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Chiu CY, Brumble LM, Vikram HR, Watt KD, Beam E. Hepatitis B Virus Reactivation in Non-Liver Solid Organ Transplantation: Incidence and Risk Analysis. Clin Transplant 2024; 38:e15389. [PMID: 38952185 DOI: 10.1111/ctr.15389] [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: 03/06/2024] [Revised: 06/05/2024] [Accepted: 06/08/2024] [Indexed: 07/03/2024]
Abstract
INTRODUCTION Hepatitis B virus reactivation (HBVr) can occur in solid organ transplant (SOT) recipients with previously inactive hepatitis B virus (HBV) infection. Previous studies have reported that HBVr is generally less than 10% in nonliver SOT recipients with past HBV infection. METHODS We conducted a retrospective study from January 2018 to August 2023 at Mayo Clinic sites in Arizona, Florida, and Minnesota. We examined the antiviral prophylaxis strategy used and the characteristics of HBVr in hepatitis B core antibody-positive (HBcAb +) nonliver SOT adult recipients. Past HBV infection was defined as HBcAb + / hepatitis B surface antigen (HBsAg) -. Chronic HBV infection was defined as HBcAb + / HBsAg +. RESULTS A total of 180 nonliver SOT recipients were identified during the study period. Indefinite antiviral prophylaxis was utilized in 77 recipients, and none developed HBVr after transplantation. In 103 recipients without antiviral prophylaxis, the incidence of HBVr was 12% (12/97) and 33% (2/6) in those with past HBV infection and chronic HBV infection. The incidence of HBVr in patients with past HBV infection is 16% (8/50), 15% (3/20), and 5% (1/22) in kidney, heart, and lungs, respectively. HBVr was more frequent in those who received alemtuzumab. Among 14 recipients with HBVr, none had HBV-associated liver failure or death. CONCLUSIONS Our study observed a higher rate of HBVr (12%) in nonliver SOT recipients with past HBV infection compared to the previous studies. Further studies are needed to identify predictors of HBVr in nonliver SOT recipients and optimize antiviral prophylaxis guidance.
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Affiliation(s)
- Chia-Yu Chiu
- Division of Public Health, Infectious Diseases, and Occupational Medicine, Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA
| | - Lisa M Brumble
- Division of Infectious Diseases, Mayo Clinic, Jacksonville, Florida, USA
| | | | - Kymberly D Watt
- Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA
- William J. von Liebig Center for Transplantation and Clinical Regeneration, Mayo Clinic, Rochester, Minnesota, USA
| | - Elena Beam
- Division of Public Health, Infectious Diseases, and Occupational Medicine, Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA
- William J. von Liebig Center for Transplantation and Clinical Regeneration, Mayo Clinic, Rochester, Minnesota, USA
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Yan Z, Luo XF, Yao SN, Wang HY, Chu JF, Zhao S, Song M, Wei XD, Zhou KS, Li YF, Zhou WP, Zhang JY, Zhang PP, Zhou LL, Wang XW, Yao ZH, Liu YY. Low incidence of hepatitis B virus reactivation in patients with hematological malignancies receiving novel anticancer drugs: A report from a high epidemic area and literature review. JOURNAL OF MICROBIOLOGY, IMMUNOLOGY, AND INFECTION = WEI MIAN YU GAN RAN ZA ZHI 2023; 56:747-756. [PMID: 37080838 DOI: 10.1016/j.jmii.2023.04.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/25/2022] [Revised: 03/23/2023] [Accepted: 04/01/2023] [Indexed: 04/22/2023]
Abstract
BACKGROUND More and more novel anticancer drugs have been approved for patients with hematological malignancies in recent years, but HBV reactivation (HBV-R) data in this population is very scarce. This study aimed to evaluated HBV-R risk in patients with hematological malignancies receiving novel anticancer drugs. METHODS HBV markers and serum HBV DNA levels of patients with hematological malignancies receiving novel anticancer drugs in a tertiary cancer hospital were retrospectively collected. HBV-R risk in the whole cohort and subgroups was described. The relevant literature was reviewed to make a pooled analysis. RESULTS Of 845 patients receiving novel anticancer drugs, 258 (30.5%) were considered at risk for HBV-R. The median duration of exposure to novel drugs was 5.6 (0.1-67.6) months. The incidence of HBV-R was 2.1% in patients with past HBV infection without prophylactic antiviral treatment (PAT) and 1.2% in all patients at risk of HBV-R. In a pooled analysis of 11 studies with 464 patients, the incidence of HBV-R was 2.4% (95% CI: 1.3-4.2) in all at-risk patients receiving novel anticancer drugs and 0.6% (95% CI: 0.03-3.5) in patients with anticancer drugs plus PAT. The incidence of death due to HBV-R was 0.4% (95% CI: 0.1-1.6) in all at-risk patients and 18.2% (95% CI: 3.2-47.7) in patients with HBV-R. CONCLUSION Most episodes of HBV-R are preventable, and most cases with HBV-R are manageable. We recommend that novel anticancer drugs should not be intentionally avoided when treating cancer patients with HBV infection.
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Affiliation(s)
- Zheng Yan
- Department of Internal Medicine, Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China
| | - Xu-Feng Luo
- Department of Clinical Research Management, Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China; Institute for Lymphoma Research, Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China
| | - Shu-Na Yao
- Department of Internal Medicine, Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China
| | - Hai-Ying Wang
- Department of Internal Medicine, Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China
| | - Jun-Feng Chu
- Department of Internal Medicine, Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China
| | - Shuang Zhao
- Department of Internal Medicine, Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China
| | - Ming Song
- Department of Clinical Research Management, Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China
| | - Xu-Dong Wei
- Hematology Department, Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China
| | - Ke-Shu Zhou
- Hematology Department, Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China
| | - Yu-Fu Li
- Hematology Department, Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China
| | - Wen-Ping Zhou
- Department of Internal Medicine, Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China; Institute for Lymphoma Research, Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China
| | - Jiu-Yang Zhang
- Department of Internal Medicine, Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China; Institute for Lymphoma Research, Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China
| | - Pei-Pei Zhang
- Department of Internal Medicine, Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China; Institute for Lymphoma Research, Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China
| | - Li-Li Zhou
- Laboratory Department, Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China
| | - Xian-Wei Wang
- Central Laboratory, Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China
| | - Zhi-Hua Yao
- Department of Internal Medicine, Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China.
| | - Yan-Yan Liu
- Department of Internal Medicine, Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China.
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Andreescu M. Risk of Infections Secondary to the Use of Targeted Therapies in Hematological Malignancies. Life (Basel) 2023; 13:1272. [PMID: 37374055 DOI: 10.3390/life13061272] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2023] [Revised: 05/24/2023] [Accepted: 05/27/2023] [Indexed: 06/29/2023] Open
Abstract
Concurrent infections in hematological malignancies (HM) are major contributors to adverse clinical outcomes, including prolonged hospitalization and reduced life expectancy. Individuals diagnosed with HM are particularly susceptible to infectious pathogens due to immunosuppression, which can either be inherent to the hematological disorder or induced by specific therapeutic strategies. Over the years, the treatment paradigm for HM has witnessed a tremendous shift, from broad-spectrum treatment approaches to more specific targeted therapies. At present, the therapeutic landscape of HM is constantly evolving due to the advent of novel targeted therapies and the enhanced utilization of these agents for treatment purposes. By initiating unique molecular pathways, these agents hinder the proliferation of malignant cells, consequently affecting innate and adaptive immunity, which increases the risk of infectious complications. Due to the complexity of novel targeted therapies and their associated risks of infection, it often becomes a daunting task for physicians to maintain updated knowledge in their clinical practice. The situation is further aggravated by the fact that most of the initial clinical trials on targeted therapies provide inadequate information to determine the associated risk of infection. In such a scenario, a cumulative body of evidence is paramount in guiding clinicians regarding the infectious complications that can arise following targeted therapies. In this review, I summarize the recent knowledge on infectious complications arising in the context of targeted therapies for HM.
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Affiliation(s)
- Mihaela Andreescu
- Department of Clinical Sciences, Hematology, Faculty of Medicine, Titu Maiorescu University of Bucharest, 040051 Bucharest, Romania
- Department of Hematology, Colentina Clinical Hospital, 020125 Bucharest, Romania
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4
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Kim E, Haag A, Nguyen J, Kesselman MM, Demory Beckler M. Vaccination of multiple sclerosis patients during the COVID-19 era: Novel insights into vaccine safety and immunogenicity. Mult Scler Relat Disord 2022; 67:104172. [PMID: 36116380 PMCID: PMC9462931 DOI: 10.1016/j.msard.2022.104172] [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] [Subscribe] [Scholar Register] [Received: 03/28/2022] [Revised: 07/13/2022] [Accepted: 09/08/2022] [Indexed: 11/15/2022]
Abstract
Multiple sclerosis (MS) is an incurable autoimmune disease known to cause widespread demyelinating lesions in the central nervous system (CNS) and a host of debilitating symptoms in patients. The development of MS is believed to be driven by the breakdown of the blood brain barrier, subsequent infiltration by CD4+ and CD8+ T cells, and widespread CNS inflammation and demyelination. Disease modifying therapies (DMTs) profoundly disrupt these processes and therefore compose an essential component of disease management. However, the effects of these therapeutic agents on vaccine safety and immunogenicity in individuals with MS are not yet fully understood. As such, the primary objective of this review article was to summarize the findings of recently conducted studies on vaccine safety and immunogenicity in MS patients treated with DMTs, particularly in the context of the ongoing coronavirus disease 2019 (COVID-19) pandemic. Discussed in this review are vaccinations against influenza, yellow fever, human papillomavirus, measles, mumps, rubella, Streptococcus pneumoniae, hepatitis B, and COVID-19. This article additionally reviews our current understanding of COVID-19 severity and incidence in this patient population, the risks and benefits of vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and vaccination guidelines set forth by MS societies and organizations.
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Affiliation(s)
- Enoch Kim
- Dr. Kiran C. Patel College of Allopathic Medicine, Nova Southeastern University, Fort Lauderdale, FL, United States of America.
| | - Alyssa Haag
- Dr. Kiran C. Patel College of Allopathic Medicine, Nova Southeastern University, Fort Lauderdale, FL, United States of America.
| | - Jackie Nguyen
- Dr. Kiran C. Patel College of Allopathic Medicine, Nova Southeastern University, Fort Lauderdale, FL, United States of America.
| | - Marc M Kesselman
- Division of Rheumatology, Dr. Kiran C. Patel College of Osteopathic Medicine, Nova Southeastern University, Fort Lauderdale, FL, United States of America.
| | - Michelle Demory Beckler
- Dr. Kiran C. Patel College of Allopathic Medicine, Nova Southeastern University, Fort Lauderdale, FL, United States of America.
