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Mikulska M, van Bömmel F, Mouliade C, Indolfi G, Kefalakes H, von Lilienfeld-Toal M, Pischke S, Hermine O, Moradpour D, Wedemeyer H, Berg T, Ljungman P, Mallet V. Updated recommendations for the management of hepatitis B, C, and E virus infections in patients with haematological malignancies and those undergoing haematopoietic cell transplantation: recommendations from the 9th European Conference on Infections in Leukaemia (ECIL-9). Lancet Haematol 2025; 12:e389-e399. [PMID: 40306834 DOI: 10.1016/s2352-3026(25)00049-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2024] [Revised: 01/09/2025] [Accepted: 02/14/2025] [Indexed: 05/02/2025]
Abstract
Viral hepatitis remains a global health challenge and immune status affects outcomes. In patients with haematological malignancies, including haematopoietic stem-cell transplantation recipients, viral hepatitis can be life-threatening due to the direct effects of the virus or the need to modify or delay chemotherapy. Additionally, haematopoietic stem-cell donors with past or current viral hepatitis infections might transmit the virus to recipients. The growing recognition of hepatitis E virus (HEV), advances in haematological therapies, and the availability of direct-acting antivirals for hepatitis C virus (HCV), led the 2022 9th European Conference on Infections in Leukaemia (ECIL-9) to update the 2013 ECIL-5 guidelines on viral hepatitis. The ECIL organising committee convened a panel of 13 impartial international experts (all authors of this Review) in viral hepatitis, both within and outside the fields of haematological malignancies and immunosuppression. The ECIL-9 panel conducted a review of the literature on hepatitis B virus (HBV), HCV, and HEV, grading the evidence based on the European Society for Clinical Microbiology and Infectious Diseases system. The panel identified key clinical questions and outcomes and built on the recommendations established during ECIL-5. A consensus conference was held in Sofia Antipolis, France, from Sept 15-17, 2022, bringing together 49 experts from 19 countries. The ECIL-9 panel presented the proposed recommendations, which were revised following expert discussions. A final consensus on updated guidelines was reached in a second plenary session. The updated ECIL-9 guidelines provide evidence-based recommendations on the prevention, screening, treatment, and long-term surveillance of viral hepatitis in patients with haematological malignancies and haematopoietic cell transplantation recipients.
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Affiliation(s)
- Malgorzata Mikulska
- Department of Health Sciences, Division of Infectious Diseases, University of Genoa, Genoa, Italy; IRCCS Ospedale Policlinico San Martino, Genoa, Italy
| | - Florian van Bömmel
- Laboratory for Clinical and Experimental Hepatology, Department of Medicine II, Leipzig University Medical Center, Leipzig, Germany; Division of Hepatology, Department of Medicine II, Leipzig University Medical Center, Leipzig, Germany; University Liver Tumor Center, Leipzig University Medical Center, Leipzig, Germany
| | - Charlotte Mouliade
- Université Paris Cité, Paris, France; AP-HP Centre, Groupe Hospitalier Cochin Port Royal, DMU Cancérologie et spécialités médico-chirurgicales, Service d'Hépatologie, Paris, France
| | | | - Helenie Kefalakes
- Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Marie von Lilienfeld-Toal
- Institut für Diversitätsmedizin, Ruhr-Universität Bochum, Bochum, Germany; Hämatologie, Onkologie, Stammzelltransplantation und Zelltherapie, Universitätsklinikum Knappschaftskrankenhaus Bochum, Bochum, Germany; Department of Haematology, Oncology and Palliative Care, St Josef Hospital, Ruhr University, Bochum, Germany
| | - Sven Pischke
- Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Olivier Hermine
- Université Paris Cité, Paris, France; Department of Haematology, Necker Hospital, Assistance Publique Hôpitaux de Paris, Paris, France; Laboratory of Physiopathology of Haematological Disorders and their Treatment, Imagine Institute INSERM U 1163, Paris, France
| | - Darius Moradpour
- Division of Gastroenterology and Hepatology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
| | - Heiner Wedemeyer
- Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Thomas Berg
- Division of Hepatology, Department of Medicine II, Leipzig University Medical Center, Leipzig, Germany
| | - Per Ljungman
- Department of Cellular Therapy and Allogeneic Stem Cell Transplantation, Karolinska University Hospital Huddinge, Karolinska Comprehensive Cancer Center, Stockholm, Sweden; Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden
| | - Vincent Mallet
- Université Paris Cité, Paris, France; AP-HP Centre, Groupe Hospitalier Cochin Port Royal, DMU Cancérologie et spécialités médico-chirurgicales, Service d'Hépatologie, Paris, France.
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Filippini G, Kruja J, Del Giovane C. Rituximab for people with multiple sclerosis. Cochrane Database Syst Rev 2025; 3:CD013874. [PMID: 40066932 PMCID: PMC11895426 DOI: 10.1002/14651858.cd013874.pub3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/15/2025]
Abstract
BACKGROUND Multiple sclerosis (MS) is the most common neurological cause of disability in young adults. Off-label rituximab for MS is used in most countries surveyed by the International Federation of MS, including high-income countries where on-label disease-modifying treatments (DMTs) are available. This updates the 2021 version of the review. OBJECTIVES To assess the benefits and harms of rituximab as 'first choice' and 'switching' treatment for adults with any form of MS. SEARCH METHODS We searched CENTRAL, MEDLINE, Embase, CINAHL, and three trials registers on 31 December 2023, together with reference checking and contacting study authors to identify unpublished studies. SELECTION CRITERIA We included randomised controlled trials (RCTs) and controlled non-randomised studies of interventions (NRSIs) comparing rituximab with placebo or another DMT for adults with any form of MS. DATA COLLECTION AND ANALYSIS We followed standard Cochrane methods. We used RoB 1 to assess risk of bias in RCTs and ROBINS-I in NRSIs. We assessed the certainty of evidence for critical and important prioritised outcomes using GRADE: disability worsening, relapse, serious adverse events (SAEs), health-related quality of life (HRQoL), common infections, cancer, and mortality. We conducted separate analyses for rituximab as 'first choice' or as 'switching' treatment, relapsing or progressive MS, comparison with placebo or another DMT, and RCTs or NRSIs. MAIN RESULTS In this update, the number of study participants increased from 16,429 (15 studies) to 37,443 (28 studies; 13 new studies: 1 RCT and 12 NRSIs). The studies were conducted worldwide; most originated from high-income countries (25 studies). Public institutions funded 22 (79%) of the studies. Most studies investigated the effects of rituximab on people with relapsing MS (19 studies; 27,500 (73%) participants). We identified 12 ongoing studies. Rituximab as 'first choice' for active relapsing MS None of the included studies compared rituximab to placebo. One RCT compared rituximab to dimethyl fumarate, with 24 months' follow-up. Rituximab may reduce the recurrence of relapse (odds ratio (OR) 0.16, 95% confidence interval (CI) 0.04 to 0.57; 195 participants; low-certainty evidence). The evidence is very uncertain on disability worsening and SAEs. Rituximab may result in little to no difference in upper respiratory tract infections (rate ratio (RR) 1.03, 95% CI 0.79 to 1.34; low-certainty evidence). The evidence is very uncertain for urinary tract, skin, and viral infections. HRQoL, cancer, and mortality were not reported. One NRSI compared rituximab to other DMTs, with 24 months' follow-up. Disability worsening was not reported. Compared with interferon beta or glatiramer acetate, rituximab likely delays relapse (hazard ratio (HR) 0.14, 95% CI 0.05 to 0.39; 1 study, 335 participants; moderate-certainty evidence). Compared with dimethyl fumarate and natalizumab, rituximab may delay relapse (dimethyl fumarate: HR 0.29, 95% CI 0.08 to 1.00; 1 study, 206 participants; low-certainty evidence; natalizumab: HR 0.24, 95% CI 0.06 to 1.00; 1 study, 170 participants; low-certainty evidence). The evidence for relapse is very uncertain when comparing rituximab to fingolimod. The effect on SAEs is uncertain due to very few events in all the comparison groups. No deaths were reported. HRQoL, common infections, and cancer were not reported. Rituximab as 'first choice' for primary progressive MS One RCT compared rituximab to placebo, with 24 months' follow-up. Rituximab likely results in little or no difference in disability worsening (OR 0.71, 95% CI 0.45 to 1.11; 439 participants; moderate-certainty evidence). The evidence is very uncertain on relapse, SAEs, common infections, cancer, and mortality. HRQoL was not reported. None of the included studies compared rituximab as 'first choice' treatment to other DMTs for primary or secondary progressive MS. Rituximab as 'switching' treatment for relapsing MS One small RCT compared rituximab to placebo, with 12 months' follow-up. Disability worsening was not reported. Rituximab may reduce recurrence of relapses (OR 0.38, 95% CI 0.16 to 0.93; 1 study, 104 participants; low-certainty evidence). The evidence is very uncertain regarding SAEs, common infections, cancer, and mortality. HRQoL was not reported. Twelve NRSIs compared rituximab to other DMTs, with 24 months' follow-up. The evidence on disability worsening is very uncertain in comparison with interferons or glatiramer acetate, natalizumab, alemtuzumab, and ocrelizumab. Rituximab likely delays time to relapse in comparison with interferons or glatiramer acetate (HR 0.18, 95% CI 0.07 to 0.49; 1 study, 1383 participants; moderate-certainty evidence), fingolimod (HR 0.08, 95% CI 0.02 to 0.32; 1 study, 256 participants; moderate-certainty evidence), and may result in little or no difference compared with natalizumab (HR 0.96, 95% CI 0.83 to 1.10; 3 studies, 1922 participants; low-certainty evidence). The evidence is very uncertain on relapse in comparison with alemtuzumab. There is uncertainty regarding SAEs when comparing rituximab to natalizumab and fingolimod. Rituximab likely increases serious common infections when compared with interferon beta or glatiramer acetate (OR 1.71, 95% CI 1.11 to 2.62; 1 study, 5477 participants; moderate-certainty evidence) and natalizumab (OR 1.58, 95% CI 1.08 to 2.32; 2 studies, 5001 participants; moderate-certainty evidence). The evidence for common infections is very uncertain when comparing rituximab to fingolimod and ocrelizumab. Rituximab may slightly reduce the risk of cancer compared with natalizumab (HR 0.79, 95% CI 0.62 to 0.99; 2 studies, 6202 participants; low-certainty evidence), whereas the evidence is very uncertain in comparison with fingolimod. The effect of rituximab on mortality is very uncertain due to very few events in all the comparison groups. HRQoL was not reported. AUTHORS' CONCLUSIONS For preventing relapses in relapsing MS, rituximab as 'first choice' and 'switching' treatment compares favourably with a wide range of approved DMTs. The protective effect of rituximab against disability worsening is uncertain. There is limited information to determine the effect of rituximab on primary progressive MS. There is limited evidence for long-term adverse events of rituximab in people with MS. Evidence for serious adverse events, cancer, and mortality was of very low certainty due to few events. There is an increased risk of serious (hospital-treated) infections with rituximab compared with other DMTs, although the absolute risk is low. High-quality (prospectively registered) NRSIs should be conducted to draw more reliable conclusions about the potential benefits and harms of rituximab in people with MS.
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Affiliation(s)
- Graziella Filippini
- Scientific Director's Office, Carlo Besta Foundation and Neurological Institute, Milan, Italy
| | - Jera Kruja
- Neurology, UHC Mother Theresa, University of Medicine, Tirana, Albania
| | - Cinzia Del Giovane
- Institute of Primary Health Care (BIHAM), University of Bern, Bern, Switzerland
- Department of Medical and Surgical Sciences for Children and Adults, University of Modena and Reggio Emilia, Modena, Italy
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Vutien P, Nguyen MH. HBV Reactivation in Immunosuppressed Patients: Screening, Prevention, and Management Including Solid Organ Transplant Recipients. Viruses 2025; 17:388. [PMID: 40143316 PMCID: PMC11945625 DOI: 10.3390/v17030388] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2025] [Revised: 03/05/2025] [Accepted: 03/07/2025] [Indexed: 03/28/2025] Open
Abstract
Hepatitis B virus (HBV) infection remains a global health challenge, affecting over 254 million individuals chronically and contributing significantly to cirrhosis, liver failure, and hepatocellular carcinoma. Despite advancements in antiviral therapy, HBV reactivation remains a critical concern, particularly in immunosuppressed individuals, including non-transplant patients undergoing immunosuppressive therapy and solid organ transplant recipients. This review provides screening and management strategies for HBV reactivation in these populations.
