHB) who were matched for sex and age. In addition, 12 patients with FH developed by acute exacerbation (AE) of asymptomatic HBV carrier (ASC) (FH-C) were also compared with 12 patients without FH by AE of chronic hepatitis B (AE-C). RESULTS Higher HBV DNA levels, subgenotype B1/Bj, A1762T/G1764A, G1896A, G1899A and A2339G mutation were significantly more frequent (P < 0.05), while hepatitis B e-antigen was less frequent in the FH-T patients than AHB. In multivariate analysis, G1896A mutation (odds ratio [OR], 13.53; 95% confidence interval [CI], 2.75-66.64), serum HBV DNA more than 5.23 log copies/mL (OR, 5.14; 95% CI, 1.10-24.15) and total bilirubin more than 10.35 mg/mL (OR, 7.81; 95% CI, 1.77-34.51) were independently associated with a fulminant outcome by transient HBV infection. On the other hand, in comparison with the patients between FH-C and AE-C groups, there was no significant difference of virological factors associated with the development of FHB. CONCLUSION A number of virological factors have been defined that may distinguish FH-T from AHB in a case-control study. The pathogenic mechanism of FHB between transient HBV infection and AE of ASC would be different.
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Affiliation(s)
- Atsunori Kusakabe
- Department of Clinical Molecular Informative Medicine, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
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Fukushima N, Mizuta T, Tanaka M, Yokoo M, Ide M, Hisatomi T, Kuwahara N, Tomimasu R, Tsuneyoshi N, Funai N, Sueoka E. Retrospective and prospective studies of hepatitis B virus reactivation in malignant lymphoma with occult HBV carrier. Ann Oncol 2009; 20:2013-7. [PMID: 19561036 DOI: 10.1093/annonc/mdp230] [Citation(s) in RCA: 90] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND In surface antigen of hepatitis B virus (HBsAg)-positive carrier for anticancer treatment of malignant lymphoma, it is well recognized that reactivation of hepatitis B virus (HBV) occasionally occurs. However, there have been only a few studies of HBV reactivation in serum HBsAg-negative and hepatitis B core antigen (HBcAb)-positive occult HBV carriers. We looked at both retrospective and prospective studies to determine the prevalence, clinical course and risk factor of HBV reactivation during chemotherapy in lymphoma patients. PATIENTS AND METHODS Forty-eight of 127 (37.8%) lymphoma patients were HBsAg negative and HBcAb positive, and 24 of these patients were then given liver function tests and HBsAg tests monthly and serum HBV DNA every 3 months. RESULTS HBV reactivation was observed in two patients (4.1%) who had received intensive chemotherapy including steroid and rituximab. Immediate administration of entecavir therapy after elevation of HBV DNA level was conducted, and this resulted in reduction of it and improvement of liver function test. CONCLUSIONS Rituximab plus steroid-containing regimens may increase the risk of HBV reactivation in HBsAg-negative and HBcAb-positive lymphoma patients. More ambitious prospective studies are required to establish clinically useful or cost-effective follow-up methods for control of HBV reactivation in lymphoma patients with occult HBV infection.
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Affiliation(s)
- N Fukushima
- Division of Hematology, Department of Internal Medicine, Faculty of Medicine, Saga University, Saga, Japan.
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Abstract
Reactivation of hepatitis B refers to the abrupt increase in hepatitis B virus (HBV) replication in a patient with inactive or resolved hepatitis B. Reactivation can occur spontaneously, but more typically is triggered by immunosuppressive therapy of cancer, autoimmune disease, or organ transplantation. Reactivation can be transient and clinically silent, but often causes a flare of disease that can be severe resulting in acute hepatic failure. Most instances of reactivation resolve spontaneously, but if immune suppression is continued, re-establishment of chronic hepatitis occurs which can lead to progressive liver injury and cirrhosis. The best-described instances of reactivation occur in hepatitis B surface antigen (HBsAg) carriers with inactive or minimally active disease who are given cancer chemotherapy for lymphoma or leukemia. Typically, serum HBV DNA rises during chemotherapy, followed by a disease flare and HBV DNA clearance with immune reconstitution after chemotherapy is stopped. Special forms of reactivation occur after solid organ and bone marrow transplantation in which chronic infection often results. Several randomized, placebo-controlled trials have shown that reactivation can be prevented by antiviral prophylaxis. Routine prophylaxis is therefore recommended for persons with HBsAg undergoing cancer chemotherapy or transplantation, but major questions remain. Which patients should be screened for HBsAg and should all be treated? Which antiviral should be used and for how long? Should persons with resolved hepatitis B without HBsAg receive prophylaxis? Future research should address the underlying molecular mechanisms of reactivation as well as its optimal means of diagnosis, treatment, and prevention in different patient populations.
