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Ogawa B, Kamoshida T, Yamamoto A, Yamaguchi Y, Hamano Y, Okawara H, Okawara A, Kakinoki N, Hirai S. Delayed Hepatitis B Virus Reactivation at 33 Months after the Completion of Rituximab-based Chemotherapy. Intern Med 2025:5179-24. [PMID: 40222940 DOI: 10.2169/internalmedicine.5179-24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 04/15/2025] Open
Abstract
We herein report a case of hepatitis B virus (HBV) reactivation in a female patient in her 70s with isolated anti-hepatitis B core (IAHBc) antibodies (HB surface antigen (HBsAg)-negative, HB surface antibody (HBsAb)-negative, and HB core antibody (HBcAb)-positive), receiving rituximab-based chemotherapy for follicular lymphoma. Her serum HBV DNA was negative. The patient was treated with rituximab for 21 months, and 33 months after completion of treatment, her HBV DNA level increased to 5.1 Log IU/mL, and the patient developed hepatic failure. Tenofovir alafenamide fumarate treatment was initiated for HBV reactivation, and DNA was not detected 9 months later.
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Affiliation(s)
- Banri Ogawa
- Department of Gastroenterology, Hitachi General Hospital, Japan
| | | | - Asaji Yamamoto
- Department of Gastroenterology, Hitachi General Hospital, Japan
| | - Yuji Yamaguchi
- Department of Gastroenterology, Hitachi General Hospital, Japan
| | - Yukako Hamano
- Department of Gastroenterology, Hitachi General Hospital, Japan
| | - Haruka Okawara
- Department of Gastroenterology, Hitachi General Hospital, Japan
| | - Atsushi Okawara
- Department of Gastroenterology, Hitachi General Hospital, Japan
| | | | - Shinji Hirai
- Department of Gastroenterology, Hitachi General Hospital, Japan
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Fu MX, Elsharkawy A, Healy B, Jackson C, Bradshaw D, Watkins E, Ushiro-Lumb I, Griffiths J, Neuberger J, Maguire K, Desai M, McDougall N, Priddee N, Barclay ST, Blackmore S, Simmonds P, Irving WL, Harvala H. Occult hepatitis B virus infection: risk for a blood supply, but how about individuals' health? EClinicalMedicine 2025; 81:103095. [PMID: 39975699 PMCID: PMC11836515 DOI: 10.1016/j.eclinm.2025.103095] [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: 11/24/2024] [Revised: 01/14/2025] [Accepted: 01/20/2025] [Indexed: 02/21/2025] Open
Abstract
The implementation of effective blood donation screening for hepatitis B virus (HBV) anti-core antibodies with highly sensitive molecular HBV DNA detection in low-endemic countries like the United Kingdom has improved blood safety. However, the linkage to care and management for blood donors with occult HBV infection (OBI) is a complex dilemma involving virological, clinical, methodological, and social issues. Limited evidence suggests that OBI may accelerate the progression of liver disease and cancer. The need for a specialist referral for donors identified with OBI carries mixed opinions from blood establishments, hepatologists, and public health. Following extensive multidisciplinary discussions, experts agree upon a need for clear messaging for donors and to consider the oncogenic implications of OBI. Proposals for future studies are identified, and the applicability of the recommendations in low-resource, high-endemic regions is considered, as well as the inclusion of OBI in global hepatitis elimination targets.
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Affiliation(s)
- Michael X. Fu
- Nuffield Department of Medicine, University of Oxford, Oxford, UK
| | - Ahmed Elsharkawy
- Liver Unit, Queen Elizabeth Hospital Birmingham, NIHR Birmingham Biomedical Research Centre, University Hospitals Birmingham, Birmingham, UK
| | - Brendan Healy
- Public Health Wales and Swansea Bay University Health Board, Swansea, UK
| | - Celia Jackson
- West of Scotland Specialist Virology Centre, Glasgow, UK
| | - Daniel Bradshaw
- Virus Reference Department, UK Health Security Agency, London, UK
| | - Emma Watkins
- Clinical Services, NHS Blood and Transplant, Birmingham, UK
| | | | | | - James Neuberger
- Liver Unit, Queen Elizabeth Hospital Birmingham, NIHR Birmingham Biomedical Research Centre, University Hospitals Birmingham, Birmingham, UK
| | | | - Monica Desai
- Blood Safety, UK Health Security Agency, London, UK
| | | | - Nicole Priddee
- Donor Services Division, Scottish National Blood Transfusion Service, Edinburgh, UK
| | | | | | - Peter Simmonds
- Nuffield Department of Medicine, University of Oxford, Oxford, UK
| | - William L. Irving
- NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust, University of Nottingham, Nottingham, UK
| | - Heli Harvala
- Microbiology Services, NHS Blood and Transplant, Colindale, UK
- Radcliffe Department of Medicine, University of Oxford, Oxford, UK
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Hou KC, Su TH, Kao CN, Cheng HR, Tseng TC, Liu CJ, Hsieh SC, Kao JH. Rituximab carries high risks of hepatitis B virus reactivation in hematologic and rheumatic patients with chronic or resolved hepatitis B. J Gastroenterol Hepatol 2024; 39:2447-2455. [PMID: 39180413 DOI: 10.1111/jgh.16725] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/15/2024] [Revised: 06/04/2024] [Accepted: 08/09/2024] [Indexed: 08/26/2024]
Abstract
BACKGROUND AND AIM Rituximab therapy is associated with a high risk of hepatitis B virus (HBV) reactivation. We aimed to assess whether the risk of reactivation differed among various underlying diseases and between hepatitis B surface antigen (HBsAg) carriers and patients with resolved HBV infection. METHODS We retrospectively analyzed patients with chronic or resolved HBV infection who received rituximab without prophylactic anti-HBV therapy at a tertiary medical center. The risks of HBV reactivation, hepatitis, and hepatic decompensation were compared between the patients with hematologic and rheumatic diseases. RESULTS There were 78 patients with hematologic diseases and 39 patients with rheumatic diseases included. Among them, 43 (59%) HBsAg-positive patients and 24 (55%) patients with resolved HBV infection experienced HBV reactivation at a median of 14.6 months after rituximab therapy. After rituximab treatment, the 1-year HBV reactivation rate among patients with hematologic and rheumatic diseases was 29% and 45% in HBsAg-positive patients, respectively, while the rates were 38% and 17% in patients with resolved HBV infection. The reactivation risk continued to increase even 2 years after rituximab therapy and was comparable between hematologic and rheumatic patients. A higher baseline HBV DNA level (≥20 IU/mL vs <20 IU/mL) was an independent predictor for HBV reactivation (adjusted hazard ratio [aHR]: 10.9, 95% confidence interval [CI]: 1.1-107) and HBV-associated hepatitis (aHR: 14.8, 95% CI: 1.4-158). CONCLUSIONS Rituximab therapy is associated with a 50-64% risk of HBV reactivation regardless of underlying diseases and HBsAg status. HBV DNA levels should be assessed before initiating rituximab.
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Affiliation(s)
- Kuan-Chu Hou
- School of Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Tung-Hung Su
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Chien-Neng Kao
- Department of Internal Medicine, National Taiwan University Hospital, Hsin-Chu Branch, Hsin-Chu, Taiwan
| | - Huei-Ru Cheng
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Tai-Chung Tseng
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
- Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan
| | - Chun-Jen Liu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Song-Chou Hsieh
- Division of Rheumatology, Immunology and Allergy, Department of Internal Medicine, National Taiwan University Hospital, 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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Otsuki K, Imaizumi M, Murono S. Seven cases illustrating difficulties in the treatment of MPO-ANCA-positive refractory otitis media. Fukushima J Med Sci 2024; 70:175-182. [PMID: 39370277 PMCID: PMC11625855 DOI: 10.5387/fms.2023-21] [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: 04/27/2023] [Accepted: 04/12/2024] [Indexed: 10/08/2024] Open
Abstract
There are increasing reports of patients with refractory otitis media caused by anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), especially myeloperoxidase (MPO)-ANCA-positive middle ear disease. However, making a definitive diagnosis can be difficult, which can adversely affect the outcome of treatment. We reviewed the diagnostic features of MPO-ANCA-positive middle ear disease and here discuss the difficulties of timely diagnosis and treatment. Seven cases were eligible (6 women, 1 man;aged 57-83 years), and all were MPO-ANCA positive and proteinase 3 (PR3)-ANCA negative. The patients were referred to our institution for management of intractable otitis media (2/7), progressive hearing loss (7/7) with facial palsy (1/7), and/or a high MPO-ANCA titer (5/7). All patients underwent tapering steroid therapy and their MPO-ANCA titer was monitored. Refractory MPO-ANCA-positive otitis media was noted:5 of 7 cases showed improvement with tapering steroid therapy but cure was not achieved in the remaining 2 cases. This study demonstrates the difficulties in the diagnosis and treatment of localized AAV. Early diagnosis and treatment can improve the prognosis of patients with AAV but global diagnostic criteria for ear disease have not been established. Additional cases should be prospectively examined to establish a treatment for MPO-ANCA-positive middle ear disease.
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Yano Y, Sato I, Imanishi T, Yoshida R, Matsuura T, Ueda Y, Kodama Y. Clinical Significance and Remaining Issues of Anti-HBc Antibody and HBV Core-Related Antigen. Diagnostics (Basel) 2024; 14:728. [PMID: 38611641 PMCID: PMC11011781 DOI: 10.3390/diagnostics14070728] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2024] [Revised: 03/17/2024] [Accepted: 03/26/2024] [Indexed: 04/14/2024] Open
Abstract
Currently, hepatitis B virus (HBV) core antibody (anti-HBc antibody) and HBV core-related antigen (HBcrAg) are widely used as serum markers for diagnosis based on the HBV core region. This review focused on anti-HBc antibodies and HBcrAg and aimed to summarize the clinical significance of currently used assay systems and the issues involved. While anti-HBc is very significant for clinical diagnosis, the clinical significance of quantitative assay of anti-HBc antibody has been reevaluated with improvements in diagnostic performance, including its association with clinical stage and prediction of carcinogenesis and reactivation. In addition, concerning the new HBcrAg, a high-sensitivity assay method has recently been established, and its diagnostic significance, including the prediction of reactivation, is being reevaluated. On the other hand, the quantitative level of anti-HBc antibody expressed in different units among assay systems complicates the interpretation of the results. However, it is difficult to standardize assay systems as they vary in advantages, and caution is needed in interpreting the assay results. In conclusion, with the development of highly sensitive HBcrAg and anti-HBc antibody, a rapid and sensitive detection assay system has been developed and used in clinical practice. In the future, it is hoped that a global standard will be created based on the many clinical findings.
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Affiliation(s)
- Yoshihiko Yano
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan; (R.Y.); (T.M.); (Y.U.); (Y.K.)
- Department of Clinical Laboratory, Kobe University Hospital, Kobe 650-0017, Japan; (I.S.); (T.I.)
| | - Itsuko Sato
- Department of Clinical Laboratory, Kobe University Hospital, Kobe 650-0017, Japan; (I.S.); (T.I.)
| | - Takamitsu Imanishi
- Department of Clinical Laboratory, Kobe University Hospital, Kobe 650-0017, Japan; (I.S.); (T.I.)
| | - Ryutaro Yoshida
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan; (R.Y.); (T.M.); (Y.U.); (Y.K.)
| | - Takanori Matsuura
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan; (R.Y.); (T.M.); (Y.U.); (Y.K.)
| | - Yoshihide Ueda
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan; (R.Y.); (T.M.); (Y.U.); (Y.K.)
| | - Yuzo Kodama
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan; (R.Y.); (T.M.); (Y.U.); (Y.K.)
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Ohkubo M, Seo E, Doki K, Suzuki Y, Sekine I, Homma M. Impact of Hepatitis B Surface and Core Antibody Levels on Hepatitis B Virus Reactivation. Biol Pharm Bull 2024; 47:941-945. [PMID: 38735754 DOI: 10.1248/bpb.b23-00907] [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] [Indexed: 05/14/2024]
Abstract
Hepatitis B virus reactivation (HBV-R) is a serious complication that can occur in patients with resolved HBV infection during cancer chemotherapy. We examined the levels of HBV surface antibody (HBsAb) and HBV core antibody (HBcAb) to assess the incidence of HBV-R in cancer patients including hematopoietic stem cell transplantation (HSCT) and rituximab administration. This retrospective cohort study included 590 patients with resolved HBV infection. The incidence of HBV-R was evaluated 761.5 (range, 90-3898) days after the inititiation of chemotherapy. Of the patients, 13 (2.2%) developed HBV-R after the start of chemotherapy. All 13 patients exhibited lower HBsAb (<100 mIU/mL) levels at baseline. A higher level of HBcAb (≥100 cut off index (C.O.I.)) was a possible risk factor for HBV-R as well as HSCT and rituximab administration. The simultaneous presence of HBsAb <100 mIU/mL and HBcAb ≥100 C.O.I. increased the risk of HBV-R by 18.5%. Patients treated with rituximab were at a higher risk of HBV-R (18.4%) despite having HBcAb <100 C.O.I. Our results suggest that assessment of HBsAb and HBcAb levels prior to the chemotherapy is important for identifying patients at high risk of HBV-R, especially in solid cancers without HSCT and rituximab administration.