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5
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Shirmast P, Shahri MA, Pashangzadeh S, Mirshahabi H, Samadi E, Motamed N. Detection of occult hepatitis B virus in patients undergoing chemotherapy in Iran. Future Virol 2022. [DOI: 10.2217/fvl-2020-0386] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
Aim: Occult hepatitis B infection (OBI) is life threatening and has a high mortality rate despite applying antiviral treatments in cancer patients. This study aimed to investigate the prevalence of OBI in patients undergoing chemotherapy in Iran. Materials & methods: A total of 342 patients undergoing chemotherapy were enrolled. OBI detection in anti-HBc positive individuals was conducted using nested PCR. Results: Among 342 subjects, 103 (30.1%) were positive for anti-HBc. Fifteen (14.6%) cases of 103 anti-HBc positive samples were also positive for HBsAg. Overall, HBV DNA was positive in three (3.4%) of 88 anti-HBc subjects. Conclusion: Our results indicated that OBI might occur in almost one in 25 anti-HBc-positive patients undergoing chemotherapy.
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Affiliation(s)
- Paniz Shirmast
- Department of Microbiology & Virology, Faculty of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Mahdi Abedinzade Shahri
- Department of Biology, Faculty of Sciences, Mashhad Branch, Islamic Azad University, Mashhad, Iran
| | - Salar Pashangzadeh
- Iranian Research Center of HIV/AIDS, Iranian Institute for Reduction of High-Risk Behaviors, Tehran University of Medical Sciences, Tehran, Iran
- Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Hessam Mirshahabi
- Department of Microbiology & Virology, Faculty of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Elham Samadi
- Department of Microbiology & Virology, Faculty of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Nima Motamed
- Department of Community Medicine, Faculty of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
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Biolato M, Bianco A, Lucchini M, Gasbarrini A, Mirabella M, Grieco A. The Disease-Modifying Therapies of Relapsing-Remitting Multiple Sclerosis and Liver Injury: A Narrative Review. CNS Drugs 2021; 35:861-880. [PMID: 34319570 PMCID: PMC8354931 DOI: 10.1007/s40263-021-00842-9] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 06/28/2021] [Indexed: 02/08/2023]
Abstract
In this narrative review, we analyze pre-registration and post-marketing data concerning hepatotoxicity of all disease-modifying therapies (DMTs) available for the treatment of relapsing-remitting multiple sclerosis, including beta interferon, glatiramer acetate, fingolimod, teriflunomide, dimethyl fumarate, cladribine, natalizumab, alemtuzumab, and ocrelizumab. We review the proposed causal mechanisms described in the literature and we also address issues like use of DMTs in patients with viral hepatitis or liver cirrhosis. Most data emerged in the post-marketing phase by reports to national pharmacovigilance agencies and published case reports or case series. Serious liver adverse events are rare, but exact incidence is largely unknown, as are predictive factors. Unfortunately, none of the DMTs currently available for the treatment of multiple sclerosis is free of potential hepatic toxic effects. Cases of acute liver failure have been reported for beta-interferon, fingolimod, natalizumab, alemtuzumab, and ocrelizumab by different mechanisms (idiosyncratic reaction, autoimmune hepatitis, or viral reactivation). Patients with multiple sclerosis should be informed about possible hepatic side effects of their treatment. Most cases of liver injury are idiosyncratic and unpredictable. The specific monitoring schedule for each DMT has been reviewed and the clinician should be ready to recognize clinical symptoms suggestive for liver injury. Not all DMTs are indicated in cirrhotic patients. For some DMTs, screening for hepatitis B virus and hepatitis C virus is required before starting treatment and a monitoring or antiviral prophylaxis schedule has been established. Beta interferon, glatiramer acetate, natalizumab, and alemtuzumab are relatively contraindicated in autoimmune hepatitis due to the risk of disease exacerbation.
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Affiliation(s)
- Marco Biolato
- Department of Medical and Surgical Sciences, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Largo A. Gemelli 8, 00168, Rome, Italy.
- Institute of Internal Medicine, Catholic University of Sacred Heart, 00168, Rome, Italy.
- Centro di ricerca per la Sclerosi Multipla (CERSM), Università Cattolica del Sacro Cuore, 00168, Rome, Italy.
| | - Assunta Bianco
- Multiple Sclerosis Center, Department of Department of Aging, Neurological, Orthopedic and Head and Neck Sciences, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168, Rome, Italy
| | - Matteo Lucchini
- Multiple Sclerosis Center, Department of Department of Aging, Neurological, Orthopedic and Head and Neck Sciences, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168, Rome, Italy
- Centro di ricerca per la Sclerosi Multipla (CERSM), Università Cattolica del Sacro Cuore, 00168, Rome, Italy
| | - Antonio Gasbarrini
- Department of Medical and Surgical Sciences, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Largo A. Gemelli 8, 00168, Rome, Italy
- Institute of Internal Medicine, Catholic University of Sacred Heart, 00168, Rome, Italy
| | - Massimiliano Mirabella
- Multiple Sclerosis Center, Department of Department of Aging, Neurological, Orthopedic and Head and Neck Sciences, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168, Rome, Italy
- Centro di ricerca per la Sclerosi Multipla (CERSM), Università Cattolica del Sacro Cuore, 00168, Rome, Italy
| | - Antonio Grieco
- Department of Medical and Surgical Sciences, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Largo A. Gemelli 8, 00168, Rome, Italy
- Institute of Internal Medicine, Catholic University of Sacred Heart, 00168, Rome, Italy
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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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Smith TE, Kister I. Infection Mitigation Strategies for Multiple Sclerosis Patients on Oral and Monoclonal Disease-Modifying Therapies. Curr Neurol Neurosci Rep 2021; 21:36. [PMID: 34009478 PMCID: PMC8132488 DOI: 10.1007/s11910-021-01117-y] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/22/2021] [Indexed: 12/17/2022]
Abstract
PURPOSE OF REVIEW The newer, higher-efficacy disease-modifying therapies (DMTs) for multiple sclerosis (MS)-orals and monoclonals-have more profound immunomodulatory and immunosuppressive properties than the older, injectable therapies and require risk mitigation strategies to reduce the risk of serious infections. This review will provide a systematic framework for infectious risk mitigation strategies relevant to these therapies. RECENT FINDINGS We classify risk mitigation strategies according to the following framework: (1) screening and patient selection, (2) vaccinations, (3) antibiotic prophylaxis, (4) laboratory and MRI monitoring, (5) adjusting dose and frequency of DMT, and (6) behavioral modifications to limit the risk of infection. We systematically apply this framework to the infections for which risk mitigations are available: hepatitis B, herpetic infections, progressive multifocal leukoencephalopathy, and tuberculosis. We also discuss up-to-date recommendations regarding COVID-19 vaccinations for patients on DMTs. We offer a practical, comprehensive, DMT-specific framework of derisking strategies designed to minimize the risk of infections associated with the newer MS therapies.
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Affiliation(s)
- Tyler Ellis Smith
- Department of Neurology, NYU-Multiple Sclerosis Care Center, NYU School of Medicine, New York, NY, USA.
- , New York, NY, USA.
| | - Ilya Kister
- Department of Neurology, NYU-Multiple Sclerosis Care Center, NYU School of Medicine, New York, NY, USA
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9
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Current Immunological and Clinical Perspective on Vaccinations in Multiple Sclerosis Patients: Are They Safe after All? Int J Mol Sci 2021; 22:ijms22083859. [PMID: 33917860 PMCID: PMC8068297 DOI: 10.3390/ijms22083859] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2021] [Revised: 04/01/2021] [Accepted: 04/06/2021] [Indexed: 12/17/2022] Open
Abstract
Vaccines work by stimulating the immune system, and their immunogenicity is key in achieving protection against specific pathogens. Questions have been raised whether in Multiple Sclerosis (MS) patients they could induce disease exacerbation and whether vaccines could possibly act as a trigger in the onset of MS in susceptible populations. So far, no correlation has been found between the vaccinations against influenza, hepatitis B, tetanus, human papillomavirus, measles, mumps, rubella, varicella zoster, tuberculosis, yellow fever, or typhoid fever and the risk of MS. Further research is needed for the potential protective implications of the tetanus and Bacillus Calmette-Guerin vaccines in MS patients. Nowadays with the emerging coronavirus disease 2019 (COVID-19) and recent vaccinations approval and arrival, the risk-benefit in MS patients with regards to safety and efficacy of COVID-19 vaccination in those treated with immunosuppressive therapies is of paramount importance. In this manuscript, we demonstrate how different vaccine types could be related to the immunopathogenesis of MS and discuss the risks and benefits of different vaccinations in MS patients.
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10
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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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11
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Japan Society of Hepatology Guidelines for the Management of Hepatitis B Virus Infection: 2019 update. Hepatol Res 2020; 50:892-923. [PMID: 32343469 DOI: 10.1111/hepr.13504] [Citation(s) in RCA: 84] [Impact Index Per Article: 16.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/20/2020] [Revised: 03/16/2020] [Accepted: 03/22/2020] [Indexed: 02/06/2023]
Abstract
The Drafting Committee for Hepatitis Management Guidelines established by the Japan Society of Hepatology published the first version of the Guidelines for the Management of Hepatitis B in 2013 (first English version in 2014), and has since been publishing updates to the Guidelines as new drugs become available, with the latest original Japanese version being Version 3.1. Herein, the Drafting Committee publishes the second English version that contains all the changes made since the first English version of the guidelines was published in 2014. This 2019 version covers: (i) the nucleos(t)ide analogs, tenofovir disoproxil fumarate and tenofovir alafenamide; (ii) updates to treatment recommendations and management of drug-resistant hepatitis B virus that reflect the new availability of these drugs; and (iii) new information about hepatitis B virus reactivation with each update. This latest update also contains information about treatment goals, indications for treatment and cessation of nucleos(t)ide analog therapy, most of which were covered by the first version.
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12
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Abstract
INTRODUCTION Hepatitis B virus (HBV) reactivation can be induced by treatments that attenuate the immunological control over HBV, leading to increased morbidity and mortality. The risk of HBV reactivation is determined by host immunity, viral factors, and the type and dose of treatments. Nevertheless, the risk of HBV reactivation for a growing number of novel therapies remains uncertain and needs to be carefully examined. Identification of patients at risk and administration of prophylactic antiviral agents are critical to prevent HBV reactivation. Early diagnosis and initiation of antiviral treatment are the keys to avoid devastating outcomes. AREA COVERED We summarized the latest evidence and recommendations for risk stratification, early diagnosis, prophylaxis, and management of HBV reactivation. EXPERT OPINION Universal screening, adequate prophylaxis, and close monitoring are essential for the prevention of HBV reactivation. Risk stratification of patients at risk with appropriate antiviral prophylaxis can prevent HBV reactivation effectively. Several emerging biomarkers have been proved to help determine the risk precisely. Early detection and timely administration of antiviral agents are crucial for management. Further studies on the precision of risk stratification as well as the optimal duration of prophylaxis and treatment are needed to establish an individualized strategy.
