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Lv W, Li X, Xu J, Wang Y, Huang H, Hu F, Cui Y, Song Y, Chen L, Wu B, Liang Y. Prognosis of hepatitis B virus reactivation in newly diagnosed multiple myeloma in modern era therapy: a retrospective study. PeerJ 2024; 12:e18475. [PMID: 39498289 PMCID: PMC11533906 DOI: 10.7717/peerj.18475] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2024] [Accepted: 10/16/2024] [Indexed: 11/07/2024] Open
Abstract
Studies on the prognosis of hepatitis B virus (HBV) reactivation following modern therapies for newly diagnosed MM (NDMM) are lacking. In this retrospective study, we aimed to assess the incidence, risk factors and prognosis of HBV reactivation in NDMM. A total of 33 of 355 patients with NDMM and HBV reactivation were included in this study. Multivariable analysis showed that hepatitis B surface antigen-positivity, hepatitis B core antibody-positivity, bortezomib-containing regimens, autologous stem cell transplantation, and gain of 1q21 were identified as independent risk factors of HBV reactivation in NDMM patients. The NDMM patients with HBV reactivation had poorer 3-year overall survival (OS) and progression-free survival (PFS) than did those without HBV reactivation, as confirmed by multivariate analysis. In conclusion, HBV reactivation in patients with NDMM constitutes a significant complication, correlating with reduced OS and PFS, and emerges as a potential adverse prognostic factor in the contemporary era of treatment.
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Affiliation(s)
- Weiran Lv
- Hematology, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Xiaojin Li
- Hematology, Faculty of Environmental Science and Engineering, Kunming University of Science and Technology, Kunming, China
| | - Jingbo Xu
- Hematology, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, China
| | - Yun Wang
- Hematology, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Hanying Huang
- Hematology, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Fang Hu
- Hematology, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Yingying Cui
- Hematology, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Yuanbin Song
- Hematology, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Lezong Chen
- Hematology, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Bingyi Wu
- Hematology, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Yang Liang
- Hematology, Sun Yat-sen University Cancer Center, Guangzhou, China
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Yi JH, Lee JL, Lee YJ, Kang HJ, Park YH, Yuh YJ, Lim SN, Kim HJ, Jung SH, Lee JJ, Cho HJ, Moon JH, Yhim HY, Kim K. Outcome of Multiple Myeloma Patients With Hepatitis B Surface Antigen: Korean Multiple Myeloma Working Party 2103 Study. CLINICAL LYMPHOMA, MYELOMA & LEUKEMIA 2024; 24:e50-e57.e2. [PMID: 37973459 DOI: 10.1016/j.clml.2023.10.004] [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: 08/30/2023] [Revised: 10/06/2023] [Accepted: 10/11/2023] [Indexed: 11/19/2023]
Abstract
BACKGROUND Hepatitis B virus reactivation (HBVr) is a well-known complication of systemic chemotherapy for particularly hematologic malignancies in HBV carriers. We performed a multicenter retrospective study to investigate the incidence and risk factors of HBVr in patients with hepatitis B surface antigen (HBsAg)-positive multiple myeloma (MM). METHODS We included 123 patients with HBsAg-positive MM who had received systemic therapy. The primary objective of the study was to evaluate the incidence of HBVr in patients with HBsAg-positive MM. RESULTS The median age was 59 years, and 72 patients were male. With a median follow-up duration of 41.4 months, there were 43 instances of HBVr in 35 patients (28.5%): 29 treatment-related HBVr occurred during 424 treatments. Treatments containing antiviral prophylaxis were associated with a significantly lower incidence of HBVr compared to those without (14.4% vs. 1.9%, P < 0.001). Moreover, treatment with cyclophosphamide (P = 0.002) and doxorubicin (P = 0.053) were risk factors for HBVr; stem cell transplantation was not associated with HBVr. There was no significant difference in overall survival between patients with and without HBVr (P = 0.753) and myeloma progression was the major cause of death. CONCLUSION Considering the low incidence of HBVr in patients who had received antiviral prophylaxis, HBsAg-positivity should not impede patients from receiving optimal antimyeloma treatment or participating in clinical trials.
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Affiliation(s)
- Jun Ho Yi
- Division of Hematology-Oncology, Department of Medicine, Chung-Ang University, Seoul, Korea
| | - Jung Lim Lee
- Department of Hemato-oncology, Daegu Fatima Hospital, Daegu, Korea
| | - Yoo Jin Lee
- Department of Hematology and Oncology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea
| | - Hye Jin Kang
- Division of Hematology/Oncology, Department of Internal Medicine, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences, Seoul, Korea
| | - Young Hoon Park
- Division of Hematology-Oncology, Department of Internal Medicine, Ewha Womans University College of Medicine, Seoul, Korea
| | - Young Jin Yuh
- Department of Internal Medicine, Sanggye-Paik Hospital, Inje University, Seoul, Korea
| | - Sung-Nam Lim
- Department of Internal Medicine, Haeundae Paik Hospital, Inje University College of Medicine, Busan, Korea
| | - Hyo Jung Kim
- Department of Internal Medicine, Hallym University Sacred Heart Hospital, Anyang, Korea
| | - Sung-Hoon Jung
- Department of Hematology-Oncology, Chonnam National University Hwasun Hospital and Chonnam National University Medical School, Hwasun-gun, Jeollanam-do, Korea
| | - Je-Jung Lee
- Department of Hematology-Oncology, Chonnam National University Hwasun Hospital and Chonnam National University Medical School, Hwasun-gun, Jeollanam-do, Korea
| | - Hee Jeong Cho
- Department of Hematology-Oncology, Kyungpook National University Hospital, Kyungpook National University, Daegu, Korea
| | - Joon Ho Moon
- Department of Hematology-Oncology, Kyungpook National University Hospital, Kyungpook National University, Daegu, Korea
| | - Ho-Young Yhim
- Department of Internal Medicine, Jeonbuk National University Medical School, Jeonju, Korea
| | - Kihyun Kim
- Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
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Mak JWY, Law AWH, Law KWT, Ho R, Cheung CKM, Law MF. Prevention and management of hepatitis B virus reactivation in patients with hematological malignancies in the targeted therapy era. World J Gastroenterol 2023; 29:4942-4961. [PMID: 37731995 PMCID: PMC10507505 DOI: 10.3748/wjg.v29.i33.4942] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/29/2023] [Revised: 07/22/2023] [Accepted: 08/15/2023] [Indexed: 09/01/2023] Open
Abstract
Hepatitis due to hepatitis B virus (HBV) reactivation can be serious and potentially fatal, but is preventable. HBV reactivation is most commonly reported in patients receiving chemotherapy, especially rituximab-containing therapy for hematological malignancies and those receiving stem cell transplantation. Patients with inactive and even resolved HBV infection still have persistence of HBV genomes in the liver. The expression of these silent genomes is controlled by the immune system. Suppression or ablation of immune cells, most importantly B cells, may lead to reactivation of seemingly resolved HBV infection. Thus, all patients with hematological malignancies receiving anticancer therapy should be screened for active or resolved HBV infection by blood tests for hepatitis B surface antigen (HBsAg) and antibody to hepatitis B core antigen. Patients found to be positive for HBsAg should be given prophylactic antiviral therapy. For patients with resolved HBV infection, there are two approaches. The first is pre-emptive therapy guided by serial HBV DNA monitoring, and treatment with antiviral therapy as soon as HBV DNA becomes detectable. The second approach is prophylactic antiviral therapy, particularly for patients receiving high-risk therapy, especially anti-CD20 monoclonal antibody or hematopoietic stem cell transplantation. Entecavir and tenofovir are the preferred antiviral choices. Many new effective therapies for hematological malignancies have been introduced in the past decade, for example, chimeric antigen receptor (CAR)-T cell therapy, novel monoclonal antibodies, bispecific antibody drug conjugates, and small molecule inhibitors, which may be associated with HBV reactivation. Although there is limited evidence to guide the optimal preventive measures, we recommend antiviral prophylaxis in HBsAg-positive patients receiving novel treatments, including Bruton's tyrosine kinase inhibitors, B-cell lymphoma 2 inhibitors, and CAR-T cell therapy. Further studies are needed to determine the risk of HBV reactivation with these agents and the best prophylactic strategy.