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Affiliation(s)
- Jay H Hoofnagle
- Division of Digestive Diseases and Nutrition, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health (NIH), Bethesda, MD 20892, USA.
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Takahashi T, Koike T, Hashimoto S, Miura T, Nakamura J, Yamada S, Miura T, Yanagi M, Yamazaki K, Okoshi S, Aoyagi Y. A case of lamivudine-sensitive de novo acute hepatitis B induced by rituximab with the CHOP regimen for diffuse large B cell lymphoma. Hepatol Int 2009; 3:316-322. [PMID: 19669383 PMCID: PMC2712308 DOI: 10.1007/s12072-008-9094-x] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/27/2008] [Accepted: 08/07/2008] [Indexed: 12/29/2022]
Abstract
A case of de novo acute hepatitis B that showed symptoms of general malaise and anorexia during rituximab therapy with the CHOP regimen for diffuse large B cell lymphoma is reported. Lamivudine was strikingly effective, showing a rapid recovery from liver damage with jaundice. Hepatitis B virus (HBV) DNA in serum became and stayed undetectable even after the withdrawal of lamivudine, although HBsAg remained positive over 42 months from the onset. Liver biopsy showed a picture suggestive of acute viral hepatitis with multinucleated giant hepatocytes and CD38-positive plasma cell infiltration into liver parenchyma. Immunohistochemically, CD3-positive T-cells were predominant cells that infiltrated in liver parenchyma, whereas CD20-positive B cells were essentially null. Hence, it is suggested from these findings that B lymphocytes might be crucial for the continuous latency in HBV infection and may give rise to de novo acute hepatitis B if totally deleted. Moreover, the CHOP regimen might have some additive effects with the repeated on-off use of corticosteroids to the onset of the disease. In addition, significance of plasma cell infiltration in this setting is discussed.
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Affiliation(s)
- Toru Takahashi
- Division of Gastroenterology and Hepatology, Nagaoka Red Cross Hospital, 2-297-1, Senshu, Nagaoka, Niigata, 940-2085, Japan,
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Miyagawa M, Minami M, Fujii K, Sendo R, Mori K, Shimizu D, Nakajima T, Yasui K, Itoh Y, Taniwaki M, Okanoue T, Yoshikawa T. Molecular characterization of a variant virus that caused de novo hepatitis B without elevation of hepatitis B surface antigen after chemotherapy with rituximab. J Med Virol 2008; 80:2069-78. [PMID: 19040281 DOI: 10.1002/jmv.21311] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
Hepatitis B virus (HBV) reactivation in hepatitis B surface antigen (HBsAg)-negative patients following treatment with rituximab has been reported increasingly. The aim of this study was to investigate the molecular mechanisms underlying HBV reactivation in an HBsAg-negative patient. HBV was reactivated in a 75-year-old man following chemotherapy with rituximab, without elevation of HBsAg. The patient's full-length HBV genome was cloned and the entire sequence was determined. Transfection studies were performed in vitro using recombinant wild-type HBV (wild-type), the patient's HBV (patient), and two chimeric HBV constructs, in which the preS/S region of the patient and wild-type virus had been exchanged with one another. Secreted HBsAg and intra- and extra-cellular HBV DNA were measured. The number of amino acid substitutions in HBV from this patient was much higher than in previous reports of HBV mutants, such as occult HBV and vaccine escape HBV mutants. Levels of HBsAg and HBV DNA production in vitro were significantly lower in the patient compared to wild-type transfections. From analyses of the chimeric constructs, the altered preS/S region was responsible mainly for this impairment. These results show that highly mutated HBV can reactivate after chemotherapy with rituximab, despite an unusually large number of mutations, resulting in impaired viral replication in vitro. Severe immune suppression, probably caused by rituximab, may permit reactivation of highly mutated HBV. These findings have important clinical implications for the prevention and management of HBV reactivation and may explain partially the mechanism of recent, unusual cases of HBV reactivation.