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Affiliation(s)
- Shang-Chin Huang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital , Taipei, Taiwan
| | - Hung-Chih Yang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital , Taipei, Taiwan.,Hepatitis Research Center, National Taiwan University Hospital , Taipei, Taiwan.,Department of Microbiology, National Taiwan University College of Medicine Taipei , Taiwan
| | - Jia-Horng Kao
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital , Taipei, Taiwan.,Hepatitis Research Center, National Taiwan University Hospital , Taipei, Taiwan.,Department of Medical Research, National Taiwan University Hospital , Taipei, Taiwan.,Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine , Taipei, Taiwan
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13
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Abstract
Hepatitis B virus (HBV) reactivation can be a serious complication for patients with chronic or resolved HBV infection when treated with biologics. For HBsAg-positive patients receiving biologics, the risk of HBV reactivation is moderate to high. HBsAg-negative/anti-HBc positive patients are at lower risk of HBV reactivation than HBsAg-positive patients. However, patients taking anti-CD20 agents, such as rituximab, have high risk of HBV reactivation (>10%), so antiviral prophylactic therapies are required. This review provides the different classes of biologics associated with HBV reactivation, stratifies the various reactivation risk levels by HBV status and biologic agent, and discusses management strategies.
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Affiliation(s)
- Eiichi Ogawa
- Department of General Internal Medicine, Kyushu University Hospital, 3-1-1 Maidashi Higashi-ku, Fukuoka 8128582, Japan
| | - Mike T Wei
- Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University Medical Center, 750 Welch Road, Suite 210, Palo Alto, CA 94304, USA
| | - Mindie H Nguyen
- Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University Medical Center, 750 Welch Road, Suite 210, Palo Alto, CA 94304, USA.
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Notsumata K, Nomura Y, Tanaka A, Nomura Y, Ueda T, Sanada T, Watanabe H, Toya D. Efficient Prophylactic Management of HBV Reactivation by an Information Technology Encoding System: Results of a 6-year Prospective Cohort Study. Intern Med 2020; 59:2457-2464. [PMID: 33055468 PMCID: PMC7662047 DOI: 10.2169/internalmedicine.4445-20] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Objective We started an information technology (IT) system that encodes the medical treatment status of hepatitis B virrus (HBV) with a 9-digit number, automatically checks for inappropriate situations occurring due to immunosuppression and chemotherapy that do not comply with the flowchart of the hepatitis B countermeasure guideline, and promotes correct HBV medical treatment in our hospital. We conducted a prospective study of HBV reactivation using this system. Methods Among 21,607 cases that were managed using this system, 1,206 patients who were HBs antigen-negative, HBc antibody- and/or HBs antibody-positive and in whom HBV DNA quantification was performed two times or more were examined for the occurrence of HBV reactivation. The study population included: malignant lymphoma patients using rituximab (n=40), patients with malignant tumors using anticancer agents (n=546), patients treated with steroids (n=274), rheumatoid arthritis (RA) patients (n=144), patients using immunosuppressants/biologics (n=26), and patients undergoing hepatitis C direct acting antiviral (DAA) treatment (n=176). Results HBV reactivation was observed in 27 cases undergoing treatment with the following agents: rituximab (n=6), anticancer agents (n=8), steroids (n=10), anti-RA agents (n=1), and hepatitis C DAA (n=2). Among the 40 patients who were using rituximab, 6 (18.2%) showed a high rate of reactivation. In 10 in which HBV reactivation occurred at a median of 10 (range, 4-32) months after steroid administration, 6 occurred after the 7th month, and 1 patient showed HBs antigen positivity and severe hepatitis. Conclusion Continuing of the operation of an automatic check system using coded medical information to check for the reactivation enabled this prospective study of HBV reactivation. Careful attention should be paid to patients using steroids, as well as malignant lymphoma patients who are treated with rituximab. The results of the present study suggest that the present IT encoding system would be useful for preventing HBV reactivation.
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Affiliation(s)
- Kazuo Notsumata
- Department of Internal Medicine, Fukui Saiseikai Hospital, Japan
| | - Yoshimoto Nomura
- Department of Internal Medicine, Fukui Saiseikai Hospital, Japan
| | - Akihiro Tanaka
- Department of Internal Medicine, Fukui Saiseikai Hospital, Japan
| | | | - Teruyuki Ueda
- Department of Internal Medicine, Fukui Saiseikai Hospital, Japan
| | - Taku Sanada
- Department of Internal Medicine, Fukui Saiseikai Hospital, Japan
| | | | - Daisyu Toya
- Department of Internal Medicine, Fukui Saiseikai Hospital, Japan
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15
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Sagnelli C, Pisaturo M, Calò F, Martini S, Sagnelli E, Coppola N. Reactivation of hepatitis B virus infection in patients with hemo-lymphoproliferative diseases, and its prevention. World J Gastroenterol 2019; 25:3299-3312. [PMID: 31341357 PMCID: PMC6639550 DOI: 10.3748/wjg.v25.i26.3299] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/15/2019] [Revised: 05/10/2019] [Accepted: 05/18/2019] [Indexed: 02/06/2023] Open
Abstract
Reactivation of hepatitis B virus (HBV) replication is characterized by increased HBV-DNA serum values of about 1 log or by HBV DNA turning positive if previously undetectable in serum, possibly associated with liver damage and seldom life-threatening. Due to HBV reactivation, hepatitis B surface antigen (HBsAg)-negative/anti-HBc-positive subjects may revert to HBsAg-positive. In patients with hemo-lymphoproliferative disease, the frequency of HBV reactivation depends on the type of lymphoproliferative disorder, the individual's HBV serological status and the potency and duration of immunosuppression. In particular, it occurs in 10%-50% of the HBsAg-positive and in 2%-25% of the HBsAg- negative/anti-HBc-positive, the highest incidences being registered in patients receiving rituximab-based therapy. HBV reactivation can be prevented by accurate screening of patients at risk and by a pharmacological prophylaxis with anti-HBV nucleo(t)sides starting 2-3 wk before the beginning of immunosuppressive treatment and covering the entire period of administration of immunosuppressive drugs and a long subsequent period, the duration of which depends substantially on the degree of immunodepression achieved. Patients with significant HBV replication before immunosuppressive therapy should receive anti-HBV nucleo(t)sides as a long-term (may be life-long) treatment. This review article is mainly directed to doctors engaged every day in the treatment of patients with onco-lymphoproliferative diseases, so that they can broaden their knowledge on HBV infection and on its reactivation induced by the drugs with high immunosuppressive potential that they use in the care of their patients.
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Affiliation(s)
- Caterina Sagnelli
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, University of Campania Luigi Vanvitelli, Naples 80127, Italy
| | - Mariantonietta Pisaturo
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, University of Campania Luigi Vanvitelli, Naples 80127, Italy
| | - Federica Calò
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, University of Campania Luigi Vanvitelli, Naples 80127, Italy
| | - Salvatore Martini
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, University of Campania Luigi Vanvitelli, Naples 80127, Italy
| | - Evangelista Sagnelli
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, University of Campania Luigi Vanvitelli, Naples 80127, Italy
| | - Nicola Coppola
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, University of Campania Luigi Vanvitelli, Naples 80127, Italy
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16
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Wang B, Mufti G, Agarwal K. Reactivation of hepatitis B virus infection in patients with hematologic disorders. Haematologica 2019; 104:435-443. [PMID: 30733266 PMCID: PMC6395346 DOI: 10.3324/haematol.2018.210252] [Citation(s) in RCA: 37] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2018] [Accepted: 01/18/2019] [Indexed: 12/16/2022] Open
Abstract
Hepatitis B reactivation is the reappearance or rise of hepatitis B virus (HBV) DNA in patients with past or chronic HBV infection, usually occurring in the context of immunosuppression. HBV reactivation has been most commonly reported in patients with hematologic disorders, with potentially serious and life-threatening consequences. In this review, we discuss the basis and presentation of HBV reactivation, and risk factors in terms of the host, the virus and the immunosuppression regimen, including newer agents used to manage hematologic malignancies. We overview the management of HBV reactivation, highlighting an up-dated recommendation on the use of newer nucleoside and nucleotide analogs, such as tenofovir and entecavir, for antiviral prophylaxis.
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Affiliation(s)
| | - Ghulam Mufti
- Department of Hematology, King's College Hospital, London, UK
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17
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Izumida K, Kaneko A, Takahashi K, Kusumoto S, Narita T, Takami A, Iida S, Aoyagi K, Tanaka Y. Clinical evaluation of a novel and highly sensitive immunoassay for anti-hepatitis B core antigen using a fully automated immunochemical analyzer. Hepatol Res 2018; 48:1081-1091. [PMID: 30006955 DOI: 10.1111/hepr.13229] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/02/2018] [Revised: 04/29/2018] [Accepted: 07/06/2018] [Indexed: 01/28/2023]
Abstract
AIM Recently, the measurement of hepatitis B surface antigen and anti-hepatitis B core antigen (HBcAb) and/or anti-hepatitis B surface antigen has been recommended before various therapies to identify patients at risk of hepatitis B virus (HBV) reactivation. However, a recent study reported that HBV reactivation occurred in HBcAb-negative patients, indicating that it is challenging to identify patients with a history of HBV infection using conventional HBcAb reagent. We developed a highly sensitive HBcAb (HBcAb-HS) assay for reducing the risk of HBV reactivation. METHODS The HBcAb-HS assay is an automated chemiluminescent enzyme immunoassay system, which is suitable for clinical use. The cut-off was set at 0.020 IU/mL from the distribution patterns of HBcAb-negative specimens, and we evaluated the performance of this assay compared with conventional reagents. RESULTS This new assay showed a 27-81-fold greater sensitivity than conventional HBcAb reagents; the quantified measurement range was from 0.005 IU/mL to 1.500 IU/mL, and it showed excellent quantitative performance and correlated well with two conventional assays, using the HBcAb-positive specimens. Moreover, it showed 100% specificity for the 469 purchased HBcAb-negative specimens. Notably, this newly developed HBcAb-HS assay showed positivity in the preserved specimens before HBV reactivation, for which conventional HBcAb reagents gave negative results, and the HBcAb-HS assay could detect the lower HBcAb levels even after intensive immunosuppressive therapies, including autologous hematopoietic stem cell transplantation. CONCLUSIONS The clinical efficacy of the newly developed, highly sensitive HBcAb assay would enable the identification of patients at risk of HBV reactivation more accurately.
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Affiliation(s)
- Kyo Izumida
- Research and Development Division, Fujirebio Inc., Hachioji, Japan
| | - Atsushi Kaneko
- Research and Development Division, Fujirebio Inc., Hachioji, Japan
| | - Kazuya Takahashi
- Research and Development Division, Fujirebio Inc., Hachioji, Japan
| | - Shigeru Kusumoto
- Department of Hematology and Oncology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Tomoko Narita
- Department of Hematology and Oncology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Akiyoshi Takami
- Division of Hematology, Department of Internal Medicine, Aichi Medical University, Nagakute, Japan
| | - Shinsuke Iida
- Department of Hematology and Oncology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Katsumi Aoyagi
- Research and Development Division, Fujirebio Inc., Hachioji, Japan
| | - Yasuhito Tanaka
- Department of Virology and Liver Unit, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
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18
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A Rare Case of Pembrolizumab-Induced Reactivation of Hepatitis B. Case Rep Oncol Med 2018; 2018:5985131. [PMID: 30416833 PMCID: PMC6207901 DOI: 10.1155/2018/5985131] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2018] [Revised: 09/06/2018] [Accepted: 09/27/2018] [Indexed: 02/07/2023] Open
Abstract
Hepatitis B virus (HBV) infection is common across the world, especially in Asia, Africa, Southern Europe, and Latin America. The association of HBV infection in patients suffering from different oncological conditions is well established. Many cases of HBV reactivation have been reported in patients on immunosuppressive chemotherapy and in patients undergoing hematopoietic bone marrow transplantations. Only one case has been reported so far of HBV reactivation in a patient treated with programmed cell death receptor 1 (PD-1) checkpoint inhibitors in the setting of HIV status. We report a case of a 51-year-old male, former smoker, diagnosed with stage IV poorly differentiated adenocarcinoma of the lung, and started on pembrolizumab, who developed reactivation of chronic hepatitis requiring antiviral therapy.