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Affiliation(s)
- Philip Vutien
- Division of Gastroenterology and Hepatology, University of Washington Medical Center, 1959 NE Pacific Street, Box 356175, Seattle, WA 98195, USA
| | - Mindie H. Nguyen
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA 94305, USA;
- Department of Epidemiology and Population Health, Stanford University Medical Center, Palo Alto, CA 94305, USA
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Androutsakos T, Dimitriadis K, Koutsompina ML, Vassilakis KD, Pouliakis A, Fragoulis GE. Hepatitis B reactivation in PsA patients: an SLR and meta-analysis for IL-17, IL-23 and JAK inhibitors. Rheumatology (Oxford) 2025; 64:935-942. [PMID: 39153010 DOI: 10.1093/rheumatology/keae445] [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: 05/29/2024] [Revised: 07/16/2024] [Accepted: 07/29/2024] [Indexed: 08/19/2024] Open
Abstract
OBJECTIVES HBV reactivation (HBVr) constitutes a side effect of the treatment of autoimmune rheumatic diseases. Even though HBVr risk of conventional synthetic DMARDs (csDMARDs) and anti-tumor necrosis factor (anti-TNF) agents has long been established, the risk of targeted synthetic (ts)DMARDs and anti-interleukin (anti-IL) agents remains largely unknown. METHODS We conducted a SLR (PubMed, Scopus and EMBASE) and meta-analysis to examine the HBVr risk for the following: anti-IL17, anti-IL12/23, anti-IL23 and JAK-inhibitors in patients with chronic HBV infection (HBsAg presence or detectable HBV-DNA) and in patients with prior HBV infection (HBcAb-positive and HBsAg-negative). Meta-analysis was performed using both the fixed and random effects method and was conducted using the R computing language. RESULTS Overall, our study revealed a low HBVr risk of <6% in all agents; the risk was significantly higher for people having chronic compared with those with resolved HBV (14.4% vs 5.1%, respectively P < 0.01). There was no difference among different drugs in the HBVr rates [anti-IL-17: 4% (95% CI: 1-9%), anti-IL-12/IL-23: 2% (95% CI: 0-5%), JAK-inhibitors: 4% (95% CI: 1-8%), anti-IL23: 0%]. Of note, HBVr rate reached 28% in patients with chronic HBV who did not receive anti-viral treatment. For patients with resolved hepatitis, the respective percentage was 4.7%. CONCLUSION Overall, our meta-analysis shows that patients with chronic HBV receiving anti-IL-17, anti-IL-12/23, anti-IL-23 and JAK-inhibitors have significant risk for HBVr, especially if they are not under anti-viral treatment. In contrast, resolved HBV seems to offer minor risk for HBVr even without anti-viral treatment.
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Affiliation(s)
- Theodoros Androutsakos
- Department of Pathophysiology, National and Kapodistrian University of Athens, Athens, Greece
| | - Konstantinos Dimitriadis
- Department of Clinical Therapeutics, 'Alexandra' hospital, National and Kapodistrian University of Athens, Athens, Greece
| | | | - Konstantinos D Vassilakis
- First Department of Internal Medicine, Propaedeutic Clinic, "Laiko" Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Avraam Pouliakis
- Second Department of Pathology, National and Kapodistrian University of Athens, Athens, Greece
| | - George E Fragoulis
- First Department of Internal Medicine, Propaedeutic Clinic, "Laiko" Hospital, National and Kapodistrian University of Athens, Athens, Greece
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Zhu D, Du Y, Zhao M, Ablikim D, Huang H, Pan W, Zeng X, Xu C, Lu M, Sutter K, Dittmer U, Zheng X, Yang D, Liu J. Functional B cell deficiency promotes intrahepatic HBV replication and impairs the development of anti-HBV T cell responses. Hepatol Int 2025; 19:93-105. [PMID: 39630171 DOI: 10.1007/s12072-024-10753-8] [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: 04/28/2024] [Accepted: 11/10/2024] [Indexed: 02/23/2025]
Abstract
BACKGROUND The pivotal role of antibody-producing B cells in controlling hepatitis B virus (HBV) infection is well-established. However, the antiviral role of B cells extends beyond antibody production, which has been insufficiently studied for HBV infection. METHODS Using an HBV hydrodynamic injection (HDI) mouse model with B cell depletion or functional blockade, we detected HBV infection markers and assessed T cell function through enzyme-linked immunosorbent assay, RT-PCR and flow cytometry. RESULTS We observed significantly delayed serum and intrahepatic HBV clearance in permanently B cell-deficient and transiently B cell-depleted mice as well as mice with a functional B cell blockade. Blocking B cell function prior to or soon after HBV HDI resulted in delayed HBV clearance indicating that B cells contribute to initiating anti-HBV immune responses after following HBV exposure. Additionally, we also found an early activation of B cells following HBV exposure, characterized by an upregulation of MHC-II, CXCR5, and PD-1. Critically, the proliferation and activation of both CD4 + and CD8 + T cells were impaired after B cell depletion prior to HBV challenge. Consistently, depleting B cells reduced the generation of Th1, Th2, and Th17 cells in the spleen and hindered HBV-specific CD8 + T cell responses in the liver. Along these lines, the HBV-exposed B cells were more efficient in inducing HBcAg-specific CD8 + T cell responses in vitro. CONCLUSIONS Collectively, our data indicate that B cells, in addition to antibody production, are essential for the development of anti-HBV cellular responses and intrahepatic HBV clearance during the early stage of HBV antigen exposure.
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Affiliation(s)
- Dan Zhu
- Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
- Institute of Infectious Diseases and Immunity, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Yanqin Du
- Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
- Institute of Infectious Diseases and Immunity, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Mengxiao Zhao
- Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
- Institute of Infectious Diseases and Immunity, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Dilhumare Ablikim
- Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
- Institute of Infectious Diseases and Immunity, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Hongming Huang
- Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
- Institute of Infectious Diseases and Immunity, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Wen Pan
- Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
- Institute of Infectious Diseases and Immunity, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Xiaoqing Zeng
- Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
- Institute of Infectious Diseases and Immunity, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Chunli Xu
- Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
- Institute of Infectious Diseases and Immunity, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Mengji Lu
- Institute for Virology, University Hospital Essen, University of Duisburg-Essen, 45147, Essen, Germany
| | - Kathrin Sutter
- Institute for Virology, University Hospital Essen, University of Duisburg-Essen, 45147, Essen, Germany
| | - Ulf Dittmer
- Institute for Virology, University Hospital Essen, University of Duisburg-Essen, 45147, Essen, Germany
| | - Xin Zheng
- Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
- Institute of Infectious Diseases and Immunity, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Dongliang Yang
- Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
- Institute of Infectious Diseases and Immunity, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Jia Liu
- Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
- Institute of Infectious Diseases and Immunity, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
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Wen H, Lei Y, Mao L. Post-marketing safety of panitumumab: a real-world pharmacovigilance study. Expert Opin Drug Saf 2024:1-9. [PMID: 39651795 DOI: 10.1080/14740338.2024.2438749] [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: 05/25/2024] [Revised: 09/30/2024] [Accepted: 10/03/2024] [Indexed: 12/11/2024]
Abstract
BACKGROUND Panitumumab has been extensively applied in antitumor therapy, and the regulation of its adverse drug reactions (ADRs) has become extremely important. This study utilized the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) database to extract real-world panitumumab ADR signals and provide relevant information for drug safety. RESEARCH DESIGN AND METHODS ROR, PRR, BCPNN, and MGPS were used to identify real-world ADR signals associated with panitumumab. RESULTS Analysis of 9,033 patients identified 263 ADR signals across 20 MedDRA System Organ Classifications. New signals including peripheral sensory neuropathy, gene mutation, decreased neutrophil count, polyneuropathy, ileus, neutropenia, and febrile neutropenia. Age and sex subgroup analyses revealed specific risks, such as polyneuropathy and gene mutation in those under 65 years of age, decreased neutrophil count and peripheral sensory neuropathy in those over 65 years of age, and febrile neutropenia in men. Ileus was highlighted as a novel ADR in gastrointestinal disorders, with no significant age or sex differences. CONCLUSION This study identified new signals of ADR associated with panitumumab, providing valuable information for the clinical use of panitumumab.
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Affiliation(s)
- Heli Wen
- Department of Gastroenterology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Yuqing Lei
- The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
- Xiaocun town Health Service Center, Wenzhou, China
| | - Lingjie Mao
- Department of Intensive Care Unit, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
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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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Alsuliman T, Musiu P, Stocker N, Desnica L, El-Cheikh J, Sestili S, Srour M, Marjanovic Z, Alrstom A. Sexually transmitted infections in the context of haematological malignancies. Lancet Haematol 2024; 11:e792-e802. [PMID: 39312925 DOI: 10.1016/s2352-3026(24)00210-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/25/2023] [Revised: 06/08/2024] [Accepted: 06/24/2024] [Indexed: 09/25/2024]
Abstract
Sexually transmitted infections (STIs) are a difficult health challenge for immunocompromised patients. Patients treated for several haematological malignancies have further compromised immune systems. Furthermore, many chemotherapies, alone or associated with haematopoietic stem-cell transplantation, make the body's natural barriers extremely fragile. STIs can negatively impact both patient morbidity and mortality. In this Series paper, we discuss Chlamydia trachomatis, Neisseria gonorrhoeae, syphilis, human immunodeficiency virus, herpes simplex virus, human papilloma virus, and hepatitis B virus, as we found them to be associated with increased risks for haematological malignancy treatments, either by incidence or by severity. Protective measures and vaccines for patients with haematological malignancies are also discussed. Large, well conducted studies should be encouraged, with the aim to systematically analyse the impacts of STIs in patients with haematological malignancies, especially given the difficulties that antimicrobial resistance can confer to patient management.
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Affiliation(s)
- Tamim Alsuliman
- Sorbonne University, Paris, France; Department of Hematology and Cellular Therapy, Saint-Antoine Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France; INSERM, Centre de Recherche Saint-Antoine, F-75012, Paris, France.
| | - Paolo Musiu
- Sorbonne University, Paris, France; Department of Hematology and Cellular Therapy, Saint-Antoine Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France; INSERM, Centre de Recherche Saint-Antoine, F-75012, Paris, France
| | - Nicolas Stocker
- Sorbonne University, Paris, France; Department of Hematology and Cellular Therapy, Saint-Antoine Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France; INSERM, Centre de Recherche Saint-Antoine, F-75012, Paris, France
| | - Lana Desnica
- Department of Hematology, University Hospital Centre Zagreb, Zagreb, Croatia
| | - Jean El-Cheikh
- Division of Hematology and Oncology, Department of Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon
| | - Simona Sestili
- Sorbonne University, Paris, France; Department of Hematology and Cellular Therapy, Saint-Antoine Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France; INSERM, Centre de Recherche Saint-Antoine, F-75012, Paris, France
| | - Micha Srour
- Service Maladie du Sang, Centre Hospitalier Universitaire de Lille, Lille, France
| | - Zora Marjanovic
- Sorbonne University, Paris, France; Department of Hematology and Cellular Therapy, Saint-Antoine Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France; INSERM, Centre de Recherche Saint-Antoine, F-75012, Paris, France
| | - Ali Alrstom
- Infectious Diseases, Santiago de Compostela University, Santiago de Compostela, Spain
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9
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Zong Y, Kamoi K, Miyagaki M, Zhang J, Yang M, Zou Y, Ohno-Matsui K. Applications of Biological Therapy for Latent Infections: Benefits and Risks. Int J Mol Sci 2024; 25:9184. [PMID: 39273134 PMCID: PMC11394918 DOI: 10.3390/ijms25179184] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2024] [Revised: 08/20/2024] [Accepted: 08/22/2024] [Indexed: 09/15/2024] Open
Abstract
Biological therapies have revolutionized medical treatment by targeting the key mediators or receptors involved in inflammatory responses, thereby effectively suppressing inflammation and achieving beneficial outcomes. They are more advanced than conventional therapies using corticosteroids and immunosuppressants, offering effective solutions for autoimmune diseases, cancer, transplant rejection, and various infectious diseases, including coronavirus disease 2019. Although they exert low immunosuppressive effects, biological therapies can reactivate specific biological targets associated with infections. This review summarizes the currently available biological therapies and discusses their immunosuppressive mechanisms and clinical applications, highlighting the variations in the types and frequencies of infection recurrence induced by different biological agents. Additionally, this review describes the risk factors associated with various biological agents, thus aiding clinicians in selecting the most appropriate biological therapy.