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Affiliation(s)
- Joyce Wing Yan Mak
- Department of Medicine and Therapeutics, Prince of Wales Hospital, Hong Kong 852, China
| | | | | | - Rita Ho
- Department of Medicine, North District Hospital, Hong Kong 852, China
| | - Carmen Ka Man Cheung
- Department of Medicine and Therapeutics, Prince of Wales Hospital, Hong Kong 852, China
| | - Man Fai Law
- Department of Medicine and Therapeutics, Prince of Wales Hospital, Hong Kong 852, China
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Shih CA, Chen WC. Prevention of hepatitis B reactivation in patients requiring chemotherapy and immunosuppressive therapy. World J Clin Cases 2021; 9:5769-5781. [PMID: 34368296 PMCID: PMC8316946 DOI: 10.12998/wjcc.v9.i21.5769] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2021] [Revised: 04/12/2021] [Accepted: 06/02/2021] [Indexed: 02/06/2023] Open
Abstract
Hepatitis B virus (HBV) reactivation can lead to severe acute hepatic failure and death in patients with HBV infection. HBV reactivation (HBVr) most commonly develops in patients undergoing cancer chemotherapy, especially B cell-depleting agent therapy such as rituximab and ofatumumab for hematological or solid organ malignancies and that receiving hematopoietic stem cell transplantation without antiviral prophylaxis. In addition, the potential consequences of HBVr is particularly a concern when patients are exposed to either immunosuppressive or biologic therapies for the management of rheumatologic diseases, inflammatory bowel disease and dermatologic diseases. Thus, screening with HBV serological markers and prophylactic or pre-emptive antiviral treatment with nucleos(t)ide analogues should be considered in these patients to diminish the risk of HBVr. This review discusses the clinical manifestation, prognosis and management of HBVr, risk stratifications of cancer chemotherapy and immunosuppressive therapy and international guideline recommendations for the prevention of HBVr in patients with HBV infection and resolved hepatitis B.
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Affiliation(s)
- Chih-An Shih
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung 813, Taiwan
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Antai Medical Care Corporation, Antai Tian-Sheng Memorial Hospital, Pingtung County 928, Taiwan
- Department of Nursing, Meiho University, Pingtung County 928, Taiwan
| | - Wen-Chi Chen
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung 813, Taiwan
- Faculty of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei 112, Taiwan
- Institute of Biomedical Sciences, College of Science, National Sun Yat-sen University, Kaohsiung 8424, Taiwan
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Hara T, Oka K, Iwai N, Inada Y, Tsuji T, Okuda T, Nagata A, Komaki T, Kagawa K. Hepatitis B Virus Reactivation 55 Months Following Chemotherapy Including Rituximab and Autologous Peripheral Blood Stem Cell Transplantation for Malignant Lymphoma. Intern Med 2021; 60:417-421. [PMID: 32963163 PMCID: PMC7925277 DOI: 10.2169/internalmedicine.5678-20] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
A 54-year-old woman underwent chemotherapy including rituximab and autologous peripheral blood stem cell transplantation (auto-PBSCT) for diffuse large B-cell lymphoma. Before the treatment, she exhibited a resolved hepatitis B virus (HBV) infection. She was diagnosed with HBV reactivation based on positive serum HBV-DNA test results, 55 months after her last treatment. Subsequently, he was treated with tenofovir alafenamide fumarate (TAF) therapy and her liver function improved. Patients undergoing chemotherapy including rituximab and auto-PBSCT are at a high risk of HBV reactivation. In such cases, careful and long-term observations may be required to detect HBV reactivation.
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Affiliation(s)
- Tasuku Hara
- Department of Gastroenterology and Hepatology, Fukuchiyama City Hospital, Japan
| | - Kohei Oka
- Department of Gastroenterology and Hepatology, Fukuchiyama City Hospital, Japan
| | - Naoto Iwai
- Department of Gastroenterology and Hepatology, Fukuchiyama City Hospital, Japan
| | - Yutaka Inada
- Department of Gastroenterology and Hepatology, Fukuchiyama City Hospital, Japan
| | - Toshifumi Tsuji
- Department of Gastroenterology and Hepatology, Fukuchiyama City Hospital, Japan
| | - Takashi Okuda
- Department of Gastroenterology and Hepatology, Fukuchiyama City Hospital, Japan
| | - Akihiro Nagata
- Department of Pathology, Fukuchiyama City Hospital, Japan
| | - Toshiyuki Komaki
- Department of Gastroenterology and Hepatology, Fukuchiyama City Hospital, Japan
| | - Keizo Kagawa
- Department of Gastroenterology and Hepatology, Fukuchiyama City Hospital, Japan
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Guo D, Xu P, Guan C, Xu Y, Yang Y, Xu J, Zhou R, Chen B. Hepatitis B virus infection and 1q21 amplification in multiple myeloma. Oncol Lett 2019; 18:6196-6206. [PMID: 31788095 DOI: 10.3892/ol.2019.10926] [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: 09/14/2018] [Accepted: 02/27/2019] [Indexed: 11/05/2022] Open
Abstract
Hepatitis B virus (HBV) is a hepatotropic and a lymphotropic virus. An association between HBV and hematologic malignancies has been determined previously; however, the association between HBV infection and multiple myeloma (MM) remains controversial. The present study aimed to assess the prevalence of HBV infection in patients with MM, and investigate their characteristics and prognostic significance. The clinical data of 165 patients with MM who had received at least four cycles of chemotherapy between April 2008 and February 2017 at Nanjing Drum Tower Hospital (Nanjing, China) were collected. HBV markers were determined using ELISA. The rates of acute or chronic HBV infection and resolved HBV infection in patients with MM were 12.12 and 26.06%, respectively. The gain of 1q21 was significantly more prevalent in the patients who were classified as HBV-positive compared with the patients who were classified as HBV-negative (54 vs. 38.2%; P=0.048), and the level of alanine transaminase in patients who were classified as HBV-positive was significantly increased compared with the non-infected group (63.29 vs. 24.66 U/l; P=0.043). Lactate dehydrogenase, serum creatinine and serum calcium levels were additionally determined to be significant risk factors of overall survival. The progression-free survival (PFS) of patients who were classified as HBV-positive was decreased compared with patients who were classified as HBV-negative (18.97 vs. 29.67 months; P=0.006), and being HBV-positive was determined to be an independent prognostic factor of PFS. HBV infection may contribute to MM progression through 1q21 amplification, and improved monitoring of HBV markers in patients with MM may be required.