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19
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Yeo SJ, Lee HS, Jang BI, Kim ES, Jeon SW, Kim SK, Kim KO, Lee YJ, Lee HJ, Park KS, Jung YJ, Kim EY, Yang CH. Nonimmunity against hepatitis B virus infection in patients newly diagnosed with inflammatory bowel disease. Intest Res 2018; 16:400-408. [PMID: 30090039 PMCID: PMC6077318 DOI: 10.5217/ir.2018.16.3.400] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/06/2017] [Revised: 01/15/2018] [Accepted: 01/16/2018] [Indexed: 12/16/2022] Open
Abstract
Background/Aims This study aimed to elucidate the prevalence of hepatitis B virus (HBV) serologic markers in Korean patients newly diagnosed with, but not yet treated for inflammatory bowel disease (IBD). Methods We prospectively enrolled 210 patients newly diagnosed with IBD (109 with ulcerative colitis and 101 with Crohn's disease). Hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (anti-HBs), and hepatitis B core antibody (anti-HBc) levels were measured and compared with those of 1,100 sex- and age-matched controls. Results The prevalence of chronic HBV infection (positive HBsAg, positive anti-HBc, and negative anti-HBs results) and past infection (negative HBsAg, positive anti-HBc, and positive or negative anti-HBs results) were not significantly different between the patients and controls (chronic HBV infection: IBD, 3.8% vs. control, 4.9%, P=0.596; past infection: IBD, 26.2% vs. control, 28.8%, P=0.625). The patients with IBD aged <20 years were at a higher susceptibility risk (nonimmune) for HBV infection than the controls (IBD, 41.5% vs. control, 22.4%; P=0.018). In the multivariate analysis, an age of <20 years (P=0.024) and symptom duration of ≥12 months before diagnosis (P=0.027) were identified as independent risk factors for nonimmunity against HBV infection. Conclusions The patients newly diagnosed with IBD were susceptible to HBV infection. The frequency of nonimmunity was high, especially in the patients aged <20 years and those with a longer duration of symptoms before diagnosis. Therefore, it is necessary to screen for HBV serologic markers and generate a detailed vaccination plan for patients newly diagnosed with IBD.
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Affiliation(s)
- Seong Jae Yeo
- Department of Internal Medicine, Kyungpook National University Hospital, School of Medicine, Kyungpook National University, Daegu, Korea
| | - Hyun Seok Lee
- Department of Internal Medicine, Kyungpook National University Hospital, School of Medicine, Kyungpook National University, Daegu, Korea
| | - Byung Ik Jang
- Department of Internal Medicine, Yeungnam University College of Medicine, Daegu, Korea
| | - Eun Soo Kim
- Department of Internal Medicine, Kyungpook National University Hospital, School of Medicine, Kyungpook National University, Daegu, Korea
| | - Seong Woo Jeon
- Department of Internal Medicine, Kyungpook National University Hospital, School of Medicine, Kyungpook National University, Daegu, Korea
| | - Sung Kook Kim
- Department of Internal Medicine, Kyungpook National University Hospital, School of Medicine, Kyungpook National University, Daegu, Korea
| | - Kyeong Ok Kim
- Department of Internal Medicine, Yeungnam University College of Medicine, Daegu, Korea
| | - Yoo Jin Lee
- Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Korea
| | - Hyun Jik Lee
- Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Korea
| | - Kyung Sik Park
- Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Korea
| | - Yun Jin Jung
- Department of Internal Medicine, Daegu Fatima Hospital, Daegu, Korea
| | - Eun Young Kim
- Department of Internal Medicine, Catholic University of Daegu School of Medicine, Daegu, Korea
| | - Chang Heon Yang
- Department of Internal Medicine, Dongguk University School of Medicine, Gyeongju, Korea
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20
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Francisci D, Falcinelli F, Schiaroli E, Capponi M, Belfiori B, Cecchini E, Baldelli F. Reactivation of Hepatitis B Virus Replication Due to Cytotoxic Therapy: A Five-Year Prospective Study. TUMORI JOURNAL 2018; 98:220-4. [DOI: 10.1177/030089161209800207] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/28/2023]
Abstract
Background and aims In hepatitis B virus (HBV) carriers receiving chemotherapy, the risk of reactivation is high, particularly if rituximab is given alone or in combination with steroids. The aim of this study was to assess the incidence, prevalence, and clinical course of HBV infection in a cohort of patients with hematological malignancies receiving cytotoxic therapy as well as to propose a strategy for managing HBV reactivation. Methods This is a prospective observational study. All consecutive patients with hematological malignancies receiving intravenous cytotoxic chemotherapy between October 2005 and June 2010 and followed up for at least six months were enrolled in the study. Viral hepatitis markers and liver function indexes were monitored prospectively. Results We enrolled 478 patients, including 263 males (55%) and 465 (97.3%) Italians. Non-Hodgkin's lymphoma was the most frequent diagnosis (66%). At least one HBV marker was positive in 96 patients (20%): 21 (4.4%) patients were HBsAg positive, 17 (3.5%) were anti-HBc positive, and 58 (12.1%) were anti-HBc/anti-HBs positive. All but one HBsAg-positive patient received therapy with nucleoside/nucleotide analogs prior to chemotherapy. All but three reached complete virological suppression at six months from the start of treatment. Of the 17 HBsAg-negative/anti-HBc-positive patients, three (18%) had reactivation with seroreversion. All three obtained viral suppression with adefovir. Regarding the 58 anti-HBc/anti-HBs-positive patients, two (3.4%) experienced seroreversion and were treated successfully with nucleoside analogs; both were taking rituximab. No severe ALT flares were observed during or after antiviral therapy. Conclusion Our data suggest that pre-treatment screening of patients at risk of viral reactivation yields benefit and therefore should be practiced by clinicians treating patients with malignancies.
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Affiliation(s)
- Daniela Francisci
- Section of Infectious Diseases, Department of Experimental Medicine and Biochemical Sciences, Department of Clinical and Experimental Medicine, University of Perugia, Perugia, Italy
| | - Flavio Falcinelli
- Section of Hematology and Clinical Immunology, Department of Clinical and Experimental Medicine, University of Perugia, Perugia, Italy
| | - Elisabetta Schiaroli
- Section of Infectious Diseases, Department of Experimental Medicine and Biochemical Sciences, Department of Clinical and Experimental Medicine, University of Perugia, Perugia, Italy
| | - Monia Capponi
- Section of Hematology and Clinical Immunology, Department of Clinical and Experimental Medicine, University of Perugia, Perugia, Italy
| | - Barbara Belfiori
- Section of Infectious Diseases, Department of Experimental Medicine and Biochemical Sciences, Department of Clinical and Experimental Medicine, University of Perugia, Perugia, Italy
| | - Enisia Cecchini
- Section of Infectious Diseases, Department of Experimental Medicine and Biochemical Sciences, Department of Clinical and Experimental Medicine, University of Perugia, Perugia, Italy
| | - Franco Baldelli
- Section of Infectious Diseases, Department of Experimental Medicine and Biochemical Sciences, Department of Clinical and Experimental Medicine, University of Perugia, Perugia, Italy
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21
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The Clinical Spectrum of Hepatic Manifestations in Chronic Lymphocytic Leukemia. CLINICAL LYMPHOMA MYELOMA & LEUKEMIA 2017; 17:863-869. [DOI: 10.1016/j.clml.2017.07.008] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/08/2017] [Accepted: 07/19/2017] [Indexed: 12/18/2022]
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Choi J, Lim YS. Characteristics, Prevention, and Management of Hepatitis B Virus (HBV) Reactivation in HBV-Infected Patients Who Require Immunosuppressive Therapy. J Infect Dis 2017; 216:S778-S784. [PMID: 29156044 DOI: 10.1093/infdis/jix178] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Hepatitis B virus (HBV) reactivation becomes a challenging issue with increasing use of immunosuppressive agents and cytotoxic chemotherapy for varied medical conditions, including cancer. The spectrum of HBV reactivation in the setting of immunosuppression may vary from asymptomatic reactivation to liver failure leading to death. HBV reactivation can hamper the course of planned therapies and diminish the effects of therapies; thus, it adversely affects the prognosis of the original disease and the survival of the patients. There is mounting evidence that HBV reactivation can be prevented and managed if patients are screened to determine their risk for HBV reactivation and are treated prophylactically before therapy with immunosuppressive agents or cytotoxic chemotherapy is initiated. In this article, we review the diagnostic criteria and clinical outcomes of HBV reactivation, discuss how immunosuppressive therapy may influence the risk of HBV reactivation, and outline strategies to prevent HBV reactivation.
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Affiliation(s)
- Jonggi Choi
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Young-Suk Lim
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
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23
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Chang CS, Tsai CY, Yan SL. Hepatitis B reactivation in patients receiving targeted therapies. Hematology 2017; 22:592-598. [DOI: 10.1080/10245332.2017.1321882] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Affiliation(s)
- Cheng-Shyong Chang
- Division of Hematology and Oncology, Department of Internal Medicine, Changhua Christian Hospital, Changhua City, Taiwan
| | - Chien-Yu Tsai
- Division of Hematology and Oncology, Department of Internal Medicine, Changhua Christian Hospital, Changhua City, Taiwan
| | - Sheng-Lei Yan
- Division of Gastroenterology, Department of Internal Medicine, Chang-Bing Show Chwan Memorial Hospital, Lugang Township, Taiwan
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24
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Prevalence of hepatitis B and C and factors for infection and nonimmune in inflammatory bowel disease patients in China. Eur J Gastroenterol Hepatol 2017; 29:509-515. [PMID: 28350740 DOI: 10.1097/meg.0000000000000838] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
OBJECTIVE The aims of this study were to investigate the prevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection in inflammatory bowel disease (IBD) patients and the risk factors related to the infection and nonimmune status. METHODS A retrospective study was carried out at two clinical centers. The prevalence of viral markers and risk factors related to HBV and HCV infection and nonimmune status were analyzed in IBD patients. Age-matched and sex-matched healthy individuals were recruited as the controls. RESULTS A total of 980 IBD patients were included in this study. Present and past HBV infection was detected in 41.21% of the IBD group, which was higher than that in the general population (P=0.003). Age older than 30 years (P=0.000), ulcerative colitis (P=0.002), and previous surgery (P=0.039) were found to be significant risk factors for HBV infection in the multivariate analysis. 36.43% of the patients in the IBD group had nonimmune status against HBV, and age less than 40 years (P=0.011) and Crohn's disease (P=0.002) were identified as independent risk factors in the multivariate analysis. The prevalence of HCV infection was low and similar to that of the general population. CONCLUSION The prevalence of HBV infection in IBD patients in China was higher than that in Europe, USA, and the general population in China, but the prevalence of HCV infection in IBD patients was similar to that in the general population in this study. The frequency of nonimmune status against HBV was high, especially in young Crohn's disease patients, and HBV vaccination should be intensified and have a targeted coverage.