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Affiliation(s)
- Masami Miyagawa
- Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
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34
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Tsutsumi Y, Shigematsu A, Hashino S, Tanaka J, Chiba K, Masauzi N, Kobayashi H, Kurosawa M, Iwasaki H, Morioka M, Asaka M, Imamura M. Analysis of reactivation of hepatitis B virus in the treatment of B cell non-Hodgkin's lymphoma in Hokkaido. Ann Hematol 2008; 88:375-7. [PMID: 18726097 DOI: 10.1007/s00277-008-0585-6] [Citation(s) in RCA: 32] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2008] [Accepted: 07/29/2008] [Indexed: 12/31/2022]
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35
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Fujiwara K, Mochida S, Matsui A, Nakayama N, Nagoshi S, Toda G. Fulminant hepatitis and late onset hepatic failure in Japan. Hepatol Res 2008; 38:646-57. [PMID: 18328067 DOI: 10.1111/j.1872-034x.2008.00322.x] [Citation(s) in RCA: 91] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
AIM A nationwide survey was performed to clarify the present state of fulminant hepatitis and late onset hepatic failure (LOHF) between 1998 and 2003 in Japan. METHODS Three hundred and sixteen, 318 and 64 patients, respectively, with acute and subacute types of fulminant hepatitis and LOHF, in which grade II or more severe hepatic encephalopathy occurred within 10 days, between 11 days and 8 weeks and between 8 and 24 weeks, respectively, after the onset of disease symptoms, were analyzed. RESULTS Complications such as metabolic syndrome were underlying in 41.5% of patients with subacute fulminant hepatitis and 51.6% of patients with LOHF, and most of such patients had received daily medications. The etiology of fulminant hepatitis was viral infection in 71.2% of the acute type and 31.8% in the subacute type. Hepatitis B virus (HBV) infection was found in most of these patients; transient infection prevailed in the acute type; and HBV carrier prevailed in the subacute type. The etiology was unknown in 42.8% and 53.1% of the subacute type and LOHF, respectively. Autoimmune hepatitis and drug allergy-induced liver injury were found in 10.7% and 11.3%, respectively, of the subacute type. Artificial liver support with plasma exchange and/or hemodiafiltration took place in more than 90% of all patients. The survival rates of the patients without liver transplantation were 53.7% in the acute and 24.4% in the subacute type, and 11.5% in LOHF. The prognosis was especially poor in HBV carriers and patients with autoimmune hepatitis. The survival rates of those who underwent liver transplantation were 56.3%, 39.3% and 23.4% in the acute type, subacute type and LOHF, respectively. CONCLUSION The etiology and prognosis differed in patients with fulminant hepatitis and LOHF depending on the disease types in Japan, and liver transplantation improved the prognosis of the patients irrespective of the disease type and etiology.
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Affiliation(s)
- Kenji Fujiwara
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Faculty of Medicine, Saitama Medical University, Saitama, Japan
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36
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He YF, Li YH, Wang FH, Jiang WQ, Xu RH, Sun XF, Xia ZJ, Huang HQ, Lin TY, Zhang L, Bao SP, He YJ, Guan ZZ. The effectiveness of lamivudine in preventing hepatitis B viral reactivation in rituximab-containing regimen for lymphoma. Ann Hematol 2008; 87:481-5. [PMID: 18299831 DOI: 10.1007/s00277-008-0454-3] [Citation(s) in RCA: 42] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2007] [Accepted: 02/01/2008] [Indexed: 01/12/2023]
Abstract
In rituximab-containing regimen for lymphoma, the role of lamivudine therapy has not been well established. Therefore, in this nonrandomized phase II clinical study, hepatitis B virus (HBV) carriers with B-cell lymphoma who received rituximab-containing regimen were treated with oral administration of lamivudine. The incidence and severity of hepatitis along with other adverse clinical outcomes were analyzed. Between January 2003 and March 2006, 29 consecutive patients were enrolled. Four of the 29 patients (13.8%) developed hepatitis during chemotherapy, none of which was attributed to HBV reactivation. According to WHO acute toxicity assessment criteria, the severity of hepatitis was grade I in two patients (6.9%) and grade II in two patients (6.9%). In these four patients, only one (3.5%) had interval delay in chemotherapy. No patient had total abnormal bilirubin. No patient had died as the result of hepatitis during the treatment. Interestingly, one of the 29 patients developed HBV activation 5.1 months after the withdrawal of lamivudine. This patient recovered after reinstallation of lamivudine therapy and is still alive. Consequently, our study confirmed previous reports that prophylactic lamivudine therapy can prevent HBV reactivation in HBV carriers who were receiving rituximab-containing regimen for lymphoma.