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Affiliation(s)
- Yuan Zong
- Department of Ophthalmology & Visual Science, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo 113-8510, Japan
| | - Koju Kamoi
- Department of Ophthalmology & Visual Science, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo 113-8510, Japan
| | - Miki Miyagaki
- Department of Ophthalmology & Visual Science, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo 113-8510, Japan
| | - Jing Zhang
- Department of Ophthalmology & Visual Science, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo 113-8510, Japan
| | - Mingming Yang
- Department of Ophthalmology & Visual Science, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo 113-8510, Japan
| | - Yaru Zou
- Department of Ophthalmology & Visual Science, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo 113-8510, Japan
| | - Kyoko Ohno-Matsui
- Department of Ophthalmology & Visual Science, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo 113-8510, Japan
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10
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Chinese Society of Infectious Diseases, Chinese Medical Association, Chinese Society of Hepatology, Chinese Medical Association, Group of Infectious Diseases, Chinese Pediatric Society, Chinese Medical Association, National Clinical Research Center for Infectious Diseases (Beijing). Expert Consensus on the Prevention and Treatment of Chronic Hepatitis B in Children. INFECTIOUS DISEASES & IMMUNITY 2024; 4:106-120. [DOI: 10.1097/id9.0000000000000122] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/27/2024]
Abstract
Abstract
The aim of this consensus is to standardize the prevention, diagnosis, and treatment of chronic hepatitis B in children and to achieve the goal of “eliminating viral hepatitis as a major public health threat by 2030” issued by the World Health Organization. Formulated by organized experts of the Chinese Society of Infectious Diseases and Chinese Society of Hepatology, Chinese Medical Association; Group of Infectious Diseases, Chinese Pediatric Society, Chinese Medical Association; and the National Clinical Research Center for Infectious Diseases (Beijing), the consensus provides the latest evidence and recommendations for the prevention, diagnosis, and treatment of chronic hepatitis B in children.
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11
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Maung ST, Deepan N, Decharatanachart P, Chaiteerakij R. Screening for viral hepatitis B infection in cancer patients before receiving chemotherapy - A systematic review and meta-analysis. Asia Pac J Clin Oncol 2024; 20:335-345. [PMID: 38512893 DOI: 10.1111/ajco.14055] [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: 12/29/2023] [Revised: 02/08/2024] [Accepted: 03/03/2024] [Indexed: 03/23/2024]
Abstract
AIM We conducted a systematic review and meta-analysis to assess the hepatitis B virus (HBV) screening rate in cancer patients before systemic chemotherapy, aiming to identify those needing antiviral prophylaxis for HBV reactivation. METHODS We searched PubMed, Embase, Scopus, and Google Scholar for relevant studies. The pooled screening rate was estimated using a random effects model. Subgroup analyses were conducted based on malignancy types, chemotherapy regimens, study period, and HBV endemic regions. RESULTS The meta-analysis included 29 studies from various endemic regions (19 low-endemic, three lower intermediate-endemic, and seven higher intermediate-endemic). These studies encompassed hematologic malignancies (n = 10), solid-organ tumors (n = 4), and combinations (n = 15). Seven studies used rituximab-containing regimens, four did not, and the remaining 11 did not specify chemotherapy regimens. The pooled screening rate was 57% (95% confidence interval [95%CI]: 46%-68%, I2 = 100%). Over time, screening rates improved from 37% (95%CI: 23%-53%) in 2006-2010 to 68% (54%-80%) in 2011-2015 and 69% (48%-84%) in 2016-2020. Screening rates were highest at 89% (74%-96%) in high endemic countries, followed by 60% (45-73%) in lower-intermediate and 49% (34-64%) in low-endemic countries. Patients with hematological malignancies had a higher screening rate than those with solid organ tumors, 65% (55%-74%) versus 37% (21%-57%), respectively. A screening rate was higher in patients receiving rituximab-containing chemotherapy than non-rituximab regimens, 68% (55%-79%) versus 45% (27%-65%). CONCLUSION Despite existing guidelines, pre-chemotherapy HBV screening rate remains unsatisfactory, with substantial heterogeneous rates globally. These findings underscore the need for effective strategies to align practices with clinical guidelines.
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Affiliation(s)
- Soe Thiha Maung
- Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand
- Ma Har Myaing Hospital, Yangon, Myanmar
| | - Natee Deepan
- Division of Academic Affairs, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | | | - Roongruedee Chaiteerakij
- Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand
- Center of Excellence for Innovation and Endoscopy in Gastrointestinal Oncology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
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12
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Fang HW, Tseng PL, Hu TH, Wang JH, Hung CH, Lu SN, Chen CH. Hepatitis B relapse after entecavir or tenofovir alafenamide cessation under anti-viral prophylaxis for cancer chemotherapy. Virol J 2024; 21:79. [PMID: 38570803 PMCID: PMC10993446 DOI: 10.1186/s12985-024-02338-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2023] [Accepted: 03/08/2024] [Indexed: 04/05/2024] Open
Abstract
BACKGROUND No study has comparing hepatitis B virus (HBV) relapse rates among patients with both cancer and hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB) who completed anti-viral prophylaxis for chemotherapy and then stopped taking entecavir or tenofovir alafenamide (TAF). METHODS A total of 227 HBeAg-negative cancer patients without cirrhosis who previously took entecavir (n = 144) or TAF (n = 83) for antiviral prophylaxis were enrolled. RESULTS The cumulative incidence of virological and clinical relapse at 2 years was 37% and 10.4%, respectively, in the entecavir group, and 46.7% and 19.5%, respectively, in the TAF group. The multivariate analysis revealed that the use of hematologic malignancy, TAF use, and high-viremia group at baseline were independent risk factors for virological relapse, and use of rituximab, TAF use, higher FIB-4 index and high-viremia group at baseline were independent risk factors for clinical relapse. After propensity score-matching, the patients who discontinued TAF therapy still exhibited higher virological (P = 0.031) and clinical relapse rates (P = 0.012) than did those who discontinued entecavir therapy. The patients were allocated to high- (> 2000 IU/mL), moderate- (between 20 and 2000 IU/mL) and low- (< 20 IU/mL) viremia groups. In the high-viremia group, those who had taken TAF for antiviral prophylaxis had higher rates of virological and clinical relapse than did those who had taken entecavir; in the moderate- and low-viremia groups, no significant difference in virological and clinical relapse rates was detected between the entecavir and TAF groups. Three patients experienced hepatic decompensation upon clinical relapse. All three patients were lymphoma and underwent rituximab therapy. One patient developed acute on chronic liver failure and died even though timely retreatment. CONCLUSIONS In patients with both cancer and CHB who underwent antiviral prophylaxis, TAF use was associated with a higher chance of HBV relapse than entecavir use after nucleos(t)ide analogue cessation, particularly in the high-viremia group. Patients who are hematologic malignancy and undergo a rituximab-containing cytotoxic therapy should be monitored closely after withdrawal from prophylactic NA treatment.
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Affiliation(s)
- Hsin-Wei Fang
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, 123 Ta Pei Road, Kaohsiung, Taiwan
| | - Po-Lin Tseng
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, 123 Ta Pei Road, Kaohsiung, Taiwan
| | - Tsung-Hui Hu
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, 123 Ta Pei Road, Kaohsiung, Taiwan
| | - Jing-Houng Wang
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, 123 Ta Pei Road, Kaohsiung, Taiwan
| | - Chao-Hung Hung
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, 123 Ta Pei Road, Kaohsiung, Taiwan
| | - Sheng-Nan Lu
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, 123 Ta Pei Road, Kaohsiung, Taiwan
| | - Chien-Hung Chen
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, 123 Ta Pei Road, Kaohsiung, Taiwan.
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De Pauli S, Grando M, Miotti G, Zeppieri M. Hepatitis B virus reactivation in patients treated with monoclonal antibodies. World J Virol 2024; 13:88487. [PMID: 38616853 PMCID: PMC11008406 DOI: 10.5501/wjv.v13.i1.88487] [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: 09/26/2023] [Revised: 11/23/2023] [Accepted: 12/19/2023] [Indexed: 03/11/2024] Open
Abstract
Hepatitis B virus (HBV) reactivation poses a significant clinical challenge, especially in patients undergoing immunosuppressive therapies, including monoclonal antibody treatments. This manuscript briefly explores the complex relationship between monoclonal antibody therapy and HBV reactivation, drawing upon current literature and clinical case studies. It delves into the mechanisms underlying this phenomenon, highlighting the importance of risk assessment, monitoring, and prophylactic measures for patients at risk. The manuscript aims to enhance the understanding of HBV reactivation in the context of monoclonal antibody therapy, ultimately facilitating informed clinical decision-making and improved patient care. This paper will also briefly review the definition of HBV activation, assess the risks of reactivation, especially in patients treated with monoclonal antibodies, and consider management for patients with regard to screening, prophylaxis, and treatment. A better understanding of patients at risk can help clinicians provide optimum management to ensure successful patient outcomes and prevent morbidity.
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Affiliation(s)
- Silvia De Pauli
- Department of Internal Medicine, Azienda Sanitaria Friuli Occidentale, San Vito al Tagliamento, Pordenone 33170, Italy
| | - Martina Grando
- Department of Internal Medicine, Azienda Sanitaria Friuli Occidentale, San Vito al Tagliamento, Pordenone 33170, Italy
| | - Giovanni Miotti
- Department of Plastic Surgery, University Hospital of Udine, Udine 33100, Italy
| | - Marco Zeppieri
- Department of Ophthalmology, University Hospital of Udine, Udine 33100, Italy
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14
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Bibas M. Plasmablastic Lymphoma. A State-of-the-Art Review: Part 2-Focus on Therapy. Mediterr J Hematol Infect Dis 2024; 16:e2024015. [PMID: 38468838 PMCID: PMC10927196 DOI: 10.4084/mjhid.2024.015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2024] [Accepted: 02/14/2024] [Indexed: 03/13/2024] Open
Abstract
The objective of this two-part review is to present a current and comprehensive understanding of the diagnosis and management of plasmablastic lymphoma. The first part, which was published previously, focused on the study of epidemiology, etiology, clinicopathological characteristics, differential diagnosis, prognostic variables, and the impact of plasmablastic lymphoma on specific populations. This second part addresses the difficult topic of the treatment of plasmablastic lymphoma, specifically examining both the conventional, consolidated approach and the novel therapeutic strategy.
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Affiliation(s)
- Michele Bibas
- Department of Clinical Research, Hematology. National Institute for Infectious Diseases "Lazzaro Spallanzani" I.R.C.S.S. Via Portuense 292 00148 Rome Italy
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15
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Prosty C, Katergi K, Nguyen A, Luo OD, Sorin M, Cherniak V, Sebag M, Demir K, McDonald EG, Lee TC, Cheng MP. Risk of infectious adverse events of venetoclax therapy for hematologic malignancies: a systematic review and meta-analysis of RCTs. Blood Adv 2024; 8:857-866. [PMID: 38154071 PMCID: PMC10875332 DOI: 10.1182/bloodadvances.2023011964] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2023] [Revised: 11/28/2023] [Accepted: 12/13/2023] [Indexed: 12/30/2023] Open
Abstract
ABSTRACT Venetoclax is a small molecule inhibitor of BCL-2 used in the treatment of acute myelogenous leukemia (AML) and chronic lymphocytic leukemia (CLL). Recent postmarketing studies of ibrutinib, another small molecule inhibitor, suggested that these agents may predispose to opportunistic infections. We sought to systematically review the randomized controlled trial (RCT) evidence of venetoclax to assess whether it predisposes patients to infectious adverse events (IAEs) and neutropenia. We systematically reviewed RCTs comparing venetoclax therapy with active or placebo controls for patients with hematologic malignancies. Data on IAEs and neutropenia were pooled by Bayesian meta-analysis, and we computed the probability of any increased risk (P[risk ratio (RR) > 1]) of IAEs or neutropenic complications. Seven RCTs were included, comprising 2067 patients. In CLL (n = 1032), there was a low probability of increased risk of high-grade (P[RR > 1] = 71.2%) and fatal IAEs (P[RR > 1] = 64.5%) and high-grade neutropenia (P[RR > 1] = 63.4%). There were insufficient data to perform a meta-analysis of IAEs in AML; however, 1 trial suggested an increased risk of IAEs with venetoclax. Furthermore, in AML (n = 642), venetoclax was associated with a high probability of increased risk of high-grade neutropenia (P[RR > 1] = 94.6%) and febrile neutropenia (P[RR > 1] = 90.6%). Our results suggest that venetoclax has a low probability of increased risk of IAEs or neutropenia in CLL. By contrast, there is likely increased risk of high-grade neutropenia and febrile neutropenia in AML. Importantly, our analyses did not identify any specific IAEs that would benefit from routine antimicrobial prophylaxis or pre-emptive testing.