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25
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Ozoya OO, Chavez J, Sokol L, Dalia S. Optimizing antiviral agents for hepatitis B management in malignant lymphomas. ANNALS OF TRANSLATIONAL MEDICINE 2017; 5:39. [PMID: 28251118 DOI: 10.21037/atm.2016.12.25] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
The global scale of hepatitis B infection is well known but its impact is still being understood. Missed hepatitis B infection impacts lymphoma therapy especially increased risk of hepatitis B virus (HBV) reactivation and poor treatment outcomes. The presence of undiagnosed chronic hepatitis also undermines chronic HBV screening methods that are based on a positive HBsAg alone. The goal of this review is to evaluate the literature for optimizing antiviral therapy for lymphoma patients with HBV infection or at risk of HBV reactivation. Relevant articles for this review were identified by searching PubMed, Embase, Ovid Medline, and Scopus using the following terms, alone and in combination: "chronic hepatitis B", "occult hepatitis B", "special groups", "malignant lymphoma", "non-Hodgkin's lymphoma", "Hodgkin's lymphoma", "immunocompromised host", "immunosuppressive agents", "antiviral", "HBV reactivation". The period of the search was restricted to a 15-year period to limit the search to optimizing antiviral agents for HBV infection in malignant lymphomas [2001-2016]. Several clinical practice guidelines recommend nucleos(t)ide analogues-entecavir, tenofovir and lamivudine among others. These agents are best initiated along with or prior to immunosuppressive therapy. Additional methods recommended for optimizing antiviral therapy include laboratory modalities such as HBV genotyping, timed measurements of HBsAg and HBV DNA levels to measure and predict antiviral treatment response. In conclusion, optimizing antiviral agents for these patients require consideration of geographic prevalence of HBV, cost of antiviral therapy or testing, screening modality, hepatitis experts, type of immunosuppressive therapy and planned duration of therapy.
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Affiliation(s)
| | - Julio Chavez
- Department of Hematological Malignancies, H. Lee Moffitt Cancer Center, Tampa, FL, USA
| | - Lubomir Sokol
- Department of Hematological Malignancies, H. Lee Moffitt Cancer Center, Tampa, FL, USA
| | - Samir Dalia
- Oncology and Hematology, Mercy Clinic Joplin, Joplin, MO, USA
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26
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Law MF, Ho R, Cheung CKM, Tam LHP, Ma K, So KCY, Ip B, So J, Lai J, Ng J, Tam THC. Prevention and management of hepatitis B virus reactivation in patients with hematological malignancies treated with anticancer therapy. World J Gastroenterol 2016; 22:6484-6500. [PMID: 27605883 PMCID: PMC4968128 DOI: 10.3748/wjg.v22.i28.6484] [Citation(s) in RCA: 65] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/01/2016] [Revised: 05/24/2016] [Accepted: 06/15/2016] [Indexed: 02/06/2023] Open
Abstract
Hepatitis due to hepatitis B virus (HBV) reactivation can be severe and potentially fatal, but is preventable. HBV reactivation is most commonly reported in patients receiving cancer chemotherapy, especially rituximab-containing therapy for hematological malignancies and those receiving stem cell transplantation. 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 (anti-HBc). Patients found to be positive for HBsAg should be given prophylactic antiviral therapy to prevent HBV reactivation. For patients with resolved HBV infection, no standard strategy has yet been established to prevent HBV reactivation. There are usually two options. One is pre-emptive therapy guided by serial HBV DNA monitoring, whereby antiviral therapy is given as soon as HBV DNA becomes detectable. However, there is little evidence regarding the optimal interval and period of monitoring. An alternative approach is prophylactic antiviral therapy, especially for patients receiving high-risk therapy such as rituximab, newer generation of anti-CD20 monoclonal antibody, obinutuzumab or hematopoietic stem cell transplantation. This strategy may effectively prevent HBV reactivation and avoid the inconvenience of repeated HBV DNA monitoring. Entecavir or tenofovir are preferred over lamivudine as prophylactic therapy. Although there is no well-defined guideline on the optimal duration of prophylactic therapy, there is growing evidence to recommend continuing prophylactic antiviral therapy for at least 12 mo after cessation of chemotherapy, and even longer for those who receive rituximab or who had high serum HBV DNA levels before the start of immunosuppressive therapy. Many novel agents have recently become available for the treatment of hematological malignancies, and these agents may be associated with HBV reactivation. Although there is currently limited evidence to guide the optimal preventive measures, we recommend antiviral prophylaxis in HBsAg-positive patients receiving novel treatments, especially the Bruton tyrosine kinase inhibitors and the phosphatidylinositol 3-kinase inhibitors, which are B-cell receptor signaling modulators and reduce proliferation of malignant B-cells. Further studies are needed to clarify the risk of HBV reactivation with these agents and the best prophylactic strategy in the era of targeted therapy for hematological malignancies.
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Ozoya OO, Sokol L, Dalia S. Hepatitis B Reactivation with Novel Agents in Non-Hodgkin's Lymphoma and Prevention Strategies. J Clin Transl Hepatol 2016; 4:143-50. [PMID: 27350944 PMCID: PMC4913070 DOI: 10.14218/jcth.2016.00005] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/13/2016] [Revised: 04/25/2016] [Accepted: 04/26/2016] [Indexed: 12/12/2022] Open
Abstract
Hepatitis B virus (HBV) infection remains an endemic disease in most parts of the world despite available prophylactic vaccines. Non-Hodgkin's lymphoma is the most common hematological malignancy, and certain patients undergoing therapy are at increased risk of HBV reactivation. Rituximab, a monoclonal antibody, is well studied in HBV reactivation, but newer agents have been implicated as well. Here, we review novel agents suspected in HBV reactivation and effective strategies to prevent HBV reactivation. Fifteen years of literature were reviewed in order to better understand the reactivation rates of hepatitis B in patients with non-Hodgkin's lymphoma. Anti-CD20 antibodies continue to be the main medications that can lead to HBV reactivation, and HBV reactivation rates have decreased with increased awareness. HBV reactivation is uncommon when using other novel agents. Entecavir and lamivudine remain the agents of choice to prevent HBV reactivation in high risk patients. In conclusion, the immunosuppressive effect of NHL and its therapy provide a pathway for HBV reactivation, especially in patients treated with anti-CD20 antibody. Since many HBV positive patients are often excluded from clinical trials of novel agents in NHL, more aggressive post-market surveillance of new agents, well-designed best practice advisories, and timely case reports are needed to reduce the incidence of HBV reactivation. Lastly, large prospective investigations coupled with well-utilized best practice advisories need to be conducted to understand the impact of more potent novel NHL therapy on HBV reactivation.
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Affiliation(s)
| | - Lubomir Sokol
- Department of Hematological Malignancies, H. Lee Moffitt Cancer Center, Tampa, FL, USA
| | - Samir Dalia
- Oncology and Hematology, Mercy Clinic Joplin, Joplin, MO, USA
- *Correspondence to: Samir Dalia, Oncology and Hematology, Mercy Clinic Joplin, 100 Mercy Way, Joplin, MO 64804, USA. Tel: +1-417-782-7722, Fax: +1-417-556-3063, E-mail: or
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Abstract
INTRODUCTION Understanding the mechanism of DILI with MTA, and how to avoid and manage these toxicities is essential for minimising inferior cancer treatment outcomes. An organised and comprehensive overview of MTA-associated hepatotoxicity is lacking; this review aims to fill the gap. AREAS COVERED A literature review was performed based on published case reports and relevant studies or articles pertaining to the topics on PubMed. Food and Drug Administration drug information documents and search on the US National Library of Medicine LiverTox database was performed for all relevant MTA. EXPERT OPINION MTA-associated hepatotoxicity is common but rarely fatal. The pattern of hepatotoxicity is predominantly idiosyncratic. Pharmacogenomics show potential in predicting patients at risk of poorly metabolising or developing immunoallergic responses to MTA, but prospective data is scant. Preventing reactivation of viral hepatitis using anti-viral drugs, and avoidance of drug combinations at high risk of negative interactions are the most readily preventable measures for DILI.
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Affiliation(s)
- Kirsty Wai-Chung Lee
- a Sir YK Pao Center for Cancer, Department of Clinical Oncology, State Key Laboratory in Oncology in South China , The Chinese University of Hong Kong, Hong Kong Cancer Institute and Prince of Wales Hospital , Shatin , Hong Kong
| | - Stephen Lam Chan
- a Sir YK Pao Center for Cancer, Department of Clinical Oncology, State Key Laboratory in Oncology in South China , The Chinese University of Hong Kong, Hong Kong Cancer Institute and Prince of Wales Hospital , Shatin , Hong Kong.,b Institute of Digestive Disease , The Chinese University of Hong Kong , Shatin , Hong Kong
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Viganò M, Serra G, Casella G, Grossi G, Lampertico P. Reactivation of hepatitis B virus during targeted therapies for cancer and immune-mediated disorders. Expert Opin Biol Ther 2016; 16:917-26. [PMID: 27088278 DOI: 10.1080/14712598.2016.1177017] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
INTRODUCTION Targeted therapies have gained popularity in the treatment of several oncologic and immune-mediated diseases. Immunosuppression caused by these drugs has been associated to reactivation of hepatitis B virus (HBV) in both hepatitis B surface antigen (HBsAg) positive patients (overt infection) and HBsAg negative/anti-hepatitis B core antigen (anti-HBc) positive carriers (resolved infection), leading to premature discontinuation of therapy and potentially fatal hepatitis. AREAS COVERED This review summarizes the evidence of HBV reactivation in patients with overt or resolved HBV infection undergoing targeted therapies for cancer or immune-mediated disorders, providing recommendations for the management of these patients. EXPERT OPINION The risk of HBV reactivation relies on the immunosuppressive potency and duration of these therapies, the underlying disease and the virological patient's profile. However, HBV reactivation is preventable by screening for HBV markers in all patients scheduled to receive targeted therapies, assessing the virological profile and patient's clinical state, followed by appropriate antiviral treatment or prophylaxis in those patients at high risk of HBV reactivation. Close monitoring of HBV carriers at low risk of reactivation is warranted with the aim to start antiviral therapy as soon as HBV reactivates.