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Affiliation(s)
- Dan Guo
- Department of Hematology, Affiliated Hospital of Nantong University, Nantong, Jiangsu, 226001, P.R. China.,Department of Hematology, Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China
| | - Peipei Xu
- Department of Hematology, Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China
| | - Chaoyang Guan
- Department of Hematology, Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China
| | - Yong Xu
- Department of Hematology, Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China
| | - Yonggong Yang
- Department of Hematology, Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China
| | - Jingyan Xu
- Department of Hematology, Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China
| | - Rongfu Zhou
- Department of Hematology, Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China
| | - Bing Chen
- Department of Hematology, Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China
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Reactivation of Hepatitis B Virus in Patients with Multiple Myeloma. Cancers (Basel) 2019; 11:cancers11111819. [PMID: 31752356 PMCID: PMC6895787 DOI: 10.3390/cancers11111819] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2019] [Revised: 11/16/2019] [Accepted: 11/17/2019] [Indexed: 12/11/2022] Open
Abstract
Reactivation of hepatitis B virus (HBV) is a well-known complication in patients with hematological malignancies during or after cytotoxic chemotherapy. If the initiation of antiviral therapy is delayed in patients with HBV reactivation, these patients can develop severe hepatitis and may die of fulminant hepatitis. The preventive strategy for HBV reactivation in patients with malignant lymphoma has already been established based on some prospective studies. As there was an increased number of novel agents being approved for the treatment of multiple myeloma (MM), the number of reported cases of HBV reactivation among MM patients has gradually increased. We conducted a Japanese nationwide retrospective study and revealed that HBV reactivation in MM patients is not rare and that autologous stem cell transplantation is a significant risk factor. In this study, around 20% of all patients with HBV reactivation developed HBV reactivation after 2 years from the initiation of therapy, unlike malignant lymphoma. This might be due to the fact that almost all of the patients received chemotherapy for a long duration. Therefore, a new strategy for the prevention of HBV reactivation in MM patients is required.
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Ataca Atilla P, Yalçıner M, Atilla E, İdilman R, Beksaç M. Hepatitis B Reactivation Rate and Fate Among Multiple Myeloma Patients Receiving Regimens Containing Lenalidomide and/or Bortezomib. Turk J Haematol 2019; 36:266-273. [PMID: 31368290 PMCID: PMC6863023 DOI: 10.4274/tjh.galenos.2019.2019.0103] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
Objective: Reactivation of the hepatitis B virus (HBV) refers to an increase in HBV replication in a patient with inactive or resolved HBV. In this retrospective study, our aim is to present and compare HBV reactivation in multiple myeloma (MM) patients who received lenalidomide and/or bortezomib at any time during treatment, evaluate the factors associated with reactivation, and demonstrate the outcome of patients. Materials and Methods: We evaluated 178 MM patients who received lenalidomide (n=102) and/or bortezomib (n=174) during their treatment schedules. The HBsAg, anti-HBc, anti-HBs, HBeAg, and anti-HBe were detected by chemiluminescence by ARCHITECT lab analyzers using commercially available kits (Abbott, USA). HBV-DNA titers were determined by quantitative PCR. The results were evaluated by IBM SPSS Statistics for Windows, Version 20.0 (IBM Corp., Armonk, NY, USA). Results: HBV reactivation was diagnosed in 6 patients (3%) after bortezomib and in 8 patients (8%) after bortezomib and lenalidomide. Three of the patients in each group had HBsAg+, HBeAg+, AntiHBeAg-, AntiHBc-, and AntiHBS+ status, whereas 5 patients in the bortezomib- and lenalidomide-treated group and 3 patients in the bortezomib-treated group had HBsAg-, HBeAg-, AntiHBeAg-, AntiHBc-, and AntiHBS+ status prior to treatment. There were no statistical differences observed between HBV reactivation in the bortezomib-treated or bortezomib- and lenalidomide-treated groups in terms of age at diagnosis, sex, International Staging System subtype, frequency of extramedullary disease, dialysis requirement, or receiving of autologous stem cell transplantation. In patients who received antiviral prophylaxis, a higher incidence of HBV reactivation was detected in HBsAg-positive patients compared to HBsAg-negative patients (4/4, 100% vs. 2/7, 29%; p=0.045). The 3-year and 5-year overall survival rates were similar in patients with or without HBV reactivation (83% vs. 84%, 73% vs. 74%, p=0.84). Conclusion: Close follow-up is recommended for not only HBsAg-positive but also HBsAg-negative patients.
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Affiliation(s)
- Pınar Ataca Atilla
- Ankara University Faculty of Medicine, Department of Hematology, Ankara, Turkey
| | - Merih Yalçıner
- Ankara University Faculty of Medicine, Department of Internal Medicine, Ankara, Turkey
| | - Erden Atilla
- Ankara University Faculty of Medicine, Department of Hematology, Ankara, Turkey
| | - Ramazan İdilman
- Ankara University Faculty of Medicine, Department of Gastroenterology, Ankara, Turkey
| | - Meral Beksaç
- Ankara University Faculty of Medicine, Department of Hematology, Ankara, Turkey
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Sasadeusz J, Grigg A, Hughes PD, Lee Lim S, Lucas M, McColl G, McLachlan SA, Peters MG, Shackel N, Slavin M, Sundararajan V, Thompson A, Doyle J, Rickard J, De Cruz P, Gish RG, Visvanathan K. Screening and Prophylaxis to Prevent Hepatitis B Reactivation: Transplant Recipients. Clin Liver Dis 2019; 23:493-509. [PMID: 31266623 DOI: 10.1016/j.cld.2019.04.010] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Organ transplantation is a lifesaving procedure for many patients. To prevent rejection or graft-versus-host disease, recipients require long-term immunosuppression. In patients who have ever been exposed to hepatitis B, it is possible for reactivation to occur; this includes patients who are anti-hepatitis B core antibody-positive only or both anti-hepatitis B core antibody-positive and hepatitis B surface antibody-positive. The susceptibility to this varies with the nature of the transplant. Hepatitis B can be transmitted from donor to recipient. It is important to assess the hepatitis B status and formulate a strategy to prevent transmission and prevent reactivation.