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Affiliation(s)
- Yi-Fu He
- Department of Medical Oncology, Sun Yat-sen University Cancer Center, 651 Dong Feng Road East, Guangzhou, 510060, People's Republic of China
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37
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Lubel JS, Testro AG, Angus PW. Hepatitis B virus reactivation following immunosuppressive therapy: guidelines for prevention and management. Intern Med J 2007; 37:705-12. [PMID: 17894766 DOI: 10.1111/j.1445-5994.2007.01479.x] [Citation(s) in RCA: 73] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
It is well known that immunosuppressive drugs or cancer chemotherapy can stimulate replication of hepatitis B virus (HBV) and precipitate severe flares of HBV infection. The risk of this syndrome of 'reactivation hepatitis B' is highest in haematopoietic stem cell or solid organ transplant recipients and in those undergoing chemotherapy for haematological malignancies; however, it has been described following almost any form of immunosuppressive treatment. Fortunately, it can be largely prevented by prophylactic therapy with oral anti-HBV nucleoside/nucleotide analogues. Importantly, chronic HBV infection is usually asymptomatic, and most patients at risk are likely to be unaware that they carry the infection. Thus, the key to avoiding this potentially fatal complication of immunosuppressive treatment is to ensure that all patients at risk of chronic HBV infection are screened for the disease before commencing immunosuppressive treatment or chemotherapy.
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Affiliation(s)
- J S Lubel
- Victorian Liver Transplant Unit, Department of Gastroenterology, Austin Health, Heidelberg, Victoria, Australia
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38
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Fabrizi F, Martin P, Elli A, Montagnino G, Banfi G, Passerini P, Campise MR, Tarantino A, Ponticelli C. Hepatitis C virus infection and rituximab therapy after renal transplantation. Int J Artif Organs 2007; 30:445-9. [PMID: 17551909 DOI: 10.1177/039139880703000513] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
BACKGROUND Rituximab, a chimeric monoclonal antibody, has been successfully given in various diseases including HCV-associated mixed cryoglobulinemia. However, only preliminary data exists on its efficacy and safety after renal transplantation. METHODS We report on a renal transplant recipient with chronic hepatitis C who received rituximab therapy for gastric cancer. Four rituximab infusions of 375 mg/m(2) were given. RESULTS Rituximab therapy was complicated by cholestatic hepatitis C with very high HCV RNA levels; liver insufficiency occurred. The patient developed bacterial pneumoniae and respiratory insufficiency was the cause of death. Although other mechanisms cannot be excluded, we found that rituximab therapy was implicated in the pathogenesis of cholestatic hepatitis C in our patient. CONCLUSIONS We suggest that rituximab therapy may be associated with significant side effects. More experience has to be accumulated before any conclusions on efficacy and safety of rituximab therapy after RT can be drawn.
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Affiliation(s)
- F Fabrizi
- Division of Nephrology and Dialysis, Maggiore Hospital, IRCCS, Milan, Italy.