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Affiliation(s)
- Maki Ohkubo
- Department of Pharmaceutical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba
- Department of Pharmacy, University of Tsukuba Hospital
| | - Emiko Seo
- Department of Gastroenterology, Faculty of Medicine, University of Tsukuba
| | - Kosuke Doki
- Department of Pharmaceutical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba
- Department of Pharmacy, University of Tsukuba Hospital
| | - Yoshiharu Suzuki
- Department of Pharmaceutical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba
- Department of Pharmacy, University of Tsukuba Hospital
| | - Ikuo Sekine
- Department of Medical Oncology, Faculty of Medicine, University of Tsukuba
| | - Masato Homma
- Department of Pharmaceutical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba
- Department of Pharmacy, University of Tsukuba Hospital
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Kim DY, Kim YR, Suh C, Yoon DH, Yang DH, Park Y, Eom HS, Lee JO, Kwak JY, Kang HJ, Hyun SY, Jo JC, Chang MH, Yoo KH, Lim SN, Shin HJ, Kim WS, Kim IH, Kim MK, Kim HJ, Lee WS, Mun YC, Kim JS. A Prospective Study of Preemptive Tenofovir Disoproxil Fumarate Therapy in HBsAg-Positive Patients With Diffuse Large B-Cell Lymphoma Receiving Rituximab Plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone. Am J Gastroenterol 2023; 118:1373-1380. [PMID: 36728217 DOI: 10.14309/ajg.0000000000002185] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/18/2022] [Accepted: 12/28/2022] [Indexed: 02/03/2023]
Abstract
INTRODUCTION This prospective study aimed to investigate the efficacy and safety of preemptive antiviral therapy with tenofovir disoproxil fumarate (TDF) for HBsAg-positive patients with newly diagnosed diffuse large B-cell lymphoma receiving rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy. METHODS We enrolled 73 patients from 20 institutions. The primary end point was the absolute risk of hepatitis B virus (HBV)-related hepatitis during preemptive TDF therapy and for 24 weeks after withdrawal from TDF. Hepatitis was defined as a more than 3-fold increase in serum alanine aminotransferase from baseline or an alanine aminotransferase level of ≥100 U/L. HBV-related hepatitis was defined as hepatitis with an increase in serum HBV-DNA to >10 times that of the pre-exacerbation baseline or an absolute increase of ≥20,000 IU/mL compared with the baseline. RESULTS No patient developed HBV reactivation or HBV-related hepatitis during preemptive antiviral therapy (until 48 weeks after completion of R-CHOP chemotherapy) with TDF. All adverse events were grade 1 or 2. HBV reactivation was reported in 17 (23.3%) patients. All HBV reactivation was developed at a median of 90 days after withdrawal from TDF (range, 37-214 days). Six (8.2%) patients developed HBV-related hepatitis at a median of 88 days after withdrawal from TDF (range, 37-183 days). DISCUSSION Preemptive TDF therapy in HBsAg-positive patients with diffuse large B-cell lymphoma receiving R-CHOP chemotherapy was safe and effective for preventing HBV-related hepatitis. However, a long-term maintenance strategy of preemptive TDF therapy should be recommended because of the relatively high rate of HBV-related hepatitis after withdrawal from TDF ( ClinicalTrials.gov ID: NCT02354846).
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Affiliation(s)
- Do Young Kim
- Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, Severance Hospital, Seoul, Korea
| | - Yu Ri Kim
- Division of Hematology, Department of Internal Medicine, Yonsei University College of Medicine, Severance Hospital, Seoul, Korea
| | - Cheolwon Suh
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Dok Hyun Yoon
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Deok-Hwan Yang
- Department of Hematology/Oncology, Chonnam National University Hwasun Hospital, Jeollanam-do, Korea
| | - Yong Park
- Department of Internal Medicine, Korea University Medical Center, Seoul, Korea
| | - Hyeon Seok Eom
- Hematology-Oncology Clinic, National Cancer Center, Goyang, Korea
| | - Jeong-Ok Lee
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Jae-Yong Kwak
- Department of Internal Medicine, Chonbuk National University Medical School, Jeonju, Korea
| | - Hye Jin Kang
- Department of Internal Medicine, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences, Seoul, Korea
| | - Shin Young Hyun
- Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Jae-Cheol Jo
- Department of Hematology and Oncology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea
| | - Myung Hee Chang
- Department of Internal Medicine, National Health Insurance Corporation Ilsan Hospital, Goyang, Korea
| | - Kwai Han Yoo
- Departments of Internal Medicine, Gachon University Gil Medical Center, Incheon, Korea
| | - Sung-Nam Lim
- Department of Internal Medicine, Inje University Haeundae Paik Hospital, Busan, Korea
| | - Ho-Jin Shin
- Department of Internal Medicine, Pusan National University School of Medicine, Pusan National University Hospital, Busan, Korea
| | - Won Seog Kim
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - In-Ho Kim
- Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - Min Kyung Kim
- Department of Internal Medicine, Yeungnam University College of Medicine, Daegu, Korea
| | - Hyo Jung Kim
- Department of Internal Medicine, Hallym University Sacred Heart Hospital, Anyang, Korea
| | - Won-Sik Lee
- Department of Internal Medicine, Inje University Busan Paik Hospital, Busan, Korea
| | - Yeung-Chul Mun
- Department of Internal Medicine, Ewha Womans University School of Medicine, Seoul, Korea
| | - Jin Seok Kim
- Division of Hematology, Department of Internal Medicine, Yonsei University College of Medicine, Severance Hospital, Seoul, Korea
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Watanabe M, Toyoda H, Kawabata T. Rapid quantification assay of hepatitis B virus DNA in human serum and plasma by Fully Automated Genetic Analyzer μTASWako g1. PLoS One 2023; 18:e0278143. [PMID: 36758029 PMCID: PMC9910706 DOI: 10.1371/journal.pone.0278143] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2022] [Accepted: 01/20/2023] [Indexed: 02/10/2023] Open
Abstract
Real-time monitoring of serum hepatitis B virus (HBV) levels is essential for the management of patients with chronic HBV infection in clinical practice, including monitoring the resistance of anti-HBV nucleotide analog or the detection of HBV reactivation. In this context, serum HBV deoxyribonucleic acid (DNA) quantification should be rapidly measured. A rapid HBV DNA quantification assay was established on the Fully Automated Genetic Analyzer, μTASWako g1. The assay performs automated sample preparation and DNA extraction, followed by the amplification and detection of quantitative polymerase chain reaction (PCR) combined with capillary electrophoresis (qPCR-CE) on integrated microfluidic chip. This study aimed to evaluate the analytical and clinical performance of HBV DNA assay on the μTASWako g1 platform in human serum and EDTA-plasma. The HBV DNA assay has a linear quantitative range from 20 to 108 IU/mL of HBV DNA with standard deviation (SD) of ≤0.14 log10 IU/mL. The limits of detection of the assay were 4.18 for the serum and 4.35 for EDTA-plasma. The HBV assay demonstrated the equivalent performance in both human serum and EDTA-plasma matrices. The HBV genotypes A to H were detected with an accuracy of ±0.34 log10 IU/mL. In quantification range, the HBV DNA assay was correlated with Roche cobas AmpliPrep/cobas TaqMan Ver2.0 (CAP/CTM v2) (r = 0.964). The mean difference (μTASWako g1-CAP/CTM v2) of the reported HBV DNA was -0.01 log10 IU/mL. Overall, the sensitivity, accuracy, and precision of the μTASWako g1 HBV assay were comparable to the existing commercial HBV DNA assay, and the assay can be completed within 110 min. This evaluation suggests that the HBV DNA assay on the μTASWako g1 is potentially applied for alternative method of the HBV viral load test, in particular with the advantage of the HBV DNA result availability within 2 h, improving the HBV infection management.
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Affiliation(s)
- Moto Watanabe
- Diagnostics Research Laboratories, FUJIFILM Wako Pure Chemical Corporation, Amagasaki, Hyogo, Japan
| | - Hidenori Toyoda
- Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Gifu, Japan
| | - Tomohisa Kawabata
- Department of Diagnostics Development, FUJIFILM Wako Pure Chemical Corporation, Chuo-Ku, Tokyo, Japan
- * E-mail:
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Yamada R, Morikawa K, Hotta K, Iwami D, Tanabe T, Murai S, Shinohara N, Yoshida S, Hosoda S, Kubo A, Tokuchi Y, Kitagataya T, Kimura M, Yamamoto K, Nakai M, Sho T, Suda G, Natsuizaka M, Ogawa K, Sakamoto N. Incidence of post-transplant hepatitis B virus reactivation with the use of kidneys from donors with resolved hepatitis B virus infection. J Viral Hepat 2022; 29:976-985. [PMID: 36031873 DOI: 10.1111/jvh.13740] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2022] [Revised: 07/11/2022] [Accepted: 07/19/2022] [Indexed: 12/09/2022]
Abstract
Donors with resolved hepatitis B virus (HBV) infection may be a solution for the organ shortage for kidney transplantation (KT). The purpose of this study was to clarify the current state of HBV markers after KT from donors with resolved HBV infection to HBV naïve recipients and the rate of HBV reactivation in recipients with resolved HBV infection. Furthermore, we investigated HBV covalently closed circular DNA (cccDNA) in transplanted organs from donors with resolved HBV infection and the capability of HBV replication in kidney cell lines. We retrospectively analysed the HBV status of 340 consecutive donors and recipients who underwent KT in a single centre. We prospectively measured cccDNA by real-time polymerase chain reaction in kidney biopsy specimens of 32 donors with resolved HBV infection. HBV reactivation was found in three recipients with resolved HBV infection (4.8%, 3/63) after KT. We analysed 45 cases of transplantation from donors with resolved HBV infection to HBV-naive recipients. One case (2.2%, 1/45) became seropositive for hepatitis B core antibody (anti-HBc) and in another case (2.2%, 1/45), HBV-DNA was detected qualitatively in an HBV naive recipient with a donor with resolved HBV infection. In the latter case, cccDNA was measured in the donor kidney during KT. HBV replication was observed in kidney cell lines with HBV plasmid transfection. In conclusion, the risk of reactivation in anti-HBc-positive donors is relatively low. However, post-transplant HBV monitoring should be conducted in all at-risk cases.
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Affiliation(s)
- Ren Yamada
- Department of Gastroenterology and Hepatology, Hokkaido University Faculty of Medicine and Graduate School of Medicine, Sapporo, Japan
| | - Kenichi Morikawa
- Department of Gastroenterology and Hepatology, Hokkaido University Faculty of Medicine and Graduate School of Medicine, Sapporo, Japan
| | - Kiyohiko Hotta
- Department of Renal and Genitourinary Surgery, Hokkaido University Faculty of Medicine and Graduate School of Medicine, Sapporo, Japan
| | - Daiki Iwami
- Department of Renal and Genitourinary Surgery, Hokkaido University Faculty of Medicine and Graduate School of Medicine, Sapporo, Japan.,Surgical Branch, Institute of Kidney Diseases, Jichi Medical University Hospital, Shimotsuke, Japan
| | - Tatsu Tanabe
- Department of Renal and Genitourinary Surgery, Hokkaido University Faculty of Medicine and Graduate School of Medicine, Sapporo, Japan
| | - Sachiyo Murai
- Department of Renal and Genitourinary Surgery, Hokkaido University Faculty of Medicine and Graduate School of Medicine, Sapporo, Japan
| | - Nobuo Shinohara
- Department of Renal and Genitourinary Surgery, Hokkaido University Faculty of Medicine and Graduate School of Medicine, Sapporo, Japan
| | - Sonoe Yoshida
- Department of Gastroenterology and Hepatology, Hokkaido University Faculty of Medicine and Graduate School of Medicine, Sapporo, Japan
| | - Shunichi Hosoda
- Department of Gastroenterology and Hepatology, Hokkaido University Faculty of Medicine and Graduate School of Medicine, Sapporo, Japan
| | - Akinori Kubo
- Department of Gastroenterology and Hepatology, Hokkaido University Faculty of Medicine and Graduate School of Medicine, Sapporo, Japan
| | - Yoshimasa Tokuchi
- Department of Gastroenterology and Hepatology, Hokkaido University Faculty of Medicine and Graduate School of Medicine, Sapporo, Japan
| | - Takashi Kitagataya
- Department of Gastroenterology and Hepatology, Hokkaido University Faculty of Medicine and Graduate School of Medicine, Sapporo, Japan
| | - Megumi Kimura
- Department of Gastroenterology and Hepatology, Hokkaido University Faculty of Medicine and Graduate School of Medicine, Sapporo, Japan
| | - Koji Yamamoto
- Department of Gastroenterology and Hepatology, Hokkaido University Faculty of Medicine and Graduate School of Medicine, Sapporo, Japan
| | - Masato Nakai
- Department of Gastroenterology and Hepatology, Hokkaido University Faculty of Medicine and Graduate School of Medicine, Sapporo, Japan
| | - Takuya Sho
- Department of Gastroenterology and Hepatology, Hokkaido University Faculty of Medicine and Graduate School of Medicine, Sapporo, Japan
| | - Goki Suda
- Department of Gastroenterology and Hepatology, Hokkaido University Faculty of Medicine and Graduate School of Medicine, Sapporo, Japan
| | - Mitsuteru Natsuizaka
- Department of Gastroenterology and Hepatology, Hokkaido University Faculty of Medicine and Graduate School of Medicine, Sapporo, Japan
| | - Koji Ogawa
- Department of Gastroenterology and Hepatology, Hokkaido University Faculty of Medicine and Graduate School of Medicine, Sapporo, Japan
| | - Naoya Sakamoto
- Department of Gastroenterology and Hepatology, Hokkaido University Faculty of Medicine and Graduate School of Medicine, Sapporo, Japan
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10
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Hagiwara S, Kusumoto S, Inoue T, Ogawa S, Narita T, Ito A, Ri M, Komatsu H, Suzuki T, Matsuura K, Yagi S, Kaneko A, Aoyagi K, Iida S, Tanaka Y. Management of hepatitis B virus (HBV) reactivation in patients with resolved HBV infection based on a highly sensitive HB core-related antigen assay. Hepatol Res 2022; 52:745-753. [PMID: 35199427 DOI: 10.1111/hepr.13761] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/16/2022] [Revised: 02/13/2022] [Accepted: 02/18/2022] [Indexed: 12/23/2022]
Abstract
AIMS To prevent hepatitis B virus (HBV) reactivation-related hepatitis, we examined the clinical usefulness of a highly sensitive HB core-related antigen (iTACT-HBcrAg) assay in patients with resolved HBV infection after nucleos(t)ide analog (NA) treatment for HBV reactivation. METHODS We retrospectively analyzed 27 patients with resolved HBV infection who experienced HBV reactivation (defined as HBV DNA levels of 1.3 log IU/ml or more), and who received systemic chemotherapies for hematological malignancies between 2008 and 2020. iTACT-HBcrAg, HBsAg-HQ, and antibodies against hepatitis B surface antigen (anti-HBs) were measured using samples stored after HBV reactivation. The lower limit of quantification for iTACT-HBcrAg was 2.0 log U/ml. RESULTS HBV reactivation was diagnosed at a median HBV DNA level of 1.8 log IU/ml, and then all patients received NA treatment. No patient had HBV-related hepatitis with a median maximum HBV DNA level of 2.0 log IU/ml. The positivities of iTACT-HBcrAg and HBsAg-HQ were 96% and 52% after HBV reactivation, respectively. Of 25 patients with detectable iTACT-HBcrAg at the initiation of NA treatment, 17 (68%) achieved iTACT-HBcrAg loss. Median durations from NA treatment to HBV DNA loss and iTACT-HBcrAg loss or the last follow-up were 35 and 175 days, respectively. Recurrence of HBV reactivation after NA cessation was not observed in seven of eight patients who achieved iTACT-HBcrAg loss or seropositive for anti-HBs during follow-up, except for one without anti-HBs after allogeneic transplantation. CONCLUSIONS iTACT-HBcrAg could be a potential surrogate marker for diagnosing early-stage HBV reactivation as well as safe cessation of NA treatment in patients with resolved HBV infection after HBV reactivation.
