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Vutien P, Nguyen MH. HBV Reactivation in Immunosuppressed Patients: Screening, Prevention, and Management Including Solid Organ Transplant Recipients. Viruses 2025; 17:388. [PMID: 40143316 PMCID: PMC11945625 DOI: 10.3390/v17030388] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2025] [Revised: 03/05/2025] [Accepted: 03/07/2025] [Indexed: 03/28/2025] Open
Abstract
Hepatitis B virus (HBV) infection remains a global health challenge, affecting over 254 million individuals chronically and contributing significantly to cirrhosis, liver failure, and hepatocellular carcinoma. Despite advancements in antiviral therapy, HBV reactivation remains a critical concern, particularly in immunosuppressed individuals, including non-transplant patients undergoing immunosuppressive therapy and solid organ transplant recipients. This review provides screening and management strategies for HBV reactivation in these populations.
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Affiliation(s)
- Philip Vutien
- Division of Gastroenterology and Hepatology, University of Washington Medical Center, 1959 NE Pacific Street, Box 356175, Seattle, WA 98195, USA
| | - Mindie H. Nguyen
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA 94305, USA;
- Department of Epidemiology and Population Health, Stanford University Medical Center, Palo Alto, CA 94305, USA
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Carvajal R, Guananga-Álvarez D, Tur C, Esperalba J, Rodríguez-Barranco M, Rando-Segura A, Borras-Bermejo B, Cobo-Calvo A, Carbonell-Mirabent P, Zules-Oña R, Rodrigo-Pendas JA, Martínez-Gómez X, Montalban X, Tintore M, Otero-Romero S. Effect of the Number of Vaccine Doses Before Starting Anti-CD20 Therapy on Seroprotection Rates Against Hepatitis B Virus in People With MS. Neurology 2025; 104:e210281. [PMID: 39819099 PMCID: PMC11737845 DOI: 10.1212/wnl.0000000000210281] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2024] [Accepted: 11/16/2024] [Indexed: 01/19/2025] Open
Abstract
BACKGROUND AND OBJECTIVES Hepatitis B vaccination (HBV) requires 6 months to complete and is recommended for patients with multiple sclerosis (PWMS), particularly those who are candidates for anti-CD20 therapy. However, limited data exist on HBV immunogenicity in PWMS receiving disease-modifying therapies (DMTs) and the impact of starting anti-CD20 therapy during immunization. We aimed to evaluate HBV immunogenicity in PWMS starting anti-CD20 therapy during vaccination, focusing on the number of doses received before anti-CD20 initiation. METHODS We conducted a retrospective analysis of a prospective cohort of adult PWMS at a single center in Spain, from April 2015 to May 2023. Eligible participants completed a 4-dose HBV course and underwent postvaccination serologic testing. We assess seroprotection rates (SRs), defined as the percentage of patients achieving anti-hepatitis B surface antibody titers ≥10 IU/L, focusing on those who switched to anti-CD20 therapy during vaccination, based on doses received before starting anti-CD20 and type of DMT at vaccination start. A multivariate generalized linear model (GLM) was used to identify factors associated with higher seroconversion. RESULTS A total of 289 PWMS (median [interquartile range (IQR)] age, 47.7 [42.8-54.4] years; 65.7% female; median [IQR] disease duration, 14.8 [6.7-21.2] years) were included. SRs progressively declined with fewer doses before anti-CD20 initiation, from 92.8% (95% CI 87.1-96.5) for 4 doses to 24.0% (95% CI 9.4-45.1) for 1 dose. Patients transitioning from sphingosine 1-phosphate (S1P) modulators showed the lowest SR at 25.0% (95% CI 7.3-52.4). The multivariate GLM confirmed these findings, with 3 doses (SR ratio 3.23 [95% CI 1.68-6.23]; p = 0.0005) or 4 doses (SR ratio 3.76 [95% CI 1.96-7.24]; p < 0.0001) before anti-CD20 therapy significantly associated with higher SRs, while starting S1P modulators at vaccination onset was significantly associated with lower SRs (SR ratio 0.42 [95% CI 0.23-0.78]; p = 0.0058). Female sex (SR ratio 1.15 [95% CI 1.01-1.32]; p = 0.0389) and younger age (SR ratio 0.90 [95% CI 0.83-0.97]; p = 0.0036) were also significantly associated with higher SRs. DISCUSSION Initiating anti-CD20 therapy during HBV negatively affects SRs, with a direct correlation with the number of doses received before anti-CD20 initiation. Early planning and execution of required vaccinations are crucial in managing PWMS. CLASSIFICATION OF EVIDENCE This study provides Class III evidence that HBV during initiation of anti-CD20 therapy is less effective in establishing seroprotection to hepatitis B than in patients in whom HBV is completed before initiation of anti-CD20 therapy.
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Affiliation(s)
- René Carvajal
- Department of Neurology-Neuroimmunology and Multiple Sclerosis Centre of Catalonia (Cemcat), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Spain
| | - David Guananga-Álvarez
- Department of Preventive Medicine and Epidemiology, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Spain
| | - Carmen Tur
- Department of Neurology-Neuroimmunology and Multiple Sclerosis Centre of Catalonia (Cemcat), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Spain
| | - Juliana Esperalba
- Department of Microbiology, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Spain
- CIBER de Enfermedades Infecciosas (CIBERINFEC), Spain
| | - Marta Rodríguez-Barranco
- Department of Neurology-Neuroimmunology and Multiple Sclerosis Centre of Catalonia (Cemcat), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Spain
| | - Ariadna Rando-Segura
- Department of Microbiology, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Spain
- CIBER de Enfermedades Hepáticas y Digestivas (CIBEREHD), Instituto de Salud Carlos III, Madrid, Spain
| | - Blanca Borras-Bermejo
- Department of Preventive Medicine and Epidemiology, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Spain
| | - Alvaro Cobo-Calvo
- Department of Neurology-Neuroimmunology and Multiple Sclerosis Centre of Catalonia (Cemcat), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Spain
| | - Pere Carbonell-Mirabent
- Department of Neurology-Neuroimmunology and Multiple Sclerosis Centre of Catalonia (Cemcat), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Spain
| | - Ricardo Zules-Oña
- Department of Preventive Medicine and Epidemiology, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Spain
- Department of Preventiva Medicine, Hospital Universitari de Girona Dr. Josep Trueta, Spain; and
| | - Jose Angel Rodrigo-Pendas
- Department of Preventive Medicine and Epidemiology, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Spain
| | - Xavier Martínez-Gómez
- Department of Preventive Medicine and Epidemiology, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Spain
| | - Xavier Montalban
- Department of Neurology-Neuroimmunology and Multiple Sclerosis Centre of Catalonia (Cemcat), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Spain
- Faculty of Medicine, University of Vic-Central University of Catalonia (UVic-UCC), Vic/Manresa, Catalonia, Spain
| | - Mar Tintore
- Department of Neurology-Neuroimmunology and Multiple Sclerosis Centre of Catalonia (Cemcat), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Spain
- Faculty of Medicine, University of Vic-Central University of Catalonia (UVic-UCC), Vic/Manresa, Catalonia, Spain
| | - Susana Otero-Romero
- Department of Preventive Medicine and Epidemiology, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Spain
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Seang S, Detruchis P, Todesco E, Valantin MA, Schneider L, Palich R, Peytavin G, Pourcher V, Marcelin AG, Katlama C. A case series of intermittent nucleoside analogue-based (NA) regimen to maintain HBV virological suppression in coinfected HBV/HIV patients with suppressed viremia. Infect Dis Now 2024; 54:104980. [PMID: 39313158 DOI: 10.1016/j.idnow.2024.104980] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2024] [Revised: 09/17/2024] [Accepted: 09/19/2024] [Indexed: 09/25/2024]
Abstract
OBJECTIVE To describe the efficacy of intermittent nucleoside analogue-based (NA) regimen to maintain HBV virological suppression in HBV/HIV-1 patients. METHODS Conducted between 2014 and 2023, this observational retrospective study included all HBV (positive AgHbs)/HIV-1 coinfected patients with HIV RNA ≤ 50 cp/mL and HBV DNA ≤ 25 UI/mL who were switched to an intermittent (<7/7 days(D)) TDF or TAF-containing antiretroviral (ART) regimen. The primary outcome was the HBV virological success rate (SR) (proportion of patients with HBV pVL < 25 UI/mL) at W48. RESULTS Among 501 HBV/HIV-1 patients, 19(3.7 %) had switched to an intermittent NA-containing regimen that included TDF/FTC or TDF/3TC or TAF/FTC or TDF alone administered 5D-a-week(n = 7), 4D-a-week(n = 7) or 3D-a-week(n = 5). HBV virological success rates were 100 % [95 %CI 82.3-100] and 100 %[95 %CI 80.5-100] at W48 and W96(n = 17), respectively; with no viral HBV or HIV rebound (61.8 months (32.4-70.3) of follow-up). CONCLUSION This case series shows the potential for intermittent NA-containing regimens to maintain long-term control of HBV replication among suppressed HBV/HIV-1 patients.
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Affiliation(s)
- S Seang
- Sorbonne University, Infectious Diseases Department, Pitié-Salpêtrière Hospital, AP-HP, Pierre Louis Epidemiology and Public Health institute (iPLESP), INSERM 1136, Paris, France.
| | - P Detruchis
- Infectious Diseases Department, Raymond-Poincaré Hospital APHP, Garches, France
| | - E Todesco
- Sorbonne University, Virology Department, Pitié-Salpêtrière Hospital, AP-HP, iPLESP, INSERM 1136, Paris, France
| | - M-A Valantin
- Sorbonne University, Infectious Diseases Department, Pitié-Salpêtrière Hospital, AP-HP, Pierre Louis Epidemiology and Public Health institute (iPLESP), INSERM 1136, Paris, France
| | - L Schneider
- Sorbonne University, Infectious Diseases Department, Pitié-Salpêtrière Hospital, AP-HP, Pierre Louis Epidemiology and Public Health institute (iPLESP), INSERM 1136, Paris, France
| | - R Palich
- Sorbonne University, Infectious Diseases Department, Pitié-Salpêtrière Hospital, AP-HP, Pierre Louis Epidemiology and Public Health institute (iPLESP), INSERM 1136, Paris, France
| | - G Peytavin
- Paris Cité University, Bichat-Claude Bernard Hospital, AP-HP, INSERM, 1137, IAME, Paris, France
| | - V Pourcher
- Sorbonne University, Infectious Diseases Department, Pitié-Salpêtrière Hospital, AP-HP, Pierre Louis Epidemiology and Public Health institute (iPLESP), INSERM 1136, Paris, France
| | - A-G Marcelin
- Sorbonne University, Virology Department, Pitié-Salpêtrière Hospital, AP-HP, iPLESP, INSERM 1136, Paris, France
| | - C Katlama
- Sorbonne University, Infectious Diseases Department, Pitié-Salpêtrière Hospital, AP-HP, Pierre Louis Epidemiology and Public Health institute (iPLESP), INSERM 1136, Paris, France
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Zhang W, Du F, Wang L, Bai T, Zhou X, Mei H. Hepatitis Virus-associated Non-hodgkin Lymphoma: Pathogenesis and Treatment Strategies. J Clin Transl Hepatol 2023; 11:1256-1266. [PMID: 37577221 PMCID: PMC10412707 DOI: 10.14218/jcth.2022.00079s] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/27/2022] [Revised: 01/21/2023] [Accepted: 03/22/2023] [Indexed: 07/03/2023] Open
Abstract
Over the last decade, epidemiological studies have discovered a link between hepatitis C virus (HCV) and hepatitis B virus (HBV) infection and non-Hodgkin lymphoma (NHL). The regression of HCV-associated NHL after HCV eradication is the most compelling proof supporting HCV infection's role in lymphoproliferative diseases. HBV infection was found to significantly enhance the incidence of NHL, according to the epidemiological data. The exact mechanism of HCV leading to NHL has not been fully clarified, and there are mainly the following possible mechanisms: (1) Indirect mechanisms: stimulation of B lymphocytes by extracellular HCV and cytokines; (2) Direct mechanisms: oncogenic effects mediated by intracellular HCV proteins; (3) hit-and-run mechanism: permanent genetic B lymphocytes damage by the transitional entry of HCV. The specific role of HBV in the occurrence of NHL is still unclear, and the research on its mechanism is less extensively explored than HCV, and there are mainly the following possible mechanisms: (1) Indirect mechanisms: stimulation of B lymphocytes by extracellular HBV; (2) Direct mechanisms: oncogenic effects mediated by intracellular HBV DNA. In fact, it is reasonable to consider direct-acting antivirals (DAAs) as first-line therapy for indolent HCV-associated B-NHL patients who do not require immediate chemotherapy. Chemotherapy for NHL is affected by HBV infection and replication. At the same time, chemotherapy can also activate HBV replication. Following recent guidelines, all patients with HBsAg positive/HBV DNA≥2,000 IU/mL should be treated for HBV. The data on epidemiology, interventional studies, and molecular mechanisms of HCV and HBV-associated B-NHL are systematically summarized in this review.