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39
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Aksoy S, Harputluoglu H, Kilickap S, Dede DS, Dizdar O, Altundag K, Barista I. Rituximab-related viral infections in lymphoma patients. Leuk Lymphoma 2007; 48:1307-12. [PMID: 17613758 DOI: 10.1080/10428190701411441] [Citation(s) in RCA: 197] [Impact Index Per Article: 10.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Recently, a human/mouse chimeric monoclonal antibody, rituximab, has been successfully used to treat cases of B-cell non-Hodgkin's lymphoma and some autoimmune diseases. However, several viral infections related to rituximab have been reported in the literature, but were not well characterized. To further investigate this topic, relevant English language studies were identified through Medline. There were 64 previously reported cases of serious viral infection after rituximab treatment. The median age of the cases was 61 years (range: 21 - 79). The median time period from the start of rituximab treatment to viral infection diagnosis was 5.0 months (range: 1 - 20). The most frequently experienced viral infections were hepatitis B virus (HBV) (39.1%, n = 25), cytomegalovirus infection (CMV) (23.4%, n = 15), varicella-zoster virus (VZV) (9.4%, n = 6), and others (28.1%, n = 18). Of the patients with HBV infections, 13 (52.0%) died due to hepatic failure. Among the 39 cases that had viral infections other than HBV, 13 died due to these specific infections. In this study, about 50% of the rituximab-related HBV infections resulted in death, whereas this was the case in only 33% of the cases with other infections. Close monitoring for viral infection, particularly HBV and CMV, in patients treated with rituximab should be recommended.
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Affiliation(s)
- Sercan Aksoy
- Department of Medical Oncology, Hacettepe University Institute of Oncology, Ankara, Turkey.
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40
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Scholing M, Schneeberger PM, van den Dries P, Drenth JPH. Clinical features of liver involvement in adult patients with listeriosis. Review of the literature. Infection 2007; 35:212-8. [PMID: 17646920 DOI: 10.1007/s15010-007-6006-2] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2005] [Accepted: 03/27/2007] [Indexed: 11/26/2022]
Abstract
Clinical features of liver involvement due to Listeria monocytogenes infection in adults are rarely reported in literature. This is surprising, regarding the current opinion that the portal system is extensively involved in the first stages of pathogenesis in invasive L. monocytogenes disease. A literature search in the PubMed and Embase database revealed 34 cases with clinical features of hepatic involvement due to listeriosis. We systematically analyzed all case reports with respect to clinical manifestations, treatment and outcome. In addition, we added clinical information on a patient diagnosed with a solitary liver abscess due to L. monocytogenes, who was seen at our institution. This review describes the different presentations of liver-involvement reported in listeriosis; solitary liver abscess, multiple liver abscesses and diffuse or granulomatous hepatitis. Distinction between these different forms of liver involvement is clinically relevant as they have a different outcome. We delve into the different pathogenic events leading to different forms of liver involvement. In addition, diagnostic modalities and possible treatments are reviewed.
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Affiliation(s)
- M Scholing
- Department of Medical Microbiology and Infection Control, VU University Medical Center, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands
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41
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Bussel JB, Giulino L, Lee S, Patel VL, Sandborg C, Stiehm ER. Update on therapeutic monoclonal antibodies. Curr Probl Pediatr Adolesc Health Care 2007; 37:118-35. [PMID: 17434008 DOI: 10.1016/j.cppeds.2007.02.001] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
Monoclonal antibodies are among the most important class of drugs introduced into the therapeutic armamentarium since the introduction of antimicrobials in the 1930s. The first therapeutic monoclonal antibody, the anti T-cell monoclonal antibody OKT4, was licensed in 1986. Since then, 18 additional antibodies have been licensed in the US, with many more in the pipeline. Before 1986, many monoclonal antibodies were available for laboratory studies, notably to identify specific cells in the blood and tissues. This is best illustrated by the cluster designation (CD) system for antigens present on hematopoietic cells, now numbering over 200.
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Affiliation(s)
- James B Bussel
- Department of Pediatrics, Cornell University School of Medicine, New York, NY, USA
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42
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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 2007; 155:1053-6. [PMID: 17034541 DOI: 10.1111/j.1365-2133.2006.07451.x] [Citation(s) in RCA: 69] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
The chimeric anti-CD20 monoclonal antibody, rituximab, is a promising treatment for cutaneous B-cell lymphomas. Classically used in combination with a multiagent-chemotherapy regimen, it can sometimes give excellent results alone. Because of its selective action on B lymphocytes, it is considered a moderate immunosuppressant in terms of infection. We describe a woman with relapsed cutaneous follicular centre B-cell lymphoma and secondary lymph-node involvement treated with rituximab alone, which induced a complete remission. One year later, she experienced a fatal hepatitis B virus (HBV) reactivation. Several such HBV reactivations were reported after combined rituximab and multiagent chemotherapy for B-cell lymphomas. This is the first case of HBV reactivation occurring during the year following rituximab monotherapy in the absence of any other immunosuppressive factor.