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Affiliation(s)
- Joe Sasadeusz
- Peter Doherty Institute for Infection and Immunity, Elizabeth Street, Melbourne, Victoria 3000, Australia; University of Melbourne, Grattan Street, Parkville, Victoria 3010, Australia.
| | - Andrew Grigg
- Olivia Newton John Cancer Research Institute, Austin Hospital, 145 Studley Road, Heidelberg, Victoria 3084, Australia
| | - Peter D Hughes
- University of Melbourne, Grattan Street, Parkville, Victoria 3010, Australia; Royal Melbourne Hospital, 300 Grattan Street, Parkville, Victoria 3050, Australia
| | - Seng Lee Lim
- National University of Singapore, 21 Lower Kent Ridge Road, Singapore 119077, Singapore
| | - Michaela Lucas
- University of Western Australia, 35 Stirling Highway, Crawley, Western Australia 6009, Australia
| | - Geoff McColl
- University of Queensland Oral Health Centre, 288 Herston Road, Queensland 4006, Australia
| | - Sue Anne McLachlan
- St Vincent's Hospital, 41 Victoria Street, Fitzroy, Victoria 3065, Australia
| | - Marion G Peters
- University of California, San Francisco, S357 Parnassus Avenue, San Francisco, CA 94143, USA
| | - Nicholas Shackel
- Ingham Institute, 1 Campbell Street, Liverpool, Sydney, New South Wales 2170, Australia
| | - Monica Slavin
- Royal Melbourne Hospital, 300 Grattan Street, Parkville, Victoria 3050, Australia; Victorian Comprehensive Cancer Centre, 305 Grattan Street, Melbourne, Victoria 3000, Australia
| | - Vijaya Sundararajan
- University of Melbourne, Grattan Street, Parkville, Victoria 3010, Australia; St Vincent's Hospital, 41 Victoria Street, Fitzroy, Victoria 3065, Australia; Department of Public Health, La Trobe University, Plenty Road, Bundoora, Victoria 3086, Australia
| | - Alexander Thompson
- University of Melbourne, Grattan Street, Parkville, Victoria 3010, Australia; St Vincent's Hospital, 41 Victoria Street, Fitzroy, Victoria 3065, Australia
| | - Joseph Doyle
- The Alfred and Monash University, 85 Commercial Road, Melbourne, Victoria 3004, Australia; Burnet Institute, 85 Commercial Road, Melbourne, Victoria 3004, Australia
| | - James Rickard
- Olivia Newton John Cancer Research Institute, Austin Hospital, 145 Studley Road, Heidelberg, Victoria 3084, Australia
| | - Peter De Cruz
- University of Melbourne, Grattan Street, Parkville, Victoria 3010, Australia
| | - Robert G Gish
- Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University, Stanford University Medical Center, 300 Pasteur Drive, Stanford, CA 94305, USA
| | - Kumar Visvanathan
- University of Melbourne, Grattan Street, Parkville, Victoria 3010, Australia; St Vincent's Hospital, 41 Victoria Street, Fitzroy, Victoria 3065, Australia
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Wu CCH, Kumar R. Hepatitis B reactivation in patients with hepatitis B core antibody positive and surface antigen negative on immunosuppressants. World J Meta-Anal 2019; 7:209-217. [DOI: 10.13105/wjma.v7.i5.209] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2019] [Revised: 05/20/2019] [Accepted: 05/22/2019] [Indexed: 02/06/2023] Open
Abstract
Hepatitis B viral (HBV) reactivation in the immunosuppressed is a significant problem even in patients who have achieved serological clearance due to the persistence of HBV as cccDNA. HBV reactivation will continue to pose a significant healthcare burden given the high prevalence of HBV and increasing use of immunosuppressants. Screening of hepatitis B surface antigen, antibody to Hepatitis B core antigen antibody and HBV DNA levels should be done routinely in all patients planned for significant immunosuppressant use. We aimed to examine the factors affecting reactivation risk. This depended on HBV disease status, the underlying disease requiring immunosuppression, and the specific immunosuppressive regime. While antiviral prophylaxis can prevent reactivation, it increases cost and still has risk of delayed reactivation after stopping antivirals and close follow-up and on-demand treatment is a good alternative for patients at risk of reactivation.
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Affiliation(s)
- Clement Chun-Ho Wu
- Department of Gastroenterology and Hepatology, Singapore General Hospital, Singapore 169608, Singapore
- Duke-NUS Medical School, Singapore 169608, Singapore
| | - Rajneesh Kumar
- Department of Gastroenterology and Hepatology, Singapore General Hospital, Singapore 169608, Singapore
- Duke-NUS Medical School, Singapore 169608, Singapore
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Chen CY, Tien FM, Cheng A, Huang SY, Chou WC, Yao M, Tang JL, Tien HF, Sheng WH. Hepatitis B reactivation among 1962 patients with hematological malignancy in Taiwan. BMC Gastroenterol 2018; 18:6. [PMID: 29310589 PMCID: PMC5759199 DOI: 10.1186/s12876-017-0735-1] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/21/2016] [Accepted: 12/22/2017] [Indexed: 01/29/2023] Open
Abstract
BACKGROUND The risk of Hepatitis B virus (HBV) reactivation in patients with different hematological malignancy except lymphoma were rarely known before. METHODS A total of 1962 patients with hematological malignancy were enrolled and followed-up at the National Taiwan University Hospital between 2008 and 2013. The clinical characteristics, HBV serology, and laboratory data were retrospectively reviewed and analyzed. RESULTS A total of 1962 patients comprising 1048 men and 914 women were studied. The median age of the patients was 55 years (range, 15-97 years). Chronic HBV carriage was documented at diagnosis of hematological malignancy in 286 (14.6%) patients. A total of 171 (59.8%) of the 286 HBV carriers received primary prophylaxis with anti-HBV agents. Of the HBV carriers, 97 (33.9%) developed hepatitis B reactivation during or after chemotherapy, including 59 patients who had discontinued antiviral therapy. The incidence of hepatitis B reactivation among patients with hematological malignancy and HBV carriage was 10.4 per 100 person-years. A multivariate analysis revealed hepatocellular carcinoma (p < 0.001) and antiviral prophylaxis use (p < 0.001) were independent risk factors of HBV reactivation in HBV carriers. Of the 1676 patients with initial negative hepatitis B surface antigen (HBsAg) counts, 41 (2.4%) experienced hepatitis B reactivation, reverse seroconversion of HBsAg, and lost their protective hepatitis B surface antibody (anti-HBs). A multivariate analysis revealed that diabetes mellitus (p = 0.005, odds ratio (OR): 0.218, 95% confidence interval (CI): 0.076-0.629), allogeneic transplantation (p = 0.013, OR: 0.182, 95% CI: 0.047-0.701), liver cirrhosis (p < 0.001, OR: 0.002, 95% CI: 0-0.047), low anti-HBs titers (p = 0.016, OR: 0.020, 95% CI: 0.001-0.480), and positive hepatitis B core antibody (p = 0.013, OR: 0.070, 95% CI: 0.009-0.571) were independent risk factors of positive seroconversion of HBsAg in patients with hematological malignancy. CONCLUSIONS The incidence of HBV reactivation among the patients with varying subtypes of hematological malignancy is similar. Prophylaxis with anti-HBV agents critically reduced the risk of hepatitis B reactivation.