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Affiliation(s)
- Wenjing Zhang
- Department of Hematology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Fan Du
- Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Li Wang
- Department of Hematology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Tao Bai
- Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Xiang Zhou
- Department of Internal Medicine II, Würzburg University Hospital, University of Würzburg, Würzburg, Germany
| | - Heng Mei
- Department of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
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Rosenberg M, Poluch M, Thomas C, Sindaco P, Khoo A, Porcu P. Hepatitis B Virus and B-cell lymphoma: evidence, unmet need, clinical impact, and opportunities. Front Oncol 2023; 13:1275800. [PMID: 37927464 PMCID: PMC10623156 DOI: 10.3389/fonc.2023.1275800] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2023] [Accepted: 10/09/2023] [Indexed: 11/07/2023] Open
Abstract
Nearly a billion people worldwide are infected with the hepatitis B Virus (HBV) and about a third of them have chronic infection. HBV is an important cause of morbidity and mortality, including acute and chronic hepatitis and hepatocellular carcinoma (HCC). Screening and control of primary HBV infection through vaccination represent a major advance in global public health, but large sections of the world population, in both developed and underdeveloped countries, remain unscreened and unvaccinated. In addition to being a global cause of liver disease, an important role of HBV in lymphoma has also emerged. First, the high risk of HBV reactivation in previously infected patients receiving chemo-immunotherapy necessitates the systematic evaluation of HBV serological status in all non-Hodgkin's lymphoma (NHL) cases and preemptive antiviral therapy for those who may have chronic or occult HBV infection. Second, HBV has been shown to infect lymphocytes, namely B-cells, and has been associated with a higher risk of developing B-cell lymphoma, most clearly in countries where HBV is endemic. While the risk of HBV reactivation with chemoimmunotherapy in NHL is well known, the role and the impact of HBV as a global lymphoma risk factor and potential oncogenic driver in B-cells are very poorly understood. Here, we review the clinical and scientific evidence supporting an association between HBV and B-cell lymphoma, with a particular focus on diffuse large B-cell lymphoma (DLBCL) and provide an overview of the estimated impact of HBV infection on the biology and clinical course of DLBCL. We also discuss ways to gain a better insight into the unmet need posed by HBV in lymphoma and whether assessing immune responses to HBV, measuring viral loads, and detecting the presence of HBV-encoded proteins in tumor tissue could be integrated into the molecular and clinical risk stratification of patients with DLBCL.
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Affiliation(s)
- Maya Rosenberg
- Department of Internal Medicine, New York University Langone Health, New York, NY, United States
- Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, United States
| | - Maria Poluch
- Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, United States
| | - Colin Thomas
- Department of Medical Oncology, Hospital of the University of Pennsylvania, Philadelphia, PA, United States
- Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, United States
| | - Paola Sindaco
- Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, United States
- Department of Medical Oncology, Thomas Jefferson University, Philadelphia, PA, United States
| | - Alan Khoo
- Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, United States
| | - Pierluigi Porcu
- Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, United States
- Department of Medical Oncology, Thomas Jefferson University, Philadelphia, PA, United States
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6
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Mak JWY, Law AWH, Law KWT, Ho R, Cheung CKM, Law MF. Prevention and management of hepatitis B virus reactivation in patients with hematological malignancies in the targeted therapy era. World J Gastroenterol 2023; 29:4942-4961. [PMID: 37731995 PMCID: PMC10507505 DOI: 10.3748/wjg.v29.i33.4942] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/29/2023] [Revised: 07/22/2023] [Accepted: 08/15/2023] [Indexed: 09/01/2023] Open
Abstract
Hepatitis due to hepatitis B virus (HBV) reactivation can be serious and potentially fatal, but is preventable. HBV reactivation is most commonly reported in patients receiving chemotherapy, especially rituximab-containing therapy for hematological malignancies and those receiving stem cell transplantation. Patients with inactive and even resolved HBV infection still have persistence of HBV genomes in the liver. The expression of these silent genomes is controlled by the immune system. Suppression or ablation of immune cells, most importantly B cells, may lead to reactivation of seemingly resolved HBV infection. Thus, all patients with hematological malignancies receiving anticancer therapy should be screened for active or resolved HBV infection by blood tests for hepatitis B surface antigen (HBsAg) and antibody to hepatitis B core antigen. Patients found to be positive for HBsAg should be given prophylactic antiviral therapy. For patients with resolved HBV infection, there are two approaches. The first is pre-emptive therapy guided by serial HBV DNA monitoring, and treatment with antiviral therapy as soon as HBV DNA becomes detectable. The second approach is prophylactic antiviral therapy, particularly for patients receiving high-risk therapy, especially anti-CD20 monoclonal antibody or hematopoietic stem cell transplantation. Entecavir and tenofovir are the preferred antiviral choices. Many new effective therapies for hematological malignancies have been introduced in the past decade, for example, chimeric antigen receptor (CAR)-T cell therapy, novel monoclonal antibodies, bispecific antibody drug conjugates, and small molecule inhibitors, which may be associated with HBV reactivation. Although there is limited evidence to guide the optimal preventive measures, we recommend antiviral prophylaxis in HBsAg-positive patients receiving novel treatments, including Bruton's tyrosine kinase inhibitors, B-cell lymphoma 2 inhibitors, and CAR-T cell therapy. Further studies are needed to determine the risk of HBV reactivation with these agents and the best prophylactic strategy.
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Affiliation(s)
- Joyce Wing Yan Mak
- Department of Medicine and Therapeutics, Prince of Wales Hospital, Hong Kong 852, China
| | | | | | - Rita Ho
- Department of Medicine, North District Hospital, Hong Kong 852, China
| | - Carmen Ka Man Cheung
- Department of Medicine and Therapeutics, Prince of Wales Hospital, Hong Kong 852, China
| | - Man Fai Law
- Department of Medicine and Therapeutics, Prince of Wales Hospital, Hong Kong 852, China
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Brakenhoff SM, Hoekstra R, Honkoop P, Roomer R, den Hollander JG, Bezemer G, de Knegt RJ, Sonneveld MJ, de Man RA. Patients treated with rituximab are poorly screened for hepatitis B infection: Data from a low-incidence country. Eur J Intern Med 2023; 108:68-73. [PMID: 36462966 DOI: 10.1016/j.ejim.2022.11.024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/25/2022] [Revised: 11/14/2022] [Accepted: 11/16/2022] [Indexed: 12/05/2022]
Abstract
BACKGROUND & AIMS Patients with chronic or resolved hepatitis B are at risk of hepatitis B reactivation (HBVr) when treated with high-risk immunosuppressive therapy such as rituximab. Therefore, international guidelines recommend HBV screening prior to rituximab treatment and subsequent antiviral prophylaxis among patients with a (resolved) infection. In this study, we evaluated the adherence to those recommendations. METHODS This is a retrospective multicentre study including patients treated with rituximab between 2000-2021. Performance of correct screening was assessed, defined as the measurement of hepatitis B surface antigen (HBsAg) and hepatitis B core antibodies (anti-HBc). Next, initiation of antiviral prophylaxis and HBVr rate among patients with a chronic or resolved HBV infection was studied. RESULTS We enrolled 3,176 patients of whom 1,448 (46%) were screened correctly. Screening rates differed significantly between academic and non-academic hospitals; respectively 65% vs 32% (p<0.001). In addition, screening rates differed across specialties and improved throughout the years; from 32% before 2012 to 75% after 2020 among academic prescribers, versus 1% to 60% among non-academic prescribers (both p<0.001). Antiviral prophylaxis was initiated in 58% vs 36% of the patients with a chronic or resolved HBV infection. Seven patients experienced HBVr, including one fatal liver decompensation. CONCLUSIONS Many patients treated with rituximab were not correctly screened for HBV infection and antiviral prophylaxis was often not initiated. Although screening rates improved over time, rates remain suboptimal. With the increasing number of indications for rituximab and other immunosuppressive agents these findings could raise awareness among all medical specialties prescribing these agents.
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Affiliation(s)
- Sylvia M Brakenhoff
- Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center, Rotterdam, the Netherlands.
| | - Roos Hoekstra
- Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center, Rotterdam, the Netherlands
| | - Pieter Honkoop
- Department of Gastroenterology and Hepatology, Albert Schweitzer Hospital, Dordrecht, the Netherlands
| | - Robert Roomer
- Department of Gastroenterology and Hepatology, Franciscus Gasthuis en Vlietland, Rotterdam, the Netherlands
| | - Jan G den Hollander
- Department of Internal Medicine, Maasstad Medical Centre, Rotterdam, the Netherlands
| | - Geert Bezemer
- Department of Gastroenterology and Hepatology, Ikazia Hospital, Rotterdam, the Netherlands
| | - Robert J de Knegt
- Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center, Rotterdam, the Netherlands
| | - Milan J Sonneveld
- Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center, Rotterdam, the Netherlands
| | - Robert A de Man
- Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center, Rotterdam, the Netherlands
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Cauchi M, Willis M, Andrews A, Backx M, Brownlee W, Ford HL, Gran B, Jolles S, Price S, Rashid W, Schmierer K, Tallantyre EC. Multiple sclerosis and the risk of infection: Association of British Neurologists consensus guideline. Pract Neurol 2022; 22:practneurol-2022-003370. [PMID: 35863879 DOI: 10.1136/practneurol-2022-003370] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/08/2022] [Indexed: 11/03/2022]
Abstract
Infection in people with multiple sclerosis (MS) is of major concern, particularly for those receiving disease-modifying therapies. This article explores the risk of infection in people with MS and provides guidance-developed by Delphi consensus by specialists involved in their management-on how to screen for, prevent and manage infection in this population.
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Affiliation(s)
- Marija Cauchi
- Division of Psychological Medicine and Clinical Neurosciences, Cardiff University, University Hospital of Wales, Cardiff, UK
| | - Mark Willis
- Division of Psychological Medicine and Clinical Neurosciences, Cardiff University, University Hospital of Wales, Cardiff, UK
| | - Angela Andrews
- Pharmacy Neurosciences Directorate, University Hospital of Wales, Cardiff, UK
| | - Matthijs Backx
- Infectious Diseases, University Hospital of Wales and Department of Microbiology, Public Health Wales, Cardiff, UK
| | - Wallace Brownlee
- Queen Square MS Centre, University College London Institute of Neurology, Queen Square Multiple Sclerosis Centre, London, UK
| | - Helen L Ford
- Centre for Neurosciences, Leeds Teaching Hospitals NHS Trust, Leeds, UK, Leeds, UK
| | - Bruno Gran
- Department of Neurology, Nottingham University Hospitals NHS Trust, Nottingham, UK
- Mental Health and Clinical Neuroscience Academic Unit, University of Nottingham School of Medicine, Nottingham, UK
| | - Stephen Jolles
- Immunodeficiency Centre for Wales, University Hospital of Wales, Cardiff, UK
| | - Sian Price
- Department of Neuroscience, University of Sheffield, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK
| | - Waqar Rashid
- Department of Neuroscience, Brighton and Sussex Medical School, University of Sussex, Brighton, UK
| | - Klaus Schmierer
- The Blizard Institute (Neuroscience, Surgery & Trauma), Queen Mary University of London Faculty of Medicine and Dentistry, London, UK
- Clinical Board Medicine (Neuroscience), The Royal London Hospital, Barts Health NHS Trust, London, UK
| | - Emma C Tallantyre
- Division of Psychological Medicine and Clinical Neurosciences, Cardiff University, University Hospital of Wales, Cardiff, UK
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Saitta C, Pollicino T, Raimondo G. Occult Hepatitis B Virus Infection: An Update. Viruses 2022; 14:v14071504. [PMID: 35891484 PMCID: PMC9318873 DOI: 10.3390/v14071504] [Citation(s) in RCA: 50] [Impact Index Per Article: 16.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2022] [Revised: 06/28/2022] [Accepted: 06/29/2022] [Indexed: 11/16/2022] Open
Abstract
Occult hepatitis B virus (HBV) infection (OBI) refers to a condition in which replication-competent viral DNA is present in the liver (with detectable or undetectable HBV DNA in the serum) of individuals testing negative for the HBV surface antigen (HBsAg). In this peculiar phase of HBV infection, the covalently closed circular DNA (cccDNA) is in a low state of replication. Many advances have been made in clarifying the mechanisms involved in such a suppression of viral activity, which seems to be mainly related to the host's immune control and epigenetic factors. OBI is diffused worldwide, but its prevalence is highly variable among patient populations. This depends on different geographic areas, risk factors for parenteral infections, and assays used for HBsAg and HBV DNA detection. OBI has an impact in several clinical contexts: (a) it can be transmitted, causing a classic form of hepatitis B, through blood transfusion or liver transplantation; (b) it may reactivate in the case of immunosuppression, leading to the possible development of even fulminant hepatitis; (c) it may accelerate the progression of chronic liver disease due to different causes toward cirrhosis; (d) it maintains the pro-oncogenic properties of the "overt" infection, favoring the development of hepatocellular carcinoma.