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Affiliation(s)
- G Perceau
- CHU de Reims, Hôpital Robert-Debré, Service de Dermatologie et Service de Gastroentérologie, avenue du Général Koenig, 51092 Reims Cedex, France
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43
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Aksoy S, Abali H, Kilickap S, Erman M, Kars A. Accelerated hepatitis C virus replication with rituximab treatment in a non-Hodgkin's lymphoma patient. ACTA ACUST UNITED AC 2006; 28:211-4. [PMID: 16706940 DOI: 10.1111/j.1365-2257.2006.00779.x] [Citation(s) in RCA: 53] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
The treatment of patients with non-Hodgkin's lymphoma (NHL) may be complicated by concomitant chronic hepatitis C virus (HCV) infection. Recent data suggest that HCV may also be a contributing factor to the development of this disease. Although antiviral treatment has occasionally been reported to result in the regression of lymphoma in patients with HCV infection, the importance of the control of this infection on the prognosis of lymphoma needs to be defined. Here we report a patient with diffuse large B-cell lymphoma who presented with a mass in her left breast. She had had HCV-related liver cirrhosis for 6 years. She was given rituximab monotherapy for three consecutive weeks, but treatment had to be discontinued as a result of hematological toxicity. HCV viral load also increased, but then decreased gradually after rituximab was stopped. She could be given no further therapy. Six months later she presented with spinal involvement with infiltration of the cauda equina. Though cranial-spinal radiotherapy and steroids were started, she died shortly thereafter. Though rituximab is an invaluable drug in the treatment of B-cell lymphomas, we believe that the use of such agents with potentially long-lasting effects on B lymphocytes requires extended vigilance for accelerated replication of hepatitis B and C viruses.
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MESH Headings
- Antibodies, Monoclonal/adverse effects
- Antibodies, Monoclonal, Murine-Derived
- Antineoplastic Agents/adverse effects
- Breast Neoplasms/complications
- Breast Neoplasms/drug therapy
- Fatal Outcome
- Female
- Hepacivirus/drug effects
- Hepacivirus/physiology
- Hepatitis C, Chronic/complications
- Humans
- Lymphoma, B-Cell/drug therapy
- Lymphoma, B-Cell/virology
- Lymphoma, Large B-Cell, Diffuse/drug therapy
- Lymphoma, Large B-Cell, Diffuse/virology
- Middle Aged
- Rituximab
- Viral Load
- Virus Replication/drug effects
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Affiliation(s)
- S Aksoy
- Hacettepe University Institute of Oncology, Ankara, Turkey.
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44
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Bestard O, Cruzado JM, Ercilla G, Gomà M, Torras J, Serón D, Rama I, Ibernon M, Viñas O, Carrera M, Grinyó JM. Rituximab induces regression of hepatitis C virus-related membranoproliferative glomerulonephritis in a renal allograft. Nephrol Dial Transplant 2006; 21:2320-4. [PMID: 16751656 DOI: 10.1093/ndt/gfl266] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
MESH Headings
- Antibodies, Monoclonal/therapeutic use
- Antibodies, Monoclonal, Murine-Derived
- Antigens, CD20/immunology
- B-Lymphocyte Subsets/drug effects
- Capillaries/chemistry
- Complement C4b/analysis
- Contraindications
- Cryoglobulinemia/drug therapy
- Cryoglobulinemia/etiology
- Fatty Liver/complications
- Female
- Follow-Up Studies
- Glomerulonephritis, Membranoproliferative/drug therapy
- Glomerulonephritis, Membranoproliferative/etiology
- Glomerulonephritis, Membranoproliferative/surgery
- Glomerulonephritis, Membranoproliferative/therapy
- Graft Survival
- HLA Antigens/immunology
- Hepatitis C, Chronic/complications
- Hepatitis C, Chronic/immunology
- Humans
- Immunosuppressive Agents/therapeutic use
- Interferon-alpha
- Kidney Transplantation
- Lymphocyte Count
- Middle Aged
- Peptide Fragments/analysis
- Postoperative Complications/drug therapy
- Postoperative Complications/etiology
- Postoperative Complications/immunology
- Recurrence
- Renal Dialysis
- Reoperation
- Rituximab
- Transplantation, Homologous
- Viral Load
- Viremia/complications
- Viremia/immunology
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Affiliation(s)
- Oriol Bestard
- Department of Nephrology, Hospital Universitari de Bellvitge, Feixa Llarga s/n, 08907 L'Hospitalet de Llobregat, Barcelona, Spain.