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Affiliation(s)
- Chien-Yuan Chen
- Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Feng-Ming Tien
- Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Aristine Cheng
- Division of Infectious Disease, Department of Internal Medicine, National Taiwan University Hospital, 7 Chung-Shan South Road, Taipei, 10002, Taiwan
| | - Shang-Yi Huang
- Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Wen-Chien Chou
- Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.,Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Ming Yao
- Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Jih-Luh Tang
- Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.,Tai-Cheng Stem Cell Therapy Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Hwei-Fang Tien
- Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Wang-Huei Sheng
- Division of Infectious Disease, Department of Internal Medicine, National Taiwan University Hospital, 7 Chung-Shan South Road, Taipei, 10002, Taiwan.
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12
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Tsukune Y, Sasaki M, Odajima T, Sunami K, Takei T, Moriuchi Y, Iino M, Isoda A, Nakaya A, Muta T, Miyake T, Miyazaki K, Shimizu T, Nakajima K, Igarashi A, Nagafuji K, Kurihara T, Aoyama T, Sugimori H, Komatsu N. Incidence and risk factors of hepatitis B virus reactivation in patients with multiple myeloma in an era with novel agents: a nationwide retrospective study in Japan. Blood Cancer J 2017; 7:631. [PMID: 29167420 PMCID: PMC5802507 DOI: 10.1038/s41408-017-0002-2] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2017] [Revised: 08/03/2017] [Accepted: 08/23/2017] [Indexed: 12/18/2022] Open
Affiliation(s)
- Yutaka Tsukune
- Department of Hematology, Juntendo University School of Medicine, Bunkyo-ku, Tokyo, 113-8421, Japan
| | - Makoto Sasaki
- Department of Hematology, Juntendo University School of Medicine, Bunkyo-ku, Tokyo, 113-8421, Japan.
| | - Takeshi Odajima
- Faculty of Health Science, Daito Bunka University, School of Sports and Health Science, Higashi-Matsuyama, Saitama, 355-8501, Japan
| | - Kazutaka Sunami
- Department of Hematology, National Hospital Organization Okayama Medical Center, Okayama, Okayama, 701-1192, Japan
| | - Tomomi Takei
- Department of Hematology, Japanese Red Cross Medical Center, Shibuya-ku, Tokyo, 150-8935, Japan
| | - Yukiyoshi Moriuchi
- Department of Hematology, Sasebo City General Hospital, Sasebo, 857-0056, Nagasaki, Japan
| | - Masaki Iino
- Department of Hematology, Yamanashi Prefectural Central Hospital, Kofu, Yamanashi, 400-8506, Japan
| | - Atsushi Isoda
- Department of Hematology, National Hospital Organization Shibukawa Medical Center, Shibukawa, Gunma, 377-0280, Japan
| | - Aya Nakaya
- First Department of Internal Medicine, Kansai Medical University, Hirakata, Osaka, 573-1010, Japan
| | - Tsuyoshi Muta
- Department of Hematology/Oncology, Japan Community Health Care Organization Kyushu Hospital, Kita-Kyusyu, Fukuoka, 806-8501, Japan
| | - Takaaki Miyake
- Department of Oncology/Hematology, Shimane University Hospital, Izumo, Shimane, 693-8501, Japan
| | - Koji Miyazaki
- Department of Transfusion and Cell Transplantation, Kitasato University School of Medicine, Sagamihara, Kanagawa, 252-0374, Japan
| | - Takayuki Shimizu
- Division of Hematology, Department of Medicine, Keio University School of Medicine, Shinjuku-ku, Tokyo, 160-8582, Japan
| | - Kei Nakajima
- Department of Hematology/Oncology, University of Yamanashi, Chuo, Yamanashi, 409-3898, Japan
| | - Aiko Igarashi
- Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Bukyo-ku, Tokyo, 113-8677, Japan
| | - Koji Nagafuji
- Division of Hematology and Oncology, Department of Medicine, Kurume University School of Medicine, Kurume, Fukuoka, 830-0011, Japan
| | - Taro Kurihara
- Department of Internal Medicine, Niigata Cancer Center Hospital, Niigata, Niigata, 951-8566, Japan
| | - Tomonori Aoyama
- Department of Gastroenterology, Juntendo University School of Medicine, Bunkyo-ku, Tokyo, 113-8421, Japan
| | - Hiroki Sugimori
- Department of Preventive Medicine, Daito Bunka University, Graduate School of Sports and Health Science, Higashi-Matsuyama, Saitama, 355-8501, Japan
| | - Norio Komatsu
- Department of Hematology, Juntendo University School of Medicine, Bunkyo-ku, Tokyo, 113-8421, Japan
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13
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Paul S, Dickstein A, Saxena A, Terrin N, Viveiros K, Balk EM, Wong JB. Role of surface antibody in hepatitis B reactivation in patients with resolved infection and hematologic malignancy: A meta-analysis. Hepatology 2017; 66:379-388. [PMID: 28128861 PMCID: PMC6485929 DOI: 10.1002/hep.29082] [Citation(s) in RCA: 129] [Impact Index Per Article: 16.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/04/2016] [Revised: 10/21/2016] [Accepted: 12/17/2016] [Indexed: 12/12/2022]
Abstract
UNLABELLED Patients with resolved hepatitis B virus (HBV) infection who are treated for hematological malignancies remain at risk for HBV reactivation. Because of conflicting studies about whether the antibody to hepatitis B surface antigen (anti-HBs) protects against reactivation in patients with resolved infection (hepatitis B surface antigen negative) receiving chemotherapy for hematological malignancies, we conducted a meta-analysis to determine if anti-HBs reduces HBV reactivation risk. We sought English-language studies through March 1, 2016, in Medline and other sources that examined reactivation in patients with resolved HBV infection receiving chemotherapy for hematologic malignancies. The absolute risks and odds ratio (OR) of reactivation with versus without anti-HBs were estimated in random-effects model meta-analyses. In 20 studies involving 1,672 patients not receiving antiviral prophylaxis, the reactivation risk was 14% (95% confidence interval [CI] 9.4%-19%) in 388 patients who had antibodies to hepatitis B core antigen only versus 5.0% (95% CI 3.0%-7.0%) in 1,284 patients who also had anti-HBs. Anti-HBs reduced reactivation risk with a pooled OR of 0.21 (95% CI 0.14-0.32) versus patients with antibody to hepatitis B core antigen only. Similar results were found when limiting the analysis to rituximab chemotherapy (OR = 0.19, 95% CI 0.11-0.32) and lymphoma (OR = 0.18, 95% CI 0.11-0.28). CONCLUSION In patients with resolved HBV receiving chemotherapy for hematological malignancies without antiviral prophylaxis, anti-HBs positivity is associated with a decreased risk of reactivation; HBV screening in this patient population should include the routine use of anti-HBs, and those who are anti-HBs-negative should receive antiviral prophylaxis. Future studies should examine the effect of anti-HBs serum titers, the potential role for booster vaccinations, and antiviral prophylaxis prior to chemotherapy in this patient population. (Hepatology 2017;66:379-388).