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Affiliation(s)
- Connor Prosty
- Faculty of Medicine, McGill University, Montréal, QC, Canada
| | - Khaled Katergi
- Faculty of Medicine, Université de Montréal, Montréal, QC, Canada
| | - Alex Nguyen
- Faculty of Medicine, McGill University, Montréal, QC, Canada
| | - Owen Dan Luo
- Faculty of Medicine, McGill University, Montréal, QC, Canada
| | - Mark Sorin
- Faculty of Medicine, McGill University, Montréal, QC, Canada
| | - Vladimir Cherniak
- Division of General Internal Medicine, Department of Medicine, McGill University Health Centre, Montréal, QC, Canada
| | - Michael Sebag
- Division of Hematology, Department of Medicine, McGill University, Montréal, QC, Canada
| | - Koray Demir
- Division of Infectious Diseases, Department of Medicine, Université de Montréal, Montréal, QC, Canada
| | - Emily G. McDonald
- Division of General Internal Medicine, Department of Medicine, McGill University Health Centre, Montréal, QC, Canada
- Division of Experimental Medicine, Department of Medicine, McGill University, Montréal, QC, Canada
- Clinical Practice Assessment Unit, Department of Medicine, McGill University Health Centre, Montréal, QC, Canada
| | - Todd C. Lee
- Division of Experimental Medicine, Department of Medicine, McGill University, Montréal, QC, Canada
- Clinical Practice Assessment Unit, Department of Medicine, McGill University Health Centre, Montréal, QC, Canada
- Division of Infectious Diseases, Department of Medicine, McGill University Health Centre, Montréal, QC, Canada
| | - Matthew P. Cheng
- Division of Experimental Medicine, Department of Medicine, McGill University, Montréal, QC, Canada
- Clinical Practice Assessment Unit, Department of Medicine, McGill University Health Centre, Montréal, QC, Canada
- Division of Infectious Diseases, Department of Medicine, McGill University Health Centre, Montréal, QC, Canada
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16
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Yi JH, Lee JL, Lee YJ, Kang HJ, Park YH, Yuh YJ, Lim SN, Kim HJ, Jung SH, Lee JJ, Cho HJ, Moon JH, Yhim HY, Kim K. Outcome of Multiple Myeloma Patients With Hepatitis B Surface Antigen: Korean Multiple Myeloma Working Party 2103 Study. CLINICAL LYMPHOMA, MYELOMA & LEUKEMIA 2024; 24:e50-e57.e2. [PMID: 37973459 DOI: 10.1016/j.clml.2023.10.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/30/2023] [Revised: 10/06/2023] [Accepted: 10/11/2023] [Indexed: 11/19/2023]
Abstract
BACKGROUND Hepatitis B virus reactivation (HBVr) is a well-known complication of systemic chemotherapy for particularly hematologic malignancies in HBV carriers. We performed a multicenter retrospective study to investigate the incidence and risk factors of HBVr in patients with hepatitis B surface antigen (HBsAg)-positive multiple myeloma (MM). METHODS We included 123 patients with HBsAg-positive MM who had received systemic therapy. The primary objective of the study was to evaluate the incidence of HBVr in patients with HBsAg-positive MM. RESULTS The median age was 59 years, and 72 patients were male. With a median follow-up duration of 41.4 months, there were 43 instances of HBVr in 35 patients (28.5%): 29 treatment-related HBVr occurred during 424 treatments. Treatments containing antiviral prophylaxis were associated with a significantly lower incidence of HBVr compared to those without (14.4% vs. 1.9%, P < 0.001). Moreover, treatment with cyclophosphamide (P = 0.002) and doxorubicin (P = 0.053) were risk factors for HBVr; stem cell transplantation was not associated with HBVr. There was no significant difference in overall survival between patients with and without HBVr (P = 0.753) and myeloma progression was the major cause of death. CONCLUSION Considering the low incidence of HBVr in patients who had received antiviral prophylaxis, HBsAg-positivity should not impede patients from receiving optimal antimyeloma treatment or participating in clinical trials.
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Affiliation(s)
- Jun Ho Yi
- Division of Hematology-Oncology, Department of Medicine, Chung-Ang University, Seoul, Korea
| | - Jung Lim Lee
- Department of Hemato-oncology, Daegu Fatima Hospital, Daegu, Korea
| | - Yoo Jin Lee
- Department of Hematology and Oncology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea
| | - Hye Jin Kang
- Division of Hematology/Oncology, Department of Internal Medicine, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences, Seoul, Korea
| | - Young Hoon Park
- Division of Hematology-Oncology, Department of Internal Medicine, Ewha Womans University College of Medicine, Seoul, Korea
| | - Young Jin Yuh
- Department of Internal Medicine, Sanggye-Paik Hospital, Inje University, Seoul, Korea
| | - Sung-Nam Lim
- Department of Internal Medicine, Haeundae Paik Hospital, Inje University College of Medicine, Busan, Korea
| | - Hyo Jung Kim
- Department of Internal Medicine, Hallym University Sacred Heart Hospital, Anyang, Korea
| | - Sung-Hoon Jung
- Department of Hematology-Oncology, Chonnam National University Hwasun Hospital and Chonnam National University Medical School, Hwasun-gun, Jeollanam-do, Korea
| | - Je-Jung Lee
- Department of Hematology-Oncology, Chonnam National University Hwasun Hospital and Chonnam National University Medical School, Hwasun-gun, Jeollanam-do, Korea
| | - Hee Jeong Cho
- Department of Hematology-Oncology, Kyungpook National University Hospital, Kyungpook National University, Daegu, Korea
| | - Joon Ho Moon
- Department of Hematology-Oncology, Kyungpook National University Hospital, Kyungpook National University, Daegu, Korea
| | - Ho-Young Yhim
- Department of Internal Medicine, Jeonbuk National University Medical School, Jeonju, Korea
| | - Kihyun Kim
- Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
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Luo C, Zhang Y, Zhang J, Jin C, Ye X, Ren Y, Shen H, Chen M, Li Y, He Q, Xu G, Shao L. Development and validation of a nomogram for predicting pulmonary infection in patients receiving immunosuppressive drugs. Front Pharmacol 2024; 14:1255609. [PMID: 38293665 PMCID: PMC10825965 DOI: 10.3389/fphar.2023.1255609] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2023] [Accepted: 12/31/2023] [Indexed: 02/01/2024] Open
Abstract
Objective: Pulmonary infection (PI), a severe complication of immunosuppressive therapy, affects patients' prognosis. As part of this study, we aimed to construct a pulmonary infection prediction (PIP) model and validate it in patients receiving immunosuppressive drugs (ISDs). Methods: Totally, 7,977 patients being treated with ISDs were randomised 7:3 to the developing (n = 5,583) versus validation datasets (n = 2,394). Our predictive nomogram was established using the least absolute shrinkage and selection operator (LASSO) and multivariate COX regression analyses. With the use of the concordance index (C-index) and calibration curve, the prediction performance of the final model was evaluated. Results: Among the patients taking immunosuppressive medication, PI was observed in 548 (6.9%). The median time of PI occurrence after immunosuppressive therapy was 123.0 (interquartile range: 63.0, 436.0) days. Thirteen statistically significant independent predictors (sex, age, hypertension, DM, malignant tumour, use of biologics, use of CNIs, use of methylprednisolone at 500 mg, use of methylprednisolone at 40 mg, use of methylprednisolone at 40 mg total dose, use of oral glucocorticoids, albumin level, and haemoglobin level) were screened using the LASSO algorithm and multivariate COX regression analysis. The PIP model built on these features performed reasonably well, with the developing C-index of 0.87 (sensitivity: 85.4%; specificity: 81.0%) and validation C-indices of 0.837, 0.829, 0.832 and 0.830 for predicting 90-, 180-, 270- and 360-day PI probability, respectively. The decision curve analysis (DCA) and calibration curves displayed excellent clinical utility and calibration performance of the nomogram. Conclusion: The PIP model presented herein could aid in the prediction of PI risk in individual patients who receive immunosuppressive treatment and help personalise clinical decision-making.
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Affiliation(s)
- Chuxuan Luo
- Department of Nephrology, Taizhou Hospital of Zhejiang Province, Wenzhou Medical University, Taizhou, Zhejiang, China
| | - Yue Zhang
- Urology and Nephrology Center, Department of Nephrology, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), Hangzhou, Zhejiang, China
| | - Jiajie Zhang
- Center for General Practice Medicine, Department of Infectious Diseases, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), Hangzhou, Zhejiang, China
| | - Chen Jin
- Urology and Nephrology Center, Department of Nephrology, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), Hangzhou, Zhejiang, China
| | - Xiaolan Ye
- Center for Clinical Pharmacy, Cancer Center, Department of Pharmacy, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), Hangzhou, Zhejiang, China
| | - Yan Ren
- Urology and Nephrology Center, Department of Nephrology, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), Hangzhou, Zhejiang, China
| | - Huajuan Shen
- Urology and Nephrology Center, Department of Nephrology, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), Hangzhou, Zhejiang, China
| | - Maosheng Chen
- Urology and Nephrology Center, Department of Nephrology, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), Hangzhou, Zhejiang, China
| | - Yiwen Li
- Urology and Nephrology Center, Department of Nephrology, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), Hangzhou, Zhejiang, China
| | - Qiang He
- Department of Nephrology, the First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine), Hangzhou, Zhejiang, China
| | - Guangbiao Xu
- Department of Nephrology, Taizhou Hospital of Zhejiang Province, Wenzhou Medical University, Taizhou, Zhejiang, China
| | - Lina Shao
- Urology and Nephrology Center, Department of Nephrology, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), Hangzhou, Zhejiang, China
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18
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Anvari S, Tsoi K. Hepatitis B Virus Reactivation with Immunosuppression: A Hidden Threat? J Clin Med 2024; 13:393. [PMID: 38256527 PMCID: PMC10816226 DOI: 10.3390/jcm13020393] [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: 11/30/2023] [Revised: 12/23/2023] [Accepted: 01/09/2024] [Indexed: 01/24/2024] Open
Abstract
Hepatitis B virus (HBV) reactivation in the setting of immunosuppressive therapy is an increasingly recognized and preventable cause of elevated liver enzymes and clinical hepatitis in treated patients. However, not all immunosuppressive therapies confer the same risk. The purpose of this article was to review the literature on risks of HBV reactivation associated with immunosuppressive agents and propose a management algorithm. We searched Google Scholar, PubMed, and MEDLINE for studies related to hepatitis B reactivation and various immunosuppressive agents. The risk of HBV reactivation was found to differ by agent and depending on whether a patient had chronic HBV (HBsAg+) or past HBV (HBsAg-, anti-HBc+). The highest risk of reactivation (>10%) was associated with anti-CD20 agents and hematopoietic stem cell transplants. Multiple societies recommend HBV-specific anti-viral prophylaxis for patients with positive HBsAg prior to the initiation of immunosuppressive therapy, while the guidance for HBsAg- patients is more variable. Clinicians should check HBV status prior to beginning an immune-suppressive therapy. Patients with positive HBsAg should be initiated on antiviral prophylaxis in the majority of cases, whereas HBsAg- individuals should be evaluated on a case-by-case basis. Further research is required to determine the optimum duration of therapy.
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Affiliation(s)
- Sama Anvari
- Division of Gastroenterology, Department of Internal Medicine, McMaster University, Hamilton, ON L8S 4L8, Canada;
- Division of Gastroenterology, St. Joseph’s Healthcare Hamilton, Hamilton, ON L8N 4A6, Canada
| | - Keith Tsoi
- Division of Gastroenterology, Department of Internal Medicine, McMaster University, Hamilton, ON L8S 4L8, Canada;
- Division of Gastroenterology, St. Joseph’s Healthcare Hamilton, Hamilton, ON L8N 4A6, Canada
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Mak JWY, Law AWH, Law KWT, Ho R, Cheung CKM, Law MF. Prevention and management of hepatitis B virus reactivation in patients with hematological malignancies in the targeted therapy era. World J Gastroenterol 2023; 29:4942-4961. [PMID: 37731995 PMCID: PMC10507505 DOI: 10.3748/wjg.v29.i33.4942] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/29/2023] [Revised: 07/22/2023] [Accepted: 08/15/2023] [Indexed: 09/01/2023] Open
Abstract
Hepatitis due to hepatitis B virus (HBV) reactivation can be serious and potentially fatal, but is preventable. HBV reactivation is most commonly reported in patients receiving chemotherapy, especially rituximab-containing therapy for hematological malignancies and those receiving stem cell transplantation. Patients with inactive and even resolved HBV infection still have persistence of HBV genomes in the liver. The expression of these silent genomes is controlled by the immune system. Suppression or ablation of immune cells, most importantly B cells, may lead to reactivation of seemingly resolved HBV infection. Thus, all patients with hematological malignancies receiving anticancer therapy should be screened for active or resolved HBV infection by blood tests for hepatitis B surface antigen (HBsAg) and antibody to hepatitis B core antigen. Patients found to be positive for HBsAg should be given prophylactic antiviral therapy. For patients with resolved HBV infection, there are two approaches. The first is pre-emptive therapy guided by serial HBV DNA monitoring, and treatment with antiviral therapy as soon as HBV DNA becomes detectable. The second approach is prophylactic antiviral therapy, particularly for patients receiving high-risk therapy, especially anti-CD20 monoclonal antibody or hematopoietic stem cell transplantation. Entecavir and tenofovir are the preferred antiviral choices. Many new effective therapies for hematological malignancies have been introduced in the past decade, for example, chimeric antigen receptor (CAR)-T cell therapy, novel monoclonal antibodies, bispecific antibody drug conjugates, and small molecule inhibitors, which may be associated with HBV reactivation. Although there is limited evidence to guide the optimal preventive measures, we recommend antiviral prophylaxis in HBsAg-positive patients receiving novel treatments, including Bruton's tyrosine kinase inhibitors, B-cell lymphoma 2 inhibitors, and CAR-T cell therapy. Further studies are needed to determine the risk of HBV reactivation with these agents and the best prophylactic strategy.