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Affiliation(s)
- Mauro Viganò
- a Hepatology Unit, Ospedale San Giuseppe , Università di Milano , Milan , Italy
| | | | | | - Glenda Grossi
- c A.M. and A. Migliavacca" Center for Liver Disease, Division of Gastroenterology and Hepatology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico , Università di Milano , Milan , Italy
| | - Pietro Lampertico
- c A.M. and A. Migliavacca" Center for Liver Disease, Division of Gastroenterology and Hepatology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico , Università di Milano , Milan , Italy
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Mallet V, van Bömmel F, Doerig C, Pischke S, Hermine O, Locasciulli A, Cordonnier C, Berg T, Moradpour D, Wedemeyer H, Ljungman P. Management of viral hepatitis in patients with haematological malignancy and in patients undergoing haemopoietic stem cell transplantation: recommendations of the 5th European Conference on Infections in Leukaemia (ECIL-5). THE LANCET. INFECTIOUS DISEASES 2016; 16:606-617. [PMID: 27599653 DOI: 10.1016/s1473-3099(16)00118-3] [Citation(s) in RCA: 103] [Impact Index Per Article: 11.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/07/2015] [Revised: 02/11/2016] [Accepted: 02/12/2016] [Indexed: 12/24/2022]
Abstract
Viral hepatitis affects millions of people worldwide, and host immunity is the key determinant of patient outcome. Viral hepatitis can be life threatening in patients with haematological malignancy, including haemopoietic stem cell transplant recipients, because of the virus itself, or through a need to decrease the dose of chemotherapy. A past or currently infected haemopoietic stem cell donor could also transmit viral hepatitis. The burden of viral hepatitis in patients with haematological malignancies and the weak evidence on which previous guidelines are based has prompted the European Conference on Infection in Leukaemia (ECIL-5) to convene a group of experts in the fields of viral hepatitis and of haematological malignancy to specifically address previously unconsidered issues and grade the available quality of evidence according to the Infectious Diseases Society of America grading system. The group recommends that all patients should be screened for hepatotropic viruses before haematological treatment and that patients or haemopoietic stem cell donors with markers of past or current viral hepatitis should be assessed by an expert. Screening, vaccination, and treatment rules are reported in this Review.
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Affiliation(s)
- Vincent Mallet
- Université Paris Descartes, Sorbonne Paris Cité, Paris, France; Institut Pasteur, Institut National de la Santé et de la Recherche Médicale Unité 1223, Paris, France; Hepatology Service, Assistance Publique-Hôpitaux de Paris, Groupe Hospitalier Cochin Port-Royal, Paris, France.
| | | | - Christopher Doerig
- Division of Gastroenterology and Hepatology, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne, Switzerland
| | - Sven Pischke
- University Medical Center Hamburg-Eppendorf, First Department of Medicine, Hamburg, Germany
| | - Olivier Hermine
- Department of Haematology, Paris Descartes University, Imagine Institute, Necker Hospital, Paris, France
| | - Anna Locasciulli
- Ematologia e Trapianto di Midollo, Ospedale SanCamillo, Roma, Italia
| | - Catherine Cordonnier
- Haematology Department, Henri Mondor Hospital, Assistance Publique-Hôpitaux de Paris, and Paris-Est Créteil University, Créteil, France
| | - Thomas Berg
- Hepatology Section, University Hospital Leipzig, Leipzig, Germany
| | - Darius Moradpour
- Division of Gastroenterology and Hepatology, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne, Switzerland
| | | | - Per Ljungman
- Karolinska University Hospital, Department of Haematology and Karolinska Institutet, Department of Medicine, Huddinge, Stockholm, Sweden
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Phipps C, Chen Y, Tan D. Lymphoproliferative Disease and Hepatitis B Reactivation: Challenges in the Era of Rapidly Evolving Targeted Therapy. CLINICAL LYMPHOMA MYELOMA & LEUKEMIA 2015; 16:5-11. [PMID: 26705677 DOI: 10.1016/j.clml.2015.11.009] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Received: 07/23/2015] [Revised: 10/27/2015] [Accepted: 11/12/2015] [Indexed: 12/14/2022]
Abstract
Reactivation of hepatitis B virus (HBV) is a known complication that occurs in patients receiving chemotherapy especially for malignant lymphoma. The increased risk in lymphoma patients parallels the potency of the immunosuppressive treatment regimens that are provided. B-cell-depleting therapy such as anti-CD20 monoclonal antibodies, especially when combined with conventional chemotherapy, significantly increases the risk of HBV reactivation, even in patients with resolved HBV infection. The first reports of HBV reactivation with anti-CD20 therapy emerged only 4 years after its US Food and Drug Administration approval. Today, these drugs carry alert warnings on the risk of hepatic dysfunction and reactivation of HBV infection. Many other new/novel agents active against lymphoma have emerged since then, targeting the different pathways involved in lymphoma pathogenesis, including histone deacetylase inhibitors, antibody-drug conjugates, and proteasome inhibitors. These various drugs have differing depths and mechanisms of immunosuppression, necessitating due diligence when administrating these compounds to prevent infective complications such as HBV reactivation, which can lead to liver failure and death. This review focuses on HBV reactivation with non-Hodgkin lymphoma treatment, in particular with the various approved novel agents. We also discuss the current recommendations for screening non-Hodgkin lymphoma patients for HBV and the role of prophylactic antiviral therapy during and after immunosuppressive treatment.
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Affiliation(s)
- Colin Phipps
- Department of Haematology, Singapore General Hospital, Singapore; Medicine Academic Clinical Programme, DUKE-NUS Graduate Medical School, Singapore.
| | - Yunxin Chen
- Department of Haematology, Singapore General Hospital, Singapore
| | - Daryl Tan
- Department of Haematology, Singapore General Hospital, Singapore; Raffles Cancer Centre, Raffles Hospital, Singapore
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Laurenti L, Autore F, Innocenti I, Vannata B, Piccirillo N, Sorà F, Speziale D, Pompili M, Efremov D, Sica S. Prevalence, characteristics and management of occult hepatitis B virus infection in patients with chronic lymphocytic leukemia: a single center experience. Leuk Lymphoma 2015; 56:2841-6. [PMID: 25682966 DOI: 10.3109/10428194.2015.1017822] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Several reports have emphasized the risk of hepatitis B virus (HBV) reactivation in patients with lymphoproliferative disorders undergoing cytotoxic treatment. To determine the prevalence of occult B infection (OBI) in a population with chronic lymphocytic leukemia (CLL) and management with universal prophylaxis (UP) in all patients undergoing chemoimmunotherapy or targeted prophylaxis (TP) in patients experiencing seroreversion during therapy, we analyzed 397 patients with CLL from our database. The prevalence of OBI in our patients with CLL was 8.6% (34 patients). When comparing patients with OBI/CLL with those with CLL, we did not find any statistical difference among clinical-biological parameters and time dependent endpoints except for a lower peripheral blood lymphocyte count in the OBI/CLL group (p = 0.036). From 2000 to 2010 careful follow-up and TP were adopted; two out of 10 patients (20%) showed seroreversion. From June 2010 we adopted UP during and 12 months after immunosuppressive treatment in all patients with CLL with OBI; no evidence of seroreversion was detected.
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Affiliation(s)
- Luca Laurenti
- a Department of Hematology , Catholic University of the Sacre Heart , Rome , Italy
| | - Francesco Autore
- a Department of Hematology , Catholic University of the Sacre Heart , Rome , Italy
| | - Idanna Innocenti
- a Department of Hematology , Catholic University of the Sacre Heart , Rome , Italy
| | - Barbara Vannata
- a Department of Hematology , Catholic University of the Sacre Heart , Rome , Italy
| | - Nicola Piccirillo
- a Department of Hematology , Catholic University of the Sacre Heart , Rome , Italy
| | - Federica Sorà
- a Department of Hematology , Catholic University of the Sacre Heart , Rome , Italy
| | - Domenico Speziale
- b Department of Laboratory Medicine , Catholic University of the Sacre Heart , Rome , Italy
| | - Maurizio Pompili
- c Internal Medicine, Catholic University of the Sacre Heart , Rome , Italy
| | - Dimitar Efremov
- d ICGEB Outstation-Monterotondo, CNR Campus "A. Buzzati-Traverso" , Rome , Italy
| | - Simona Sica
- a Department of Hematology , Catholic University of the Sacre Heart , Rome , Italy
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Entecavir as a first-line treatment for hepatitis B virus reactivation following polychemotherapy for chronic lymphocytic leukemia and invasive ductal carcinoma: a report of two cases and review of the literature. Eur J Gastroenterol Hepatol 2015; 27:39-45. [PMID: 25076063 DOI: 10.1097/meg.0000000000000115] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
OBJECTIVE Hepatitis B reactivation has been reported in chronic carriers of hepatitis B [hepatitis B surface antigen (HBsAg)] or in patients with prior hepatitis B virus (HBV) infection who are HBsAg-negative and have antibodies against hepatitis B core antigen (anti-HBc) with or without antibodies to HBsAg (anti-HBs). Lamivudine has been the first and commonly used nucleoside analog to inhibit HBV replication; however, prolonged therapy has been associated with an increased risk for drug-resistant mutations and mortality rates. Entecavir, a deoxyguanosine analog, offers several advantages over lamivudine for the treatment of HBV reactivation following chemotherapy while exhibiting more potent antiviral activity and a lower resistance rate. METHODS Herein, we report rapid and sustained suppression of polychemotherapy-related HBV reactivation by entecavir administered as a prompt antiviral therapy in the cases of two patients with chronic lymphocytic leukemia and invasive ductal carcinoma. A review of the literature is discussed. RESULTS Entecavir produced a rapid and sustained suppression of polychemotherapy-related HBV reactivation as a prompt antiviral therapy in the cases of two patients with chronic lymphocytic leukemia and invasive ductal carcinoma. CONCLUSION Allowing a rapid and sustained control of HBV replication, entecavir seems to be a promising drug for first-line prompt treatment of HBV reactivation in patients undergoing chemotherapy for hematological as well as solid organ malignancies, with safe long-term use enabling maintenance of resolved hepatitis.
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Bojito-Marrero L, Pyrsopoulos N. Hepatitis B and Hepatitis C Reactivation in the Biologic Era. J Clin Transl Hepatol 2014; 2:240-6. [PMID: 26355300 PMCID: PMC4548361 DOI: 10.14218/jcth.2014.00033] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/02/2014] [Revised: 12/02/2014] [Accepted: 12/08/2014] [Indexed: 02/07/2023] Open
Abstract
Hepatitis B (HBV) and hepatitis C (HCV) reactivation may occur after the use of biologic agents. During the last decade, utilization of biologics has changed the fate of many treated for cancer, autoimmune and connective tissue disease, maintenance of transplanted organs, and the prevention of graft-versus-host disease among others. HBV reactivation has been reported in up to 50% of HBV carriers undergoing immunosuppressive therapy, and there is emerging data pointing towards an increased risk for HCV reactivation. If reactivation of HBV and HCV occurs, the spectrum of clinical manifestations can range from asymptomatic hepatitis flares to hepatic decompensation, fulminant hepatic failure, and death. Therefore, identifying patients at risk and early diagnosis are imperative to decrease significant morbidity and mortality. The purpose of this article is to review the pathophysiology of the reactivation of HBV and HCV infection in patients receiving biologic therapies and the approaches used to diagnose, prevent, and treat HBV and HCV reactivation.