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Affiliation(s)
- Sonali Paul
- Section of Gastroenterology, Center for Liver Diseases; The University of Chicago Medicine, Chicago, IL 60637
| | - Aaron Dickstein
- Division of Gastroenterology and Hepatology, Tufts Medical Center, Boston, MA 02111
| | - Akriti Saxena
- Division of Gastroenterology, Boston Medical Center, Boston, MA 02118
| | - Norma Terrin
- Institute for Clinical Research and Health Policy Studies, Tufts Medical Center, Boston, MA 02111, and Biostatistics, Epidemiology and Research Design (BERD) Center, Tufts Clinical and Translational Science Institute, Tufts University, Boston, MA 02111
| | - Kathleen Viveiros
- Division of Gastroenterology and Hepatology, Tufts Medical Center, Boston, MA 02111
| | - Ethan M. Balk
- Brown Center for Evidence-Based Medicine, Brown University School of Public Health, Providence, RI 02912
| | - John B. Wong
- Division of Clinical Decision Making, Tufts Medical Center, Boston, MA 02111
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14
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Gentile G, Andreoni M, Antonelli G, Sarmati L. Screening, monitoring, prevention, prophylaxis and therapy for hepatitis B virus reactivation in patients with haematologic malignancies and patients who underwent haematologic stem cell transplantation: a systematic review. Clin Microbiol Infect 2017; 23:916-923. [PMID: 28668465 DOI: 10.1016/j.cmi.2017.06.024] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2017] [Revised: 06/15/2017] [Accepted: 06/17/2017] [Indexed: 02/07/2023]
Abstract
BACKGROUND The growth of new therapeutic options and practices increases the risk of hepatitis B virus (HBV) reactivation in patients with haematologic malignancies and/or patients undergoing haematologic stem cell transplantation (HSCT). OBJECTIVES To provide a systematic review supporting recommendations for prevention, monitoring, prophylaxis and therapy of HBV reactivation in patients with haematologic malignancies and HSCT. DATA SOURCES The systematic review was based on a strategy using PubMed and the Cochrane Library searching literature published from 1991 to December 31, 2016. PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guidelines were followed. SELECTION CRITERIA Randomized control trials, prospective and retrospective cohort studies. RISK-OF-BIAS ASSESSMENT Cochrane Risk of Bias Tool and Newcastle Ottawa Quality Assessment Scale. RESULTS Forty-two studies of fair or good quality were included in this systematic review. The following main results were obtained: haematologic patients should be screened for HBV before chemotherapy; HBV DNA levels should be monthly monitored in all HBV-positive patients not receiving prophylaxis; hepatitis B surface antigen (HBsAg)-positive haematologic patients and patients undergoing HSCT should receive prophylaxis and third-generation HBV drugs should be provided; and anti-hepatitis B core protein-positive lymphoma patients and patients who underwent HSCT should receive antiviral prophylaxis. CONCLUSIONS A higher quality of evidence is needed. However, the level of evidence was sufficient to support the recommendations published in this issue of the journal.
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Affiliation(s)
- G Gentile
- Department of Cellular Biotechnologies and Haematology, La Sapienza University, Rome, Italy
| | - M Andreoni
- Clinical Infectious Diseases, Department of System Medicine, Tor Vergata University, Rome, Italy
| | - G Antonelli
- Department of Molecular Medicine, La Sapienza University, Rome, Italy
| | - L Sarmati
- Clinical Infectious Diseases, Department of System Medicine, Tor Vergata University, Rome, Italy.
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15
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Severe Acute Hepatitis B in HBV-Vaccinated Partner of a Patient with Multiple Myeloma Treated with Cyclophosphamide, Bortezomib, and Dexamethasone and Autologous Stem Cell Transplant. Case Reports Hepatol 2017; 2017:2463953. [PMID: 28428898 PMCID: PMC5385905 DOI: 10.1155/2017/2463953] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2017] [Accepted: 03/06/2017] [Indexed: 01/25/2023] Open
Abstract
Hepatitis B reactivation can occur with various forms of immunosuppression. Cyclophosphamide, Bortezomib, and Dexamethasone (CYBOR-D) chemotherapy is commonly used for the treatment of multiple myeloma and has not been noted in guidelines to be causative in HBV reactivation. Indeed, current guidelines do not recommend providing antiviral prophylaxis to patients with prior HBV infection. We present a case of HBV reactivation as a result of CYBOR-D and autologous stem cell transplant which is complicated by the patient's partner who developed acute hepatitis B. Our case highlights the need to review the role of antiviral prophylaxis for patients undergoing treatment of multiple myeloma and also the role of ensuring immunity for close contacts of these patients who may also be at risk.
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16
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Akbar SMF, Al-Mahtab M, Jahan M, Yoshida O, Hiasa Y. Novel insights into immunotherapy for hepatitis B patients. Expert Rev Gastroenterol Hepatol 2016; 10:267-76. [PMID: 26626120 DOI: 10.1586/17474124.2016.1112266] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
The possible use of immunotherapy for hepatitis B has emerged for two major reasons: (1) chronic hepatitis B (CHB) is an immune-mediated pathological condition, and (2) commercially available antiviral drugs are of limited efficacy. Although various immunomodulatory agents have been used to treat patients with CHB during the last three decades, there is currently no consensus among physicians and hepatologists regarding the suitability of immunotherapy for patients with CHB. However, new insights into immunotherapy for CHB have emerged; these may facilitate design of effective and tolerable immunotherapy regimens for these patients. This review provides a comprehensive overview of immunotherapy for CHB.