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45
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Tsutsumi Y, Kanamori H, Mori A, Tanaka J, Asaka M, Imamura M, Masauzi N. Reactivation of hepatitis B virus with rituximab. Expert Opin Drug Saf 2006; 4:599-608. [PMID: 15934864 DOI: 10.1517/14740338.4.3.599] [Citation(s) in RCA: 107] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Rituximab has become a useful drug for the treatment of non-Hodgkin's lymphoma (NHL) and such autoimmune diseases as idiopathic thrombocytopenic purpura and rheumatoid arthritis. When combined with cytotoxic agents, rituximab showed synergistic effects for the treatment of NHL. In such treatment, hepatitis B virus (HBV) reactivation is a crucial complication when patients are treated with immunosuppressive or chemotherapeutic agents. Despite its treatment efficacy, several studies have pointed out unusual viral infections after its administration that resulted in fatal hepatitis due to HBV reactivation. In the cases at the authors' institute, the authors analysed the kinetics of HBV antibodies, HBV-reactivation timing, and the prophylactic efficacy of lamivudine. The authors reviewed their cases and the previous literature to clarify the characteristics of HBV-reactivated patients who were administered rituximab.
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Affiliation(s)
- Yutaka Tsutsumi
- Department of Internal Medicine, Hakodate Municipal Hospital, Hakodate 041-8680, Japan.
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46
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Sera T, Hiasa Y, Michitaka K, Konishi I, Matsuura K, Tokumoto Y, Matsuura B, Kajiwara T, Masumoto T, Horiike N, Onji M. Anti-HBs-positive liver failure due to hepatitis B virus reactivation induced by rituximab. Intern Med 2006; 45:721-4. [PMID: 16819252 DOI: 10.2169/internalmedicine.45.1590] [Citation(s) in RCA: 98] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/13/2023] Open
Abstract
A 59-year-old man developed acute hepatitis with reactivated hepatitis B virus (HBV) following administration of rituximab (anti-CD20 monoclonal antibody). The patient was diagnosed with malignant lymphoma in 1998, and virus marker testing indicated HBV surface antigen (HBsAg)-negative and anti-HBs antibody (anti-HBs)-positive results when chemotherapy including rituximab was started. Levels of aminotransferases were elevated, and HBsAg results turned positive. Despite therapy for late-onset hepatic failure, the patient died. Rituximab appears likely to have induced HBV reactivation in this case. Anti-viral agents should be administered for both HBsAg-positive and anti-HBs-positive patients who are scheduled to receive rituximab.
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Affiliation(s)
- Toshiki Sera
- Ehime University Graduate School of Medicine, Department of Gastroenterology and Metabology, Shitsukawa, Toon
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47
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Niscola P, Del Principe MI, Maurillo L, Venditti A, Buccisano F, Piccioni D, Amadori S, Del Poeta G. Fulminant B hepatitis in a surface antigen-negative patient with B-cell chronic lymphocytic leukaemia after rituximab therapy. Leukemia 2005; 19:1840-1. [PMID: 16094417 DOI: 10.1038/sj.leu.2403914] [Citation(s) in RCA: 47] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
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48
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Qazilbash MH, Qu Z, Hosing C, Couriel D, Donato M, Giralt S, Champlin R. Rituximab-induced acute liver failure after an allogeneic transplantation for chronic myeloid leukemia. Am J Hematol 2005; 80:43-5. [PMID: 16138357 DOI: 10.1002/ajh.20413] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
Autoimmune hemolytic anemia (AIHA) is a well-recognized complication of allogeneic bone marrow transplantation (BMT) and can affect up to 5% patients. Several recent case reports suggested the efficacy of anti-CD20 monoclonal antibody, rituximab, in treating this condition. We report our experience with a 21-year-old female with accelerated-phase chronic myeloid leukemia who underwent allogeneic hematopoietic stem cell transplantation from a matched, unrelated donor. The patient developed autoimmune hemolytic anemia that failed to respond to steroids, intravenous immunoglobulins, and plasma exchange. She was then treated with rituximab that resulted in fatal acute liver toxicity.