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Affiliation(s)
- Shinya Hagiwara
- Department of Hematology and Oncology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Shigeru Kusumoto
- Department of Hematology and Oncology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Takako Inoue
- Department of Clinical Laboratory Medicine, Nagoya City University Hospital, Nagoya, Japan
| | - Shintaro Ogawa
- Department of Virology and Liver Unit, 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
| | - Asahi Ito
- Department of Hematology and Oncology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Masaki Ri
- Department of Hematology and Oncology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Hirokazu Komatsu
- Department of Hematology and Oncology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Takanori Suzuki
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Kentaro Matsuura
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Shintaro Yagi
- Department of Research and Development, Advanced Life Science Institute, Inc., Hachioji, Japan
| | - Atsushi Kaneko
- Research and Development Division, Fujirebio Inc., Hachioji, Japan
| | - Katsumi Aoyagi
- Department of Research and Development, Advanced Life Science Institute, Inc., Hachioji, Japan
- Research and Development Division, Fujirebio Inc., Hachioji, Japan
| | - Shinsuke Iida
- Department of Hematology and Oncology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Yasuhito Tanaka
- Department of Virology and Liver Unit, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
- Department of Gastroenterology and Hepatology, Kumamoto University, Kumamoto, Japan
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11
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Li Z, Meng F, Li J, Wu T. Donor-Derived CD7 CAR-T Therapy Followed by Allogeneic Hematopoietic Stem Cell Transplantation for Acute T-Lymphocytic Leukemia Associated With Hepatitis B: A Case Report. Front Immunol 2022; 13:931452. [PMID: 35903089 PMCID: PMC9314645 DOI: 10.3389/fimmu.2022.931452] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2022] [Accepted: 06/14/2022] [Indexed: 12/14/2022] Open
Abstract
The use of chimeric antigen receptor T cells (CAR-Ts) is effective in the treatment of hematological malignancies. It has been reported that HBV is reactivated after CAR-T immunotherapy for refractory/relapsed hematological malignant B-cell tumors. However, there is little literature on donor-derived CAR-T therapy combined with allogeneic hematopoietic stem cell transplantation in hepatitis B patients with acute T-lymphocytic leukemia. We report the case of one patient with hepatitis B associated with relapsed/refractory acute T-lymphocytic leukemia (T-ALL) treated with donor-derived CD7 CAR-T therapy and allogeneic hematopoietic stem cell transplantation. During treatment, the copy number of hepatitis B virus continuously decreased, and AST, ALT, DBIL and TBIL remained within the controllable ranges. CD7-negative MRD recurred 4.5 months after transplantation, and the flow cytometry results became negative after immunosuppressive reduction. Seven months after transplantation, the patient had complete remission, and the copy number of hepatitis B virus decreased to below 102. This is the first study on the safety and effectiveness of donor-derived CD7 CAR-T therapy bridging to allogeneic hematopoietic stem cell transplantation in a patient with relapsed/refractory acute T-lymphocytic leukemia and hepatitis B.
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12
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Saitta C, Pollicino T, Raimondo G. Occult Hepatitis B Virus Infection: An Update. Viruses 2022; 14:v14071504. [PMID: 35891484 PMCID: PMC9318873 DOI: 10.3390/v14071504] [Citation(s) in RCA: 47] [Impact Index Per Article: 15.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2022] [Revised: 06/28/2022] [Accepted: 06/29/2022] [Indexed: 11/16/2022] Open
Abstract
Occult hepatitis B virus (HBV) infection (OBI) refers to a condition in which replication-competent viral DNA is present in the liver (with detectable or undetectable HBV DNA in the serum) of individuals testing negative for the HBV surface antigen (HBsAg). In this peculiar phase of HBV infection, the covalently closed circular DNA (cccDNA) is in a low state of replication. Many advances have been made in clarifying the mechanisms involved in such a suppression of viral activity, which seems to be mainly related to the host's immune control and epigenetic factors. OBI is diffused worldwide, but its prevalence is highly variable among patient populations. This depends on different geographic areas, risk factors for parenteral infections, and assays used for HBsAg and HBV DNA detection. OBI has an impact in several clinical contexts: (a) it can be transmitted, causing a classic form of hepatitis B, through blood transfusion or liver transplantation; (b) it may reactivate in the case of immunosuppression, leading to the possible development of even fulminant hepatitis; (c) it may accelerate the progression of chronic liver disease due to different causes toward cirrhosis; (d) it maintains the pro-oncogenic properties of the "overt" infection, favoring the development of hepatocellular carcinoma.
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Affiliation(s)
- Carlo Saitta
- Division of Medicine and Hepatology, University Hospital of Messina, 98124 Messina, Italy;
- Department of Clinical and Experimental Medicine, University of Messina, 98124 Messina, Italy
| | - Teresa Pollicino
- Department of Human Pathology, University Hospital of Messina, 98124 Messina, Italy;
| | - Giovanni Raimondo
- Division of Medicine and Hepatology, University Hospital of Messina, 98124 Messina, Italy;
- Department of Clinical and Experimental Medicine, University of Messina, 98124 Messina, Italy
- Correspondence: ; Tel.: +39-(0)-902212392
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13
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Sagnelli C, Sica A, Creta M, Borsetti A, Ciccozzi M, Sagnelli E. Prevention of HBV Reactivation in Hemato-Oncologic Setting during COVID-19. Pathogens 2022; 11:567. [PMID: 35631088 PMCID: PMC9144674 DOI: 10.3390/pathogens11050567] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2022] [Revised: 05/06/2022] [Accepted: 05/10/2022] [Indexed: 02/04/2023] Open
Abstract
Onco-hematologic patients are highly susceptible to SARS-CoV-2 infection and, once infected, frequently develop COVID-19 due to the immunosuppression caused by tumor growth, chemotherapy and immunosuppressive therapy. In addition, COVID-19 has also been recognized as a further cause of HBV reactivation, since its treatment includes the administration of corticosteroids and some immunosuppressive drugs. Consequently, onco-hematologic patients should undergo SARS-CoV-2 vaccination and comply with the rules imposed by lockdowns or other forms of social distancing. Furthermore, onco-hematologic facilities should be adapted to new needs and provided with numerically adequate health personnel vaccinated against SARS-CoV-2 infection. Onco-hematologic patients, both HBsAg-positive and HBsAg-negative/HBcAb-positive, may develop HBV reactivation, made possible by the support of the covalently closed circular DNA (cccDNA) persisting in the hepatocytic nuclei of patients with an ongoing or past HBV infection. This occurrence must be prevented by administering high genetic barrier HBV nucleo(t)side analogues before and throughout the antineoplastic treatment, and then during a long-term post-treatment follow up. The prevention of HBV reactivation during the SARS-CoV-2 pandemic is the topic of this narrative review.
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Affiliation(s)
- Caterina Sagnelli
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, University of Campania “Luigi Vanvitelli”, 80131 Naples, Italy;
| | - Antonello Sica
- Department of Precision Medicine, University of Campania “Luigi Vanvitelli”, 80131 Naples, Italy;
| | - Massimiliano Creta
- Department of Neurosciences, Reproductive Sciences and Odontostomatology, University of Naples Federico II, 80131 Naples, Italy;
| | - Alessandra Borsetti
- National HIV/AIDS Research Center, Istituto Superiore di Sanità, 00161 Rome, Italy;
| | - Massimo Ciccozzi
- Medical Statistics and Molecular Epidemiology Unit, Campus Bio-Medico University, 00128 Rome, Italy;
| | - Evangelista Sagnelli
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, University of Campania “Luigi Vanvitelli”, 80131 Naples, Italy;
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14
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Franzè MS, Pollicino T, Raimondo G, Squadrito G. Occult hepatitis B virus infection in hepatitis C virus negative chronic liver diseases. Liver Int 2022; 42:963-972. [PMID: 35246933 PMCID: PMC9310828 DOI: 10.1111/liv.15233] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/11/2021] [Revised: 01/09/2022] [Accepted: 02/16/2022] [Indexed: 01/26/2023]
Abstract
Data concerning the prevalence of hepatitis B virus (HBV) occult infection (OBI) varies greatly in the different studies according to the sensitivity and specificity of the diagnostic approaches and the HBV prevalence in the different populations examined. The clinical implications of OBI are still debated. While the impact of OBI in HBV transmission as well as in HBV reactivation under immunosuppression are well established, the role of OBI in liver disease and hepatocellular carcinoma (HCC) development are still not definitively elucidated. It has been hypothesized that OBI might contribute to worsening the liver disease course when other causes of liver damage co-exist. Furthermore, much evidence suggests a role of OBI in the hepato-carcinogenesis processes through both indirect and direct oncogenic mechanisms that might favour HCC development. Data on the OBI clinical implications mainly come from studies performed in patients with hepatitis C virus (HCV) infection. However, HCV prevalence has dramatically fallen in the past years also because of the advent of specific and highly effective direct acting antivirals, with a consequent abrupt change of the worldwide scenario of chronic liver disease. Information about OBI prevalence and possible clinical impact in non-HCV-related liver disease are fragmentary, and the objective of this review is to critically summarize the available data in this field.
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Affiliation(s)
- Maria Stella Franzè
- Department of Clinical and Experimental MedicineMessina UniversityMessinaItaly
- Division of Medicine and HepatologyMessina University HospitalMessinaItaly
| | - Teresa Pollicino
- Department of Human PathologyMessina UniversityMessinaItaly
- Division of Advanced Diagnostic LaboratoriesMessina University HospitalMessinaItaly
| | - Giovanni Raimondo
- Department of Clinical and Experimental MedicineMessina UniversityMessinaItaly
- Division of Medicine and HepatologyMessina University HospitalMessinaItaly
| | - Giovanni Squadrito
- Department of Clinical and Experimental MedicineMessina UniversityMessinaItaly
- Division of Internal MedicineMessina University HospitalMessinaItaly
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15
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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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16
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Matsuno T, Matsuura H, Fujii S, Tanaka A, Satake M, Kinoshita T, Tomita A, Matsui Y, Sugiura Y, Miura Y. Prolonged incubation period of hepatitis B in a recipient of a nucleic acid amplification test-negative hepatitis B virus window donation. Transfusion 2021; 61:2782-2787. [PMID: 34258757 DOI: 10.1111/trf.16557] [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: 02/02/2021] [Revised: 05/24/2021] [Accepted: 05/27/2021] [Indexed: 11/30/2022]
Abstract
BACKGROUND The occurrence of transfusion-transmitted hepatitis B virus (HBV) infection has fallen dramatically due to continuous improvements in pre-transfusion laboratory testing. However, the characteristics of transfusion-transmitted HBV infection caused by individual donor nucleic acid amplification test (ID-NAT)-negative blood products are unclear. CASE PRESENTATION A 76-year-old woman with acute myeloid leukemia was diagnosed with transfusion-transmitted HBV infection after receiving apheresis platelets derived from an ID-NAT-negative blood donation. This case was diagnosed definitively as transfusion-mediated because complete nucleotide homology of a 1556 bp region of the HBV Pol/preS1-preS2-S genes and a 23 bp region of the HBV core promoter/precore between the donor and recipient strains was confirmed by PCR-directed sequencing. The case is uncommon with respect to the unexpectedly prolonged HBV-DNA incubation period of nearly 5 months after transfusion (previously, the longest period observed since the recent implementation of ID-NAT pre-transfusion laboratory testing in Japan was 84 days). Slow-replicating HBV genotype A2 may contribute to the prolonged incubation period; also, the quantity of apheresis platelets delivered in a large volume of plasma, and/or the immune response of the recipient suffering from a hematological neoplasm, may have contributed to establishment of HBV infection in the recipient. This was supported by analysis of three previously documented cases of transfusion-transmitted HBV infection by blood products derived from ID-NAT-negative donations in Japan. CONCLUSION Continuous monitoring of HBV infection for longer periods (>3 months) may be required after transfusion of blood components from an ID-NAT-negative HBV window donation.