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Affiliation(s)
- Carlo Saitta
- Division of Medicine and Hepatology, University Hospital of Messina, 98124 Messina, Italy;
- Department of Clinical and Experimental Medicine, University of Messina, 98124 Messina, Italy
| | - Teresa Pollicino
- Department of Human Pathology, University Hospital of Messina, 98124 Messina, Italy;
| | - Giovanni Raimondo
- Division of Medicine and Hepatology, University Hospital of Messina, 98124 Messina, Italy;
- Department of Clinical and Experimental Medicine, University of Messina, 98124 Messina, Italy
- Correspondence: ; Tel.: +39-(0)-902212392
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10
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Detection of occult hepatitis B virus infection among subjects with isolated hepatitis B core antibodies: Results from a 3-year survey in an Italian tertiary-care hospital. Clin Res Hepatol Gastroenterol 2022; 46:101892. [PMID: 35202845 DOI: 10.1016/j.clinre.2022.101892] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/16/2021] [Revised: 02/09/2022] [Accepted: 02/13/2022] [Indexed: 02/04/2023]
Abstract
BACKGROUND Hepatitis B virus (HBV) infection causes hepatitis, liver cirrhosis, hepatocellular carcinoma, and death. This study examines the subjects with isolated anti-HBV core antigen antibody (anti-HBcAg), a pattern characterized by the persistent HBV carriage in the absence of HBV surface antigen (HBsAg) and anti-HBsAg antibody. METHODS Based on medical orders, from 2017 to 2019, serological and molecular assays were performed on serum/plasma samples of 33,048 subjects (71.4% Italians, 28.6% foreigners), who referred to the Virology Unit of the University-Hospital of Parma (Northern Italy) for the laboratory diagnosis of HBV infection. RESULTS The seroprevalence was 4.6% for HBsAg and 11% for anti-HBcAg. The occurrence of the isolated anti-HBcAg status was 3.1%, with higher frequency in males than in females (66.3% vs. 33.7%, P < 0.0001), in Italians than in foreigners (54.8% vs. 45.2%, P < 0.001), and in outpatients than in inpatients (57.4% vs. 42.6%, P < 0.0001). Foreigners with isolated anti-HBcAg came mostly from Africa (67.9%) and Eastern Europe (26.2%). Among subjects with isolated anti-HBcAg, 14.8% had occult HBV infection, 26.3% hepatitis C virus co-infection, 2% human immunodeficiency virus co-infection, and 3.3% both of these latter co-infections. CONCLUSIONS The anti-HBcAg assay accurately evaluates the HBV exposure; subjects with isolated anti-HBcAg antibody should be further analysed for HBV DNA. The HBV infection prevalence in Italy is increasing, due to growing migratory flows from endemic areas.
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11
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Anti-rheumatic drug-induced hepatitis B virus reactivation and preventive strategies for hepatocellular carcinoma. Pharmacol Res 2022; 178:106181. [PMID: 35301112 DOI: 10.1016/j.phrs.2022.106181] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2022] [Revised: 03/10/2022] [Accepted: 03/11/2022] [Indexed: 12/13/2022]
Abstract
To date, an estimated 3 million people worldwide have been infected with chronic hepatitis B virus (HBV). Although anti-HBV therapies have improved the long-term survival profile of chronic carriers, viral reactivation still poses a significant challenge for preventing HBV-related hepatitis, hepatocellular carcinoma (HCC), and death. Immuno-modulating drugs, which are widely applied in managing rheumatic conditions, are commonly associated with HBV reactivation (HBVr) as a result of drug-induced immune suppression. However, there are few reports on the risk of HBVr and the medication management plan for HBV carriers, especially rheumatic patients. In this review, we summarize immuno-modulating drug-induced HBVr during rheumatoid therapy and its preventive strategies for HBVr-induced liver diseases, especially cirrhosis and HCC. These findings will assist with developing treatments for rheumatic patients, and prevent HBV-related cirrhosis and HCC.
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12
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Cencioni MT, Genchi A, Brittain G, de Silva TI, Sharrack B, Snowden JA, Alexander T, Greco R, Muraro PA. Immune Reconstitution Following Autologous Hematopoietic Stem Cell Transplantation for Multiple Sclerosis: A Review on Behalf of the EBMT Autoimmune Diseases Working Party. Front Immunol 2022; 12:813957. [PMID: 35178046 PMCID: PMC8846289 DOI: 10.3389/fimmu.2021.813957] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2021] [Accepted: 12/29/2021] [Indexed: 12/18/2022] Open
Abstract
Multiple sclerosis (MS) is a central nervous system (CNS) disorder, which is mediated by an abnormal immune response coordinated by T and B cells resulting in areas of inflammation, demyelination, and axonal loss. Disease-modifying treatments (DMTs) are available to dampen the inflammatory aggression but are ineffective in many patients. Autologous hematopoietic stem cell transplantation (HSCT) has been used as treatment in patients with a highly active disease, achieving a long-term clinical remission in most. The rationale of the intervention is to eradicate inflammatory autoreactive cells with lympho-ablative regimens and restore immune tolerance. Immunological studies have demonstrated that autologous HSCT induces a renewal of TCR repertoires, resurgence of immune regulatory cells, and depletion of proinflammatory T cell subsets, suggesting a "resetting" of immunological memory. Although our understanding of the clinical and immunological effects of autologous HSCT has progressed, further work is required to characterize the mechanisms that underlie treatment efficacy. Considering that memory B cells are disease-promoting and stem-like T cells are multipotent progenitors involved in self-regeneration of central and effector memory cells, investigating the reconstitution of B cell compartment and stem and effector subsets of immunological memory following autologous HSCT could elucidate those mechanisms. Since all subjects need to be optimally protected from vaccine-preventable diseases (including COVID-19), there is a need to ensure that vaccination in subjects undergoing HSCT is effective and safe. Additionally, the study of vaccination in HSCT-treated subjects as a means of evaluating immune responses could further distinguish broad immunosuppression from immune resetting.
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Affiliation(s)
- Maria Teresa Cencioni
- Division of Neurology, Department of Brain Sciences, Imperial College London, London, United Kingdom
| | - Angela Genchi
- Department of Neurology, Neurology Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy
| | - Gavin Brittain
- South Yorkshire Regional Department of Infection and Tropical Medicine, Sheffield Teaching Hospitals National Health Service (NHS) Foundation Trust, Sheffield, United Kingdom.,Institute for Translational Neuroscience and Sheffield Neuroscience Biomedical Research Centre (BRC), Sheffield, United Kingdom
| | - Thushan I de Silva
- South Yorkshire Regional Department of Infection and Tropical Medicine, Sheffield Teaching Hospitals National Health Service (NHS) Foundation Trust, Sheffield, United Kingdom.,Department of Infection, Immunity and Cardiovascular Disease, The University of Sheffield, Sheffield, United Kingdom
| | - Basil Sharrack
- South Yorkshire Regional Department of Infection and Tropical Medicine, Sheffield Teaching Hospitals National Health Service (NHS) Foundation Trust, Sheffield, United Kingdom.,Institute for Translational Neuroscience and Sheffield Neuroscience Biomedical Research Centre (BRC), Sheffield, United Kingdom
| | - John Andrew Snowden
- Department of Haematology, Sheffield Teaching Hospitals National Health Service (NHS) Foundation Trust, Sheffield, United Kingdom.,Department of Oncology and Metabolism, The University of Sheffield, Sheffield, United Kingdom
| | - Tobias Alexander
- Charité - Universitätsmedizin Berlin, Corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Rheumatology and Clinical Immunology, Berlin, Germany.,Deutsches Rheuma-Forschungszentrum, ein Leibniz Institut, Berlin, Germany
| | - Raffaella Greco
- Unit of Haematology and Bone Marrow Transplantation, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy
| | - Paolo A Muraro
- Division of Neurology, Department of Brain Sciences, Imperial College London, London, United Kingdom
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13
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Smets I, Giovannoni G. Derisking CD20-therapies for long-term use. Mult Scler Relat Disord 2021; 57:103418. [PMID: 34902761 DOI: 10.1016/j.msard.2021.103418] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2021] [Revised: 09/15/2021] [Accepted: 11/20/2021] [Indexed: 11/16/2022]
Abstract
Anti-CD20 have quickly become the mainstay in the treatment of multiple sclerosis (MS) and other neuroinflammatory conditions. However, when they are used as a maintenance therapy the balance between risks and benefits changes. In this review, we suggested six steps to derisk anti-CD20. Firstly and secondly, adequate infectious screening followed by vaccinations before starting anti-CD20 are paramount. Third, family planning needs to be discussed upfront with every woman of childbearing age. Fourth, infusion reactions should be adequately managed to avoid treatment interruption. After repeated infusions, it becomes important to detect and prevent anti-CD20-related adverse events. Fifth, we recommended measuring immunoglobulin levels and reviewing vaccinations annually as well as counselling adequate fever management. For female patients, we emphasised the importance to engage with the local breast cancer screening programs. Sixth, to fundamentally derisk anti-CD20 therapies, we need evidence-based approaches to reduce dosing intervals and guide retreatment.
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Affiliation(s)
- Ide Smets
- Blizard Institute, Centre for Neuroscience, Surgery and Trauma, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, 4 Newark St, Whitechapel, London E1 2AT, United Kingdom; Clinical Board Medicine (Neuroscience), Royal London Hospital, Barts Health NHS Trust, Whitechapel Road, London E1 1FR, United Kingdom
| | - Gavin Giovannoni
- Blizard Institute, Centre for Neuroscience, Surgery and Trauma, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, 4 Newark St, Whitechapel, London E1 2AT, United Kingdom; Clinical Board Medicine (Neuroscience), Royal London Hospital, Barts Health NHS Trust, Whitechapel Road, London E1 1FR, United Kingdom.
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14
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Pei SN, Liu YF, Kuo CY, Wang MC, Ma MC, Liao CK, Ng HY, Chen CH. Role of quantitative hepatitis B surface antibodies in preventing hepatitis B virus-related hepatitis in patients treated with rituximab. Leuk Lymphoma 2021; 62:2899-2906. [PMID: 34323157 DOI: 10.1080/10428194.2021.1948034] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
Hepatitis B virus (HBV) reactivation is a well-known complication after rituximab-based chemotherapy in patients with B cell lymphoma (BCL) who have resolved HBV infection. This retrospective cohort study used electronic medical records from the Kaohsiung Chang Gung Memorial Hospital. There were 128 patients with BCL and resolved HBV infection treated with 1st-line rituximab-containing therapy from 2008 to 2013. No patient received antiviral prophylaxis. Patients with high pretreatment hepatitis B surface antibody (anti-HBs titer ≥100 mIU/mL), had significantly less HBV reactivation (2.0%, 1/49) than patients with low (10-100 mIU/mL, 10.8%, 4/37) or negative anti-HBs (<10 mIU/mL, 23.8%, 10/42) (p = 0.001). No patient in the high group vs. 1 (2.7%) low group vs. 6 (14.3%) negative group developed HBV-related hepatitis (p = 0.002). Patients with high pretreatment anti-HBs have a low risk of HBV-related complications and may not require antiviral prophylaxis. We propose an algorithm for the management of HBV reactivation risk in BCL.
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Affiliation(s)
- Sung-Nan Pei
- Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.,Department of Hematology Oncology, E-Da Cancer Hospital, Kaohsiung, Taiwan.,College of Medicine, I-Shou University, Kaohsiung, Taiwan
| | - Yan-Fang Liu
- Global Epidemiology, Janssen Research & Development, Singapore, Singapore
| | - Chin-Yuan Kuo
- Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Ming-Chung Wang
- Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Ming-Chun Ma
- Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Chun-Kai Liao
- Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Hwee-Yeong Ng
- Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Chien-Hung Chen
- Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.,College of Medicine, Chang Gung University, Taoyuan, Taiwan
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15
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Borojevic B, Chauhan A, Patterson S. Liver failure from delayed hepatitis B reactivation in anti-HBc-positive patient following rituximab for B-cell lymphoma. BMJ Case Rep 2021; 14:14/7/e243526. [PMID: 34244190 DOI: 10.1136/bcr-2021-243526] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
A 93-year-old man was admitted with 1 week of frank jaundice and abdominal pain. His medical history included diffuse large B-cell lymphoma treated with rituximab and cyclophosphamide, hydroxydaunomycin, oncovin and prednisolone (R-CHOP) chemotherapy 10 months prior. His investigations revealed marked hyperbilirubinemia with a total bilirubin of 355 μmol/L, along with a 17-fold elevation in alanine transaminase and impaired hepatic synthetic function. He tested hepatitis B surface antigen (HBsAg) and hepatitis B surface antibody (HBsAb) negative, hepatitis B core antibody (HBcAb) positive and had elevated hepatitis B virus DNA level at 13 691 IU/L. This was in the setting of radiological evidence of suspected cirrhosis. He was later found to have tested positive for HBcAb and negative for HBsAg and HBsAb prior to chemotherapy, but had not received antiviral prophylaxis. He was diagnosed with fulminant hepatitis secondary to delayed hepatitis B reactivation in the setting of rituximab. Hepatitis B reactivation and the role of screening and antiviral prophylaxis in isolated HBcAb-positive patients is reviewed.
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Affiliation(s)
- Branko Borojevic
- General Medicine, Austin Health, Heidelberg, Victoria, Australia
| | - Ayushi Chauhan
- General Medicine, Eastern Health, Box Hill, Victoria, Australia
| | - Scott Patterson
- Gastroenterology and General Medicine, Austin Health, Heidelberg, Victoria, Australia
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16
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Cheng CL, Fang WQ, Lin YJ, Yuan CT, Ko BS, Tang JL, Tien HF. Hepatitis B surface antigen positivity is associated with progression of disease within 24 months in follicular lymphoma. J Cancer Res Clin Oncol 2021; 148:1211-1222. [PMID: 34228224 DOI: 10.1007/s00432-021-03719-y] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2021] [Accepted: 06/26/2021] [Indexed: 11/29/2022]
Abstract
PURPOSE Studies have reported a positive association between hepatitis B surface antigen (HBsAg)-positive hepatitis B virus (HBV) infection and follicular lymphoma (FL). Nevertheless, clinical information concerning chronic HBV infection in FL is sparse. METHODS This retrospective cohort study investigated the prognostic impact of HBsAg in immunocompetent patients with FL treated with frontline rituximab-containing chemoimmunotherapy in an HBV-endemic area between 2006 and 2016. RESULTS Among the 149 analyzed patients, 32 (21.5%) were HBsAg-positive. HBsAg positivity was positively associated with symptomatic splenomegaly, significant serous effusions, and peritreatment hepatic dysfunction. HBsAg-positive patients had a trend of lower complete remission rate (59.4% vs. 76.9%, P = 0.07), significantly poorer overall survival (hazard ratio for death, 2.68; 95% confidence interval, 1.21-5.92), and shorter progression-free survival than had HBsAg-negative patients. Multivariate analysis revealed that HBsAg is an independent adverse prognostic factor for overall survival. Intriguingly, HBsAg-positive patients had a higher incidence of progression of disease within 24 months (POD24) than had HBsAg-negative patients (cumulative incidence rate, 25.8% vs. 12.4%, P = 0.045). CONCLUSION This study revealed that patients with FL and chronic HBV infection represent a distinct subgroup with a markedly poor prognosis. HBsAg was positively associated with POD24 and might serve as a new prognostic predictor of the survival of FL patients in endemic regions for HBV infection.