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MESH Headings
- Adult
- Antibodies, Monoclonal/adverse effects
- Antibodies, Monoclonal, Murine-Derived
- Antineoplastic Agents/adverse effects
- Fatal Outcome
- Female
- Histocompatibility Testing
- Humans
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive/therapy
- Liver/pathology
- Liver Failure, Acute/chemically induced
- Liver Failure, Acute/pathology
- Necrosis
- Rituximab
- Transplantation, Homologous
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Affiliation(s)
- Muzaffar H Qazilbash
- Department of Blood and Marrow Transplantation, UT-MD Anderson Cancer Center, Houston, 77030, USA.
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49
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Foxton MR, Knight L, Knisely AS, Mufti GJ, O'Grady J, Muiesan P, Norris S. Liver transplantation for HCV-related cirrhosis in a patient with gastric mucosa-associated lymphoma (MALToma) pretreated with rituximab. Liver Transpl 2005; 11:839-842. [PMID: 15973713 DOI: 10.1002/lt.20403] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Abstract
End-stage liver disease due to chronic hepatitis C virus (HCV) infection is now the most frequent indication for liver transplantation. HCV infection is associated with extrahepatic disease including cryoglobulinemia and lymphoma. The number of patients requiring liver transplantation (LT) for cirrhosis secondary to HCV infection has increased over the past 10 years; consequently, associated extrahepatic manifestations (in particular hematological malignancies) will be more commonly observed in this patient group. The management of patients with both end-stage liver disease and significant HCV-related extrahepatic disease is undefined. We report a 59-year-old man in whom extranodal marginal-zone B-cell lymphoma arising in gastric mucosa-associated lymphoid tissue (MALToma) was successfully eradicated by rituximab administration and gastrectomy at LT for HCV-related cirrhosis. Our experience with rituximab in this patient suggests that it can be used safely in the setting of severe liver disease due to HCV infection. Rituximab may be useful in preventing progression of NHL until surgical extirpation is possible.
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Affiliation(s)
| | - Lisa Knight
- Institute of Liver Studies, Kings' College Hospital, London, UK
| | - Alex S Knisely
- Institute of Liver Studies, Kings' College Hospital, London, UK
| | - Ghulam J Mufti
- Department of Haematological Medicine, Kings' College Hospital, London, UK
| | - John O'Grady
- Institute of Liver Studies, Kings' College Hospital, London, UK
| | - Paolo Muiesan
- Department of Liver Transplantation and Hepatobiliary Surgery, Kings' College Hospital, London, UK
| | - Suzanne Norris
- Institute of Liver Studies, Kings' College Hospital, London, UK
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50
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Park YW, Pryshchep S, Seyler TM, Goronzy JJ, Weyand CM. B cells as a therapeutic target in autoimmune diseases. Expert Opin Ther Targets 2005; 9:431-45. [PMID: 15948665 DOI: 10.1517/14728222.9.3.431] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
Historically, the pathogenic role of B cells in autoimmune disease has been attributed to the formation of autoantibodies which, as soluble immunoglobulins or immunocomplexes, can trigger cellular damage and initiate the inflammatory cascade. Recent results from clinical trials applying B cell-directed therapeutics in rheumatoid arthritis and systemic lupus erythematosus have challenged such traditional views and encouraged novel ideas about the disease involvement of B cells. Suppression of disease activity, often disconnected from effects on autoantibody titers, has supported the notion that B cells may promote autoimmune disease by serving as antigen-presenting cells that sustain T cell activation. Likewise, B cells have been implicated in supporting the process of ectopic lymphoid neogenesis, a mechanism that stabilises pathogenic immune responses in target tissues and thus contributes to disease chronicity. As a general rule, clinical effects of B cell-directed therapeutics have often been unanticipated and unpredicted by experimental models, emphasis-ing the need to explore and verify disease principles in the patient.
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Affiliation(s)
- Yong Wook Park
- Department of Medicine, Lowance Center for Human Immunology, Emory University School of Medicine, Woodruff Memorial Research Building, 101 Woodruff Circle, Atlanta, GA 30322, USA
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