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Affiliation(s)
- Takahiro Matsuno
- Department of Blood Transfusion, Fujita Health University Hospital, Toyoake, Aichi, Japan
| | - Hideaki Matsuura
- Department of Blood Transfusion, Fujita Health University Hospital, Toyoake, Aichi, Japan.,Department of Molecular Laboratory Medicine, Fujita Health University School of Medical Sciences, Toyoake, Aichi, Japan
| | - Sumie Fujii
- Department of Transfusion Medicine and Cell Therapy, Fujita Health University School of Medicine, Toyoake, Aichi, Japan
| | - Ami Tanaka
- Central Blood Institute, Blood Service Headquarters, Japanese Red Cross Society, Tokyo, Japan
| | - Masahiro Satake
- Central Blood Institute, Blood Service Headquarters, Japanese Red Cross Society, Tokyo, Japan
| | | | - Akihiro Tomita
- Department of Hematology, Fujita Health University School of Medicine, Toyoake, Aichi, Japan
| | - Yusuke Matsui
- School of Public Health, Division of Infectious Diseases and Vaccinology, University of California, Berkeley, California, USA
| | - Yukari Sugiura
- Department of Blood Transfusion, Fujita Health University Hospital, Toyoake, Aichi, Japan
| | - Yasuo Miura
- Department of Blood Transfusion, Fujita Health University Hospital, Toyoake, Aichi, Japan.,Department of Transfusion Medicine and Cell Therapy, Fujita Health University School of Medicine, Toyoake, Aichi, Japan
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17
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Nayak SP, Roy S. Immune phase transition under steroid treatment. Phys Rev E 2021; 103:062401. [PMID: 34271610 DOI: 10.1103/physreve.103.062401] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2020] [Accepted: 05/11/2021] [Indexed: 11/07/2022]
Abstract
The steroid hormone glucocorticoid (GC) is a well-known immunosuppressant that controls T-cell-mediated adaptive immune response. In this work, we have developed a minimal kinetic network model of T-cell regulation connecting relevant experimental and clinical studies to quantitatively understand the long-term effects of GC on pro-inflammatory T-cell (T_{pro}) and anti-inflammatory T-cell (T_{anti}) dynamics. Due to the antagonistic relation between these two types of T cells, their long-term steady-state population ratio helps us to characterize three classified immune regulations: (i) weak ([T_{pro}]>[T_{anti}]), (ii) strong ([T_{pro}]<[T_{anti}]), and (iii) moderate ([T_{pro}]∼[T_{anti}]), holding the characteristic bistability. In addition to the differences in their long-term steady-state outcome, each immune regulation shows distinct dynamical phases. In the presteady state, a characteristic intermediate stationary phase is observed to develop only in the moderate regulation regime. In the medicinal field, the resting time in this stationary phase is distinguished as a clinical latent period. GC dose-dependent steady-state analysis shows an optimal level of GC to drive a phase transition from the weak or autoimmune prone to the moderate regulation regime. Subsequently, the presteady state clinical latent period tends to diverge near that optimal GC level where [T_{pro}]:[T_{anti}] is highly balanced. The GC-optimized elongated stationary phase explains the rationale behind the requirement of long-term immune diagnostics, especially when long-term GC-based chemotherapeutics and other immunosuppressive drugs are administrated. Moreover, our study reveals GC sensitivity of clinical latent period, which might serve as an early warning signal in diagnosing different immune phases and determining immune phasewise steroid treatment.
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Affiliation(s)
| | - Susmita Roy
- Department of Chemical Sciences, Indian Institute of Science Education and Research Kolkata, Campus Road, Mohanpur, West Bengal 741246, India
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18
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Takakusagi S, Takagi H, Yokoyama Y, Kizawa K, Marubashi K, Kosone T, Nagashima S, Takahashi M, Murata K, Okamoto H. Spontaneous reactivation of hepatitis B virus with a frameshift mutation in the precore region in an elderly hepatitis B virus carrier with lifestyle-related diseases. Clin J Gastroenterol 2021; 14:1202-1210. [PMID: 33959934 DOI: 10.1007/s12328-021-01423-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2021] [Accepted: 04/21/2021] [Indexed: 12/20/2022]
Abstract
A 76-year-old woman with spontaneous reactivation of hepatitis B virus (HBV) without any immunosuppressants who had been successfully treated with tenofovir alafenamide fumarate (TAF) was reported. The patient was admitted to our hospital because of acute exacerbation of the liver function and jaundice. She had been found to have chronic HBV infection with a normal liver function and had been treated for lifestyle-related diseases, such as diabetes mellitus, dyslipidemia and hypertension, for over 10 years at a local clinic. At admission, her serum HBV DNA was high (7.3 log IU/mL), and anti-hepatitis B core protein immunoglobulin M was slightly elevated (1.47 S/CO). Due to the absence of known risk factors for HBV reactivation, the reactivation was regarded as "spontaneous". After the initiation of the nucleotide analog TAF, her liver function gradually improved with a decrease in the HBV DNA load. Her HBV genome was typed as subgenotype B1 and possessed a frameshift mutation due to an insertion of T after nucleotide (nt) 1817 and G to A mutations at nt 1896 and nt 1899 (G1896A/G1899A) in the precore region as well as serine to glutamine substitution of amino acid 21 in the core protein. In addition to these viral mutations, aging and complications of lifestyle-related diseases in the present case may have been responsible for the spontaneous HBV reactivation. Careful observation and management of aged HBV carriers with underlying diseases are needed even when persistent HBV infection is free from symptoms and liver dysfunction and no immunosuppressive conditions are involved.
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Affiliation(s)
- Satoshi Takakusagi
- Department of Gastroenterology and Hepatology, Kusunoki Hospital, 607-22, Fujioka, Gunma, 375-0024, Japan
| | - Hitoshi Takagi
- Department of Gastroenterology and Hepatology, Kusunoki Hospital, 607-22, Fujioka, Gunma, 375-0024, Japan.
| | - Yozo Yokoyama
- Department of Gastroenterology and Hepatology, Kusunoki Hospital, 607-22, Fujioka, Gunma, 375-0024, Japan
| | - Kazuko Kizawa
- Department of Gastroenterology and Hepatology, Kusunoki Hospital, 607-22, Fujioka, Gunma, 375-0024, Japan
| | - Kyoko Marubashi
- Department of Gastroenterology and Hepatology, Kusunoki Hospital, 607-22, Fujioka, Gunma, 375-0024, Japan
| | - Takashi Kosone
- Department of Gastroenterology and Hepatology, Kusunoki Hospital, 607-22, Fujioka, Gunma, 375-0024, Japan
| | - Shigeo Nagashima
- Division of Virology, Department of Infection and Immunity, Jichi Medical University School of Medicine, 3311-1 Yakushiji, Shimotsuke, Tochigi, 329-0498, Japan
| | - Masaharu Takahashi
- Division of Virology, Department of Infection and Immunity, Jichi Medical University School of Medicine, 3311-1 Yakushiji, Shimotsuke, Tochigi, 329-0498, Japan
| | - Kazumoto Murata
- Division of Virology, Department of Infection and Immunity, Jichi Medical University School of Medicine, 3311-1 Yakushiji, Shimotsuke, Tochigi, 329-0498, Japan
| | - Hiroaki Okamoto
- Division of Virology, Department of Infection and Immunity, Jichi Medical University School of Medicine, 3311-1 Yakushiji, Shimotsuke, Tochigi, 329-0498, Japan
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19
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Yamauchi N, Maruyama D, Choi I, Atsuta Y, Sakai R, Miyashita K, Moriuchi Y, Tsujimura H, Kubota N, Yamamoto G, Igarashi T, Izutsu K, Yoshida S, Kojima K, Uchida T, Inoue Y, Tsukamoto N, Ohtsuka E, Suzuki S, Inaguma Y, Ichikawa S, Gomyo H, Ushijima Y, Nosaka K, Kurata M, Tanaka Y, Ueda R, Mizokami M, Kusumoto S. Prophylactic antiviral therapy for hepatitis B virus surface antigen-positive patients with diffuse large B-cell lymphoma treated with rituximab-containing chemotherapy. Cancer Sci 2021; 112:1943-1954. [PMID: 33576088 PMCID: PMC8088933 DOI: 10.1111/cas.14846] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2020] [Revised: 02/08/2021] [Accepted: 02/09/2021] [Indexed: 12/15/2022] Open
Abstract
We conducted a nationwide retrospective analysis of 116 hepatitis B virus (HBV) surface antigen (HBsAg)-positive patients with diffuse large B-cell lymphoma (DLBCL) and 278 HBsAg-negative patients with DLBCL, as a control cohort, who received rituximab-containing regimens as an induction chemotherapy at 30 Japanese medical centers between January 2004 and December 2014. Hepatitis was defined as an absolute serum alanine aminotransferase (ALT) level of ≥100 U/L. HBV reactivation-related hepatitis was defined as hepatitis with an absolute serum HBV DNA level of ≥3.3 log IU/mL or an absolute increase of ≥2 log compared with the baseline value. HBsAg-positive patients were divided into three groups based on anti-HBV prophylactic therapy: no nucleos(t)ide analogue (non-NA, n = 9), lamivudine (LAM, n = 20), and entecavir (ETV, n = 87). The 4-year cumulative incidence (CI) of hepatitis in HBsAg-positive and HBsAg-negative patients was 21.1% and 14.6% (P = .081), respectively. The 4-year CI of HBV reactivation-related hepatitis was higher in HBsAg-positive patients than in HBsAg-negative patients (8.0% vs 0.4%; P < .001). Among HBsAg-positive patients, the 4-year CI of HBV reactivation-related hepatitis was the highest in the non-NA group (33.3%), followed by the LAM (15.0%) and ETV (3.8%) groups (P < .001). Of note, 3 non-NA patients (33%) and 1 LAM patient (5%) (but no ETV patients) died due to HBV hepatitis. Based on Cox multivariate analysis, HBsAg positivity was not associated with poor overall survival. Prophylactic use of ETV would reduce the occurrence of HBV reactivation-related hepatitis and mortality in HBsAg-positive DLBCL patients receiving rituximab-containing chemotherapy.
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MESH Headings
- Adult
- Aged
- Aged, 80 and over
- Alanine Transaminase/blood
- Antineoplastic Agents, Immunological/therapeutic use
- Antineoplastic Combined Chemotherapy Protocols/administration & dosage
- Antineoplastic Combined Chemotherapy Protocols/therapeutic use
- Antiviral Agents/therapeutic use
- Case-Control Studies
- Cyclophosphamide/administration & dosage
- DNA, Viral/blood
- Doxorubicin/administration & dosage
- Doxorubicin/analogs & derivatives
- Female
- Hepatitis B/blood
- Hepatitis B/drug therapy
- Hepatitis B/epidemiology
- Hepatitis B Surface Antigens/blood
- Hepatitis B virus/genetics
- Humans
- Incidence
- Induction Chemotherapy/methods
- Japan/epidemiology
- Liver Function Tests
- Lymphoma, Large B-Cell, Diffuse/blood
- Lymphoma, Large B-Cell, Diffuse/drug therapy
- Lymphoma, Large B-Cell, Diffuse/immunology
- Lymphoma, Large B-Cell, Diffuse/virology
- Male
- Middle Aged
- Prednisone/administration & dosage
- Retrospective Studies
- Rituximab/administration & dosage
- Rituximab/therapeutic use
- Survival Analysis
- Vincristine/administration & dosage
- Virus Activation
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Affiliation(s)
- Nobuhiko Yamauchi
- Department of HematologyNational Cancer Center East HospitalKashiwaJapan
| | - Dai Maruyama
- Department of HematologyNational Cancer Center HospitalTokyoJapan
| | - Ilseung Choi
- Department of HematologyNational Hospital Organization Kyushu Cancer CenterFukuokaJapan
| | - Yoshiko Atsuta
- Japanese Data Center for Hematopoietic Cell TransplantationNagoyaJapan
| | - Rika Sakai
- Department of Hematology and Medical OncologyKanagawa Cancer CenterYokohamaJapan
| | - Kazuho Miyashita
- Department of HematologyYokohama City University Medical CenterYokohamaJapan
| | | | | | - Nobuko Kubota
- Department of HematologySaitama Cancer CenterSaitamaJapan
| | - Go Yamamoto
- Department of HematologyToranomon HospitalTokyoJapan
| | | | - Koji Izutsu
- Department of HematologyNational Cancer Center HospitalTokyoJapan
| | - Shinichiro Yoshida
- Department of HematologyNational Hospital Organization Nagasaki Medical CenterOhmuraJapan
| | - Kensuke Kojima
- Division of Hematology, Respiratory Medicine and OncologyDepartment of Internal MedicineFaculty of MedicineSaga UniversitySagaJapan
| | - Toshiki Uchida
- Department of Hematology and OncologyJapanese Red Cross Nagoya Daini HospitalNagoyaJapan
| | - Yoshiko Inoue
- Department of HematologyNational Hospital Organization Kumamoto Medical CenterKumamotoJapan
| | | | - Eiichi Ohtsuka
- Department of HematologyOita prefectural HospitalOitaJapan
| | - Sachiko Suzuki
- Department of HematologyNational Hospital Organization Hokkaido Cancer CenterSapporoJapan
| | - Yoko Inaguma
- Division of HematologyFujita Health UniversityToyoakeJapan
| | - Satoshi Ichikawa
- Hematology and RheumatologyTohoku University Graduate School of MedicineSendaiJapan
| | - Hiroshi Gomyo
- Division of HematologyHyogo Cancer CenterAkashiJapan
| | - Yoko Ushijima
- Hematology and OncologyNagoya University Graduate School of MedicineNagoyaJapan
| | - Kisato Nosaka
- Department of HematologyKumamoto University HospitalKumamotoJapan
| | - Mio Kurata
- Japanese Data Center for Hematopoietic Cell TransplantationNagoyaJapan
| | - Yasuhito Tanaka
- Department of Virology and Liver unitNagoya City University Graduate School of Medical SciencesNagoyaJapan
- Department of Gastroenterology and HepatologyFaculty of Life SciencesKumamoto UniversityKumamotoJapan
| | - Ryuzo Ueda
- Department of Tumor ImmunologyAichi Medical University School of MedicineNagakuteJapan
| | - Masashi Mizokami
- Genome Medical Sciences ProjectNational Center for Global Health and MedicineIchikawaJapan
| | - Shigeru Kusumoto
- Department of Hematology and OncologyNagoya City University Graduate School of Medical SciencesNagoyaJapan
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20
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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: 6] [Impact Index Per Article: 1.5] [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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21
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Tsuruya K, Anzai K, Shioyama S, Ito A, Arase Y, Hirose S, Tanaka Y, Suzuki H, Kagawa T. Case of hepatitis B virus reactivation after ibrutinib therapy in which the patient remained negative for hepatitis B surface antigens throughout the clinical course. Hepatol Res 2021; 51:239-244. [PMID: 32978866 DOI: 10.1111/hepr.13575] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2020] [Revised: 08/28/2020] [Accepted: 09/08/2020] [Indexed: 12/17/2022]
Abstract
A 71-year-old man was diagnosed with B-cell chronic lymphocytic leukemia. He was negative for hepatitis B surface antigen (HBsAg), positive for antibodies against the hepatitis B surface and core, and negative for hepatitis B virus (HBV)-DNA before starting chemotherapy. A total of 13 months after the initiation of ibrutinib (a Bruton's tyrosine kinase inhibitor), the patient's alanine aminotransferase levels suddenly increased to 427 U/L. As the level of serum HBV-DNA increased to 5.2 logIU/mL, a diagnosis of HBV reactivation was made, whereas the patient remained negative for HBsAg. The patient's serum alanine aminotransferase levels normalized after the initiation of entecavir at a dose of 1 mg/day. However, it took >1 year to achieve an undetectable level of HBV-DNA, even with an add-on therapy of tenofovir disoproxil fumarate. Interestingly, the patient remained negative for HBsAg throughout the clinical course owing to triple HBsAg escape mutations: Q101K, M133L, and G145A.