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Affiliation(s)
- Chieh-Lung Cheng
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei City, Taiwan. .,Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, College of Medicine, National Taiwan University, No. 7, Chung-Shan South Road, Taipei, 10002, Taiwan. .,Department of Hematological Oncology, National Taiwan University Cancer Center, Taipei, Taiwan.
| | - Wei-Quan Fang
- Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan
| | - Yu-Jen Lin
- Department of Hematological Oncology, National Taiwan University Cancer Center, Taipei, Taiwan
| | - Chang-Tsu Yuan
- Department of Pathology, National Taiwan University Cancer Center, Taipei, Taiwan
| | - Bor-Sheng Ko
- Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, College of Medicine, National Taiwan University, No. 7, Chung-Shan South Road, Taipei, 10002, Taiwan
| | - Jih-Luh Tang
- Department of Hematological Oncology, National Taiwan University Cancer Center, Taipei, Taiwan
| | - Hwei-Fang Tien
- Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, College of Medicine, National Taiwan University, No. 7, Chung-Shan South Road, Taipei, 10002, Taiwan
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17
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Cao X, Wang Y, Li P, Huang W, Lu X, Lu H. HBV Reactivation During the Treatment of Non-Hodgkin Lymphoma and Management Strategies. Front Oncol 2021; 11:685706. [PMID: 34277431 PMCID: PMC8281013 DOI: 10.3389/fonc.2021.685706] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2021] [Accepted: 06/16/2021] [Indexed: 12/14/2022] Open
Abstract
Hepatitis B virus reactivation (HBV-R), which can lead to HBV-related morbidity and mortality, is a common and well-known complication that occurs during the treatment of non-Hodgkin lymphoma (NHL) patients with current or past exposure to HBV infection. HBV-R is thought to be closely associated with chemotherapeutic or immunosuppressive therapies. However, immunosuppressive agents such as anti-CD20 antibodies (e.g., rituximab and ofatumumab), glucocorticoids, and hematopoietic stem cell transplantation (HSCT) administered to NHL patients during treatment can cause deep immunodepression and place them at high risk of HBV-R. In this review, we explore the current evidence, the guidelines of several national and international organizations, and the recommendations of expert panels relating to the definition, risk factors, screening and monitoring strategies, whether to use prophylaxis or pre-emptive therapy, and the optimal antiviral agent and duration of antiviral therapy for HBV-R.
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Affiliation(s)
- Xing Cao
- Department of Oncology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yafei Wang
- Department of Respiratory and Critical Care Medicine, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Panyun Li
- Department of Oncology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Wei Huang
- Department of Oncology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xiaojuan Lu
- Department of Oncology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Hongda Lu
- Department of Oncology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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18
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[The consensus on the prophylaxis and treatment of HBV reactivation in B or plasma cell-directed CAR-T cell therapy(2021)]. ZHONGHUA XUE YE XUE ZA ZHI = ZHONGHUA XUEYEXUE ZAZHI 2021; 42:441-446. [PMID: 34384148 PMCID: PMC8295609 DOI: 10.3760/cma.j.issn.0253-2727.2021.06.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/10/2021] [Indexed: 12/14/2022]
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19
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Management of Hepatitis B Virus Reactivation in Malignant Lymphoma Prior to Immunosuppressive Treatment. J Pers Med 2021; 11:jpm11040267. [PMID: 33918206 PMCID: PMC8066124 DOI: 10.3390/jpm11040267] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2021] [Revised: 03/29/2021] [Accepted: 03/30/2021] [Indexed: 12/25/2022] Open
Abstract
Hepatitis B reactivation is a common complication in lymphoma patients under immunosuppressive treatment with potentially serious and life-threating consequences. In this review, we discuss the basis of chronic Hepatitis B virus (HBV) infection, the definition and risk factors for HBV reactivation. We overview the management of HBV reactivation based on virological status and immunosuppressive regimen risk stratification. We also highlight and update information about the HBV reactivation in lymphoma patients under novel agent treatment, including newer monoclonal antibodies, small molecule inhibitors, and even chimeric antigen receptor T-cell immunotherapy.
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20
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Hu S, Chen N, Lu K, Zhen C, Sui X, Fang X, Li Y, Luo Y, Zhou X, Wang X. The prognostic roles of hepatitis B virus antibody in diffuse large B-cell lymphoma patients. Leuk Lymphoma 2021; 62:1335-1343. [PMID: 33399486 DOI: 10.1080/10428194.2020.1867726] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Diffuse large B-cell lymphoma (DLBCL) has been correlated with virus infection and immunity status. We retrospectively analyzed the association between HBV antibody and DLBCL development in HBsAg- patients. Compared with HBeAb- patients, HBeAb+ patients displayed unique clinical features. HBV antibody-negative patients had better therapeutic efficiency (p < .05). The media progression-free survival (PFS) and overall survival (OS) of HBV antibody-positive group were shorter than the negative group (p < .05). Furthermore, we found positive association between CD21 and HBsAb and their synergistic effect for prognostic predication. Interestingly, the effect of Rituximab in prognostic improvement was more significant in HBV antibody-positive group than negative group. Univariate analysis showed that HBV antibody was independent risk factor for disease prognosis. Altogether, our investigations identified for the first time the close association between HBV antibody and clinical prognosis in DLBCL patients. These findings provide potential biomarker to predict the effect of Rituximab and prognosis in DLBCL patients.
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Affiliation(s)
- Shunfeng Hu
- Department of Hematology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Na Chen
- Department of Hematology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Kang Lu
- Department of Hematology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Changqing Zhen
- Department of Hematology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Xiaohui Sui
- Department of Hematology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Xiaosheng Fang
- Department of Hematology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.,Department of Hematology, Shandong Provincial Hospital, Shandong First Medical University, Jinan, China.,School of Medicine, Shandong University, Jinan, China.,Shandong Provincial Engineering Research Center of Lymphoma, Jinan, China.,Branch of National Clinical Research Center for Hematologic Diseases, Jinan, China.,National Clinical Research Center for Hematologic Diseases, the First Affiliated Hospital of Soochow University, Suzhou, China
| | - Ying Li
- Department of Hematology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Yingshu Luo
- Department of Gastroenterology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Xiangxiang Zhou
- Department of Hematology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.,Department of Hematology, Shandong Provincial Hospital, Shandong First Medical University, Jinan, China.,School of Medicine, Shandong University, Jinan, China.,Shandong Provincial Engineering Research Center of Lymphoma, Jinan, China.,Branch of National Clinical Research Center for Hematologic Diseases, Jinan, China.,National Clinical Research Center for Hematologic Diseases, the First Affiliated Hospital of Soochow University, Suzhou, China
| | - Xin Wang
- Department of Hematology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.,Department of Hematology, Shandong Provincial Hospital, Shandong First Medical University, Jinan, China.,School of Medicine, Shandong University, Jinan, China.,Shandong Provincial Engineering Research Center of Lymphoma, Jinan, China.,Branch of National Clinical Research Center for Hematologic Diseases, Jinan, China.,National Clinical Research Center for Hematologic Diseases, the First Affiliated Hospital of Soochow University, Suzhou, China
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21
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Pisaturo M, Onorato L, Russo A, Coppola N. Prevalence of occult HBV infection in Western countries. J Med Virol 2020; 92:2917-2929. [PMID: 32275083 DOI: 10.1002/jmv.25867] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2019] [Accepted: 03/19/2020] [Indexed: 12/11/2022]
Abstract
Due to a lack of standardized tests, it is difficult to obtain prevalence data and define the real impact of occult HBV infection (OBI) in Western countries. The present review article addresses the prevalence of OBI, defined as presence of hepatitis B virus (HBV) DNA in liver tissue or plasma in HBsAg-negative subjects, in Western countries. This varies in different studies according to the different methodologies used (based on serology vs virology), to the sample analyzed for the diagnosis (liver tissue vs plasma), to the different populations studied, to the different geographical variations in the HBV spread, to the host characteristics (age, gender, risk factors for acquiring HBV infection) and to the presence of other parenteral infections (hepatitis C virus and/or human immunodeficiency virus [HIV] infections). Considering the different liver diseases analyzed, that is in patients with cryptogenic cirrhosis or advanced liver fibrosis, the prevalence of OBI ranges 4% to 38%. Considering the different populations studied, in the case of parenteral blood exposure it is about 45%, in patients with chronic hepatitis C it is estimated at about 52%, in HIV-infected patients it ranges from 0% to 45%, in blood donors from 0% to 22.7% and in hemodialysis patients it ranges from 0% to 54%. In conclusion, OBI is a virological entity to be considered when performing the patient's evaluation for immunosuppressive diseases, liver pathologies, or for blood transfusions. Knowing the prevalence and clinical impact of OBI will allow better patient management.
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Affiliation(s)
- Mariantonietta Pisaturo
- Department of Mental Health and Public Medicine-Infectious Diseases Unit, University of Campania Luigi Vanvitelli, Naples, Italy
| | - Lorenzo Onorato
- Department of Mental Health and Public Medicine-Infectious Diseases Unit, University of Campania Luigi Vanvitelli, Naples, Italy
| | - Antonio Russo
- Department of Mental Health and Public Medicine-Infectious Diseases Unit, University of Campania Luigi Vanvitelli, Naples, Italy
| | - Nicola Coppola
- Department of Mental Health and Public Medicine-Infectious Diseases Unit, University of Campania Luigi Vanvitelli, Naples, Italy
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22
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Abstract
Hepatitis B virus (HBV) infection causes chronic hepatitis and has long term complications. Individuals ever infected with HBV are at risk of viral reactivation under certain circumstances. This review summarizes studies on HBV persistence and reactivation with a focus on the definitions and mechanisms. Emphasis is placed on the interplay between HBV replication and host immunity as this interplay determines the patterns of persistence following viral acquisition. Chronic infections exhibit as overt persistence when a defective immune response fails to control the viral replication. The HBV genome persists despite an immune response in the form of covalently closed circular DNA (cccDNA) and integrated DNA, rendering an occult state of viral persistence in individuals whose infection appears to have been resolved. We have described HBV reactivation that occurs because of changes in the virus or the immune system. This review aims to raise the awareness of HBV reactivation and to understand how HBV persists, and discusses the risks of HBV reactivation in a variety of clinical settings.
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Affiliation(s)
- Yu Shi
- The State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital of School of Medicine, Zhejiang University, Hangzhou, China
- Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China
- National Clinical Research Center for Infectious Diseases, China
| | - Min Zheng
- The State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital of School of Medicine, Zhejiang University, Hangzhou, China
- Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China
- National Clinical Research Center for Infectious Diseases, China
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Cheng CL, Huang SC, Chen JH, Wei CH, Fang WQ, Su TH, Yuan CT, Liu JH, Chuang MK, Tien HF. Hepatitis B Surface Antigen Positivity Is an Independent Unfavorable Prognostic Factor in Diffuse Large B-Cell Lymphoma in the Rituximab Era. Oncologist 2020; 25:793-802. [PMID: 32275807 DOI: 10.1634/theoncologist.2019-0756] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2019] [Accepted: 03/25/2020] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND Patients with diffuse large B-cell lymphoma (DLBCL) with concurrent hepatitis B surface antigen (HBsAg)-positive hepatitis B virus (HBV) infection have distinct clinical features. Nevertheless, the prognostic value of HBsAg in DLBCL in the rituximab era remains unclear. MATERIALS AND METHODS We conducted a retrospective cohort study to investigate the clinical relevance of HBsAg in immunocompetent patients with DLBCL treated with homogeneous rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone between 2002 and 2016. RESULTS Among 416 analyzed patients, 98 (23.6%) were HBsAg positive. HBsAg positivity was associated with a younger age and more advanced stage at diagnosis, more frequent hepatic impairment during perichemotherapy, and a trend of higher National Comprehensive Cancer Network-International Prognostic Index (NCCN-IPI) score at diagnosis. Compared with the HBsAg-negative patients, the HBsAg-positive patients had a lower overall response rate (76.5% vs. 85.5%, p = .043), poorer 5-year overall survival (OS) rate (57.2% vs. 73.5%, p < .001), and shorter 5-year progression-free survival (PFS) rate (47.2% vs. 60.7%, p = .013). Multivariate analyses showed that HBsAg positivity was an independent unfavorable prognostic indicator for OS and PFS. A scoring system incorporating HBsAg positivity, the NCCN-IPI score, and serum albumin levels proved to be useful for stratifying prognostically relevant subgroups of patients with DLBCL. CONCLUSION This study demonstrated that HBV infection is uniquely relevant to DLBCL. HBsAg might serve as a novel biomarker to improve clinical risk stratification of patients with DLBCL in areas with high prevalence of HBV infection. Further research investigating the etiopathogenesis of HBV infection in DLBCL is imperative. IMPLICATIONS FOR PRACTICE A considerable disparity exists regarding the prognostic relevance of hepatitis B surface antigen (HBsAg)-positive hepatitis B virus (HBV) infection in patients with diffuse large B-cell lymphoma (DLBCL). In this large, retrospective cohort study from an area with high prevalence of HBV infection, the authors demonstrated that HBsAg was an independent unfavorable factor significantly associated with survival, highlighting its potential as a novel prognostic indicator to improve the risk stratification of patients with DLBCL in the rituximab era.