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Affiliation(s)
- Joyce Wing Yan Mak
- Department of Medicine and Therapeutics, Prince of Wales Hospital, Hong Kong 852, China
| | | | | | - Rita Ho
- Department of Medicine, North District Hospital, Hong Kong 852, China
| | - Carmen Ka Man Cheung
- Department of Medicine and Therapeutics, Prince of Wales Hospital, Hong Kong 852, China
| | - Man Fai Law
- Department of Medicine and Therapeutics, Prince of Wales Hospital, Hong Kong 852, China
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Luo J, Zheng Z, Yu R. Analysis of medical malpractice liability disputes related to novel antineoplastic drugs and research on risk prevention and control strategies. PLoS One 2023; 18:e0286623. [PMID: 37276214 DOI: 10.1371/journal.pone.0286623] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2022] [Accepted: 05/22/2023] [Indexed: 06/07/2023] Open
Abstract
OBJECTIVE To investigate the general characteristics of litigation cases of medical malpractice liability disputes (MMLDs) related to novel antineoplastic drugs (NADs), the drugs involved, as well as the common types of medical errors related to NADs and their damages in the process of diagnosis and treatment, with the aims of improving the level of rational medication use in the clinical application of NADs and actively prevent medical disputes. METHODS The China Judgments Online was searched for the cause of action using the key word "MMLDs" along with the name of 77 kinds of NADs. A total of 39 NAD litigation cases meeting the inclusion criteria from 1 January 2009 to 31 December 2021 were analyzed, and each potential adverse drug reaction (ADR) was reviewed to determine a causality assessment using the Naranjo algorithm for non-drug-induced liver injury (DILI) cases and the updated Roussel Uclaf Causality Assessment Method (RUCAM) for the DILI cases. Risk prevention and control strategies were recommended. RESULTS Cases that met the inclusion criteria increased substantially each year during the last six years, from three cases in 2009-2015 to 36 cases in 2016-2021. There were more cases in Eastern China than in other geographic regions. Most cases involved tertiary hospitals, patients between 25 and 60 years of age, and patients who were predominately male. There were 18 kinds of NADs involved in medical errors. The most common consequences of NADs were closely related to the death, disability, and increased treatment costs caused by ADRs, inadequate indications, delayed diagnosis and treatment, and misdiagnosis and mistreatment. The most frequent medical errors were medical technology errors, medical ethics errors and medical record writing/safekeeping errors. In two cases involving DILI, one case was unable to undergo further RUCAM scoring because the liver function indicators of the patient before and after treatment were not published. CONCLUSION The establishment of mechanisms to reduce the risks associated with the clinical application of NADs is warranted. Healthcare services must maintain strict adherence to the specific requirements of GPCANADs and drug instructions and strictly grasp the indications, contraindications, usage, and dosage of drugs, and strengthen the notification and management of off-label drug use. Monitoring patients for ADRs and preparing rescue and treatment measures for high-risk drugs may serve to reduce damages related to NADs. For DILI cases, medical and appraisal institutions should use RUCAM score to assess causal relationships.
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Affiliation(s)
- Jinyu Luo
- Division of Nursing, Hemopurification Center, Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang Province, People's Republic of China
| | - Zaoqian Zheng
- Department of Pharmacy, Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang, People's Republic of China
- Division of Medical Administration, Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang, People's Republic of China
- Division of Medical Administration, Zhejiang Academy of Traditional Chinese Medicine, Hangzhou, Zhejiang, People's Republic of China
| | - Rongliang Yu
- Division of Medical Administration, Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang, People's Republic of China
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21
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Ho JCL, Mak JWY, Yip TCF, Lam HM, Cheng TY, Lam TO, Tam LS, Law MF, Cheung CKM, Ng SC, Wong VWS, Wong GLH. Risk of alanine aminotransferase flare in patients with previous hepatitis B virus exposure on biological modifier therapies-A population-based study. Liver Int 2023; 43:588-598. [PMID: 36516362 DOI: 10.1111/liv.15499] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/11/2022] [Revised: 09/22/2022] [Accepted: 11/28/2022] [Indexed: 01/01/2023]
Abstract
BACKGROUND It is uncertain whether biological therapies would increase the risk of hepatitis among patients with past hepatitis B virus (HBV) infection. This study aimed to evaluate the risk of alanine aminotransferase (ALT) flare in patients with past HBV infection while using biological therapies. METHODOLOGY Patients who received biological therapies for ≥3 months from 2000 to 2019 were identified from a population-based database in Hong Kong. Patients with past HBV infection were compared with a control group without prior HBV exposure. The primary endpoint was development of ALT flare within 5 years of starting biological therapies, defined as ALT >80 IU/L. RESULTS There were 2471 and 2394 patients with and without past HBV infection respectively. There was a non-significant increase in risk of ALT flare among the HBV-exposed group (27.6% vs. 23.7%, p = .055). In multivariable analysis, using prednisolone-equivalent dose of >20 mg daily, male sex and concomitant immunosuppressants were risk factors for ALT flare. The risk of ALT flare was significantly higher with anti-CD20 when compared to other biological agents (36.1% vs. 14.5%, p < .01), but was not significantly different among anti-tumour necrosis factor, anti-cytokine, Janus kinase inhibitors and T cell/B cell inhibitors or anti-integrin (15.2% vs. 14.6% vs. 11.7% vs. 11.1%, p = .82). Among patients with documented hepatitis B surface antigen seroreversion, 96% were on anti-CD20. CONCLUSIONS Our study further supports the current suggestion of prophylactic anti-viral before starting anti-CD20 in HBV-exposed patients. While other biological therapies appear to have a lower risk for ALT flare, this result needs further confirmation.
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Affiliation(s)
- Jacky C L Ho
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, Hong Kong
| | - Joyce W Y Mak
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, Hong Kong
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, Hong Kong
- Medical Data Analytics Centre, The Chinese University of Hong Kong, Hong Kong, Hong Kong
| | - Terry C F Yip
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, Hong Kong
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, Hong Kong
- Medical Data Analytics Centre, The Chinese University of Hong Kong, Hong Kong, Hong Kong
| | - Hong Man Lam
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, Hong Kong
| | - Tsz Yan Cheng
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, Hong Kong
| | - Tsz On Lam
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, Hong Kong
| | - Lai Shan Tam
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, Hong Kong
| | - Man Fai Law
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, Hong Kong
| | - Carmen K M Cheung
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, Hong Kong
| | - Siew C Ng
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, Hong Kong
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, Hong Kong
| | - Vincent W S Wong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, Hong Kong
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, Hong Kong
- Medical Data Analytics Centre, The Chinese University of Hong Kong, Hong Kong, Hong Kong
| | - Grace L H Wong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, Hong Kong
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, Hong Kong
- Medical Data Analytics Centre, The Chinese University of Hong Kong, Hong Kong, Hong Kong
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22
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Shui LP, Zhu Y, Duan XQ, Chen YT, Yang L, Tang XQ, Zhang HB, Xiao Q, Wang L, Liu L, Luo XH. HBsAg (-)/HBsAb (-)/HBeAg (-)/HBeAb (+)/HBcAb (+) predicts a high risk of hepatitis B reactivation in patients with B-cell lymphoma receiving rituximab based immunochemotherapy. J Med Virol 2023; 95:e28549. [PMID: 36734081 DOI: 10.1002/jmv.28549] [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: 08/13/2022] [Revised: 12/30/2022] [Accepted: 01/24/2023] [Indexed: 02/04/2023]
Abstract
Patterns of hepatitis B virus reactivation (HBV-R) in HBsAg (-)/HBcAb (+) patients with B-cell non-Hodgkin lymphoma (NHL) receiving rituximab based immunochemotherapy have not been well described. The retrospective study included 222 HBsAg (-)/HBcAb (+) NHL patients as training cohort and 127 cases as validation cohort. The incidence of HBV-R in HBsAg (-)/HBcAb (+) B-cell NHL patients was 6.3% (14/222), of which that in HBsAg (-)/HBsAb (-)/HBeAg (-)/HBeAb (+)/HBcAb (+) population was 23.7% (9/38). Multivariate analysis showed that HBsAg (-)/HBsAb (-)/HBeAg (-)/HBeAb (+)/HBcAb (+) correlated with a high risk of HBV-R in B-cell lymphoma patients (training phase hazard ratio [HR], 10.123; 95% confidence interval [CI], 3.389-30.239; p < 0.001; validation phase HR, 18.619; 95% CI, 1.684-205.906; p = 0.017; combined HR, 12.264; 95% CI, 4.529-33.207; p < 0.001). In the training cohort, the mortality rate of HBsAg (-)/HBcAb (+) B-cell NHL caused by HBV-R was 14.3% (2/14) while that for HBV reactivated HBsAg (-)/HBsAb (-)/HBeAg (-)/HBeAb (+)/HBcAb (+) population was up to 44.4% (4/9). As a high incidence of HBV-R and high mortality after HBV-R was found in HBsAg (-)/HBsAb (-)/HBcAb (+)/HBeAg (-)/HBeAb (+) patients with B-cell NHL receiving rituximab based immunochemotherapy, prophylactic antiviral therapy is recommended for these patients.
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Affiliation(s)
- Li-Ping Shui
- Department of Hematology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Yan Zhu
- Department of Hematology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
| | - Xiao-Qin Duan
- Department of Hematology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Yu-Ting Chen
- Department of Hematology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Li Yang
- Department of Hematology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Xiao-Qiong Tang
- Department of Hematology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Hong-Bin Zhang
- Department of Hematology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Qing Xiao
- Department of Hematology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Li Wang
- Department of Hematology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Lin Liu
- Department of Hematology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Xiao-Hua Luo
- Department of Hematology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
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Brakenhoff SM, Hoekstra R, Honkoop P, Roomer R, den Hollander JG, Bezemer G, de Knegt RJ, Sonneveld MJ, de Man RA. Patients treated with rituximab are poorly screened for hepatitis B infection: Data from a low-incidence country. Eur J Intern Med 2023; 108:68-73. [PMID: 36462966 DOI: 10.1016/j.ejim.2022.11.024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/25/2022] [Revised: 11/14/2022] [Accepted: 11/16/2022] [Indexed: 12/05/2022]
Abstract
BACKGROUND & AIMS Patients with chronic or resolved hepatitis B are at risk of hepatitis B reactivation (HBVr) when treated with high-risk immunosuppressive therapy such as rituximab. Therefore, international guidelines recommend HBV screening prior to rituximab treatment and subsequent antiviral prophylaxis among patients with a (resolved) infection. In this study, we evaluated the adherence to those recommendations. METHODS This is a retrospective multicentre study including patients treated with rituximab between 2000-2021. Performance of correct screening was assessed, defined as the measurement of hepatitis B surface antigen (HBsAg) and hepatitis B core antibodies (anti-HBc). Next, initiation of antiviral prophylaxis and HBVr rate among patients with a chronic or resolved HBV infection was studied. RESULTS We enrolled 3,176 patients of whom 1,448 (46%) were screened correctly. Screening rates differed significantly between academic and non-academic hospitals; respectively 65% vs 32% (p<0.001). In addition, screening rates differed across specialties and improved throughout the years; from 32% before 2012 to 75% after 2020 among academic prescribers, versus 1% to 60% among non-academic prescribers (both p<0.001). Antiviral prophylaxis was initiated in 58% vs 36% of the patients with a chronic or resolved HBV infection. Seven patients experienced HBVr, including one fatal liver decompensation. CONCLUSIONS Many patients treated with rituximab were not correctly screened for HBV infection and antiviral prophylaxis was often not initiated. Although screening rates improved over time, rates remain suboptimal. With the increasing number of indications for rituximab and other immunosuppressive agents these findings could raise awareness among all medical specialties prescribing these agents.