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Affiliation(s)
- Kota Tsuruya
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Tokai University School of Medicine, Isehara, Japan
| | - Kazuya Anzai
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Tokai University School of Medicine, Isehara, Japan
| | - Shunsuke Shioyama
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Tokai University School of Medicine, Isehara, Japan
| | - Ayano Ito
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Tokai University School of Medicine, Isehara, Japan
| | - Yoshitaka Arase
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Tokai University School of Medicine, Isehara, Japan
| | - Shunji Hirose
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Tokai University School of Medicine, Isehara, Japan
| | - Yasuhito Tanaka
- Department of Gastroenterology and Hepatology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan
| | - Hidekazu Suzuki
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Tokai University School of Medicine, Isehara, Japan
| | - Tatehiro Kagawa
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Tokai University School of Medicine, Isehara, Japan
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22
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Ito S. Updates on management strategies of hepatitis B virus reactivation in patients with resolved hepatitis virus B infection undergoing immunosuppressive therapy in rheumatology and the current situation in Niigata Rheumatic Center. Mod Rheumatol 2020; 31:775-782. [PMID: 33021133 DOI: 10.1080/14397595.2020.1832731] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
With the introduction of methotrexate, biological disease-modifying antirheumatic drugs (bDMARDs), and targeted synthetic DMARDs (tsDMARDs), the disease activity of patients with rheumatoid arthritis has been dramatically ameliorated. However, these drugs have strong immunosuppressive effects and can cause reactivation of hepatitis B virus (HBV) in patients with resolved HBV infection. Corticosteroids or immunosuppressants used for other connective tissue diseases or vasculitis also carry a risk of inducing reactivation of HBV. Therefore, every rheumatologist should know how to detect the resolved infection of HBV in patients with rheumatic diseases receiving immunosuppressive therapy and how to monitor it when resolved infection is revealed. Of note, the cut-off index was changed from 2.1 log copies/ml to 20 IU/ml (1.3 Log IU/ml) in 2017. Rheumatologists should start nucleic acid analog administration at reactivation of HBV while performing ongoing immunosuppressive therapy in order to prevent severe or fulminant hepatitis. A low titer of HBs antibody (Ab) or lack of HBs Ab is a risk factor of reactivation of HBV. However, the reactivation of HBV cannot be prevented by HBs Ab titers at baseline or changes overtime. Rheumatologists should recognize that every immunosuppressive therapy, regardless of the mode of action, has a potential risk of reactivation. To facilitate proper management of patients with HBV infection, collaboration between rheumatologists and hepatologists is strongly encouraged. Patients' education, systems for checking electronic medical charts, and multidisciplinary efforts are considered important for detecting HBV reactivation.
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Affiliation(s)
- Satoshi Ito
- Department of Rheumatology, Niigata Rheumatic Center, Shibata City, Niigata, Japan
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23
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Kusumoto S, Tanaka Y, Suzuki R, Watanabe T, Nakata M, Sakai R, Fukushima N, Fukushima T, Moriuchi Y, Itoh K, Nosaka K, Choi I, Sawa M, Okamoto R, Tsujimura H, Uchida T, Suzuki S, Okamoto M, Takahashi T, Sugiura I, Onishi Y, Kohri M, Yoshida S, Kojima M, Takahashi H, Tomita A, Atsuta Y, Maruyama D, Tanaka E, Suzuki T, Kinoshita T, Ogura M, Ueda R, Mizokami M. Ultra-high sensitivity HBsAg assay can diagnose HBV reactivation following rituximab-based therapy in patients with lymphoma. J Hepatol 2020; 73:285-293. [PMID: 32194183 DOI: 10.1016/j.jhep.2020.03.009] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2019] [Revised: 03/04/2020] [Accepted: 03/05/2020] [Indexed: 12/15/2022]
Abstract
BACKGROUND & AIMS HBV reactivation is a risk in patients receiving anti-CD20 antibodies for the treatment of lymphoma. The purpose of this post hoc analysis was to evaluate the efficacy of an ultra-high sensitivity HBsAg assay to guide preemptive antiviral treatment in patients with lymphoma and resolved HBV infections using prospectively stored samples from an HBV DNA monitoring study. METHODS HBV reactivation (defined as HBV DNA levels of ≥11 IU/ml) was confirmed in 22 of 252 patients. A conventional HBsAg assay (ARCHITECT, cut-off value: 0.05 IU/ml) and an ultra-high sensitivity HBsAg assay employing a semi-automated immune complex transfer chemiluminescence enzyme technique (ICT-CLEIA, cut-off value: 0.0005 IU/ml) were performed at baseline, at confirmed HBV reactivation and monitored after HBV reactivation. RESULTS Baseline HBsAg was detected using ICT-CLEIA in 4 patients; in all of whom precore mutants with high replication capacity were reactivated. Of the 6 patients with HBV DNA detected below the level of quantification at baseline, 5 showed HBV reactivation and 3 of the 5 had precore mutations. Sensitivity for detection by ARCHITECT and ICT-CLEIA HBsAg assays at HBV reactivation or the next sampling after HBV reactivation was 18.2% (4 of 22) and 77.3% (17 of 22), respectively. Of the 5 patients undetectable by ICT-CLEIA, HBV reactivation resolved spontaneously in 2 patients. All 6 patients reactivated with precore mutations including preS deletion could be diagnosed by ICT-CLEIA HBsAg assay at an early stage of HBV reactivation. Multivariate analysis showed that an anti-HBs titer of less than 10 mIU/ml, HBV DNA detected but below the level of quantification, and HBsAg detected by ICT-CLEIA at baseline were independent risk factors for HBV reactivation (adjusted hazard ratios, 15.4, 31.2 and 8.7, respectively; p <0.05). CONCLUSIONS A novel ICT-CLEIA HBsAg assay is an alternative method to diagnose HBV reactivation. CLINICAL TRIAL NUMBER UMIN000001299. LAY SUMMARY Hepatitis B virus can be reactivated in lymphoma patients receiving anti-CD20 antibodies such as rituximab. Currently, reactivation requires the monitoring of HBV DNA, but monitoring of the surface antigen (HBsAg) could provide a relatively inexpensive, quick and easy alternative. We assessed the performance of an ultra-high sensitivity HBsAg assay and showed that it could be effective for the diagnosis and monitoring of HBV reactivation.
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Affiliation(s)
- Shigeru Kusumoto
- Department of Hematology and Oncology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Yasuhito Tanaka
- Department of Virology and Liver unit, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Ritsuro Suzuki
- Department of Oncology/Hematology, Shimane University Hospital, Izumo, Japan
| | - Takashi Watanabe
- Department of Immuno-Gene Therapy, Mie University Graduate School of Medicine, Mie, Japan
| | - Masanobu Nakata
- Department of Internal Medicine, Sapporo Hokuyu Hospital, Sapporo, Japan
| | - Rika Sakai
- Department of Hematology and Medical Oncology, Kanagawa Cancer Center, Yokohama, Japan
| | - Noriyasu Fukushima
- Division of Hematology, Department of Internal Medicine, Faculty of Medicine, Saga University, Saga, Japan
| | - Takuya Fukushima
- Department of Hematology, Atomic Bomb Disease and Hibakusha Medicine Unit, Atomic Bomb Disease Institute, Nagasaki University, Nagasaki, Japan
| | | | - Kuniaki Itoh
- Divisions of Oncology and Hematology, National Cancer Center Hospital East, Kashiwa, Japan
| | - Kisato Nosaka
- Department of Hematology and Infectious Diseases, Kumamoto University School of Medicine, Kumamoto, Japan
| | - Ilseung Choi
- Department of Hematology, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan
| | - Masashi Sawa
- Department of Hematology and Oncology, Anjo Kosei Hospital, Anjo, Japan
| | - Rumiko Okamoto
- Department of Oncology, Chibanishi general Hospital, Chiba, Japan
| | - Hideki Tsujimura
- Division of Hematology-Oncology, Chiba Cancer Center, Chiba, Japan
| | - Toshiki Uchida
- Department of Hematology and Oncology, Japanese Red Cross Nagoya Daini Hospital, Nagoya, Japan
| | - Sachiko Suzuki
- Department of Hematology, National Hospital Organization Hokkaido Cancer Center, Sapporo, Japan
| | - Masataka Okamoto
- Department of Hematology, Fujita Health University School of Medicine, Toyoake, Japan
| | - Tsutomu Takahashi
- Department of Oncology/Hematology, Shimane University Hospital, Izumo, Japan
| | - Isamu Sugiura
- Division of Hematology and Oncology, Toyohashi Municipal Hospital, Toyohashi, Japan
| | - Yasushi Onishi
- Department of Hematology and Rheumatology, Tohoku University Hospital, Sendai, Japan
| | - Mika Kohri
- Department of Hematology, International Medical Center, Saitama Medical University, Hidaka, Japan
| | - Shinichiro Yoshida
- Department of Hematology, National Hospital Organization Nagasaki Medical Center, Ohmura, Japan
| | - Minoru Kojima
- Department of Hematology and Oncology, Tokai University School of Medicine, Isehara, Japan
| | - Hiroyuki Takahashi
- Department of Hematology and Clinical Immunology, Yokohama City University School of Medicine, Yokohama, Japan
| | - Akihiro Tomita
- Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Yoshiko Atsuta
- Department of Hematopoietic Stem Cell Transplantation Data Management and Biostatistics, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Dai Maruyama
- Department of Hematology, National Cancer Center Hospital, Tokyo, Japan
| | - Eiji Tanaka
- Department for the Promotion of Regional Medicine, Shinshu University School of Medicine, Matsumoto, Japan
| | - Takayo Suzuki
- Department of Hematology, Kusatsu General Hospital, Kusatsu, Japan
| | | | - Michinori Ogura
- Department of Hematology and Oncology, Kasugai Municipal Hospital, Kasugai, Japan
| | - Ryuzo Ueda
- Department of Tumor Immunology, Aichi Medical University School of Medicine, Aichi, Japan
| | - Masashi Mizokami
- Genome Medical Science Project, National Center for Global Health and Medicine, Ichikawa, Japan.
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Kikuchi T, Kusumoto S, Tanaka Y, Oshima Y, Fujinami H, Suzuki T, Totani H, Kinoshita S, Asao Y, Narita T, Ito A, Ri M, Komatsu H, Iida S. Hepatitis B virus reactivation in a myeloma patient with resolved infection who received daratumumab-containing salvage chemotherapy. J Clin Exp Hematop 2020; 60:51-54. [PMID: 32404569 PMCID: PMC7337267 DOI: 10.3960/jslrt.19034] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2019] [Revised: 02/16/2020] [Accepted: 02/28/2020] [Indexed: 12/14/2022] Open
Abstract
A 72-year-old female complaining of back pain was diagnosed with IgG-κ multiple myeloma. After osteosynthesis for fracture of the left femoral shaft due to myeloma, she received bortezomib, melphalan, and prednisolone as an initial regimen for multiple myeloma, but discontinued it after three courses due to progressive disease. The patient subsequently received lenalidomide and dexamethasone as a second-line regimen for 2.5 years, and pomalidomide and dexamethasone as a third-line regimen for only 2 months. An anti-CD38 monoclonal antibody, daratumumab (DARA), and bortezomib and dexamethasone (DVd) as a fourth-line regimen were administered for refractory myeloma. However, hepatitis B virus (HBV) reactivation occurred on day 15 of the third course of DVd. The HBV DNA level in peripheral blood suddenly increased to 2.2 log IU/mL. An anti-HBV nucleotide analog, entecavir, was subsequently administered when the HBV DNA level increased to 2.6 log IU/mL. No HBV-related hepatitis was observed during follow-up. DARA can improve the prognosis of patients with multiple myeloma, but also potentially increase the risk of HBV reactivation. Host and viral risk factors need to be identified in such patients in order to implement a more cost-effective strategy against HBV reactivation.