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Affiliation(s)
- Chieh-Lung Cheng
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei City, Taiwan
- Department of Hematological Oncology, National Taiwan University Cancer Center, Taipei, Taiwan
- Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Sheng-Chuan Huang
- Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Jia-Hong Chen
- Division of Hematology/Oncology, Department of Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
- Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
| | - Chao-Hung Wei
- Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Wei-Quan Fang
- Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan
| | - Tung-Hung Su
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Chang-Tsu Yuan
- Department of Pathology, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Jia-Hau Liu
- Taicheng Stem Cell Therapy Center, National Taiwan University, Taipei, Taiwan
| | - Ming-Kai Chuang
- Department of Laboratory Medicine, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Hwei-Fang Tien
- Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan
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Lee PH, Lee TY, Chang GC. Hepatitis B flare during osimertinib targeted therapy in a lung cancer patient with a resolved hepatitis B virus infection. Eur J Cancer 2020; 130:272-274. [PMID: 32204966 DOI: 10.1016/j.ejca.2020.02.026] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2020] [Accepted: 02/22/2020] [Indexed: 01/06/2023]
Affiliation(s)
- Po-Hsin Lee
- Division of Chest Medicine, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.
| | - Teng-Yu Lee
- Division of Gastroenterology & Hepatology, Taichung Veterans General Hospital, Taichung, Taiwan; Department of Medicine, Chung Shan Medical University, Taichung, Taiwan.
| | - Gee-Chen Chang
- Division of Chest Medicine, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan; Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan.
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25
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Koutsianas C, Thomas K, Vassilopoulos D. Reactivation of hepatitis B virus infection in rheumatic diseases: risk and management considerations. Ther Adv Musculoskelet Dis 2020; 12:1759720X20912646. [PMID: 32206094 PMCID: PMC7076579 DOI: 10.1177/1759720x20912646] [Citation(s) in RCA: 36] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2019] [Accepted: 02/11/2020] [Indexed: 12/14/2022] Open
Abstract
In patients with rheumatic diseases undergoing immunosuppressive treatment, hepatitis B virus reactivation (HBVr) has been long recognized as a major treatment-related adverse event with substantial morbidity and mortality. Because HBVr is easily preventable with appropriate screening and monitoring strategies, and, when indicated, prophylactic antiviral treatment, awareness of this complication is of the utmost importance, especially in the era of biologic treatments. As a condition, it continues to be topical, in view of the emergence of novel classes of immunosuppressive drugs (i.e. Janus kinase inhibitors) acquiring licenses for a variety of rheumatic diseases. The class-specific risk of these agents for HBVr has not yet been determined. Moreover, ambiguity still exists for the management of patients planned to be treated with traditional agents, such as cyclophosphamide and glucocorticoids, particularly in the setting of resolved HBV infection. Clinicians in the field of rheumatic diseases should be tailoring their practice according to the host's profile and treatment-specific risk for HBVr. In this review, the authors attempt to critically review the existing literature and provide practical advice on these issues.
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Affiliation(s)
- Christos Koutsianas
- Clinical Immunology-Rheumatology Unit, 2nd Department of Medicine and Laboratory, National and Kapodistrian University of Athens School of Medicine, Hippokration General Hospital, Athens, Greece
| | - Konstantinos Thomas
- Clinical Immunology-Rheumatology Unit, 2nd Department of Medicine and Laboratory, National and Kapodistrian University of Athens School of Medicine, Hippokration General Hospital, Athens, Greece
| | - Dimitrios Vassilopoulos
- Clinical Immunology-Rheumatology Unit, 2nd Department of Medicine and Laboratory, National and Kapodistrian University of Athens School of Medicine, Hippokration General Hospital, 114 Vass. Sophias Ave., Athens, 115 27, Greece
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26
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Quality Initiative in Clinical Practice: A Single-Institution Appraisal of Quality Metrics in the Management of Newly Diagnosed Diffuse Large B-Cell Lymphoma. Mayo Clin Proc Innov Qual Outcomes 2020; 3:485-494. [PMID: 31993568 PMCID: PMC6978588 DOI: 10.1016/j.mayocpiqo.2019.08.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2018] [Revised: 05/30/2019] [Accepted: 08/23/2019] [Indexed: 11/22/2022] Open
Abstract
Objective To assess our adherence to treatment guidelines for diffuse large B-cell lymphoma (DLBCL) established by the American Society of Hematology in 2014 through implementation of a quality improvement initiative (QII) at our institution in 2015. Patients and Methods Patients with newly diagnosed DLBCL treated from January 1, 2006, through December 31, 2017, were identified. Electronic medical records were reviewed for documentation of American Society of Hematology Practice Improvement Module quality measures (eg, key pathologic features of DLBCL, lymphoma staging, and screening for hepatitis B virus [HBV] infection in patients receiving rituximab-based chemotherapy). We also reviewed assessment of prognosis by revised International Prognostic Index score, testing for hepatitis C virus, HBV, and HIV, chemotherapy education, and the addition of rituximab in the treatment regimen of CD20+ DLBCL. Results Following QII implementation, we saw improvements in most metrics, including reporting of key molecular features (fluorescence in situ hybridization for c-MYC, BCL2, and BCL6, from 45.5% [75 of 165 patients] before QII to 91.7% [22 of 24 patients] after QII; P<.001), screening for HBV (41.8% [69 of 165 patients] to 91.7% [22 of 24 patients]; P<.001) and HIV infections (33.9% [56 of 165 patients] to 87.5% [21 of 24 patients]; P<.0001), providing chemotherapy education (92.7% [153 of 165 patients] to 100%), and use of rituximab for CD20+ DLBCL (83.6% [138 of 165 patients] to 100%; P=.05). All patients had positron emission tomography–computed tomography for DLBCL staging, and there was significantly lower use of bone marrow biopsy (P=.011). Conclusion Implementating a QII and employing standardized metrics can aid in improving quality of care for patients with newly diagnosed DLBCL and allow opportunities to build and ensure better adherence to evolving patient care guidelines.
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Key Words
- ASH-PIM, American Society of Hematology Practice Improvement Module
- BMB, bone marrow biopsy
- CT, computed tomography
- DLBCL, diffuse large B-cell lymphoma
- EMR, electronic medical record
- G-CSF, granulocyte colony-stimulating factor
- HAART, highly active antiretroviral therapy
- HBV, hepatitis B virus
- HCV, hepatitis C virus
- NHL, non-Hodgkin lymphoma
- PET, positron emission tomography
- QII, quality improvement initiative
- R-CHOP, rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone
- VMMC, Virginia Mason Medical Center
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27
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Cheah JT, Faragon JJ, Marks KM. Management of hepatitis B and C infections in rheumatologic disease. Best Pract Res Clin Rheumatol 2019; 32:848-868. [PMID: 31427059 DOI: 10.1016/j.berh.2019.04.001] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Hepatitis B and C viruses present dual considerations in rheumatic disease as both etiologic factors and important comorbidities that must be assessed and addressed. This review summarizes the link between hepatitis B and arthritis and polyarteritis nodosa as well as hepatitis C and arthritis, Sicca syndrome and cryoglobulinemic vasculitis. Recent data pertaining to the antiviral management in these conditions, especially regarding the use of the direct-acting antivirals in hepatitis C, are also presented. Additionally, guidance on testing and treatment of hepatitis B and C as comorbidities in the context of systemic inflammatory rheumatic conditions and the use of disease-modifying antirheumatic therapy are discussed.
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Affiliation(s)
- Jonathan Tl Cheah
- Department of Medicine, Hospital for Special Surgery, 535 E 70th St., New York, NY, 10021, USA.
| | - John J Faragon
- Department of Pharmacy and Medicine, Albany Medical Center, 43 New Scotland Avenue, Albany, NY, 12208, USA.
| | - Kristen M Marks
- Division of Infectious Diseases, Weill Cornell Medicine, 525 East 70th St., New York, NY, 10065, USA.
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28
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Smalls DJ, Kiger RE, Norris LB, Bennett CL, Love BL. Hepatitis B Virus Reactivation: Risk Factors and Current Management Strategies. Pharmacotherapy 2019; 39:1190-1203. [PMID: 31596963 DOI: 10.1002/phar.2340] [Citation(s) in RCA: 61] [Impact Index Per Article: 10.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Hepatitis B virus (HBV) is a global disease with significant morbidity and mortality. Worldwide, ~257 million people are chronically infected with HBV, defined as having a positive hepatitis B surface antigen, but millions more have prior HBV exposure indicated by positive hepatitis B core antibody. Reactivation of hepatitis B implies a sudden increase in viral replication in a patient with chronic HBV infection or prior HBV exposure. Hepatitis B virus reactivation (HBVr) can occur spontaneously, but it is more commonly triggered by immunosuppressive therapies for cancer, immunologic diseases, or transplantation. Elimination of hepatitis C virus (HCV) in HBV-HCV coinfected individuals treated with direct-acting antivirals (DAAs) has also been identified as an important cause of HBVr. Hepatitis B virus reactivation is an underappreciated but important complication of common medical therapies that can delay treatment or result in clinical episodes of hepatitis, hepatic failure, or death. In this review, factors associated with HBVr, particularly medication-related risks, are explored. We review data involving rituximab and ofatumumab, doxorubicin, corticosteroids, tumor necrosis factor antagonists, tyrosine kinases, bortezomib, hematologic stem cell transplantation, and DAAs for HCV treatment. In addition, we discuss screening strategies, choice of antiviral prophylaxis, and the optimal duration of therapy for HBVr. With additional awareness, screening, and appropriate antiviral therapy, it is expected that most cases of HBVr can be prevented.
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Affiliation(s)
- Danielle J Smalls
- Department of Clinical Pharmacy and Outcomes Sciences, University of South Carolina College of Pharmacy, Columbia, South Carolina
| | - Reagan E Kiger
- Department of Clinical Pharmacy and Outcomes Sciences, University of South Carolina College of Pharmacy, Columbia, South Carolina
| | - LeAnn B Norris
- Department of Clinical Pharmacy and Outcomes Sciences, University of South Carolina College of Pharmacy, Columbia, South Carolina.,South Carolina Center of Economic Excellence for Medication Safety, University of South Carolina College of Pharmacy, Columbia, South Carolina
| | - Charles L Bennett
- Department of Clinical Pharmacy and Outcomes Sciences, University of South Carolina College of Pharmacy, Columbia, South Carolina.,South Carolina Center of Economic Excellence for Medication Safety, University of South Carolina College of Pharmacy, Columbia, South Carolina.,William Jennings Bryan Dorn VA Medical Center, Columbia, South Carolina.,Arnold School of Public Health, University of South Carolina, Columbia, South Carolina.,Hollings Cancer Center, Medical University of South Carolina, Charleston, South Carolina
| | - Bryan L Love
- Department of Clinical Pharmacy and Outcomes Sciences, University of South Carolina College of Pharmacy, Columbia, South Carolina.,South Carolina Center of Economic Excellence for Medication Safety, University of South Carolina College of Pharmacy, Columbia, South Carolina.,William Jennings Bryan Dorn VA Medical Center, Columbia, South Carolina
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29
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Yeo D, Hossain I, Lim ST, Farid M, Tao M, Quek R, Tang T, Chan A. Management of hepatitis B reactivation in lymphoma patients on rituximab with past hepatitis B exposure: An observational study. J Oncol Pharm Pract 2019; 25:1042-1052. [PMID: 29554828 DOI: 10.1177/1078155218763039] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
BACKGROUND Currently, a standardized approach to prevent and manage hepatitis B reactivation in lymphoma patients with past hepatitis exposure receiving rituximab in Singapore is lacking. This study is designed to report the current management approach and outcomes associated with hepatitis B reactivation. OBJECTIVES The primary objective was to report 6-, 12-, 24-month cumulative hepatitis B reactivation-related outcomes. Secondary objectives were to report monitoring frequencies of hepatitis B DNA and liver function tests performed in lymphoma patients with resolved hepatitis B receiving rituximab, and anti-viral prophylaxis use. METHODOLOGY This was a single centre, retrospective observational study. Patients with resolved hepatitis B initiated on rituximab from January 2011 to December 2015 were identified and reviewed over a two-year period starting from the date of rituximab initiation. Relevant parameters were obtained from electronic medical records. Hepatitis B reactivation was defined by hepatitis B DNA levels 20 IU/ml (1.30 log/ml) and above. Data were analysed using descriptive statistics. RESULTS Seventy-five patients were retrospectively reviewed over a two-year period. Hepatitis B reactivation was defined as hepatitis B DNA levels ≥20 IU/ml (1.30 log/ml). The 24-month cumulative hepatitis B reactivation rate was 4.0%. The median (interquartile range) number of hepatitis B DNA tests performed during treatment, initial six-month follow-up, and subsequent follow-up were 1.0 (0.0-2.6), 1.0 (0.0-2.0), and 1.0 (0.0-3.1), respectively. CONCLUSION Large variations in hepatitis B reactivation monitoring and management strategies were observed. Further studies are required to develop and determine a standardised protocol that could contribute to safer and more cost-effective care for lymphoma patients with resolved hepatitis B on rituximab.