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Affiliation(s)
- Sylvia M Brakenhoff
- Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center, Rotterdam, the Netherlands.
| | - Roos Hoekstra
- Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center, Rotterdam, the Netherlands
| | - Pieter Honkoop
- Department of Gastroenterology and Hepatology, Albert Schweitzer Hospital, Dordrecht, the Netherlands
| | - Robert Roomer
- Department of Gastroenterology and Hepatology, Franciscus Gasthuis en Vlietland, Rotterdam, the Netherlands
| | - Jan G den Hollander
- Department of Internal Medicine, Maasstad Medical Centre, Rotterdam, the Netherlands
| | - Geert Bezemer
- Department of Gastroenterology and Hepatology, Ikazia Hospital, Rotterdam, the Netherlands
| | - Robert J de Knegt
- Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center, Rotterdam, the Netherlands
| | - Milan J Sonneveld
- Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center, Rotterdam, the Netherlands
| | - Robert A de Man
- Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center, Rotterdam, the Netherlands
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Quartuccio L, Bortoluzzi A, Scirè CA, Marangoni A, Del Frate G, Treppo E, Castelnovo L, Saccardo F, Zani R, Candela M, Fraticelli P, Mazzaro C, Renoldi P, Scaini P, Filippini DA, Visentini M, Scarpato S, Giuggioli D, Mascia MT, Sebastiani M, Zignego AL, Lauletta G, Fiorilli M, Casato M, Ferri C, Pietrogrande M, Pioltelli PE, De Vita S, Monti G, Galli M. Management of mixed cryoglobulinemia with rituximab: evidence and consensus-based recommendations from the Italian Study Group of Cryoglobulinemia (GISC). Clin Rheumatol 2023; 42:359-370. [PMID: 36169798 PMCID: PMC9873783 DOI: 10.1007/s10067-022-06391-w] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2022] [Revised: 09/06/2022] [Accepted: 09/21/2022] [Indexed: 01/28/2023]
Abstract
Cryoglobulinemic vasculitis (CV) or mixed cryoglobulinemic syndrome (MCS) is a systemic small-vessel vasculitis characterized by the proliferation of B-cell clones producing pathogenic immune complexes, called cryoglobulins. It is often secondary to hepatitis C virus (HCV), autoimmune diseases, and hematological malignancies. CV usually has a mild benign clinical course, but severe organ damage and life-threatening manifestations can occur. Recently, evidence in favor of rituximab (RTX), an anti-CD 20 monoclonal antibody, is emerging in CV: nevertheless, questions upon the safety of this therapeutic approach, especially in HCV patients, are still being issued and universally accepted recommendations that can help physicians in MCS treatment are lacking. A Consensus Committee provided a prioritized list of research questions to perform a systematic literature review (SLR). A search was made in Medline, Embase, and Cochrane library, updated to August 2021. Of 1227 article abstracts evaluated, 27 studies were included in the SLR, of which one SLR, 4 RCTs, and 22 observational studies. Seventeen recommendations for the management of mixed cryoglobulinemia with rituximab from the Italian Study Group of Cryoglobulinemia (GISC) were developed to give a valuable tool to the physician approaching RTX treatment in CV.
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Affiliation(s)
- Luca Quartuccio
- Unit of Rheumatology, Department of Medicine (DAME), University of Udine, ASUFC, Udine, Italy.
| | - Alessandra Bortoluzzi
- Section of Rheumatology, Department of Medical Sciences, University of Ferrara and Azienda Ospedaliera, Universitaria Di Ferrara, Cona, FE, Italy
| | | | - Antonio Marangoni
- Section of Rheumatology, Department of Medical Sciences, University of Ferrara and Azienda Ospedaliera, Universitaria Di Ferrara, Cona, FE, Italy
| | - Giulia Del Frate
- Unit of Rheumatology, Department of Medicine (DAME), University of Udine, ASUFC, Udine, Italy
| | - Elena Treppo
- Unit of Rheumatology, Department of Medicine (DAME), University of Udine, ASUFC, Udine, Italy
| | - Laura Castelnovo
- Department of Internal Medicine, Hospital of Legnano, Legnano, Italy
| | | | | | | | - Paolo Fraticelli
- Ematologia Ed Immunologia Clinica, Clinica Medica Generale, University of Ancona, Ancona, Italy
| | - Cesare Mazzaro
- Clinical Experimental Onco-Haematology Unit, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, 33081, Aviano, Italy
| | - Piero Renoldi
- UOS Di Immunologia Clinica, Ospedale S. Carlo Borromeo, Milan, Italy
| | | | | | - Marcella Visentini
- Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy
| | | | - Dilia Giuggioli
- Department of Internal Medicine, Rheumatology Unit, University of Modena and Reggio Emilia, Modena, Italy
| | - Maria Teresa Mascia
- Department of Internal Medicine, Rheumatology Unit, University of Modena and Reggio Emilia, Modena, Italy
| | - Marco Sebastiani
- Department of Internal Medicine, Rheumatology Unit, University of Modena and Reggio Emilia, Modena, Italy
| | | | | | - Massimo Fiorilli
- Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy
| | - Milvia Casato
- Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy
| | - Clodoveo Ferri
- Department of Internal Medicine, Rheumatology Unit, University of Modena and Reggio Emilia, Modena, Italy
| | - Maurizio Pietrogrande
- Department of Medicine, Surgery and Dentistry, Medicina Interna, Policlinico San Marco of Zingonia, University of Milan, Milan, Italy
| | | | - Salvatore De Vita
- Unit of Rheumatology, Department of Medicine (DAME), University of Udine, ASUFC, Udine, Italy
| | - Giuseppe Monti
- Medicina Interna, Ospedale Di Saronno, AO Busto Arsizio, Italy
| | - Massimo Galli
- Infectious Disease Unit, L. Sacco, Department of Clinical Sciences, University of Milan, Milan, Italy
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25
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Giordano C, Picardi M, Pugliese N, Vincenzi A, Abagnale DP, De Fazio L, Giannattasio ML, Fatigati C, Ciriello M, Salemme A, Muccioli Casadei G, Vigliar E, Mascolo M, Troncone G, Pane F. Lamivudine 24-month-long prophylaxis is a safe and efficient choice for the prevention of hepatitis B virus reactivation in HBsAg-negative/HBcAb-positive patients with advanced DLBCL undergoing upfront R-CHOP-21. Front Oncol 2023; 13:1130899. [PMID: 36890828 PMCID: PMC9986962 DOI: 10.3389/fonc.2023.1130899] [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: 12/23/2022] [Accepted: 01/30/2023] [Indexed: 02/17/2023] Open
Abstract
Introduction Occult hepatitis B infection (OBI) is a condition where replication-competent hepatitis B virus-DNA (HBV-DNA) is present in the liver, with or without HBV-DNA in the blood [<200 international units (IU)/ml or absent] in HB surface antigen (HBsAg)-negative/HB core antibody (HBcAb)-positive individuals. In patients with advanced stage diffuse large B-cell lymphoma (DLBCL) undergoing 6 cycles of R-CHOP-21+2 additional R, OBI reactivation is a frequent and severe complication. There is no consensus among recent guidelines on whether a pre-emptive approach or primary antiviral prophylaxis is the best solution in this setting of patients. In addition, questions still unresolved are the type of prophylactic drug against HBV and adequate prophylaxis duration. Methods In this case-cohort study, we compared a prospective series of 31 HBsAg-/HBcAb+ patients with newly diagnosed high-risk DLBCL receiving lamivudine (LAM) prophylaxis 1 week before R-CHOP-21+2R until 18 months after (24-month LAM series) versus 96 HBsAg-/HBcAb+ patients (from January 2005 to December 2011) undergoing a pre-emptive approach (pre-emptive cohort) and versus 60 HBsAg-/HBcAb+ patients, from January 2012 to December 2017, receiving LAM prophylaxis [1 week before immunochemotherapy (ICHT) start until 6 months after] (12-month LAM cohort). Efficacy analysis focused primarily on ICHT disruption and secondarily on OBI reactivation and/or acute hepatitis. Results In the 24-month LAM series and in the 12-month LAM cohort, there were no episodes of ICHT disruption versus 7% in the pre-emptive cohort (P = 0.05). OBI reactivation did not occur in any of the 31 patients in the 24-month LAM series versus 7 out of 60 patients (10%) in the 12-month LAM cohort or 12 out of 96 (12%) patients in the pre-emptive cohort (P = 0.04, by χ 2 test). No patients in the 24-month LAM series developed acute hepatitis compared with three in the 12-month LAM cohort and six in the pre-emptive cohort. Discussion This is the first study collecting data regarding a consistent and homogeneous large sample of 187 HBsAg-/HBcAb+ patients undergoing standard R-CHOP-21 for aggressive lymphoma. In our study, 24-month-long prophylaxis with LAM appears to be the most effective approach with a null risk of OBI reactivation, hepatitis flare-up, and ICHT disruption.
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Affiliation(s)
- Claudia Giordano
- Department of Clinical Medicine and Surgery, Federico II University Medical School, Naples, Italy
| | - Marco Picardi
- Department of Clinical Medicine and Surgery, Federico II University Medical School, Naples, Italy
| | - Novella Pugliese
- Department of Clinical Medicine and Surgery, Federico II University Medical School, Naples, Italy
| | - Annamaria Vincenzi
- Department of Clinical Medicine and Surgery, Federico II University Medical School, Naples, Italy
| | - Davide Pio Abagnale
- Department of Clinical Medicine and Surgery, Federico II University Medical School, Naples, Italy
| | - Laura De Fazio
- Department of Clinical Medicine and Surgery, Federico II University Medical School, Naples, Italy
| | - Maria Luisa Giannattasio
- Department of Clinical Medicine and Surgery, Federico II University Medical School, Naples, Italy
| | - Carmina Fatigati
- Department of Clinical Medicine and Surgery, Federico II University Medical School, Naples, Italy
| | - Mauro Ciriello
- Department of Clinical Medicine and Surgery, Federico II University Medical School, Naples, Italy
| | - Alessia Salemme
- Department of Clinical Medicine and Surgery, Federico II University Medical School, Naples, Italy
| | - Giada Muccioli Casadei
- Department of Clinical Medicine and Surgery, Federico II University Medical School, Naples, Italy
| | - Elena Vigliar
- Department of Public Health, Federico II University Medical School Naples, Naples, Italy
| | - Massimo Mascolo
- Department of Advanced Biomedical Sciences, Federico II University Medical School, Naples, Italy
| | - Giancarlo Troncone
- Department of Public Health, Federico II University Medical School Naples, Naples, Italy
| | - Fabrizio Pane
- Department of Clinical Medicine and Surgery, Federico II University Medical School, Naples, Italy
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Pan C, Cao M, Yan C, Ou X, Zhang X, Xu W, Xu Y, Cui X. Hepatitis B virus reactivation associated with Janus kinase (JAK) inhibitors: a retrospective study of pharmacovigilance databases and review of the literature. Expert Opin Drug Saf 2023; 22:469-476. [PMID: 36794347 DOI: 10.1080/14740338.2023.2181339] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2022] [Accepted: 01/06/2023] [Indexed: 02/17/2023]
Abstract
BACKGROUND Recently, there have been clinical reports of hepatitis B virus reactivation (HBVr) related with Janus kinase (JAK) inhibitors. However, there were no studies to investigate the association between HBVr and different JAK inhibitors. RESEARCH DESIGN AND METHODS This study was a retrospective review utilizing the FAERS pharmacovigilance database and a systematic literature search for all cases of HBVr reported with JAK inhibitors. Disproportionality analysis and Bayesian analysis were used in data detection to screen the suspected HBVr after the administration of different JAK inhibitors, based on the FDA Adverse Event Reporting System (FAERS) pharmacovigilance database from Q4 2011 to Q1 2022. RESULTS There were a total number of 2097 (0.02%) reports of HBVr in FAERS, of which 41 (1.96%) were associated with JAK inhibitors. Baricitinib appeared to have the strongest signal among four JAK inhibitors, based on the highest reporting odds ratio (ROR = 4.45, 95% confidence interval [CI] 1.67-11.89). Ruxolitinib also showed signals, whereas no signals were detected among Tofacitinib and Upadacitinib. CONCLUSION While there may be an association between JAK inhibitors and HBVr, it appears to be a numerically uncommon occurrence. Further studies are needed to optimize the safety profiles of JAK inhibitors.