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Affiliation(s)
| | - Nikolaos Pyrsopoulos
- Correspondence to: Nikolaos Pyrsopoulos, Division of Gastroenterology and Hepatology, Rutgers New Jersey Medical School, 185 South Orange Ave, MSB, Room H-536, Newark NJ 07101, USA. Tel: +01-973-972-5252, Fax: +01-973-972-3144. E-mail:
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Riveiro-Barciela M, Buti M. [Hepatitis B virus infection in pregnancy and the immunosuppressed patient]. GASTROENTEROLOGIA Y HEPATOLOGIA 2014; 38:31-9. [PMID: 25066320 DOI: 10.1016/j.gastrohep.2014.05.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/01/2014] [Revised: 05/15/2014] [Accepted: 05/20/2014] [Indexed: 10/25/2022]
Abstract
Hepatitis B virus (HBV) infection continues to be a major public health problem worldwide. Although treatment indications are well established in clinical practice guidelines, there are some risk groups, such as pregnant women and immunosuppressed patients, who require different and specific management of HBV infection. In pregnant women, treatment indication should be individualized and the risk of HBV transmission to the newborn evaluated because cases of vertical transmission continue to be reported, despite active and passive immunoprophylaxis. In patients receiving immunosuppressive therapy, HBV reactivation is associated with high morbidity and mortality, even in patients with past HBV infection, highlighting the importance of screening and the need to evaluate prophylactic therapy in some cases.
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Affiliation(s)
- Mar Riveiro-Barciela
- Servicio de Hepatología, Medicina Interna, Hospital Universitario Vall d'Hebron, Barcelona, España
| | - María Buti
- Servicio de Hepatología, Medicina Interna, Hospital Universitario Vall d'Hebron, Barcelona, España.
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Abstract
After hepatitis B virus (HBV) infection, HBV DNA persists in minute amounts in hepatocyte nuclei even in individuals with “resolved” infection. Viral replication and development of liver disease depend on the balance between viral mechanisms promoting persistence and host immune control. Patients with active or inactive disease or resolved HBV infection are at risk for reactivation with immunosuppressive therapy use. HBV reactivation varies from a clinically asymptomatic condition to one associated with acute liver failure and death. We review recent studies on HBV reactivation during immunomodulatory therapies for oncologic, gastroenterological, rheumatic, and dermatologic disorders. Risk calculation should be determined through HBV screening and assessment of immunosuppressive therapy potency. We also discuss monitoring for reactivation, prophylactic antiviral therapy, and treatment of reactivation. Prophylactic antiviral treatment is needed for all HBsAg carriers and selected patients who have anti-HBc without HBsAg and is critical for preventing viral reactivation and improving outcomes.
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Affiliation(s)
- Anil Seetharam
- Banner Transplant and Advanced Liver Disease Center, Phoenix, AZ USA ; University of Arizona College of Medicine, Phoenix, AZ USA
| | - Robert Perrillo
- Hepatology Division, Baylor University Medical Center, Dallas, TX USA ; Department of Internal Medicine, University of Texas Southwestern Medical School, Dallas, TX USA
| | - Robert Gish
- St. Joseph's Hospital Medical Center/Liver Center, Phoenix, AZ USA ; 6022 La Jolla Mesa Drive, San Diego, CA 92037 USA
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Yazici O, Şendur MAN, Aksoy S. Hepatitis C virus reactivation in cancer patients in the era of targeted therapies. World J Gastroenterol 2014; 20:6716-6724. [PMID: 24944464 PMCID: PMC4051913 DOI: 10.3748/wjg.v20.i22.6716] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/04/2013] [Revised: 12/26/2013] [Accepted: 03/05/2014] [Indexed: 02/06/2023] Open
Abstract
The purpose of this review is to summarize the evidence of hepatitis C reactivation in cancer patients in the era of targeted therapies. Targeted therapies are novel therapeutics frequently used in cancer patients. During treatment with targeted therapies, viral replication is one of the major problems that can occur. The PubMed database, ASCO, and ASCO Gastrointestinal Cancer Symposium abstracts were searched up until September 15, 2013 using the following search keywords: “targeted therapies, rituximab, alemtuzumab, brentuximab, hepatitis, hepatitis C reactivation, tyrosine kinase inhibitors, imatinib, mammalian target of rapamycin (mTOR) inhibitors, everolimus, anti-HER therapies, trastuzumab, pertuzumab, lapatinib, anti-epidermal growth factor receptor therapies, cetuximab, panitumumab, and ipilimumab”. Papers considered relevant for the aim of this review were selected by the authors. The data about rituximab-induced hepatic flare in hepatitis C virus (HCV) positive patients is controversial. However, there is the possibility of life-threatening hepatic flare that can develop after HCV ribonucleic acid (HCV-RNA) viral load increases. Routine follow-up of liver function tests should be advised. Especially in high-risk patients, such as those with baseline chronic active hepatitis and cirrhosis, and where there are plans to administer rituximab concomitantly with corticosteroids, it is advised to have close follow-up of HCV viral load. The data is insufficient to make accurate statements about the association of alemtuzumab therapy and HCV reactivation. However, alemtuzumab may cause deep immunosuppression. Due to this, it is better to follow up with liver function tests and HCV RNA levels during alemtuzumab therapy. Brentuximab has effects on antibody dependent cellular toxicity and may decrease humoral immunity. Thus, we believe that during brentuximab treatment of HCV infected patients, clinicians may encounter hepatitis C reactivation. There have been no reported cases of hepatitis C reactivation with imatinib therapy. However, there are many reports of hepatitis B reactivation with imatinib treatment. Based on the evidence of hepatitis B reactivation with imatinib and the effects of imatinib on immune system functions, we suggest that imatinib therapy might be a risk factor for HCV reactivation. Anti-human epidermal growth factor receptor 2 therapies are not associated with hepatic flare in HCV infected patients. Post-transplant studies reported that mTOR was safely administered to patients with active hepatitis C without causing hepatic flare. Cetuximab and panitumumab have not been associated with HCV reactivation. Two cases of HCV infected melanoma were safely treated with ipilimumab without any HCV reactivation or hepatic flare. Targeted therapies are a new and emerging area of oncology treatment modalities. While treating HCV infected cancer patients, clinicians should be mindful of the immunosuppressive properties of targeted therapies. Further randomized trials are needed to establish algorithms for this issue.
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Skupsky J, Hu KQ. Current hepatitis B treatment guidelines and future research directions. Front Med 2014; 8:145-57. [PMID: 24871443 DOI: 10.1007/s11684-014-0335-1] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2014] [Accepted: 03/12/2014] [Indexed: 12/18/2022]
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Huang ML, Xu XT, Shen J, Qiao YQ, Dai ZH, Ran ZH. Prevalence and factors related to hepatitis B and C infection in inflammatory bowel disease patients in China: a retrospective study. J Crohns Colitis 2014; 8:282-7. [PMID: 24067604 DOI: 10.1016/j.crohns.2013.08.017] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/09/2013] [Revised: 08/29/2013] [Accepted: 08/29/2013] [Indexed: 02/08/2023]
Abstract
OBJECTIVES The objectives of this retrospective study were to assess the prevalence of HBV and HCV infection in Chinese IBD patients, identify potential risk factors of the infection in this population, and discuss the prevalence of HBV and HCV in the general Chinese population. METHODS A total of 714 IBD patients who had been investigated for HBV and/or HCV infection were consecutively enrolled in the study. Clinical and laboratory data on IBD and hepatitis infection were collected. A control group of 22,373 healthy individuals was also included in the study. RESULTS Present and past HBV infection was found in 40.62% of IBD patients (ulcerative colitis: HBsAg+, 5.68%; anti-HBc+, 41.64%; Crohn's disease: HBsAg+, 5.29%; anti-HBc+, 39.80%;), and 27.58% of the non-IBD group (HBsAg+, 5.52%; anti-HBc+, 27.58% [P = 0.00]). HCV infection was found in 0.42% of IBD patients and 0.36% of the non-IBD group (P=0.80). One hundred and fifty-four of the IBD patients (21.57%) had been effectively vaccinated for HBV. In a multivariate analysis, age, family history of hepatitis B, and IBD-related admission were significantly related to HBV infection in IBD patients. Potential risk factors for HCV were not analyzed due to the limited number of HCV-positive patients in the study. CONCLUSIONS Prevalence of HBV infection in IBD patients was higher than that in the non-IBD patients, whereas prevalence of HCV infection was similar to that of the non-IBD group. Effective vaccination for HBV was present in only a small proportion of IBD patients.
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Affiliation(s)
- Mei Lan Huang
- Department of Gastroenterology, Renji Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai Institute of Digestive Disease, Shanghai Inflammatory Bowel Disease Research Center, 160# Pu Jian Ave., 200127 Shanghai, China
| | - Xi Tao Xu
- Department of Gastroenterology, Renji Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai Institute of Digestive Disease, Shanghai Inflammatory Bowel Disease Research Center, 160# Pu Jian Ave., 200127 Shanghai, China
| | - Jun Shen
- Department of Gastroenterology, Renji Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai Institute of Digestive Disease, Shanghai Inflammatory Bowel Disease Research Center, 160# Pu Jian Ave., 200127 Shanghai, China
| | - Yu Qi Qiao
- Department of Gastroenterology, Renji Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai Institute of Digestive Disease, Shanghai Inflammatory Bowel Disease Research Center, 160# Pu Jian Ave., 200127 Shanghai, China
| | - Zhang Han Dai
- Department of Gastroenterology, Renji Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai Institute of Digestive Disease, Shanghai Inflammatory Bowel Disease Research Center, 160# Pu Jian Ave., 200127 Shanghai, China
| | - Zhi Hua Ran
- Department of Gastroenterology, Renji Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai Institute of Digestive Disease, Shanghai Inflammatory Bowel Disease Research Center, 160# Pu Jian Ave., 200127 Shanghai, China.
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Abstract
Patients with chronic HBV infection are at risk of reactivation of HBV should they require immunosuppressive therapies for a variety of clinical settings, including chemotherapy for patients with cancer, immunosuppression for solid organ and stem cell transplant recipients, and use of anti-CD20 antibodies, TNF inhibitors, or corticosteroids in patients with oncological, gastrointestinal, rheumatological or dermatological conditions. The key to preventing HBV reactivation is the identification of patients with HBV infection prior to immunosuppressive therapy, initiation of prophylactic antiviral therapy in patients at moderate or high risk of HBV reactivation, and close monitoring of other patients so that antiviral therapy can be initiated at the first sign of HBV reactivation. Unfortunately, many patients infected with HBV are unaware of their infection or risk factors, and physicians often do not have sufficient time to systematically assess patients for risk factors for HBV prior to starting immunosuppressive therapy. In this article, we review the incidence, risk factors and outcomes of HBV reactivation, and the efficacy of antiviral therapy in preventing its occurrence. We also propose an algorithm for managing patients with HBV infection who require immunosuppressive therapy.