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Affiliation(s)
- Denise Yeo
- 1 Department of Pharmacy, National University of Singapore, Singapore
| | - Ihtimam Hossain
- 2 Department of Pharmacy, Singapore General Hospital, Singapore
| | - Soon Thye Lim
- 3 Division of Medical Oncology, National Cancer Centre Singapore, Singapore
| | - Mohamad Farid
- 3 Division of Medical Oncology, National Cancer Centre Singapore, Singapore
| | - Miriam Tao
- 3 Division of Medical Oncology, National Cancer Centre Singapore, Singapore
| | - Richard Quek
- 3 Division of Medical Oncology, National Cancer Centre Singapore, Singapore
| | - Tiffany Tang
- 3 Division of Medical Oncology, National Cancer Centre Singapore, Singapore
| | - Alexandre Chan
- 1 Department of Pharmacy, National University of Singapore, Singapore
- 4 Department of Pharmacy, National Cancer Centre Singapore, Singapore
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30
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Javanmard D, Namaei MH, Farahmand M, Ziaee A, Amini E, Ziaee M. Molecular and serological characterization of occult hepatitis B virus infection among patients with hemophilia. J Med Virol 2019; 91:1519-1527. [PMID: 30908666 DOI: 10.1002/jmv.25470] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2018] [Revised: 03/09/2019] [Accepted: 03/22/2019] [Indexed: 12/19/2022]
Abstract
BACKGROUND The occult hepatitis B virus infection (OBI) is a health concern among high-risk groups and immunosuppressed individuals. There is still a paucity of data regarding the occult hepatitis B virus infection among hemophilic patients. With this in mind, we aimed to evaluate the molecular prevalence of OBI among clients with hemophilia. METHODS Totally, 87 hemophilic patients were selected to be studied. To detect OBI, nested polymerase chain reaction test was used to amplify HBV-S, X, and Core regions. Viral load was determined using an in-house real-time PCR assay. Finally, sequence of S gene was used for genotyping and analysis of mutations. RESULTS The mean age of patients was 28.4 ± 5.3 years old, with 90.7% of whom were men. HBV-DNA was detected in eight subjects (9.3%). The rate of OBI was much higher in anti-HBs seronegative subjects than that in other patients (P = 0.019). All OBI cases had HBV genotype D, subgenotype D1. In addition, five out of eight cases (62.5%) showed detectable viral loads (a mean viral load of 4.5 × 10 2 copies/mL). sR73H, sI110L, sP120A, sP127T, sQ129H, sG130R, and sC137S were shown to be the most determinant escape mutation and OBI-relevant mutants. CONCLUSION The rate of OBI among the studied population of hemophilia seems to be remarkable. Therefore, screening for OBI must be a routine practice in patients with hemophilia and also patients undergoing immunosuppressive treatments. Amino acid substitutions were observed in the major hydrophilic region. However further investigations are needed for analysis of exact function.
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Affiliation(s)
- Davod Javanmard
- Infectious Diseases Research Center, Birjand University of Medical Sciences, Birjand, Iran.,Department of Virology, Iran University of Medical Sciences, Tehran, Iran
| | - Mohammad Hasan Namaei
- Infectious Diseases Research Center, Birjand University of Medical Sciences, Birjand, Iran
| | - Mohammad Farahmand
- Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | - Arash Ziaee
- Infectious Diseases Research Center, Birjand University of Medical Sciences, Birjand, Iran
| | - Elham Amini
- Infectious Diseases Research Center, Birjand University of Medical Sciences, Birjand, Iran
| | - Masood Ziaee
- Infectious Diseases Research Center, Birjand University of Medical Sciences, Birjand, Iran
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31
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Klotz L, Havla J, Schwab N, Hohlfeld R, Barnett M, Reddel S, Wiendl H. Risks and risk management in modern multiple sclerosis immunotherapeutic treatment. Ther Adv Neurol Disord 2019; 12:1756286419836571. [PMID: 30967901 PMCID: PMC6444778 DOI: 10.1177/1756286419836571] [Citation(s) in RCA: 78] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2018] [Accepted: 02/14/2019] [Indexed: 12/13/2022] Open
Abstract
In recent years, there has been a paradigm shift in the treatment of multiple
sclerosis (MS) owing to the approval of a number of new drugs with very distinct
mechanisms of action. All approved disease-modifying drugs primarily work
directly on the immune system. However, the identification of an ‘optimal
choice’ for individual patients with regard to treatment efficacy, treatment
adherence and side-effect profile has become increasingly complex including
conceptual as well as practical considerations. Similarly, there are
peculiarities and specific requirements with regard to treatment monitoring,
especially in relation to immunosuppression, the development of secondary
immune-related complications, as well as the existence of drug-specific on- and
off-target effects. Both classical immunosuppression and selective immune
interventions generate a spectrum of potential therapy-related complications.
This article provides a comprehensive overview of available immunotherapeutics
for MS and their risks, detailing individual mechanisms of action and
side-effect profiles. Furthermore, practical recommendations for patients
treated with modern MS immunotherapeutics are provided.
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Affiliation(s)
- Luisa Klotz
- Department of Neurology with Institute of Translational Neurology, University of Münster, Building A1, Albert Schweitzer Campus 1, 48149 Münster, Germany
| | - Joachim Havla
- Institute of Clinical Neuroimmunology, University Hospital; Data Integration for Future Medicine consortium (DIFUTURE), Ludwig-Maximilians University, Munich, Germany
| | - Nicholas Schwab
- Department of Neurology with Institute of Translational Neurology, University of Münster, Münster, Germany
| | - Reinhard Hohlfeld
- Institute of Clinical Neuroimmunology, University Hospital, Ludwig-Maximilians University, Munich, Germany Munich Cluster for Systems Neurology, Ludwig-Maximilians University, Munich, Germany
| | | | - Stephen Reddel
- Brain and Mind Centre, University of Sydney, NSW, Australia
| | - Heinz Wiendl
- Department of Neurology with Institute of Translational Neurology, University of Münster, Building A1, Albert Schweitzer Campus 1, 48149 Münster, Germany
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Azarkar Z, Ziaee M, Ebrahimzadeh A, Sharifzadeh G, Javanmard D. Epidemiology, risk factors, and molecular characterization of occult hepatitis B infection among anti-hepatitis B core antigen alone subjects. J Med Virol 2018; 91:615-622. [PMID: 30345529 DOI: 10.1002/jmv.25343] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2018] [Accepted: 10/11/2018] [Indexed: 12/15/2022]
Abstract
OBJECTIVES Features of occult hepatitis B virus (HBV) infection among the anti-hepatitis B core antigen (anti-HBc) positives have yet to be described in more details. This study aimed to determine the molecular prevalence of occult HBV infection (OBI), and association to risk factors among seropositives for anti-HBc. METHODS This was part of a community-based screening project that included 5234 cases. All participants completed a questionnaire on demographic and socio-epidemiological information. Then, the blood samples were collected and tested for anti-HBc and HBsAg using ELISA method. To identify OBI, nested-polymerase chain reaction (PCR) assays were performed for HBV-S and X genes, and viral load was determined using an in-house real-time PCR. Sequencing and phylogenetic analysis have been implemented for genotyping. RESULTS Overall, 596 cases, positive only for anti-HBc were included in the study. OBI was detected among 61 cases (10.2%). The genotype and subgenotype of HBV among all of them was D1, except one that was D4. Most of them had low viral loads ranged from 1.2 × 102 to 1.34 × 10 3 copies/mL; 19.6% had undetectable viral loads. Important mutations in surface protein and reverse transcriptase were sI92T, sQ129H, rtL80I, rtS85F, rtL91I. The prevalence of OBI was related to some risk factors, such as tattooing (P = 0.02), sexual activities (P = 0.009), and diabetes (P = 0.031). CONCLUSION Our study suggests that OBI should be considered among anti-HBc seropositive subjects. This form of HBV infection was accompanied with some mutations, risk factors, and diseases. However, further investigations are needed to determine virological importance of documented mutations.
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Affiliation(s)
- Zohreh Azarkar
- Infectious Diseases Research Center, Birjand University of Medical Sciences, Birjand, Iran
| | - Masood Ziaee
- Infectious Diseases Research Center, Birjand University of Medical Sciences, Birjand, Iran
| | - Azadeh Ebrahimzadeh
- Infectious Diseases Research Center, Birjand University of Medical Sciences, Birjand, Iran
| | - Gholamreza Sharifzadeh
- Infectious Diseases Research Center, Birjand University of Medical Sciences, Birjand, Iran
| | - Davod Javanmard
- Infectious Diseases Research Center, Birjand University of Medical Sciences, Birjand, Iran.,Department of Virology, Iran University of Medical Sciences, Tehran, Iran
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33
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Epstein DJ, Dunn J, Deresinski S. Infectious Complications of Multiple Sclerosis Therapies: Implications for Screening, Prophylaxis, and Management. Open Forum Infect Dis 2018; 5:ofy174. [PMID: 30094293 PMCID: PMC6080056 DOI: 10.1093/ofid/ofy174] [Citation(s) in RCA: 111] [Impact Index Per Article: 15.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2018] [Accepted: 07/12/2018] [Indexed: 12/12/2022] Open
Abstract
Multiple sclerosis therapies include interferons, glatiramer, and multiple immunosuppressive drugs. Discerning infectious risks of immunosuppressive drugs requires understanding their mechanisms of action and analyzing interventional studies and postmarketing observational data. Though identical immunosuppressive therapies are sometimes used in non-neurologic conditions, infectious risks may differ in this population. Screening for and treatment of latent tuberculosis (TB) infection should be prioritized for patients receiving alemtuzumab; ocrelizumab is likely not associated with an increased risk of TB. Hepatitis B virus (HBV) reactivation can be devastating for patients treated with ocrelizumab and alemtuzumab, whereas the small molecule oral agents do not likely pose substantial risk of HBV. Progressive multifocal leukoencephalopathy is a particular concern with natalizumab. Alemtuzumab, and possibly natalizumab and fingolimod, risks herpes virus reactivation and may warrant prophylaxis. Unusual opportunistic infections have been described. Vaccination is an important tool in preventing infections, though vaccine timing and contraindications can be complex.
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Affiliation(s)
- David J Epstein
- Division of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University, Stanford, California
| | - Jeffrey Dunn
- Department of Neurology and Neurological Sciences, Stanford University, Stanford, California
| | - Stan Deresinski
- Division of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University, Stanford, California
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34
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Schrezenmeier E, Budde K, Staeck O, Lehner L, Duerr M, Khadzhynov D, Dörner T, Halleck F. Incidence of Infectious Disease and Malignancies After Rituximab Therapy in Kidney Transplant Recipients: Results From a Cohort in Germany. Transplant Proc 2018; 49:2269-2273. [PMID: 29198659 DOI: 10.1016/j.transproceed.2017.09.042] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND Rituximab is frequently used in solid organ transplantation off-label, especially in patients with renal allografts. Few data are available on the safety aspects of solid organ transplant recipients receiving rituximab. There is a knowledge gap on long-term follow-up data, in particular on infectious complications. PATIENTS AND METHODS A retrospective observational registry study (German Registry on Autoimmune Diseases) comprising a total of 681 patients was conducted. The data of 63 adult kidney transplant recipients who received rituximab between 2006 and 2013 were used in this analysis. RESULTS Median follow-up was 42 (1-109) months. At least 1 severe infection occurred in 57% of patients. The median time between the first rituximab infusion and the first infection was 4 (1-48) months. Of the overall 88 infections, 74 were severe bacterial infections, 5 were severe viral infections, 3 were severe fungal infections, 2 were combined severe bacterial and fungal infections, and 4 were combined severe viral, fungal and bacterial infections. Seven patients died during the observational period, 2 of them due to infectious complications. In the observational period, 1 case of squamous cell carcinoma but no other malignancies were observed. CONCLUSION Consistent with previous data, a high incidence of infections was observed after rituximab treatment in kidney transplant recipients. Most infections occurred within 6 months after rituximab initiation. With more than 3 years of follow-up, we were able to document a low incidence of secondary malignancies after rituximab with only 1 case in our cohort.