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25
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High hepatitis B virus screening rate among patients receiving systemic anticancer treatment in Japan. Int J Clin Oncol 2020; 25:1327-1333. [PMID: 32200482 DOI: 10.1007/s10147-020-01655-4] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2019] [Accepted: 03/08/2020] [Indexed: 10/24/2022]
Abstract
BACKGROUND Patients with hepatitis B virus (HBV) infection have a risk of reactivation after chemotherapy. All patients undergoing chemotherapy should be screened for HBV infection. No large-scale studies have been conducted to examine HBV screening practice in Japan. METHODS We analyzed health insurance claims equivalent data linked with a nationwide hospital-based cancer registry. Patients diagnosed with cancer in 2014, who were aged 20 years and older and those who underwent systemic anticancer treatment in 2014-15 were included. We assessed the HBV screening rates by the HBsAg or anti-HBc tests, HBV-DNA tests, and entecavir prescriptions. Multiple logistic regression models were used to identify factors related to the receipt of screening. RESULTS Of 177,597 patients (mean [SD] age, 65.6 [12.2] years), 82.6% and 12.9% patients had a solid tumor and hematologic malignancy, respectively. Among them, 88.1%, 6.3%, and 5.5% received cytotoxic chemotherapy, targeted therapy, and anti-CD20 antibodies, respectively. Overall, 70.6% of patients were screened. The positive predictor of HBV screening was receiving anti-CD20 antibodies [odds ratio (OR); 2.23, 95% confidence interval (CI) 2.06-2.41, p < 0.001] and negative predictors were age ≥ 85 (OR 0.76, 95% CI 0.71-0.81), age 75-84 (OR 0.77, 95% CI 0.75-0.79) and targeted therapy (OR 0.69, 95% CI 0.67-0.72). Among the screened patients, 13.2% were tested for HBV-DNA, and 1.49% were prescribed entecavir. CONCLUSIONS The HBV screening rate in Japan is higher than in other countries. Further improvement of the HBV screening rate is needed to prevent reactivation and avoidable deaths of patients with HBV infection.
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26
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Li Z, Dong Y, Fan M, Yin Y, Zhu J, Li B, Huang W. Analysis of Hepatitis B Virus Reactivation After Radiotherapy in Patients With Hepatocellular Carcinoma Using the Lyman NTCP Model. Technol Cancer Res Treat 2020; 18:1533033819875136. [PMID: 31526114 PMCID: PMC6749789 DOI: 10.1177/1533033819875136] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023] Open
Abstract
Purpose: To analyze the correlation of hepatitis B virus reactivation with patient-related and treatment-related dose–volume factors and to describe the feasibility of hepatitis B virus reactivation analyzed by a normal tissue complication probability model for patients with hepatocellular carcinoma treated with radiotherapy. Materials and Methods: Ninety patients with hepatitis B virus-related hepatocellular carcinoma treated with radiotherapy were enrolled in this retrospective study and were followed from June 2009 to December 2015. Of the 90 patients, 78 had received conventional fractionation radiotherapy to a mean dose of 39.6 to 50.4 Gy and 12 patients were scheduled to receive hypofractionation. The physical doses were converted into 2 Gy equivalents for analysis. The parameters, TD50 (1), n, and m, of the Lyman-Kutcher-Burman normal tissue complication probability model were derived using maximum likelihood estimation. Bootstrap and leave-one-out were employed to against model overfitting and improve the model stability. Results: Radiation-induced liver diseases were 17.8%, hepatitis B virus reactivation was 22.2%, and hepatitis B virus reactivation-induced hepatitis was 21.1%, respectively. In multivariate analysis, the V5Gy was associated with hepatitis B virus reactivation; TD50 (1), m, and n were 32.3, 0.55, and 0.71 Gy, respectively, for hepatitis B virus reactivation. Bootstrap and leave-one-out results showed that the hepatitis B virus parameter fits were extremely robust. Conclusion: A Lyman-Kutcher-Burman normal tissue complication probability model has been established to predict hepatitis B virus reactivation for patients with hepatocellular carcinoma who received radiotherapy.
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Affiliation(s)
- Zhenjiang Li
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China
| | - Yinping Dong
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China.,School of Medicine and Life Sciences, University of Jinan-Shandong Academy of Medical Sciences, Jinan, Shandong, China
| | - Min Fan
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China
| | - Yong Yin
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China
| | - Jian Zhu
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China
| | - Baosheng Li
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China
| | - Wei Huang
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China
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27
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Kuo MH, Tseng CW, Lee CH, Tung CH, Tseng KC, Lai NS. Moderate Risk of Hepatitis B Virus Reactivation in HBsAg -/HBcAb + Carriers Receiving Rituximab for Rheumatoid Arthritis. Sci Rep 2020; 10:2456. [PMID: 32051458 PMCID: PMC7016116 DOI: 10.1038/s41598-020-59406-4] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2019] [Accepted: 01/28/2020] [Indexed: 12/26/2022] Open
Abstract
To investigate the incidence and risk factors of hepatitis B virus (HBV) reactivation in HBV surface antigen (HBsAg)-/ HBV core antibody (HBcAb)+ patients who underwent rituximab (RTX) therapy for rheumatoid arthritis (RA). From January 2000 through December 2017, a total of 134 RA patients with various HBV serostatuses who received RTX at Dalin Tzu Chi Hospital were screened. Finally, 50 HBsAg-/HBcAb+ patients were enrolled in this retrospective study. Baseline characteristics, comedications, and the occurrence of HBV reactivation were recorded. Four HBsAg-/HBcAb+ RA patients (8%; 4/50) experienced HBV reactivation after treatment with RTX. Hepatitis flare-up occurred in 2 of these 4 patients, with a fatal outcome in one. HBV reactivation occurred approximately 1-4 years after the first dose of RTX and 0.5-1.5 years after the last one. In HBsAg-/HBcAb+ patients, HBV reactivation was significantly more common in those who were HBV surface antibody (HBsAb)- at baseline than in those who were HBsAb+ (30% vs 4%; p = 0.02). A history of adalimumab use was associated with HBV reactivation (100% vs 39%; p = 0.02). A moderate risk of HBV reactivation was observed in HBsAg-/HBcAb+ RA patients receiving RTX therapy. The reactivation may induce acute hepatitis and even death. To reduce the risk of HBV reactivation, regular monitoring of liver function is insufficient; monitoring of viral load and HBsAg or prophylaxis with antiviral therapy should be considered.
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Affiliation(s)
- Meng Hsuan Kuo
- Department of Pharmacy, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chia-Yi, Taiwan
- School of Medicine, Tzuchi University, Hualien, Taiwan
| | - Chih-Wei Tseng
- School of Medicine, Tzuchi University, Hualien, Taiwan.
- Division of Gastroenterology, Department of Internal Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chia-Yi, Taiwan.
| | - Chi-Hui Lee
- Department of Pharmacy, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chia-Yi, Taiwan
- School of Medicine, Tzuchi University, Hualien, Taiwan
| | - Chien-Hsueh Tung
- School of Medicine, Tzuchi University, Hualien, Taiwan
- Division of Rheumatology, Department of Internal Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chia-Yi, Taiwan
| | - Kuo-Chih Tseng
- School of Medicine, Tzuchi University, Hualien, Taiwan
- Division of Gastroenterology, Department of Internal Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chia-Yi, Taiwan
| | - Ning-Sheng Lai
- School of Medicine, Tzuchi University, Hualien, Taiwan
- Division of Rheumatology, Department of Internal Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chia-Yi, Taiwan
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28
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Ujiie I, Ujiie H, Yoshimoto N, Iwata H, Shimizu H. Prevalence of infectious diseases in patients with autoimmune blistering diseases. J Dermatol 2020; 47:378-384. [PMID: 32043652 DOI: 10.1111/1346-8138.15244] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2019] [Accepted: 01/05/2020] [Indexed: 01/10/2023]
Abstract
A long-term immunosuppressive treatment can provoke latent infections. Autoimmune blistering diseases (AIBD) are mostly treated with systemic immunosuppressive agents. To prevent the reactivation or exacerbation of existing latent infections, patients must be screened for infectious diseases before immunosuppressive treatments are initiated. However, the prevalence of infectious diseases in AIBD remains to be elucidated. To evaluate the necessity of screening infectious diseases in AIBD, we retrospectively reviewed the clinical records of 215 patients at a single center with AIBD for hepatitis B virus (HBV), hepatitis C virus (HCV), Mycobacterium tuberculosis, Treponema pallidum, human T-cell leukemia virus type 1 (HTLV-1) and HIV infections. Approximately 40% of patients were infected with HBV. During systemic corticosteroid treatment, HBV DNA became positive in 3.4% of cases. Antibodies to HCV, interferon-γ release assays for M. tuberculosis and the T. pallidum latex agglutination test were positive in 0.6%, 6.6% and 1.2% cases, respectively. Neither HTLV-1 nor HIV infections were detected. In conclusion, checks for HBV and M. tuberculosis infections should be made before immunosuppressive treatments are started, because of the high prevalence of these potentially life-threatening infections. Other infections should be tested for depending on the patient's risk factors.
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Affiliation(s)
- Inkin Ujiie
- Department of Dermatology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan
| | - Hideyuki Ujiie
- Department of Dermatology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan
| | - Norihiro Yoshimoto
- Department of Dermatology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan
| | - Hiroaki Iwata
- Department of Dermatology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan
| | - Hiroshi Shimizu
- Department of Dermatology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan
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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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Sano T, Akuta N, Suzuki Y, Kasuya K, Fujiyama S, Kawamura Y, Sezaki H, Hosaka T, Saitoh S, Kobayashi M, Suzuki F, Kobayashi M, Arase Y, Ikeda K, Kumada H. Fulminant Hepatitis due to de novo Hepatitis B after Cord Blood Transplantation Rescued by Medical Treatment. Intern Med 2020; 59:1519-1524. [PMID: 32536678 PMCID: PMC7364250 DOI: 10.2169/internalmedicine.4190-19] [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: 11/30/2022] Open
Abstract
A 53-year-old man presented with fulminant hepatitis due to de novo hepatitis B. He had been diagnosed previously with adult T-cell leukemia (ATL) and previously resolved hepatitis B virus infection. The ATL had been treated with cord blood transplantation (CBT). He developed fulminant hepatitis 18 months after CBT, 15 months after the withdrawal of immunosuppressants, and 10 months after vitreous injections of methotrexate for ATL-related retinal infiltration. The aggressive medical protocol included entecavir, prednisolone, plasma exchange, hemodialysis, and bilirubin adsorption. We herein report successful medical treatment for fulminant de novo hepatitis B in a patient considered unsuitable for liver transplantation.
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Affiliation(s)
- Tomoya Sano
- Department of Hepatology, Toranomon Hospital, Japan
| | - Norio Akuta
- Department of Hepatology, Toranomon Hospital, Japan
| | | | | | | | | | | | | | | | | | | | | | - Yasuji Arase
- Department of Hepatology, Toranomon Hospital, Japan
| | - Kenji Ikeda
- Department of Hepatology, Toranomon Hospital, Japan
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Wei J, Zhu X, Mao X, Huang L, Meng F, Zhou J. Severe early hepatitis B reactivation in a patient receiving anti-CD19 and anti-CD22 CAR T cells for the treatment of diffuse large B-cell lymphoma. J Immunother Cancer 2019; 7:315. [PMID: 31753002 PMCID: PMC6868854 DOI: 10.1186/s40425-019-0790-y] [Citation(s) in RCA: 42] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2019] [Accepted: 10/25/2019] [Indexed: 02/07/2023] Open
Abstract
Background Hepatitis B virus (HBV) reactivation is commonly seen in HBsAg-positive hematologic patients undergoing immunosuppressive chemotherapy. Little is known about the risk of HBV reactivation after chimeric antigen receptor T-cell (CAR T) immunotherapy for the treatment of refractory/relapsed malignant B-cell lymphoma. Case presentation We report a patient who underwent antiviral prophylaxis for 26 months and who discontinued treatment by herself 1 month after the sequential infusion of two specific, third-generation anti-CD19 and anti-CD22 CAR T cell immunotherapies for refractory/relapsed diffuse large B-cell lymphoma. Remission of the primary disease was achieved after two and half months, but she was admitted with a 7-day history of vomiting, jaundice, itching and dark urine. After excluding other possible causes of acute liver damage, HBV reactivation was suspected. HBV-DNA was 4,497,000 IU/mL at that time. Following the reintroduction of entecavir, a decline in the HBV-DNA copies was observed, but ALT, AST and bilirubin were elevated, and there was no improvement of the clinical conditions. She passed away because of hepatic encephalopathy and multiple organ dysfunction syndrome 40 days after admission. Conclusions Our study provides the first report of the severe, early reactivation of an inactive HBsAg carrier after CAR T cell therapy in DLBCL. Trial registration ChiCTR-OPN-16008526.