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Affiliation(s)
| | - Mamun Al-Mahtab
- b Department of Hepatology , Bangabandhu Sheikh Mujib Medical University , Dhaka , Bangladesh
| | - Munira Jahan
- c Department of Virology , Bangabandhu Sheikh Mujib Medical University , Dhaka , Bangladesh
| | - Osamu Yoshida
- d Department of Gastroenterology and Metabology , Ehime University Graduate School of Medicine , Toon , Japan
| | - Yoichi Hiasa
- d Department of Gastroenterology and Metabology , Ehime University Graduate School of Medicine , Toon , Japan
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17
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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: 66] [Impact Index Per Article: 7.3] [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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18
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Tsukune Y, Sasaki M, Odajima T, Isoda A, Matsumoto M, Koike M, Tamura H, Moriya K, Ito S, Asahi M, Imai Y, Tanaka J, Handa H, Koiso H, Tanosaki S, Hua J, Hagihara M, Yahata Y, Suzuki S, Watanabe S, Sugimori H, Komatsu N. Incidence and clinical background of hepatitis B virus reactivation in multiple myeloma in novel agents' era. Ann Hematol 2016; 95:1465-72. [PMID: 27358178 DOI: 10.1007/s00277-016-2742-7] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2016] [Accepted: 06/24/2016] [Indexed: 01/16/2023]
Abstract
There are some reports regarding hepatitis B virus (HBV) reactivation in patients with myeloma who are HBV carriers or who have had a resolved HBV infection, and there is no standard prophylaxis strategy for these patients. We performed a retrospective multicenter study to determine the incidence and characteristics of HBV reactivation in patients with multiple myeloma. We identified 641 patients with multiple myeloma who had been treated using novel agents and/or autologous stem cell transplantation with high-dose chemotherapy between January 2006 and June 2014 at nine Japanese hospitals. The patients' characteristics, laboratory data, and clinical courses were retrieved and statistically analyzed. During a median follow-up of 101 weeks, one of eight (12.5 %) HBV carriers developed hepatitis and 9 of 99 (9.1 %) patients with resolved HBV infection experienced HBV reactivation; the cumulative incidences of HBV reactivation at 2 years (104 weeks) and 5 years (260 weeks) were 8 and 14 %, respectively. The nine cases of reactivation after resolved HBV infection had received entecavir as preemptive therapy or were carefully observed by monitoring their HBV DNA levels, and none of these cases developed hepatitis. Among patients with multiple myeloma, HBV reactivation was not rare. Therefore, long-term monitoring of HBV DNA levels is needed to prevent hepatitis that is related to HBV reactivation in these patients.
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Affiliation(s)
- Yutaka Tsukune
- Department of Hematology, Juntendo University School of Medicine, 2-1-1, Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan
| | - Makoto Sasaki
- Department of Hematology, Juntendo University School of Medicine, 2-1-1, Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan.
| | - Takeshi Odajima
- Faculty of Health Science, Daito Bunka University School of Sports and Health Science, Saitama, Japan
| | - Atsushi Isoda
- Department of Hematology, National Hospital Organization Nishigunma Hospital, Gunma, Japan
| | - Morio Matsumoto
- Department of Hematology, National Hospital Organization Nishigunma Hospital, Gunma, Japan
| | - Michiaki Koike
- Department of Hematology, Juntendo University Shizuoka Hospital, Shizuoka, Japan
| | - Hideto Tamura
- Division of Hematology, Department of Medicine, Nippon Medical School, Tokyo, Japan
| | - Keiichi Moriya
- Division of Hematology, Department of Medicine, Nippon Medical School, Tokyo, Japan
| | - Shigeki Ito
- Department of Medical Oncology, Iwate Medical University School of Medicine, Iwate, Japan
| | - Maki Asahi
- Hematology and Oncology, Department of Internal Medicine, Iwate Medical University School of Medicine, Iwate, Japan
| | - Yoichi Imai
- Department of Hematology, Tokyo Women's Medical University, Tokyo, Japan
| | - Junji Tanaka
- Department of Hematology, Tokyo Women's Medical University, Tokyo, Japan
| | - Hiroshi Handa
- Department of Medicine and Clinical Science, Gunma University, Gunma, Japan
| | - Hiromi Koiso
- Infection Control and Prevention Center, Gunma University Hospital, Gunma, Japan
| | - Sakae Tanosaki
- Department of Hematology, The Fraternity Memorial Hospital, Tokyo, Japan
| | - Jian Hua
- Department of Hematology, Eiju General Hospital, Tokyo, Japan
| | - Masao Hagihara
- Department of Hematology, Eiju General Hospital, Tokyo, Japan
| | - Yuriko Yahata
- Department of Hematology, Juntendo University School of Medicine, 2-1-1, Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan
| | - Satoko Suzuki
- Department of Gastroenterology, Tokyo Metropolitan Health and Medical Treatment Corporation Tobu Chiiki Hospital, Tokyo, Japan
| | - Sumio Watanabe
- Department of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan
| | - Hiroki Sugimori
- Department of Preventive Medicine, Daito Bunka University Graduate School of Sports and Health Science, Saitama, Japan
| | - Norio Komatsu
- Department of Hematology, Juntendo University School of Medicine, 2-1-1, Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan
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19
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Pattullo V. Prevention of Hepatitis B reactivation in the setting of immunosuppression. Clin Mol Hepatol 2016; 22:219-37. [PMID: 27291888 PMCID: PMC4946398 DOI: 10.3350/cmh.2016.0024] [Citation(s) in RCA: 88] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2016] [Accepted: 04/27/2016] [Indexed: 12/13/2022] Open
Abstract
Advances in the treatment of malignant and inflammatory diseases have developed over time, with increasing use of chemotherapeutic and immunosuppressive agents of a range of drug classes with varying mechanism and potency in their effects on the immune system. These advances have been met with the challenge of increased risk of hepatitis B virus (HBV) reactivation in susceptible individuals. The magnitude of risk of HBV reactivation is associated with the individual’s HBV serological status and the potency and duration of immunosuppression. Individuals with chronic hepatitis B (CHB) and previously infected but serologically cleared HBV infection are both susceptible to HBV reactivation. HBV reactivation in the setting of immunosuppression is a potentially life threatening condition leading to liver failure and death in extreme cases. It is important to recognize that HBV reactivation in the setting of immunosuppression is potentially preventable. Therefore, identification of patients at risk of HBV reactivation and institution of prophylactic antiviral therapy prior to initiation of immunosuppression is essential.