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Affiliation(s)
- E Schrezenmeier
- Department of Nephrology and Medical Intensive Care, Charité - Universitätsmedizin Berlin, Berlin, Germany; Department of Medicine/Rheumatology and Clinical Immunology and DRFZ, Charité Campus Mitte, Berlin, Germany.
| | - K Budde
- Department of Nephrology and Medical Intensive Care, Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - O Staeck
- Department of Nephrology and Medical Intensive Care, Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - L Lehner
- Department of Nephrology and Medical Intensive Care, Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - M Duerr
- Department of Nephrology and Medical Intensive Care, Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - D Khadzhynov
- Department of Nephrology and Medical Intensive Care, Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - T Dörner
- Department of Medicine/Rheumatology and Clinical Immunology and DRFZ, Charité Campus Mitte, Berlin, Germany
| | - F Halleck
- Department of Nephrology and Medical Intensive Care, Charité - Universitätsmedizin Berlin, Berlin, Germany
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Cholongitas E, Haidich AB, Apostolidou-Kiouti F, Chalevas P, Papatheodoridis GV. Hepatitis B virus reactivation in HBsAg-negative, anti-HBc-positive patients receiving immunosuppressive therapy: a systematic review. Ann Gastroenterol 2018; 31:480-490. [PMID: 29991894 PMCID: PMC6033767 DOI: 10.20524/aog.2018.0266] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/08/2018] [Accepted: 02/27/2018] [Indexed: 12/17/2022] Open
Abstract
Background: The optimal management of HBsAg-negative, anti-HBc-positive patients who receive immunosuppression remains unclarified. We systematically reviewed the available data on potential predictors of the risk of hepatitis B virus (HBV) reactivation in such patients. Methods: A literature search identified 55 studies with 3640 HBsAg-negative, anti-HBc-positive patients who received immunosuppressive regimens. Results: HBV reactivation was reported in 236 (6.5%) patients. The pooled HBV reactivation rates did not differ between patients with detectable or undetectable HBV DNA in studies with hematological diseases or regimens containing rituximab, but it was higher in patients with detectable than in those with undetectable HBV DNA who were taking rituximab-free regimens (14% vs. 2.6%; risk ratio [RR] 12.67, 95% CI: 95%CI 2.39-67.04, P=0.003) or had non-hematological diseases, although the latter was not confirmed by sensitivity analysis (RR 8.80, 95%CI 0.71-109.00, P=0.09). The pooled HBV reactivation rates were lower in patients with positive than in those with negative anti-HBs in studies with hematological (7.1% vs. 21.8%; RR 0.29, 95%CI 0.19-0.46, P<0.001) or non-hematological (2.5% vs. 10.7%; RR 0.28, 95%CI 0.11-0.76, P=0.012) diseases, and rituximab-containing (6.6% vs. 19.8%; RR 0.32, 95%CI 0.15-0.69, P=0.003) or rituximab-free (3.3% vs. 9.2%; RR 0.36, 95%CI 0.14-0.96, P=0.042) regimens. Conclusions: The risk of HBV reactivation is high; therefore, anti-HBV prophylaxis should be recommended in HBsAg-negative, anti-HBc-positive patients with hematological diseases and/or rituximab-containing regimens, regardless of HBV DNA and anti-HBs status. In contrast, patients with non-hematological diseases or rituximab-free regimens have a low risk of HBV reactivation and may not require anti-HBV prophylaxis if they have undetectable HBV DNA and positive anti-HBs.
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Affiliation(s)
- Evangelos Cholongitas
- 1st Department of Internal Medicine, Medical School of National & Kapodistrian University, Athens (Evangelos Cholongitas), Greece
| | - Anna-Bettina Haidich
- Department of Hygiene and Epidemiology, Medical School of Aristotle University of Thessaloniki (Anna-Bettina Haidich, Fani Apostolidou-Kiouti), Greece
| | - Fani Apostolidou-Kiouti
- Department of Hygiene and Epidemiology, Medical School of Aristotle University of Thessaloniki (Anna-Bettina Haidich, Fani Apostolidou-Kiouti), Greece
| | - Parthenis Chalevas
- 4th Department of Internal Medicine, Medical School of Aristotle University, Hippokration General Hospital of Thessaloniki (Parthenis Chalevas), Greece
| | - George V Papatheodoridis
- Department of Gastroenterology, Medical School of National and Kapodistrian University of Athens, Laiko General Hospital of Athens (George V. Papatheodoridis), Greece
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Wu T, Kwok RM, Tran TT. Isolated anti-HBc: The Relevance of Hepatitis B Core Antibody-A Review of New Issues. Am J Gastroenterol 2017; 112:1780-1788. [PMID: 29087395 DOI: 10.1038/ajg.2017.397] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/02/2017] [Accepted: 09/01/2017] [Indexed: 02/06/2023]
Abstract
Hepatitis B core antibody (anti-HBc) is considered the most sensitive serological marker for history of hepatitis B virus (HBV) infection. In a subset of anti-HBc carriers, anti-HBc is present in the absence of hepatitis B surface antigen and hepatitis B surface antibody-a serological pattern known as "isolated anti-HBc" (IAHBc). IAHBc has been of clinical interest over the past several years, with growing data to suggest its role as a serological marker for occult HBV infection (OBI). This article reviews the clinical significance and association of IAHBc with hepatitis C virus (HCV) co-infection, risk of HBV reactivation during direct-acting antiviral therapy for HCV as well as immune suppression, and development of hepatocellular carcinoma (HCC). Hepatitis B core-related antigen is also highlighted as an emerging laboratory assay that may identify OBI and predict HCC development in non-cirrhotic patients receiving nucleoside/nucleotide analog therapy.
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Affiliation(s)
- Tiffany Wu
- Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California, USA
| | - Ryan M Kwok
- Division of Gastroenterology and Hepatology, Walter Reed National Military Medical Center, Bethesda, Maryland, USA
| | - Tram T Tran
- Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, California, USA
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Pivnik AV, Tumanova MV, Chistyakova AV, Dudina GA, Dubnitskaya MG, Mukhin OV, Sergeeva EP. [Analysis of inpatient care for HIV-positive patients with malignant lymphomas and hepatitis over 5 years (2011-2015) at the A.S.Loginov Moscow Clinical Research Center, Moscow Healthcare Department]. TERAPEVT ARKH 2017; 89:105-111. [PMID: 28766549 DOI: 10.17116/terarkh2017897105-111] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
The authors give their own data in the first Russian publication on 170 patients with lymphomas and hepatitis concurrent with HIV infection, on the distribution of therapy regimens by nosological entities and the number of deaths. Conventional protocols and programs were used for diagnosis and treatment. All the patients received highly active antiretroviral therapy. Lymphoma was treated according to the conventional programs using rituximab in people without hepatitis B. Aggressive lymphomas, such as diffuse large B-cell lymphoma, Burkitt lymphoma, and plasmablastic lymphoma, were identified in most patients. Hodgkin's lymphoma is the matter of a separate study; it differs in its pathogenesis from other lymphomas. The rate of coinfection with hepatitis was high in the entire group of patients with lymphomas. The major prognostic indicators included low CD4 T-cell counts (less than 50), stage IVB lymphoma, and hepatitis. Complete remissions were achieved in 40% of patients. Forty-one (24%) patients died.
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Affiliation(s)
- A V Pivnik
- A.S. Loginov Moscow Clinical Research Center, Moscow Healthcare Department, Moscow, Russia
| | - M V Tumanova
- A.S. Loginov Moscow Clinical Research Center, Moscow Healthcare Department, Moscow, Russia
| | - A V Chistyakova
- Peoples' Friendship University of Russia, Ministry of Education and Science of Russia, Moscow, Russia
| | - G A Dudina
- A.S. Loginov Moscow Clinical Research Center, Moscow Healthcare Department, Moscow, Russia
| | - M G Dubnitskaya
- A.S. Loginov Moscow Clinical Research Center, Moscow Healthcare Department, Moscow, Russia
| | - O V Mukhin
- A.S. Loginov Moscow Clinical Research Center, Moscow Healthcare Department, Moscow, Russia
| | - E P Sergeeva
- A.S. Loginov Moscow Clinical Research Center, Moscow Healthcare Department, Moscow, Russia
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Downie ML, Gallibois C, Parekh RS, Noone DG. Nephrotic syndrome in infants and children: pathophysiology and management. Paediatr Int Child Health 2017; 37:248-258. [PMID: 28914167 DOI: 10.1080/20469047.2017.1374003] [Citation(s) in RCA: 87] [Impact Index Per Article: 10.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
Abstract
Nephrotic syndrome is defined by nephrotic-range proteinuria (≥40 mg/m2/hour or urine protein/creatinine ratio ≥200 mg/mL or 3+ protein on urine dipstick), hypoalbuminaemia (<25 g/L) and oedema. This review focuses on the classification, epidemiology, pathophysiology, management strategies and prognosis of idiopathic nephrotic syndrome of childhood, and includes a brief overview of the congenital forms.
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Affiliation(s)
- Mallory L Downie
- a Department of Paediatrics , Univeristy of Toronto , Toronto , Canada.,b Division of Nephrology , The Hospital for Sick Children , Toronto , Canada.,c Department of Paediatrics , University of Toronto , Toronto , Canada
| | - Claire Gallibois
- d Department of Medicine , Royal College of Surgeons in Ireland , Dublin , Ireland
| | - Rulan S Parekh
- a Department of Paediatrics , Univeristy of Toronto , Toronto , Canada.,b Division of Nephrology , The Hospital for Sick Children , Toronto , Canada.,c Department of Paediatrics , University of Toronto , Toronto , Canada.,d Department of Medicine , Royal College of Surgeons in Ireland , Dublin , Ireland.,e Child Health Evaluative Sciences, Research Institute , The Hospital for Sick Children , Toronto , Canada.,f Division of Nephrology , University Health Network , Toronto , Canada.,g Dalla Lana School of Public Health , University of Toronto , Toronto , Canada
| | - Damien G Noone
- a Department of Paediatrics , Univeristy of Toronto , Toronto , Canada.,b Division of Nephrology , The Hospital for Sick Children , Toronto , Canada.,c Department of Paediatrics , University of Toronto , Toronto , Canada
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39
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Coluccio C, Begini P, Marzano A, Pellicelli A, Imperatrice B, Anania G, Delle Fave G, Marignani M. Hepatitis B in patients with hematological diseases: An update. World J Hepatol 2017; 9:1043-1053. [PMID: 28951776 PMCID: PMC5596311 DOI: 10.4254/wjh.v9.i25.1043] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/27/2017] [Revised: 07/13/2017] [Accepted: 08/04/2017] [Indexed: 02/06/2023] Open
Abstract
Hepatitis B virus (HBV) reactivation (HBVr) in patients undergoing immunosuppressive therapy is still a hot topic worldwide. Its prevention and management still represents a challenge for specialists dealing with immunosuppressed patients. Aim of this paper is to provide a critical review of the relevant information emerged in the recent literature regarding HBV reactivation following immunosuppressive treatments for oncohematological tumors. A computerized literature search in MEDLINE was performed using appropriate terms arrangement, including English-written literature only or additional relevant articles. Articles published only in abstract form and case reports not giving considerable news were excluded. Clinical manifestation of HBVr can be manifold, ranging from asymptomatic self-limiting anicteric hepatitis to life-threatening fulminant liver failure. In clusters of patients adverse outcomes are potentially predictable. Clinicians should be aware of the inherent risk of HBVr among the different virological categories (active carriers, occult HBV carriers and inactive carriers, the most intriguing category), and classes of immunosuppressive drugs. We recommend that patients undergoing immunosuppressive treatments for hematological malignancies should undergo HBV screening. In case of serological sign(s) of current or past infection with the virus, appropriate therapeutic or preventive strategies are suggested, according to both virological categories, risk of HBVr by immunosuppressive drugs and liver status. Either antiviral drug management and surveillance and pre-emptive approach are examined, commenting the current international recommendations about this debated issue.
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Affiliation(s)
- Chiara Coluccio
- Digestive and Liver Diseases Department, Sant’Andrea Hospital, School of Medicine and Psychology, Sapienza University, 00189 Rome, Italy
| | - Paola Begini
- Digestive and Liver Diseases Department, Sant’Andrea Hospital, School of Medicine and Psychology, Sapienza University, 00189 Rome, Italy
| | - Alfredo Marzano
- Division of Gastroenterology and Hepatology, San Giovanni Battista Hospital, 10126 Turin, Italy
| | | | - Barbara Imperatrice
- Digestive and Liver Diseases Department, Sant’Andrea Hospital, School of Medicine and Psychology, Sapienza University, 00189 Rome, Italy
| | - Giulia Anania
- Digestive and Liver Diseases Department, Sant’Andrea Hospital, School of Medicine and Psychology, Sapienza University, 00189 Rome, Italy
| | - Gianfranco Delle Fave
- Digestive and Liver Diseases Department, Sant’Andrea Hospital, School of Medicine and Psychology, Sapienza University, 00189 Rome, Italy
| | - Massimo Marignani
- Digestive and Liver Diseases Department, Sant’Andrea Hospital, School of Medicine and Psychology, Sapienza University, 00189 Rome, Italy
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40
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Chronic Hepatitis B, C, and D. Microbiol Spectr 2017; 4. [PMID: 27726758 DOI: 10.1128/microbiolspec.dmih2-0025-2015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
Chronic hepatitis B, C, and D virus infections contribute significantly to the morbidity and mortality of immunocompromised individuals. To contextualize discussion of these infections in immunocompromised patients, this paper provides an overview of aspects of infection in normal hosts. It then describes differences in disease, diagnostic testing, and therapeutic management observed in immunocompromised patients.
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41
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Mittal M, Hu KQ. Clinical Implications and Management of Chronic Occult Hepatitis B Virus Infection. CURRENT HEPATOLOGY REPORTS 2017; 16:90-96. [DOI: 10.1007/s11901-017-0339-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/16/2025]
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Zhang MY, Zhu GQ, Zheng JN, Cheng Z, Van Poucke S, Shi KQ, Huang HH, Chen FY, Zheng MH. Nucleos(t)ide analogues for preventing HBV reactivation in immunosuppressed patients with hematological malignancies: a network meta-analysis. Expert Rev Anti Infect Ther 2017; 15:503-513. [PMID: 28317397 DOI: 10.1080/14787210.2017.1309291] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2016] [Accepted: 03/17/2017] [Indexed: 12/31/2022]
Abstract
BACKGROUND We aimed to evaluate the efficacy of five oral nucleos(t)ide analogues (NAs), including lamivudine, entecavir, adefovir, telbivudine and tenofovir, for the prevention of hepatitis B virus (HBV) reactivation and HBV-related complications in chronic hepatitis B virus (CHB) infected patients with hematological malignancies receiving chemotherapy or hematopoietic stem cell transplantation (HSCT) by network meta-analysis. METHODS The search identified 28 articles involving 5 different prophylactic regimens covering 1478 participants. RESULTS Among five prophylactic regimes, tenofovir (predicted probability, 90%), was the most effective intervention followed by entecavir (88%) in preventing HBV reactivation. There was no significant difference between tenofovir and entecavir for preventing HBV reactivation. With regards to other outcomes, tenofovir and telbivudine was not included to evaluate due to lack of relevant studies. Entecavir was the most effective intervention in reducing the risk of HBV related hepatitis (100%), HBV related death (61%) and all other causes of hepatitis (98%). CONCLUSION Tenofovir and entecavir might be the most potent regimes in prevention of HBV reactivation for CHB infected patients with hematological malignancies undergoing chemotherapy or HSCT.