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Affiliation(s)
- Jia Wei
- Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China
| | - Xiaojian Zhu
- Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China
| | - Xia Mao
- Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China
| | - Liang Huang
- Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China
| | - Fankai Meng
- Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China.
| | - Jianfeng Zhou
- Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, 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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Kanda T, Lau GKK, Wei L, Moriyama M, Yu ML, Chuang WL, Ibrahim A, Lesmana CRA, Sollano J, Kumar M, Jindal A, Sharma BC, Hamid SS, Kadir Dokmeci A, Mamun-Al-Mahtab, McCaughan GW, Wasim J, Crawford DHG, Kao JH, Ooka Y, Yokosuka O, Sarin SK, Omata M. APASL HCV guidelines of virus-eradicated patients by DAA on how to monitor HCC occurrence and HBV reactivation. Hepatol Int 2019; 13:649-661. [PMID: 31541423 PMCID: PMC6861433 DOI: 10.1007/s12072-019-09988-7] [Citation(s) in RCA: 68] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2019] [Accepted: 08/30/2019] [Indexed: 12/13/2022]
Abstract
In the direct-acting antiviral (DAA) era for hepatitis C virus (HCV) infection, sustained virological response (SVR) is very high, but close attention must be paid to the possible occurrence of hepatocellular carcinoma (HCC) and reactivation of hepatitis B virus (HBV) in patients with co-infection who achieved SVR in short term. HCC occurrence was more often observed in patients with previous HCC history. We found occurrence of HCC in 178 (29.6%) of 602 patients with previous HCC history (15.4 months mean follow-up post-DAA initiation) but, in contrast, in only 604 (1.3%) of 45,870 patients without previous HCC history (18.2 months mean follow-up). Thus, in these guidelines, we recommend the following: in patients with previous HCC history, surveillance at 4-month intervals for HCC by ultrasonography (US) and tumor markers should be performed. In patients without previous HCC history, surveillance at 6- to 12-month intervals for HCC including US is recommended until the long-term DAA treatment effects, especially for the resolution of liver fibrosis, are confirmed. This guideline also includes recommendations on how to follow-up patients who have been infected with both HCV and HBV. When HCV was eradicated in these HBsAg-positive patients or patients with previous HBV infection (anti-HBc and/or anti-HBs-positive), it was shown that HBV reactivation or HBV DNA reappearance was observed in 67 (41.4%) of 162 or 12 (0.9%) of 1317, respectively. For these co-infected patients, careful attention should be paid to HBV reactivation for 24 weeks post-treatment.
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Affiliation(s)
- Tatsuo Kanda
- Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan
| | - George K K Lau
- Humanity and Health Medical Center, Hong Kong SAR, China
| | - Lai Wei
- Tsinghua Changgung Hospital, Tsinghua University, Beijing, China
| | - Mitsuhiko Moriyama
- Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan
| | - Ming-Lung Yu
- College of Biological Science and Technology, National Chiao Tung University, Hsin-Chu, Taiwan
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Wang-Long Chuang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Alaaeldin Ibrahim
- GI/Liver Division, Department of Internal Medicine, University of Benha, Banha, Egypt
| | - Cosmas Rinaldi Adithya Lesmana
- Digestive Disease and GI Oncology Centre, Medistra Hospital, Jakarta, Indonesia
- Hepatobiliary Division, Department of Internal Medicine, Dr. Cipto Mangunkusumo Hospital, Universitas Indonesia, Jakarta, Indonesia
| | - Jose Sollano
- University Santo Tomas Hospital, Manila, Philippines
| | - Manoj Kumar
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Ankur Jindal
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | | | - Saeed S Hamid
- Department of Medicine, Aga Khan University and Hospital, Stadium Road, Karachi, 74800, Pakistan
| | - A Kadir Dokmeci
- Department of Gastroenterology, Ankara University School of Medicine, Ankara, Turkey
| | - Mamun-Al-Mahtab
- Department of Hepatology, Bangabandhu Sheikh Mujib Medical University, Dhaka, 1000, Bangladesh
| | - Geoffrey W McCaughan
- Royal Prince Alfred Hospital, Centenary Institute, University of Sydney, Sydney, Australia
| | - Jafri Wasim
- Department of Medicine, Aga Khan University and Hospital, Stadium Road, Karachi, 74800, Pakistan
| | - Darrell H G Crawford
- University of Queensland, School of Medicine, Woolloongabba, QLD, 4102, Australia
| | - Jia-Horng Kao
- National Taiwan University College of Medicine, and National Taiwan University Hospital, Taipei, Taiwan
| | - Yoshihiko Ooka
- Chiba University, Graduate School of Medicine, Chiba, Japan
| | - Osamu Yokosuka
- Chiba University, Graduate School of Medicine, Chiba, Japan
| | - Shiv Kumar Sarin
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Masao Omata
- Yamanashi Prefectural Central Hospital, 1-1-1 Fujimi, Kofu-shi, Yamanashi, 400-8506, Japan.
- The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
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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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Hayashi M, Abe K, Fujita M, Okai K, Takahashi A, Ohira H. Hepatitis B Virus Reactivation in a Patient with Nonalcoholic Steatohepatitis 41 Months after Rituximab-containing Chemotherapy. Intern Med 2019; 58:375-380. [PMID: 30210131 PMCID: PMC6395117 DOI: 10.2169/internalmedicine.1587-18] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/26/2022] Open
Abstract
Hepatitis B virus (HBV) reactivation occasionally occurs long after immunosuppressive therapy. The characteristics of late HBV reactivation remain unclear. We herein present a case of HBV reactivation in a patient with nonalcoholic steatohepatitis (NASH) more than 3 years after rituximab-containing chemotherapy for diffuse large B-cell lymphoma. Increased transaminase levels, which were induced by NASH, were observed after chemotherapy and were alleviated with statin treatment. HBV reactivation was identified incidentally. The patient developed hepatitis that improved with entecavir therapy. Our case might indicate that the presence of NASH is associated with HBV reactivation long after treatment and that statins, as immune-modulatory agents, affect HBV reactivation.
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Affiliation(s)
- Manabu Hayashi
- Department of Gastroenterology, Fukushima Medical University School of Medicine, Japan
| | - Kazumichi Abe
- Department of Gastroenterology, Fukushima Medical University School of Medicine, Japan
| | - Masashi Fujita
- Department of Gastroenterology, Fukushima Medical University School of Medicine, Japan
| | - Ken Okai
- Department of Gastroenterology, Fukushima Medical University School of Medicine, Japan
| | - Atsushi Takahashi
- Department of Gastroenterology, Fukushima Medical University School of Medicine, Japan
| | - Hiromasa Ohira
- Department of Gastroenterology, Fukushima Medical University School of Medicine, Japan
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Chen YM, Yang SS, Chen DY. Risk-stratified management strategies for HBV reactivation in RA patients receiving biological and targeted therapy: A narrative review. JOURNAL OF MICROBIOLOGY, IMMUNOLOGY, AND INFECTION = WEI MIAN YU GAN RAN ZA ZHI 2019; 52:1-8. [DOI: 10.1016/j.jmii.2017.10.002] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/18/2017] [Revised: 09/26/2017] [Accepted: 10/17/2017] [Indexed: 02/06/2023]
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Kusumoto S, Arcaini L, Hong X, Jin J, Kim WS, Kwong YL, Peters MG, Tanaka Y, Zelenetz AD, Kuriki H, Fingerle-Rowson G, Nielsen T, Ueda E, Piper-Lepoutre H, Sellam G, Tobinai K. Risk of HBV reactivation in patients with B-cell lymphomas receiving obinutuzumab or rituximab immunochemotherapy. Blood 2019; 133:137-146. [PMID: 30341058 PMCID: PMC6337873 DOI: 10.1182/blood-2018-04-848044] [Citation(s) in RCA: 85] [Impact Index Per Article: 14.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2018] [Accepted: 10/02/2018] [Indexed: 02/06/2023] Open
Abstract
Risk of hepatitis B virus (HBV) reactivation was assessed in B-cell non-Hodgkin lymphoma (NHL) patients with resolved HBV infection (hepatitis B surface antigen negative, hepatitis B core antibody positive) who received obinutuzumab- or rituximab-containing immunochemotherapy in the phase 3 GOYA and GALLIUM studies. HBV DNA monitoring was undertaken monthly to 1 year after the last dose of study drug. In case of HBV reactivation (confirmed, HBV DNA ≥29 IU/mL), immunochemotherapy was withheld and nucleos(t)ide analog treatment (preemptive NAT) started. Immunochemotherapy was restarted if HBV DNA became undetectable or reactivation was not confirmed, and discontinued if HBV DNA exceeded 100 IU/mL on NAT. Prophylactic NAT was allowed by investigator discretion. Among 326 patients with resolved HBV infection, 27 (8.2%) had HBV reactivation, occurring a median of 125 days (interquartile range, 85-331 days) after the first dose. In 232 patients without prophylactic NAT, 25 (10.8%) had HBV reactivation; all received preemptive NAT. Ninety-four patients received prophylactic NAT; 2 (2.1%) had HBV reactivation. No patients developed HBV-related hepatitis. On multivariate Cox analysis, detectable HBV DNA at baseline was strongly associated with an increased risk of reactivation (adjusted hazard ratio [HR], 18.22; 95% confidence interval [CI], 6.04-54.93; P < .0001). Prophylactic NAT was strongly associated with a reduced risk (adjusted HR, 0.09; 95% CI, 0.02-0.41; P = .0018). HBV DNA monitoring-guided preemptive NAT was effective in preventing HBV-related hepatitis during anti-CD20-containing immunochemotherapy in B-cell NHL patients with resolved HBV infection. Antiviral prophylaxis was also effective and may be appropriate for high-risk patients. These trials were registered at www.clinicaltrials.gov as NCT01287741 (GOYA) and NCT01332968 (GALLIUM).
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Affiliation(s)
- Shigeru Kusumoto
- Department of Hematology and Oncology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Luca Arcaini
- Division of Hematology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
- Department of Molecular Medicine, University of Pavia, Pavia, Italy
| | - Xiaonan Hong
- Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Jie Jin
- Department of Hematology, The First Affiliated Hospital, Zhejiang University College of Medicine, Hangzhou, China
| | - Won Seog Kim
- Department of Hematology-Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Yok Lam Kwong
- Department of Medicine, Queen Mary Hospital, Hong Kong, China
| | - Marion G Peters
- Department of Medicine, University of California, San Francisco, San Francisco, CA
| | - Yasuhito Tanaka
- Department of Virology and Liver Unit, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Andrew D Zelenetz
- Department of Medicine, Lymphoma Service, Memorial Sloan Kettering Cancer Center, New York, NY
- Department of Medicine, Weill Cornell Medical Center, New York, NY
| | - Hiroshi Kuriki
- Clinical Science & Strategy Department, Oncology Clinical Science & Strategy, Chugai Pharmaceutical Co. Ltd., Tokyo, Japan
| | | | - Tina Nielsen
- Product Development Oncology, F. Hoffmann-La Roche Ltd., Basel, Switzerland; and
| | - Eisuke Ueda
- Clinical Science & Strategy Department, Oncology Clinical Science & Strategy, Chugai Pharmaceutical Co. Ltd., Tokyo, Japan
| | - Hanna Piper-Lepoutre
- Product Development Oncology, F. Hoffmann-La Roche Ltd., Basel, Switzerland; and
| | - Gila Sellam
- Product Development Oncology, F. Hoffmann-La Roche Ltd., Basel, Switzerland; and
| | - Kensei Tobinai
- Department of Hematology, National Cancer Center Hospital, Tokyo, Japan
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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] [Grants] [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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Fujita M, Sugiyama M, Sato Y, Nagashima K, Takahashi S, Mizokami M, Hata A. Hepatitis B virus reactivation in patients with rheumatoid arthritis: Analysis of the National Database of Japan. J Viral Hepat 2018; 25:1312-1320. [PMID: 29770539 DOI: 10.1111/jvh.12933] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/09/2018] [Accepted: 04/03/2018] [Indexed: 02/06/2023]
Abstract
This study aimed to determine the incidence and risk factors for hepatitis B virus (HBV) reactivation in patients with rheumatoid arthritis (RA) undergoing immunosuppressive therapy. The National Database of Japan, in which insurance claim data have been comprehensively accumulated, was utilized. The subjects were 76 641 RA patients who were plausibly initiated on immunosuppressive therapy from April 2013 to March 2014. Laboratory tests of the hepatitis B surface antigen, anti-hepatitis B virus surface antibody, and anti-hepatitis B virus core antibody were performed in 28.23%, 12.52% and 14.63% of patients, respectively, when the therapy was initiated. We found that HBV reactivation and fulminant hepatitis occurred in both the patients with and without HBV DNA monitoring, indicating insufficient monitoring in Japan during the study. The cumulative incidence of HBV reactivation over 24 months was 1.57% (95% confidence interval [CI] = 1.28%-1.92%) in the monitoring group, which consisted of those with resolved HBV infection. Glucocorticoid administration was a potent risk factor for HBV reactivation (hazard ratio [HR] = 1.70, 95% CI = 1.26-2.29, P = .001 in all subjects, and HR = 1.82, 95% CI = 1.18-2.81, P = .007 in the nonmonitoring group), although it was not statistically significant in the monitoring group (HR = 1.49, 95% CI = 0.99-2.26 and P = .057). No significant risk difference was observed between single administration of methotrexate and biological drugs.