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Affiliation(s)
- Chen Pan
- Department of Pharmacy, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Mingnan Cao
- Department of Pharmacy, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Cilin Yan
- School of Automation Science and Electrical Engineering, Beihang University, Beijing, China
| | - Xiaojuan Ou
- National Clinical Research Center for Digestive Diseases, Beijing, China
- Beijing Key Laboratory of Translational Medicine on Liver Cirrhosis, Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Xia Zhang
- Department of Rheumatology, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Wanyi Xu
- Department of Pharmacy, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Ye Xu
- Department of Pharmacy, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Xiangli Cui
- Department of Pharmacy, Beijing Friendship Hospital, Capital Medical University, Beijing, China
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Papatheodoridis GV, Lekakis V, Voulgaris T, Lampertico P, Berg T, Chan HLY, Kao JH, Terrault N, Lok AS, Reddy KR. Hepatitis B virus reactivation associated with new classes of immunosuppressants and immunomodulators: A systematic review, meta-analysis, and expert opinion. J Hepatol 2022; 77:1670-1689. [PMID: 35850281 DOI: 10.1016/j.jhep.2022.07.003] [Citation(s) in RCA: 61] [Impact Index Per Article: 20.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/07/2022] [Revised: 07/01/2022] [Accepted: 07/06/2022] [Indexed: 12/27/2022]
Abstract
HBV reactivation (HBVr) can be prevented by nucleos(t)ide analogues (NAs). We conducted a systematic review and meta-analysis on the risk of HBVr associated with new classes of immunosuppressive and immunomodulatory therapies and developed guidance on NA prophylaxis. An expert panel reviewed the data and categorised the risk of HBVr associated with each class of drugs into low (<1%), intermediate (1-10%), and high (>10%). Our search uncovered 59 studies, including 3,424 HBsAg+ and 5,799 HBsAg-/anti-HBc+ patients, which met our eligibility criteria. Based on medium-high quality evidence, immune checkpoint inhibitors, tyrosine kinase inhibitors, cytokine inhibitors, chimeric antigen receptor T-cell immunotherapies, and corticosteroids were associated with high HBVr risk in HBsAg+ patients; cytokine inhibitors, chimeric antigen receptor T-cell immunotherapies, and corticosteroids with intermediate risk in HBsAg-/anti-HBc+ patients; and anti-tumour necrosis factor agents and immune checkpoint inhibitors with low risk in HBsAg-/anti-HBc+ patients. Provisional recommendations are provided for drugs with low quality evidence. NA prophylaxis is recommended when using drugs associated with a high HBVr risk, while monitoring with on-demand NAs is recommended for low-risk drugs - either approach may be appropriate for intermediate-risk drugs. Consensus on definitions and methods of reporting HBVr, along with inclusion of HBsAg+, and HBsAg-/anti-HBc+ patients in clinical trials, will be key to gathering reliable data on the risk of HBVr associated with immunosuppressive or immunomodulatory therapies.
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Affiliation(s)
- George V Papatheodoridis
- Academic Department of Gastroenterology, National and Kapodistrian University of Athens, General Hospital of Athens "Laiko", Athens, Greece
| | - Vasileios Lekakis
- Academic Department of Gastroenterology, National and Kapodistrian University of Athens, General Hospital of Athens "Laiko", Athens, Greece
| | - Thodoris Voulgaris
- Academic Department of Gastroenterology, National and Kapodistrian University of Athens, General Hospital of Athens "Laiko", Athens, Greece
| | - Pietro Lampertico
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Milan, Italy; CRC "A. M. and A. Migliavacca" Center for Liver Disease, Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
| | - Thomas Berg
- Division of Hepatology, Department of Medicine, Leipzig University Hospital, Leipzig, Germany
| | - Henry L Y Chan
- Division of Gastroenterology and Hepatology, Union Hospital and Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong
| | - Jia-Horng Kao
- Graduate Institute of Clinical Medicine and Hepatitis Research Center, National Taiwan University College of Medicine and Hospital, Taipei, Taiwan
| | - Norah Terrault
- Division of Gastrointestinal and Liver Diseases, University of Southern California, Los Angeles, California, USA
| | - Anna S Lok
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan, USA.
| | - K Rajender Reddy
- Division of Gastroenterology and Hepatology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
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Abstract
Purpose of Review Rituximab has transformed the treatment of B-cell malignancies and rheumatoid arthritis in the past 2 decades. More recently, this anti-CD20 monoclonal antibody has seen increasing usage in the field of dermatology. This review highlights the evidence supporting its use in several important dermatologic conditions. Recent Findings Key recent findings include the 2018 FDA approval of rituximab for the treatment of moderate-to-severe pemphigus. Summary Data from randomized controlled trials have demonstrated the efficacy of rituximab in pemphigus, ANCA-associated vasculitis, and cryoglobulinemic vasculitis. More limited data suggests its use in recalcitrant cases of diseases such as pemphigoid, epidermolysis bullosa acquisita, and dermatomyositis. There is scarce evidence and mixed results for rituximab when studied in cutaneous polyarteritis nodosa and cutaneous lupus erythematosus.
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Affiliation(s)
- Connor Cole
- Division of Dermatology, Rush University Medical Center, Chicago, IL USA
| | - Kyle T. Amber
- Division of Dermatology, Rush University Medical Center, Chicago, IL USA
- Department of Internal Medicine, Rush University Medical Center, Chicago, IL USA
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Bilajac E, Mahmutović L, Lundstrom K, Glamočlija U, Šutković J, Sezer A, Hromić-Jahjefendić A. Viral Agents as Potential Drivers of Diffuse Large B-Cell Lymphoma Tumorigenesis. Viruses 2022; 14:2105. [PMID: 36298660 PMCID: PMC9610751 DOI: 10.3390/v14102105] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2022] [Accepted: 09/19/2022] [Indexed: 04/22/2025] Open
Abstract
Among numerous causative agents recognized as oncogenic drivers, 13% of total cancer cases occur as a result of viral infections. The intricacy and diversity of carcinogenic processes, however, raise significant concerns about the mechanistic function of viruses in cancer. All tumor-associated viruses have been shown to encode viral oncogenes with a potential for cell transformation and the development of malignancies, including diffuse large B-cell lymphoma (DLBCL). Given the difficulties in identifying single mechanistic explanations, it is necessary to combine ideas from systems biology and viral evolution to comprehend the processes driving viral cancer. The potential for more efficient and acceptable therapies lies in targeted medicines that aim at viral proteins or trigger immune responses to either avoid infection or eliminate infected or cancerous cells. In this review, we aim to describe the role of viral infections and their mechanistic approaches in DLBCL tumorigenesis. To the best of our knowledge, this is the first review summarizing the oncogenic potential of numerous viral agents in DLBCL development.
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Affiliation(s)
- Esma Bilajac
- Department of Genetics and Bioengineering, Faculty of Engineering and Natural Sciences, International University of Sarajevo, Hrasnička cesta 15, 71000 Sarajevo, Bosnia and Herzegovina
| | - Lejla Mahmutović
- Department of Genetics and Bioengineering, Faculty of Engineering and Natural Sciences, International University of Sarajevo, Hrasnička cesta 15, 71000 Sarajevo, Bosnia and Herzegovina
| | | | - Una Glamočlija
- Department of Pharmaceutical Biochemistry and Laboratory Diagnostics, University of Sarajevo, Faculty of Pharmacy, Zmaja od Bosne 8, 71 000 Sarajevo, Bosnia and Herzegovina
- School of Medicine, University of Mostar, Zrinskog Frankopana 34, 88 000 Mostar, Bosnia and Herzegovina
- Scientific-Research Unit, Bosnalijek JSC, Jukićeva 53, 71 000 Sarajevo, Bosnia and Herzegovina
| | - Jasmin Šutković
- Department of Genetics and Bioengineering, Faculty of Engineering and Natural Sciences, International University of Sarajevo, Hrasnička cesta 15, 71000 Sarajevo, Bosnia and Herzegovina
| | - Abas Sezer
- Department of Genetics and Bioengineering, Faculty of Engineering and Natural Sciences, International University of Sarajevo, Hrasnička cesta 15, 71000 Sarajevo, Bosnia and Herzegovina
| | - Altijana Hromić-Jahjefendić
- Department of Genetics and Bioengineering, Faculty of Engineering and Natural Sciences, International University of Sarajevo, Hrasnička cesta 15, 71000 Sarajevo, Bosnia and Herzegovina
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İNANÇ Y, NAZİK S. OCRELİZUMAB KULLANAN MULTİPL SKLEROZ HASTALARINDA HEPATİT B VİRÜSÜ SEROLOJİK DURUMU. KAHRAMANMARAŞ SÜTÇÜ İMAM ÜNIVERSITESI TIP FAKÜLTESI DERGISI 2022. [DOI: 10.17517/ksutfd.1158614] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/31/2023] Open
Abstract
IN PATIENTS WITH MULTIPLE SCLEROSIS USING OCRELIZUMAB
SEROLOGICAL STATUS OF HEPATITIS B VIRUS
Abstract
Objective
B-cell depleting treatments are associated with potential risks of viral infections. Hepatitis B virus (HBV) infection is the most common chronic viral infection and it is estimated that 30% of the world population has serological evidence of current or past infection
Material end methods
Our study is a single-center, retrospective, cross-sectional study. We retrospectively reviewed the clinical records of MS patients receiving ocrelizumab. Demographic and clinical characteristics of patients, Expanded Disability Status Scale (EDSS), drug history before ocrelizumab for MS; Mean ocrelizumab intake times, smoking status, hepatitis C virus, HIV serological status, HBV serological status, HBV treatment status were recorded.
Results
The study included 64 MS patients treated with ocrelizumab. The mean age was 41.6±9.8 years (min-max: 21-62 years). 75% of the cases were female (n:48), 25% were male (n:16).
HIV and hepatitis C virus serological tests were negative in all cases. HBsAg was found to be positive in 1.6% (n:1) and Anti-HBcIgG in 12.5% (n:8). The number of patients who were started on hepatitis B treatment was 12.5% (n:8), and tenofovir disoproxil was started in 2 patients (25%), entecavir in 5 patients (62.5%), and tenofovir alafenamide in 1 patient (12.5). The mean duration of taking ocrelizumab for the patients was 28.5±13.1 months (min-max: 6-46 months).
Conclusion
In conclusion, all patients should be screened for HBV before starting ocrelizumab therapy. Both HBsAg and Anti-HBcIg G tests should be used. The isolated presence of Anti-HBcIg G may cause HBV reactivation. Therefore, Anti-HBcIg G should be screened before immunosuppressive therapy.
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31
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Nuersulitan R, Li M, Mi L, Wu M, Ji X, Liu Y, Zhao H, Wang G, Song Y, Zhu J, Liu W. Effect of infection with hepatitis B virus on the survival outcome of diffuse large B-cell lymphoma in the prophylactic antiviral era. Front Oncol 2022; 12:989258. [PMID: 36072805 PMCID: PMC9441704 DOI: 10.3389/fonc.2022.989258] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2022] [Accepted: 08/08/2022] [Indexed: 11/13/2022] Open
Abstract
Patients with lymphoma who are also infected with Hepatitis B virus (HBV) have a poor prognosis. This could be partly explained by the delay or premature termination of anti-tumor treatment because of HBV reactivation. However, there is limited data on the survival outcome of patients HBV-related lymphoma in the era of prophylactic antivirals. Data for 128 patients with HBV surface antigen-positive diffuse large B-cell lymphoma was collected. The median age was 54 years and the ratio of men to women was 1.2:1. All patients received immune-chemotherapy and prophylactic antiviral therapy. The median number of cycles of immune-chemotherapy was six. The overall response rate was 82%, with a complete remission rate of 75%. With a median follow-up of 58.4 months, the 5-year progression-free survival and overall survival rates were 75.7% and 74.7%, respectively. Nine patients experienced HBV reactivation but none experienced HBV-associated hepatitis. Patients with low and high HBV DNA loads had comparable survival outcomes. In conclusion, HBV infection had no negative effect on the prognosis of DLBCL in the era of prophylactic antiviral therapy.