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Affiliation(s)
- Min-Yue Zhang
- a Division of Hematology , Renji Hospital, School of Medicine, Shanghai Jiaotong University , Shanghai , China
| | - Gui-Qi Zhu
- b Department of Hepatology , Liver Research Center, the First Affiliated Hospital of Wenzhou Medical University , Wenzhou , China
- c School of the First Clinical Medical Sciences , Wenzhou Medical University , Wenzhou , China
| | - Ji-Na Zheng
- b Department of Hepatology , Liver Research Center, the First Affiliated Hospital of Wenzhou Medical University , Wenzhou , China
- c School of the First Clinical Medical Sciences , Wenzhou Medical University , Wenzhou , China
| | - Zhang Cheng
- b Department of Hepatology , Liver Research Center, the First Affiliated Hospital of Wenzhou Medical University , Wenzhou , China
- c School of the First Clinical Medical Sciences , Wenzhou Medical University , Wenzhou , China
| | - Sven Van Poucke
- d Department of Anesthesiology , Intensive Care, Emergency Medicine and Pain Therapy, Ziekenhuis Oost-Limburg , Genk , Belgium
| | - Ke-Qing Shi
- b Department of Hepatology , Liver Research Center, the First Affiliated Hospital of Wenzhou Medical University , Wenzhou , China
- e Institute of Hepatology, Wenzhou Medical University , Wenzhou , China
| | - Hong-Hui Huang
- a Division of Hematology , Renji Hospital, School of Medicine, Shanghai Jiaotong University , Shanghai , China
| | - Fang-Yuan Chen
- a Division of Hematology , Renji Hospital, School of Medicine, Shanghai Jiaotong University , Shanghai , China
| | - Ming-Hua Zheng
- b Department of Hepatology , Liver Research Center, the First Affiliated Hospital of Wenzhou Medical University , Wenzhou , China
- e Institute of Hepatology, Wenzhou Medical University , Wenzhou , China
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Guarino M, Picardi M, Vitiello A, Pugliese N, Rea M, Cossiga V, Pane F, Caporaso N, Morisco F. Viral Outcome in Patients with Occult HBV Infection or HCV-Ab Positivity Treated for Lymphoma. Ann Hepatol 2017. [DOI: 10.5604/16652681.1231579] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/26/2023]
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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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Federico A, Brancaccio G, Dallio M, Iodice P, Fabozzi A, Del Prete S, Ciardiello F, Loguercio C, Gaeta GB. Reactivation of hepatitis B virus in cancer patients treated with chemotherapy for solid tumors. Is the prophylaxis really required? Dig Liver Dis 2017; 49:197-201. [PMID: 27899262 DOI: 10.1016/j.dld.2016.11.004] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/02/2016] [Revised: 11/05/2016] [Accepted: 11/08/2016] [Indexed: 12/11/2022]
Abstract
BACKGROUND Reactivation of hepatitis B virus during cancer chemotherapy for non-hematological tumors is not fully clear. AIM To evaluate the risk of hepatitis B virus reactivation in carriers of hepatitis B virus cancer patients treated with chemotherapy for solid tumors. METHODS Two hundred sixty-seven patients with solid tumors were consecutively enrolled: 13 (4.8%) were hepatitis B s-antigen positive, of whom 6 were documented inactive carriers and 7 had chronic liver disease. Thirty-two patients (12%) were hepatitis B s-antigen negative/hepatitis B c-antibody positive. Hepatitis B virus inactive carriers were followed every 3 months by alanine aminotransferases, hepatitis B virus-DNA; whereas hepatitis B virus occult carriers were followed every 3 months by alanine aminotransferases and hepatitis B s-antigen. RESULTS None of the 38 total patients with inactive or occult B infection who did not receive prophylaxis presented hepatitis B virus reactivation during the follow-up period. CONCLUSION This study suggests that, in hepatitis B s-antigen negative patients who undergo chemotherapy for solid tumors, hepatitis B and c-antibody screening results are not relevant to clinical decision and can be avoided. Larger studies are needed to establish whether the risk of reactivation of HBV during chemotherapy is negligible in this subset of patients and they could not be monitored for HBV reactivation.
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Affiliation(s)
- Alessandro Federico
- Division of Hepatogastroenterology, Second University of Naples, Naples, Italy.
| | | | - Marcello Dallio
- Division of Hepatogastroenterology, Second University of Naples, Naples, Italy
| | - Patrizia Iodice
- Division of Oncology, S. Giovanni di Dio Hospital, Frattamaggiore, Italy
| | - Alessio Fabozzi
- Division of Oncology, Second University of Naples, Naples, Italy
| | | | | | - Carmela Loguercio
- Division of Hepatogastroenterology, Second University of Naples, Naples, Italy
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Marchetti O, Tissot F, Calandra T. Infections in the Cancer Patient. Infect Dis (Lond) 2017. [DOI: 10.1016/b978-0-7020-6285-8.00079-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
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Efficacy of prophylactic antiviral therapy and outcomes in HBsAg-negative, anti-HBc-positive patients receiving chemotherapy: a real-life experience. Eur J Gastroenterol Hepatol 2017; 29:56-60. [PMID: 27669175 DOI: 10.1097/meg.0000000000000749] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
OBJECTIVE The aim of this study is to evaluate the outcomes of hepatitis B surface antigen (HBsAg)-negative, anti-HBc-positive patients who received immunosuppressive therapies. PATIENTS AND METHODS We retrospectively evaluated the medical records of HBsAg-negative, anti-HBc-positive patients with hematological diseases or solid tumors who underwent immunosuppressive therapies and were referred because of positive baseline hepatitis B virus (HBV) serology or HBV reactivation. The referral date was according to the judgment of the treating physician at the time of identification of any signs of HBV infection. RESULTS We included 55 HBsAg-negative, anti-HBc-positive patients. Of these, 31 received antiviral prophylaxis (group 1), whereas 24 patients did not receive any anti-HBV agent (group 2). The majority of patients [49/55 (89%)] had hematological malignancies and most of them 39/55 (71%) received rituximab-containing regimens. Lamivudine was used as antiviral prophylaxis in 13/31 (42%) patients of group 1. One patient in this group experienced HBV reactivation and was treated successfully with tenofovir add-on therapy. All patients in the second group experienced HBV reactivation and most of them [19/24 (79%)] were treated with tenofovir or entecavir as rescue therapy. Two of these patients (one of the tenofovir/entecavir subgroup and one of the lamivudine subgroup) eventually died because of hepatic failure despite rescue treatment. CONCLUSION Patients with serological markers of previous HBV infection are still at risk for HBV reactivation. Screening of both anti-HBs and anti-HBc is mandatory before chemotherapy. Pre-emptive antiviral prophylaxis, including lamivudine, is highly effective in all subgroups of such patients, whereas deferring treatment upon HBV reactivation is not enough to rescue all cases.
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Hepatitis B reactivation in HBsAg-negative/HBcAb-positive patients receiving immunosuppressive therapy for glomerulonephritis: a retrospective analysis. Int Urol Nephrol 2016; 49:475-482. [PMID: 28032257 DOI: 10.1007/s11255-016-1487-5] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2016] [Accepted: 12/09/2016] [Indexed: 12/18/2022]
Abstract
PURPOSE The aim of this study is to investigate the prevalence and risk factors for hepatitis B virus (HBV) reactivation in HBsAg-negative/HBcAb-positive patients receiving immunosuppressive therapy for glomerulonephritis. METHODS We performed a retrospective study of 745 HBsAg-negative/HBcAb-positive patients undergoing immunosuppressive therapy for glomerulonephritis from years 2003 to 2012 at the department of nephrology, China-Japan Friendship Hospital, Beijing, China. The patients were divided into HBV reactivation group (n = 27) and non-HBV reactivation group (n = 718). RESULTS The prevalence of HBV reactivation in patients receiving immunosuppressive therapy for glomerulonephritis was up to 3.62% in serological status of HBsAg-negative/HBcAb-positive. HBV reactivation was associated with several findings: greater proportion of lupus nephritis (25.93 vs. 9.61%, p = 0.014), much higher percentage of HBsAb-negative (74.07 vs. 23.82%, p < 0.001), longer duration of immunosuppressive treatment (100 vs. 70.06%, p < 0.001), as well as more cases of combined immunosuppressant (92.59 vs. 61.56%, p = 0.001). After univariate and multivariate analysis, three variables remained as independent risk factors for HBV reactivation: serological status of HBsAb-negative (OR 8.375, 95% CI 3.674-19.776, p = 0.001), length of immunosuppressive treatment more than 1 year (OR 1.308, 95% CI 1.121-1.358, p = 0.024), and combined immunosuppressant (OR 6.342, 95% CI 1.675-30.166, p = 0.003). CONCLUSIONS HBV reactivation is not uncommon in HBsAg-negative/HBcAb-positive glomerulonephritis patients treated with immunosuppressant, and the prevalence was up to 3.62%. Patients with serological status of HBsAb-negative, more than 1 year of immunosuppressive therapy, and combined immunosuppressant are independent risk factors for HBV reactivation.
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Baghbanian M, Halvani M, Roghani HS, Lotfi MH, Yazdi MF, Vahedian-Ardakani HA. PREVALENCE OF OCCULT HEPATITIS B INFECTION IN IRANIAN CANCER PATIENTS BEFORE CHEMOTHERAPY TREATMENT. ARQUIVOS DE GASTROENTEROLOGIA 2016; 53:175-9. [PMID: 27438423 DOI: 10.1590/s0004-28032016000300010] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/01/2015] [Accepted: 03/30/2016] [Indexed: 01/06/2023]
Abstract
BACKGROUND Occult hepatitis B infection is characterized by negative hepatitis B surface antigen (HBsAg) and also detectable hepatitis B virus (HBV) -DNA, with or without hepatitis B core antibody (anti-HBc). HBV reactivation in individuals under immunosuppressive therapy is critical, occurring in occult HBV. OBJECTIVE In this study, we aimed to determine the prevalence of occult HBV infection among hepatitis B surface antigen negative in cancer patients before receiving chemotherapy. METHODS Sera from 204 cancer patients who were negative for HBsAg, were tested for anti-HBc antibodies. The samples that were negative for HBsAg but positive for anti-HBc also examined for HBV-DNA by polymerase chain reaction (PCR). RESULTS Of the 204 HBsAg negative blood samples, 11 (5.4%) samples were positive for anti-HBc antibodies. HBV-DNA was detected in 9/11 (81%) of anti-HBc positive samples. Occult HBV infection in hematological cancers was more than solid cancers, 4.8% and 4.3% respectively. There was no significant difference in HBc antibody positivity based on vaccination, previous blood transfusions, history of familial hepatitis or biochemical parameters (ALT, AST, total and direct bilirubin levels) (P>0.05). CONCLUSION Screening of occult HBV infection by HBsAg, HBV DNA and anti HB core antibody should be suggested as a routine investigation in cancer patients before receiving chemotherapy.
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Affiliation(s)
- Mahmud Baghbanian
- Department of Gastroenterology, Shahid Sadoughi University of Medical Sciences and Health Services, Yazd, Iran
| | - Mehdi Halvani
- Department of Internal Medicine, Shahid Sadoughi University of Medical Sciences and Health Services, Yazd, Iran
| | - Hassan Salman Roghani
- Department of Gastroenterology, Shahid Sadoughi University of Medical Sciences and Health Services, Yazd, Iran
| | - Mohammad Hassan Lotfi
- Biostatistics & Epidemiology, Health Faculty, Shaheed Sadoughi University of Medical Sciences, Daneshju Blv. Yazd, Iran
| | - Mohammad Frahat Yazdi
- Department of haematology, Shahid Sadoughi University of Medical Sciences and Health Services, Yazd, Iran
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Abstract
PURPOSE OF REVIEW Rheumatoid arthritis (RA) patients experience increased infectious disease-related morbidity and mortality, and vaccinations represent an important element in their care. However, vaccine immunogenicity can be affected by disease-modifying antirheumatic drug (DMARD) therapy, such that vaccine choice and timing can be clinically challenging. We review the indications, safety, and immunogenicity of vaccines in the setting of RA. RECENT FINDINGS Recent recommendations highlight the use of influenza, pneumococcal, and shingles vaccines in RA patients. Studies suggest influenza and pneumococcal vaccines are underutilized, but well tolerated in RA patients and generally immunogenic during DMARD use with the exception of rituximab. Though data for other nonlive vaccines are more limited, hepatitis B virus and human papilloma virus vaccines also appear well tolerated and immunogenic in this population. Live vaccines for shingles and yellow fever remain contraindicated in some RA patients; however, limited data suggest they might be well tolerated in certain individuals. SUMMARY The review updates rheumatologists on the optimal use and timing of routine vaccinations in the care of RA.
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