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Affiliation(s)
- M Fujita
- Department of Public Health, Chiba University Graduate School of Medicine, Chiba City, Japan
| | - M Sugiyama
- Genome Medical Sciences Project, National Center for Global Health and Medicine, Ichikawa City, Japan
| | - Y Sato
- Department of Global Clinical Research, Chiba University Graduate School of Medicine, Chiba City, Japan
| | - K Nagashima
- Department of Global Clinical Research, Chiba University Graduate School of Medicine, Chiba City, Japan
| | - S Takahashi
- Clinical Research Center, Chiba University Hospital, Chiba City, Japan
| | - M Mizokami
- Genome Medical Sciences Project, National Center for Global Health and Medicine, Ichikawa City, Japan
| | - A Hata
- Department of Public Health, Chiba University Graduate School of Medicine, Chiba City, Japan
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Yoshida Y, Yonezawa M, Okamoto T, Fujiwara Y, Suzuki A, Suzuki Y, Endo K, Kakisaka K, Oikawa T, Kuroda H, Miyasaka A, Takikawa Y. Occurrence of hepatocellular carcinoma 24 years after successful interferon therapy in a patient with chronic hepatitis C: a case report. Clin J Gastroenterol 2018; 12:120-127. [DOI: 10.1007/s12328-018-0915-8] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/17/2018] [Accepted: 10/13/2018] [Indexed: 01/25/2023]
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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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Matsuda H, Hiramatsu K, Akazawa Y, Nosaka T, Saito Y, Ozaki Y, Hayama R, Takahashi K, Naito T, Ofuji K, Ohtani M, Nemoto T, Hida Y, Kimura H, Soya Y, Nakamoto Y. Genetic polymorphism and decreased expression of HLA class II DP genes are associated with HBV reactivation in patients treated with immunomodulatory agents. J Med Virol 2018; 90:712-720. [PMID: 29283185 DOI: 10.1002/jmv.25011] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2016] [Accepted: 11/14/2017] [Indexed: 12/16/2022]
Abstract
Hepatitis B virus (HBV) reactivation can be triggered by immunosuppressive chemotherapy. HLA class II molecules may play a role in HBV reactivation. Genetic polymorphism and mRNA expression of HLA class II were examined in patients with latent HBV infection treated with immunosuppressive therapies. Subjects with resolved HBV infection who had undergone treatment with immunosuppressive chemotherapies were retrospectively enrolled (n = 42) and divided into reactivated (n = 9) and non-reactivated groups (n = 33). Patients were genotyped for 17 single nucleotide polymorphisms (SNPs) within HLA class II DPA1, and DPB1, and mRNA expression levels of HLA class II genes were assessed. The frequency of the AA genotype of rs872956, a SNP in HLA-DPB1, was significantly higher in the reactivated group than in the non-reactivated group (55.6% vs 12.1%, P < 0.05). The frequencies of the T allele and non-AA genotypes (AT/TT) of rs3116996 (located in DPB1) were significantly higher in the reactivated group (T allele frequency: 16.7% vs 0.0% [P < 0.01], non-AA genotype frequency: 22.2% vs 0.0% [P < 0.05]). Multivariate logistic regression identified the AA genotype of rs872956 as an independent protective factor against HBV reactivation (odds ratio [OR] = 18.1, 95% confidence interval [CI] = 2.6-126.7, P < 0.01). mRNA expression of HLA-DPB1 was lower in the HBV reactivated group than in the non-reactivated group (median 276.1 ± 165.6/β-actin vs 371.4 ± 407.5/β-actin [P < 0.05]). These results suggest the involvement of HLA class II molecules in HBV reactivation after treatment with immunomodulatory agents.
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Affiliation(s)
- Hidetaka Matsuda
- Second Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, Japan
| | - Katsushi Hiramatsu
- Second Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, Japan
| | - Yu Akazawa
- Second Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, Japan
| | - Takuto Nosaka
- Second Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, Japan
| | - Yasushi Saito
- Second Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, Japan
| | - Yoshihiko Ozaki
- Second Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, Japan
| | - Ryoko Hayama
- Second Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, Japan
| | - Kazuto Takahashi
- Second Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, Japan
| | - Tatsushi Naito
- Second Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, Japan
| | - Kazuya Ofuji
- Second Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, Japan
| | - Masahiro Ohtani
- Second Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, Japan
| | - Tomoyuki Nemoto
- Second Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, Japan
| | - Yukio Hida
- Department of Clinical Laboratories, Faculty of Medical Sciences, University of Fukui, Fukui, Japan
| | - Hideki Kimura
- Department of Clinical Laboratories, Faculty of Medical Sciences, University of Fukui, Fukui, Japan
| | - Yoshihiro Soya
- Tsuruga Institute of Biotechnology, Toyobo Co., Ltd., Osaka, Japan
| | - Yasunari Nakamoto
- Second Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, Japan
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Shinkai N, Kusumoto S, Murakami S, Ogawa S, Ri M, Matsui T, Tamori A, Toyoda H, Ishida T, Iida S, Tanaka Y. Novel monitoring of hepatitis B reactivation based on ultra-high sensitive hepatitis B surface antigen assay. Liver Int 2017; 37:1138-1147. [PMID: 27992664 DOI: 10.1111/liv.13349] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2016] [Accepted: 12/12/2016] [Indexed: 12/12/2022]
Abstract
BACKGROUND & AIMS Occult hepatitis B virus (HBV) infection should be evaluated before systemic chemotherapy to prevent HBV reactivation-related hepatitis. We investigated HBV reactivation using high sensitivity HB surface antigen (HBsAg) chemiluminescent enzyme immunoassay (HBsAg-HQ) and ultra-high sensitive HBsAg assay employing a semi-automated immune complex transfer chemiluminescence enzyme technique (ICT-CLEIA). METHODS Of 120 HBV-resolved patients with haematological malignancy receiving systemic chemotherapy from 2012 to 2015 in our hospital, 13 patients had HBV DNA reactivation (in 12/13 patients HBV DNA became quantifiable) according to HBV DNA monitoring. These patients were applied for Architect HBsAg-QT (detection limit:50 mIU/mL), HBsAg-HQ (5 mIU/mL) and ICT-CLEIA (0.5 mIU/mL) using stored samples. RESULTS When HBV DNA was firstly quantifiable by regular HBV DNA monitoring, HBsAg-QT was detected in 1/12 patients (8%), HBsAg-HQ was detected in 4/12 patients (33%) and ICT-CLEIA was detected in all 12 patients (100%), suggesting that the sensitivity of ICT-CLEIA was comparable to that of HBV DNA quantification. Interestingly, two patients were HBsAg positive by ICT-CLEIA before HBV DNA became detectable. Median difference of detectable point between HBV DNA and ICT-CLEIA was zero (range from -28 to 56 days), while median delay by HBsAg-QT or HBsAg-HQ was 52.5 days after HBV DNA became detectable. Although anti-HBs titres were high (131.9 mIU, 80.4 mIU) in two patients with escape mutations (Saa126V, Saa145R), HBsAg by ICT-CLEIA and HBV DNA were detectable concurrently. CONCLUSIONS ICT-CLEIA is a novel assay for HBV monitoring to prevent hepatitis caused by HBV reactivation.
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Affiliation(s)
- Noboru Shinkai
- Departments of Virology & Liver unit, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Shigeru Kusumoto
- Department of Hematology and Oncology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Shuko Murakami
- Departments of Virology & Liver unit, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Shintaro Ogawa
- Departments of Virology & Liver unit, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Masaki Ri
- Department of Hematology and Oncology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Tekeshi Matsui
- Departments of Virology & Liver unit, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
- Center for Gastroenterology, Teine-Keijinkai Hospital, Sapporo, Japan
| | - Akihiro Tamori
- Department of Hepatology, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Hidenori Toyoda
- Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Takashi Ishida
- Department of Hematology and Oncology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Shinsuke Iida
- Department of Hematology and Oncology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Yasuhito Tanaka
- Departments of Virology & Liver unit, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
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Mittal M, Hu KQ. Clinical Implications and Management of Chronic Occult Hepatitis B Virus Infection. CURRENT HEPATOLOGY REPORTS 2017; 16:90-96. [DOI: 10.1007/s11901-017-0339-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/16/2025]
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Guarino M, Picardi M, Vitiello A, Pugliese N, Rea M, Cossiga V, Pane F, Caporaso N, Morisco F. Viral Outcome in Patients with Occult HBV Infection or HCV-Ab Positivity Treated for Lymphoma. Ann Hepatol 2017. [DOI: 10.5604/16652681.1231579] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/26/2023]
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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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Yamamoto M. New strategies for the treatment of IgG4-related disease. ACTA ACUST UNITED AC 2017; 39:485-490. [PMID: 28049956 DOI: 10.2177/jsci.39.485] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
IgG4-related disease is a chronic and fibroinflammatory disorder, which is characterized with elevated levels of serum IgG4, and prominent infiltration of IgG4-bearing plasma cells in the involved organs. It often affects with lacrimal glands, salivary glands, pancreas, kidneys, lungs, and retroperitoneal cavity. Now, the first line of the induction therapy for IgG4-related disease is glucocorticoid, but almost patients need the maintenance treatment and experience the relapse. It is recently reported that biologic agents, including rituximab and abatacept, are effective for the relapse of IgG4-related disease. It is clear that the tapering effect of glucocorticoid is better than conventional oral immunosuppressants. We can use it in safely if we choose the appropriate cases. The investigator-initiated trial of rituximab for IgG4-related disease is scheduled in Japan. This article reviews the new strategies for the treatment of IgG4-related disease with our data of SMART registry, and discuss the problems of each biologic agents for IgG4-related disease.
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Affiliation(s)
- Motohisa Yamamoto
- Department of Rheumatology, Sapporo Medical University School of Medicine
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Yamada T, Nannya Y, Suetsugu A, Shimizu S, Sugihara J, Shimizu M, Seishima M, Tsurumi H. Late Reactivation of Hepatitis B Virus after Chemotherapies for Hematological Malignancies: A Case Report and Review of the Literature. Intern Med 2017; 56:115-118. [PMID: 28049989 PMCID: PMC5313436 DOI: 10.2169/internalmedicine.56.7468] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/31/2022] Open
Abstract
Reactivation of hepatitis B virus (HBV) is a serious complication of immunosuppressive therapy and cytotoxic chemotherapy. The optimal duration of HBV-DNA monitoring for at-risk patients depends on the clinical features of reactivation, especially the range of potency from therapies to reactivation. We present a case of very late reactivation after chemotherapy for lymphoma and review previous reports of late reactivation cases. We also underscore the significance of developing an indicator for anti-HBV immunity which can be used to determine the optimal monitoring period.
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Affiliation(s)
- Toshiki Yamada
- Department of Hematology, Gifu Prefectural Medical Center, Japan
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Muraishi J, Shibata M, Honma Y, Hiura M, Abe S, Harada M. Reactivation of Occult Hepatitis B Virus Infection 27 Months after the End of Chemotherapy Including Rituximab for Malignant Lymphoma. Intern Med 2017; 56:1967-1971. [PMID: 28768965 PMCID: PMC5577071 DOI: 10.2169/internalmedicine.56.8233] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/05/2023] Open
Abstract
A 68-year-old man with occult hepatitis B virus (HBV) infection was diagnosed with malignant lymphoma and achieved complete remission after treatment with a chemotherapy regimen including rituximab for 5 months. Entecavir (ETV) was also used during and after chemotherapy and was ended at 14 months after chemotherapy. However, reactivation of HBV was observed in blood tests, which showed not only elevation of HBV-DNA but also HBsAg and HBeAg, at 27 months after the end of chemotherapy. After restarting ETV, the HBV-DNA levels immediately subsided. In addition, anti-HBs became and remained positive at 31 months after chemotherapy. ETV was re-discontinued at 36 months after chemotherapy.
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Affiliation(s)
- Junichi Muraishi
- Third Department of Internal Medicine, Japan School of Medicine, University of Occupational and Environmental Health, Japan
| | - Michihiko Shibata
- Third Department of Internal Medicine, Japan School of Medicine, University of Occupational and Environmental Health, Japan
| | - Yuichi Honma
- Third Department of Internal Medicine, Japan School of Medicine, University of Occupational and Environmental Health, Japan
| | - Masaaki Hiura
- Third Department of Internal Medicine, Japan School of Medicine, University of Occupational and Environmental Health, Japan
| | - Shintaro Abe
- Third Department of Internal Medicine, Japan School of Medicine, University of Occupational and Environmental Health, Japan
| | - Masaru Harada
- Third Department of Internal Medicine, Japan School of Medicine, University of Occupational and Environmental Health, Japan
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Makvandi M. Update on occult hepatitis B virus infection. World J Gastroenterol 2016; 22:8720-8734. [PMID: 27818588 PMCID: PMC5075547 DOI: 10.3748/wjg.v22.i39.8720] [Citation(s) in RCA: 102] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2016] [Revised: 06/13/2016] [Accepted: 07/20/2016] [Indexed: 02/06/2023] Open
Abstract
The event of mutations in the surface antigen gene of hepatitis B virus (HBV) results in undetectable hepatitis B surface antigen with positive/negative anti-hepatitis B core (anti-HBc) antibody status in serum and this phenomenon is named occult hepatitis B infection (OBI). The presence of anti-HBc antibody in serum is an important key for OBI tracking, although about 20% of OBI cases are negative for anti-HBc antibody. The diagnosis of OBI is mainly based on polymerase chain reaction (PCR) and real-time PCR assays. However, real-time PCR is a more reliable method than PCR. OBI is a great issue for the public health problem and a challenge for the clinical entity worldwide. The persistence of OBI may lead to the development of cirrhosis and hepatocellular carcinoma. With regard to OBI complications, the screening of HBV DNA by the highly sensitive molecular means should be implemented for: (1) patients with a previous history of chronic or acute HBV infection; (2) patients co-infected with hepatitis C virus/human immunodeficiency virus; (3) patients undergoing chemotherapy or anti-CD20 therapy; (4) recipients of organ transplant; (5) blood donors; (6) organ transplant donors; (7) thalassemia and hemophilia patients; (8) health care workers; (9) patients with liver related disease (cryptogenic); (10) hemodialysis patients; (11) patients undergoing lamivudine or interferon therapy; and (12) children in time of HBV vaccination especially in highly endemic areas of HBV. Active HBV vaccination should be implemented for the close relatives of patients who are negative for OBI markers. Thus, the goal of this review is to evaluate the rate of OBI with a focus on status of high risk groups in different regions of the world.
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