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Hwang JP, Fisch MJ, Lok ASF, Zhang H, Vierling JM, Suarez-Almazor ME. Trends in hepatitis B virus screening at the onset of chemotherapy in a large US cancer center. BMC Cancer 2013; 13:534. [PMID: 24209764 PMCID: PMC3827843 DOI: 10.1186/1471-2407-13-534] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2013] [Accepted: 10/31/2013] [Indexed: 12/21/2022] Open
Abstract
Background National organizations recommend screening for hepatitis B virus (HBV) before chemotherapy but differ regarding which patients should be screened. We aimed to determine contemporary screening rates at a cancer center and the possible influence on these rates of publication of national recommendations. Methods We conducted a retrospective cohort study of HBV screening in cancer patients registered during the period from January 2004 through April 2011. Screening was defined as HBsAg and anti-HBc tests ordered around the time of initial chemotherapy. We compared screening rates for 3 periods: January 1, 2004, through December 18, 2008 (Food and Drug Administration and American Association for the Study of Liver Diseases 2007 recommendations); December 19, 2008, through September 30, 2010 (Centers for Disease Control and Prevention, National Comprehensive Cancer Network, American Association for the Study of Liver Diseases 2009, Institute of Medicine, and American Society of Clinical Oncology recommendations); and October 1, 2010, through April 30, 2011. Logistic regression models were used to identify predictors of screening. Results Of 141,877 new patients, 18,688 received chemotherapy, and 3020 (16.2%) were screened. HBV screening rates increased over the 3 time periods (14.8%, 18.2%, 19.9%; P < 0.0001), but <19% of patients with HBV risk factors were screened. Among patients with hematologic malignancies, over 66% were screened, and odds of screening nearly doubled after publication of the recommendations (P < 0.0001). Less than 4% of patients with solid tumors were screened, although odds of screening increased 70% after publication of the recommendations (P = 0.003). Other predictors of screening included younger age, planned rituximab therapy, and known risk factors for HBV infection. Conclusions Most patients with solid tumors or HBV risk factors remained unscreened, although screening rates increased after publication of national recommendations. Efforts are needed to increase awareness of the importance of HBV screening before chemotherapy to identify patients who should start antiviral prophylaxis.
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Affiliation(s)
- Jessica P Hwang
- Department of General Internal Medicine, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd,, Unit 1465, Houston, Texas 77030, USA.
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Namberger K, Weiss L, Krause B, Melchardt T, Greil R. A case of long-term remission with ofatumumab maintenance therapy in multiply relapsed and rituximab-refractory chronic lymphocytic leukaemia with deletion 17p. Eur J Haematol 2013; 90:349-50. [DOI: 10.1111/ejh.12065] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Affiliation(s)
- Konrad Namberger
- 3rd Medical Department of Haematology; Medical Oncology, Haemostaseology, Rheumatology and Infectious Disease; Paracelsus Medical University; Salzburg, Austria Laboratory for Immunological and Molecular Cancer Research; Salzburg; Austria
| | - Lukas Weiss
- 3rd Medical Department of Haematology; Medical Oncology, Haemostaseology, Rheumatology and Infectious Disease; Paracelsus Medical University; Salzburg, Austria Laboratory for Immunological and Molecular Cancer Research; Salzburg; Austria
| | - Barbara Krause
- 3rd Medical Department of Haematology; Medical Oncology, Haemostaseology, Rheumatology and Infectious Disease; Paracelsus Medical University; Salzburg, Austria Laboratory for Immunological and Molecular Cancer Research; Salzburg; Austria
| | - Thomas Melchardt
- 3rd Medical Department of Haematology; Medical Oncology, Haemostaseology, Rheumatology and Infectious Disease; Paracelsus Medical University; Salzburg, Austria Laboratory for Immunological and Molecular Cancer Research; Salzburg; Austria
| | - Richard Greil
- 3rd Medical Department of Haematology; Medical Oncology, Haemostaseology, Rheumatology and Infectious Disease; Paracelsus Medical University; Salzburg, Austria Laboratory for Immunological and Molecular Cancer Research; Salzburg; Austria
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Wu C, Shi H, Lu M, Xu Y, Chen X. A case of hepatitis B reactivation in an anti-HBs positive, anti-HBc positive non-Hodgkin's lymphoma patient. Virol Sin 2013; 28:49-52. [PMID: 23385354 DOI: 10.1007/s12250-013-3285-x] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2012] [Accepted: 01/14/2013] [Indexed: 12/12/2022] Open
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Asahina Y, Izumi N, Oketani M, Kumada H, Kurosaki M, Koike K, Suzuki F, Takikawa H, Tanaka A, Tanaka E, Tanaka Y, Tsubouchi H, Hayashi N, Hiramatsu N, Yotsuyanagi H. Guidelines for the management of hepatitis B virus infection. ACTA ACUST UNITED AC 2013. [DOI: 10.2957/kanzo.54.402] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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Hwang JP, Vierling JM, Zelenetz AD, Lackey SC, Loomba R. Hepatitis B virus management to prevent reactivation after chemotherapy: a review. Support Care Cancer 2012; 20:2999-3008. [PMID: 22933131 PMCID: PMC3469760 DOI: 10.1007/s00520-012-1576-7] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2012] [Accepted: 08/13/2012] [Indexed: 12/11/2022]
Abstract
PURPOSE Reactivation of hepatitis B virus (HBV) infection after chemotherapy can lead to liver failure and death. Conflicting recommendations regarding HBV screening in cancer patients awaiting chemotherapy mean that some patients at risk for HBV reactivation are not being identified and treated with prophylactic antiviral therapy. METHODS We performed a narrative review of the existing evidence regarding screening for and management of HBV infection among patients with cancer using Ovid Medline, PubMed, and the Cochrane Library. RESULTS Our review showed inconsistencies in the definition and management strategies for HBV reactivation. The timeframe of reactivation is variable, and its molecular mechanisms are not clear. There are five effective antiviral agents that can be used as prophylaxis to prevent reactivation of HBV infection in cancer patients; however, the optimal drug and duration of therapy are unknown. Reactivation is more commonly reported in patients with hematologic malignancies receiving rituximab treatment, but reactivation can occur after other chemotherapies and in patients with solid tumors. Screening with all three screening tests-HBsAg, anti-HBc, and anti-HBs-allows the most thorough interpretation of a patient's serologic profile and assessment of reactivation risk; however, decision-making and cost-effectiveness studies are needed to determine optimal screening strategies. CONCLUSIONS Prevention of reactivation of HBV infection depends on identification of patients at risk and initiation of antiviral prophylaxis, but data to guide screening and treatment strategies are lacking. Additional research is necessary to accurately define and predict reactivation, identify best antiviral treatment strategies, and identify cost-effective HBV screening strategies.
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Affiliation(s)
- Jessica P Hwang
- The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
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Shiba S, Kondo S, Ueno H, Morizane C, Ikeda M, Okusaka T. Hepatitis B Virus Reactivation during Treatment with Multi-Tyrosine Kinase Inhibitor for Hepatocellular Carcinoma. Case Rep Oncol 2012; 5:515-9. [PMID: 23139664 PMCID: PMC3492963 DOI: 10.1159/000342913] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
Abstract
Hepatitis B virus (HBV) reactivation is well documented in individuals with cancer who receive certain cytotoxic or immunosuppressive therapies including rituximab treatment. As a general rule, the risk is greatest upon withdrawal of chemotherapy. The risk ranges from approximately 20 to 50% among HBsAg-positive carriers. A 67-year-old man was diagnosed with inoperable multiple hepatocellular carcinoma accompanied by an increase in alpha-fetoprotein and protein induced by vitamin K absence or antagonist II level. Eighteen weeks after starting on the oral multi-tyrosine kinase inhibitor TSU-68, laboratory investigations showed a substantial increase in serum transaminase levels (AST: 302 IU/l; ALT: 324 IU/l) and an elevation of the HBV-DNA level (6.9 log copies/ml). The diagnosis was that the cause of the acute hepatitis was HBV reactivation and we immediately administered entecavir. Two months after the initiation of daily entecavir treatment, laboratory findings showed that the serum levels of transaminases and ALP had improved (AST: 18 IU/l; ALT: 10 IU/l; ALP: 197 U/l). When the HBV markers were examined 4 months later, they were altered: HBeAg was negative and HBeAb was positive. Entecavir treatment was discontinued after 6 months. Although reactivation with rituximab has been reported, reactivation with a tyrosine kinase inhibitor is extremely unusual in a patient who is HBsAg negative but anti-HBc positive. This is the first report describing HBV reactivation with an increasing HBV-DNA level in a HBsAg-negative/HBcAb-positive/HBsAb-positive patient who was treated with TSU-68 for hepatocellular carcinoma.
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Affiliation(s)
- Satoshi Shiba
- Hepatobiliary and Pancreatic Oncology Division, National Cancer Center Hospital, Tokyo, Japan
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Occult Hepatitis B (OBH) in Clinical Settings. HEPATITIS MONTHLY 2012. [DOI: 10.5812/hapatmon.6126] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/13/2023]
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Alavian SM, Miri SM, Hollinger FB, Jazayeri SM. Occult Hepatitis B (OBH) in Clinical Settings. HEPATITIS MONTHLY 2012; 12:e6126. [PMID: 23087749 PMCID: PMC3475016 DOI: 10.5812/hepatmon.6126] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 05/20/2012] [Revised: 06/20/2012] [Accepted: 07/08/2012] [Indexed: 12/11/2022]
Abstract
CONTEXT Occult hepatitis B (OHB), or persistent HBV DNA in patients who are hepatitis B surface antigen (HBsAg) negative, is a recently recognized entity. In an attempt to summarize the issues, this review presents an overview of the current proposed hypothesis on the clinical relevance and also updates the knowledge on the classification of OHB in different clinical settings. EVIDENCE ACQUISITION OHB COULD BE FOUND IN DIFFERENT POPULATION AND CLINICAL BACKGROUNDS INCLUDING: viral co-infections (with either human immunodeficiency or hepatitis C viruses), HBV chronic carriers, dialysis patients, transplantation settings and certain clinical situations (named in here: special clinical settings) with no apparent distinguishable clinical parameters. RESULTS The exact magnitude, pathogenesis, and clinical relevance of OHB are unclear. Even the possible role exerted by this cryptic infection on liver disease outcome, and hepatocellular carcinoma development remains unknown. CONCLUSIONS Monitoring of Individuals with positive anti-HBc, mass immunization programs and improvement in diagnostic tools seem to be important to control the probability of transmission of HBV through cryptic HBV infection.
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Affiliation(s)
- Seyed Moayed Alavian
- Baqiyatallah Research Center for Gastroenterology and Liver Disease, Baqiyatallah University of Medical Sciences, Tehran, IR Iran
| | - Seyed Mohammad Miri
- Baqiyatallah Research Center for Gastroenterology and Liver Disease, Baqiyatallah University of Medical Sciences, Tehran, IR Iran
| | | | - Seyed Mohammad Jazayeri
- Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, IR Iran
- Corresponding author: Seyed Mohammad Jazayeri, Department of Virology, School of Public Health, Tehran University of Medical Sciences, P.O. Box: 15155-6446, Tehran, IR Iran.Tel.: +98-2188992660, Fax: +98-2188992660, E-mail:
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