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Affiliation(s)
- Venessa Pattullo
- Department of Gastroenterology, Royal North Shore Hospital, Sydney, Australia
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20
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Han JW, Yang H, Lee HL, Bae SH, Choi JY, Lee JW, Kim HJ, Lee S, Cho SG, Min CK, Kim DW, Yoon SK. Risk factors and outcomes of hepatitis B virus reactivation in hepatitis B surface antigen negative patients with hematological malignancies. Hepatol Res 2016; 46:657-68. [PMID: 26445232 DOI: 10.1111/hepr.12603] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/12/2015] [Revised: 09/28/2015] [Accepted: 10/05/2015] [Indexed: 12/25/2022]
Abstract
AIM Current guidelines recommend all patients scheduled to receive chemotherapy should be screened for hepatitis B surface antigen (HBsAg) and antibodies to hepatitis B virus core antigen (anti-HBc) status. However, still, more research is needed to identify the risk factors for hepatitis B virus (HBV) reactivation. We retrospectively investigated the incidence, risk factors and outcome of HBV reactivation in HBsAg negative patients with hematological malignancies. METHODS Seven hundred and thirty-eight HBsAg negative patients with hematological malignancies were included in the study. HBV reactivation was defined as reverse seroconversion of HBsAg (HBsAg reappearance). Risk factors, cumulative incidence and overall survival of HBV reactivation were analyzed. RESULTS Reactivation occurred in 23 of the 738 (3.1%) enrolled patients. As expected, the reactivation rate of the anti-HBc positive group was significantly higher than that of the anti-HBc negative group (5.4% vs 0.8%). Multivariate analysis indicated that loss of antibody to the hepatitis B surface antigen (anti-HBs) was an independent risk factor. Patients with acute lymphoblastic leukemia and multiple myeloma showed significantly higher reactivation rate than those with other diseases. The cumulative incidence of HBV reactivation after starting chemotherapy in the anti-HBc positive subgroup was 0.3% at 1 year, 1.7% at 2 years and 10.5% at 3 years. CONCLUSION Close monitoring of HBV markers, including anti-HBs, should be performed for longer than 24 months. Further study is needed to establish a strategy to prevent HBV reactivation after chemotherapy in HBsAg negative patients with hematological malignancies.
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Affiliation(s)
- Ji Won Han
- Division of Hepatology, Department of Internal Medicine, Seoul St Mary's Hospital, College of Medicine, The Catholic University of South Korea, Seoul, Korea
| | - Hyun Yang
- Division of Hepatology, Department of Internal Medicine, Seoul St Mary's Hospital, College of Medicine, The Catholic University of South Korea, Seoul, Korea
| | - Hae Lim Lee
- Division of Hepatology, Department of Internal Medicine, Seoul St Mary's Hospital, College of Medicine, The Catholic University of South Korea, Seoul, Korea
| | - Si Hyun Bae
- Division of Hepatology, Department of Internal Medicine, Seoul St Mary's Hospital, College of Medicine, The Catholic University of South Korea, Seoul, Korea
| | - Jong Young Choi
- Division of Hepatology, Department of Internal Medicine, Seoul St Mary's Hospital, College of Medicine, The Catholic University of South Korea, Seoul, Korea
| | - Jong-Wook Lee
- Division of Hematology, Department of Internal Medicine, Seoul St Mary's Hospital, College of Medicine, The Catholic University of South Korea, Seoul, Korea
| | - Hee Je Kim
- Division of Hematology, Department of Internal Medicine, Seoul St Mary's Hospital, College of Medicine, The Catholic University of South Korea, Seoul, Korea
| | - Seok Lee
- Division of Hematology, Department of Internal Medicine, Seoul St Mary's Hospital, College of Medicine, The Catholic University of South Korea, Seoul, Korea
| | - Seok Goo Cho
- Division of Hematology, Department of Internal Medicine, Seoul St Mary's Hospital, College of Medicine, The Catholic University of South Korea, Seoul, Korea
| | - Chang Ki Min
- Division of Hematology, Department of Internal Medicine, Seoul St Mary's Hospital, College of Medicine, The Catholic University of South Korea, Seoul, Korea
| | - Dong Wook Kim
- Division of Hematology, Department of Internal Medicine, Seoul St Mary's Hospital, College of Medicine, The Catholic University of South Korea, Seoul, Korea
| | - Seung Kew Yoon
- Division of Hepatology, Department of Internal Medicine, Seoul St Mary's Hospital, College of Medicine, The Catholic University of South Korea, Seoul, Korea
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Pondé RAA. Acute hepatitis B virus infection or acute exacerbation of chronic hepatitis B infection: the differential serological diagnosis. Eur J Clin Microbiol Infect Dis 2015; 35:29-40. [PMID: 26581426 DOI: 10.1007/s10096-015-2522-7] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2015] [Accepted: 11/02/2015] [Indexed: 12/15/2022]
Abstract
Acute exacerbations of chronic hepatitis B are common, and may even be the first presentation of hepatitis B virus (HBV) infection. Sometimes, patients involved in these scenarios may have mistaken diagnosis of acute hepatitis B. The reason for the confusion is that the two forms of infection manifestation resemble remarkably in clinical, biochemical, and serological features, such as apparent rapid onset of severe disease, advanced grades of encephalopathy, high aminotransferases and prolonged international normalized ratios (INRs), as well as positivity for HBsAg and for IgM anti-HBc antibodies and DNA detection. Therefore, these two entities cannot be distinguished easily without historical information of HBV-associated chronic infection or recent HBV exposure, information that is often inaccurate. Considering the different prognoses, treatment strategies, and the epidemiological impact in the public health context, the correct diagnosis is extremely important. Despite the lack of effective and reliable tests to differentiate between acute infection and acute exacerbation of chronic HBV infection, the expression and kinetic evaluation of viral markers present in the circulation of individuals infected, the observation of physical-chemical properties of specific antibodies, and the combination of these findings represent some strategies in serology that could assist in differentiating between the two entities, or at least in the guidance for the correct diagnosis.
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Affiliation(s)
- R A A Pondé
- Laboratory of Human Virology, Institute of Tropical Pathology and Public Health, Federal University of Goiás, Goiânia, Goiás, Brazil. .,Central Goiana de Sorologia, Imuno-hematologia e Biologia Molecular, Goiânia, Goiás, Brazil. .,SUVISA-Superintendência de Vigilância em Saúde, Secretaria Estadual de Saúde, Coordenação Estadual de Controle das Hepatites Virais (CECHV), Goiânia, Goiás, Brazil. .,, Rua 7A Edifício RIOL, Nº 158, 1º andar, sala 101, setor aeroporto, Goiânia, Goiás, 74-075-030, Brazil.
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