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Affiliation(s)
- Reyizha Nuersulitan
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Lymphoma, Peking University Cancer Hospital & Institute, Beijing, China
| | - Miaomiao Li
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Lymphoma, Peking University Cancer Hospital & Institute, Beijing, China
| | - Lan Mi
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Lymphoma, Peking University Cancer Hospital & Institute, Beijing, China
| | - Meng Wu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Lymphoma, Peking University Cancer Hospital & Institute, Beijing, China
| | - Xinqiang Ji
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Medical Record Statistics, Peking University Cancer Hospital & Institute, Beijing, China
| | - Yiqi Liu
- Department of Infectious Diseases, Peking University First Hospital, Beijing, China
| | - Hong Zhao
- Department of Infectious Diseases, Peking University First Hospital, Beijing, China
| | - Guiqiang Wang
- Department of Infectious Diseases, Peking University First Hospital, Beijing, China
| | - Yuqin Song
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Lymphoma, Peking University Cancer Hospital & Institute, Beijing, China
| | - Jun Zhu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Lymphoma, Peking University Cancer Hospital & Institute, Beijing, China
- *Correspondence: Jun Zhu, ; Weiping Liu,
| | - Weiping Liu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Lymphoma, Peking University Cancer Hospital & Institute, Beijing, China
- *Correspondence: Jun Zhu, ; Weiping Liu,
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32
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Dual-targeting magnetic fluorescent mesoporous organosilicon hollow nanospheres for gambogic acid loading, sustained release and anti-tumor properties. J Mol Liq 2022. [DOI: 10.1016/j.molliq.2022.119412] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
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Cauchi M, Willis M, Andrews A, Backx M, Brownlee W, Ford HL, Gran B, Jolles S, Price S, Rashid W, Schmierer K, Tallantyre EC. Multiple sclerosis and the risk of infection: Association of British Neurologists consensus guideline. Pract Neurol 2022; 22:practneurol-2022-003370. [PMID: 35863879 DOI: 10.1136/practneurol-2022-003370] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/08/2022] [Indexed: 11/03/2022]
Abstract
Infection in people with multiple sclerosis (MS) is of major concern, particularly for those receiving disease-modifying therapies. This article explores the risk of infection in people with MS and provides guidance-developed by Delphi consensus by specialists involved in their management-on how to screen for, prevent and manage infection in this population.
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Affiliation(s)
- Marija Cauchi
- Division of Psychological Medicine and Clinical Neurosciences, Cardiff University, University Hospital of Wales, Cardiff, UK
| | - Mark Willis
- Division of Psychological Medicine and Clinical Neurosciences, Cardiff University, University Hospital of Wales, Cardiff, UK
| | - Angela Andrews
- Pharmacy Neurosciences Directorate, University Hospital of Wales, Cardiff, UK
| | - Matthijs Backx
- Infectious Diseases, University Hospital of Wales and Department of Microbiology, Public Health Wales, Cardiff, UK
| | - Wallace Brownlee
- Queen Square MS Centre, University College London Institute of Neurology, Queen Square Multiple Sclerosis Centre, London, UK
| | - Helen L Ford
- Centre for Neurosciences, Leeds Teaching Hospitals NHS Trust, Leeds, UK, Leeds, UK
| | - Bruno Gran
- Department of Neurology, Nottingham University Hospitals NHS Trust, Nottingham, UK
- Mental Health and Clinical Neuroscience Academic Unit, University of Nottingham School of Medicine, Nottingham, UK
| | - Stephen Jolles
- Immunodeficiency Centre for Wales, University Hospital of Wales, Cardiff, UK
| | - Sian Price
- Department of Neuroscience, University of Sheffield, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK
| | - Waqar Rashid
- Department of Neuroscience, Brighton and Sussex Medical School, University of Sussex, Brighton, UK
| | - Klaus Schmierer
- The Blizard Institute (Neuroscience, Surgery & Trauma), Queen Mary University of London Faculty of Medicine and Dentistry, London, UK
- Clinical Board Medicine (Neuroscience), The Royal London Hospital, Barts Health NHS Trust, London, UK
| | - Emma C Tallantyre
- Division of Psychological Medicine and Clinical Neurosciences, Cardiff University, University Hospital of Wales, Cardiff, UK
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34
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Wong GLH, Gane E, Lok ASF. How to achieve functional cure of HBV: Stopping NUCs, adding interferon or new drug development? J Hepatol 2022; 76:1249-1262. [PMID: 35589248 DOI: 10.1016/j.jhep.2021.11.024] [Citation(s) in RCA: 142] [Impact Index Per Article: 47.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/25/2021] [Revised: 11/16/2021] [Accepted: 11/17/2021] [Indexed: 12/20/2022]
Abstract
Functional cure of hepatitis B is defined as sustained undetectable circulating HBsAg and HBV DNA after a finite course of treatment. Barriers to HBV cure include the reservoirs for HBV replication and antigen production (covalently closed circular DNA [cccDNA] and integrated HBV DNA), the high viral burden (HBV DNA and HBsAg) and the impaired host innate and adaptive immune responses against HBV. Current HBV therapeutics, 1 year of pegylated-interferon-α (PEG-IFNα) and long-term nucleos(t)ide analogues (NUCs), rarely achieve HBV cure. Stopping NUC therapy may lead to functional cure in some Caucasian patients but rarely in Asian patients. Switching from a NUC to IFN after HBV DNA suppression increases the chance of HBsAg clearance mainly in those with low HBsAg levels. Novel antiviral strategies that inhibit viral entry, translation and secretion of HBsAg, modulate capsid assembly, or target cccDNA transcription/degradation have shown promise in clinical trials. Novel immunomodulatory approaches including checkpoint inhibitors, metabolic modulation of T cells, therapeutic vaccines, adoptive transfer of genetically engineered T cells, and stimulation of innate and B-cell immune responses are being explored. These novel approaches may be further combined with NUCs or PEG-IFNα in personalised strategies, according to virologic and disease characteristics, to maximise the chance of HBV cure. The development of curative HBV therapies should be coupled with the development of standardised and validated virologic and immunologic assays to confirm target engagement and to assess response. In addition to efficacy, curative therapies must be safe and affordable to meet the goal of global elimination of hepatitis B.
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Affiliation(s)
- Grace L H Wong
- Medical Data Analytics Centre, Department of Medicine and Therapeutics, and Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong
| | - Ed Gane
- New Zealand Liver Transplant Unit, Auckland City Hospital, University of Auckland, New Zealand
| | - Anna S F Lok
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
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35
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Immuno-pathogenesis of neuromyelitis optica and emerging therapies. Semin Immunopathol 2022; 44:599-610. [DOI: 10.1007/s00281-022-00941-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2022] [Accepted: 04/20/2022] [Indexed: 01/01/2023]
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36
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Silva GD, de Oliveira VF, Mendonça LO. Challenges and insights in immunization in patients with demyelinating diseases: a bench-to-bedside and evidence-based review. ARQUIVOS DE NEURO-PSIQUIATRIA 2022; 80:173-181. [PMID: 35976311 PMCID: PMC9491426 DOI: 10.1590/0004-282x-anp-2022-s121] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/15/2022] [Accepted: 04/29/2022] [Indexed: 05/28/2023]
Abstract
BACKGROUND Infections are among the main causes of death in patients with demyelinating diseases of the central nervous system (CNSDD). Vaccines are effective methods in reducing hospitalization and death from infectious diseases, but they are challenging in patients with CNSDD because of autoimmunity and immunosuppression. OBJECTIVES To summarize the pathophysiological rationale and main evidence for vaccine recommendations in patients with CNSDD. METHODS Specialists with different backgrounds on the subject: a neurologist specialized in demyelinating diseases, an infectious diseases specialist and an immunologist, presented a critical narrative review of vaccination literature in patients with CNSDD, highlighting which vaccines should or should not be administered and the best time for it. RESULTS Patients with DDSNC are at increased risk of vaccine-preventable viral and bacterial infections. Vaccines can prevent herpes zoster, hepatitis B reactivation, HPV-associated warts and tumors, viral and bacterial pneumonia, and meningitis. Live attenuated virus vaccines should not be used when the patient is on immunosuppression. Vaccines should be avoided during relapses. The greatest vaccine efficacy is given before treatment or at the end of medication. CONCLUSION Patients with DDSNC need differentiated immunization in relation to additional vaccines, contraindicated vaccines and timing of vaccination.
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Affiliation(s)
- Guilherme Diogo Silva
- Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, Departamento de Neurologia, São Paulo SP, Brazil
| | - Vítor Falcão de Oliveira
- Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, Departamento de Moléstias Infecciosas e Parasitárias, São Paulo SP, Brazil
| | - Leonardo Oliveira Mendonça
- Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, Departamento de Imunologia Clínica e Alergia, São Paulo SP, Brazil
- Rede DASA-Hospital 9 de Julho, Divisão de Imunologia Clínica e Alergia, São Paulo SP, Brazil
- Rede DASA-Hospital 9 de Julho, Centro de Doenças Raras e da Imunidade, São Paulo SP, Brazil
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37
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Otani IM, Lehman HK, Jongco AM, Tsao LR, Azar AE, Tarrant TK, Engel E, Walter JE, Truong TQ, Khan DA, Ballow M, Cunningham-Rundles C, Lu H, Kwan M, Barmettler S. Practical guidance for the diagnosis and management of secondary hypogammaglobulinemia: A Work Group Report of the AAAAI Primary Immunodeficiency and Altered Immune Response Committees. J Allergy Clin Immunol 2022; 149:1525-1560. [PMID: 35176351 DOI: 10.1016/j.jaci.2022.01.025] [Citation(s) in RCA: 92] [Impact Index Per Article: 30.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2021] [Revised: 12/31/2021] [Accepted: 01/21/2022] [Indexed: 11/17/2022]
Abstract
Secondary hypogammaglobulinemia (SHG) is characterized by reduced immunoglobulin levels due to acquired causes of decreased antibody production or increased antibody loss. Clarification regarding whether the hypogammaglobulinemia is secondary or primary is important because this has implications for evaluation and management. Prior receipt of immunosuppressive medications and/or presence of conditions associated with SHG development, including protein loss syndromes, are histories that raise suspicion for SHG. In patients with these histories, a thorough investigation of potential etiologies of SHG reviewed in this report is needed to devise an effective treatment plan focused on removal of iatrogenic causes (eg, discontinuation of an offending drug) or treatment of the underlying condition (eg, management of nephrotic syndrome). When iatrogenic causes cannot be removed or underlying conditions cannot be reversed, therapeutic options are not clearly delineated but include heightened monitoring for clinical infections, supportive antimicrobials, and in some cases, immunoglobulin replacement therapy. This report serves to summarize the existing literature regarding immunosuppressive medications and populations (autoimmune, neurologic, hematologic/oncologic, pulmonary, posttransplant, protein-losing) associated with SHG and highlights key areas for future investigation.
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Affiliation(s)
- Iris M Otani
- Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, UCSF Medical Center, San Francisco, Calif.
| | - Heather K Lehman
- Division of Allergy, Immunology, and Rheumatology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY
| | - Artemio M Jongco
- Division of Allergy and Immunology, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Great Neck, NY
| | - Lulu R Tsao
- Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, UCSF Medical Center, San Francisco, Calif
| | - Antoine E Azar
- Division of Allergy and Clinical Immunology, Johns Hopkins University School of Medicine, Baltimore
| | - Teresa K Tarrant
- Division of Rheumatology and Immunology, Duke University, Durham, NC
| | - Elissa Engel
- Division of Hematology and Oncology, Cincinnati Children's Hospital, Cincinnati, Ohio
| | - Jolan E Walter
- Division of Allergy and Immunology, Johns Hopkins All Children's Hospital, St Petersburg, Fla; Division of Allergy and Immunology, Morsani College of Medicine, University of South Florida, Tampa; Division of Allergy and Immunology, Massachusetts General Hospital for Children, Boston
| | - Tho Q Truong
- Divisions of Rheumatology, Allergy and Clinical Immunology, National Jewish Health, Denver
| | - David A Khan
- Division of Allergy and Immunology, University of Texas Southwestern Medical Center, Dallas
| | - Mark Ballow
- Division of Allergy and Immunology, Morsani College of Medicine, Johns Hopkins All Children's Hospital, St Petersburg
| | | | - Huifang Lu
- Department of General Internal Medicine, Section of Rheumatology and Clinical Immunology, The University of Texas MD Anderson Cancer Center, Houston
| | - Mildred Kwan
- Division of Rheumatology, Allergy, and Immunology, Department of Medicine, University of North Carolina School of Medicine, Chapel Hill
| | - Sara Barmettler
- Allergy and Immunology, Massachusetts General Hospital, Boston.
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Effects of B-Cell Lymphoma on the Immune System and Immune Recovery after Treatment: The Paradigm of Targeted Therapy. Int J Mol Sci 2022; 23:ijms23063368. [PMID: 35328789 PMCID: PMC8952275 DOI: 10.3390/ijms23063368] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2022] [Revised: 03/07/2022] [Accepted: 03/09/2022] [Indexed: 12/10/2022] Open
Abstract
B-cell lymphoma and lymphoproliferative diseases represent a heterogeneous and complex group of neoplasms that are accompanied by a broad range of immune regulatory disorder phenotypes. Clinical features of autoimmunity, hyperinflammation, immunodeficiency and infection can variously dominate, depending on the immune pathway most involved. Immunological imbalance can play a role in lymphomagenesis, also supporting the progression of the disease, while on the other hand, lymphoma acts on the immune system to weaken immunosurveillance and facilitate immunoevasion. Therefore, the modulation of immunity can have a profound effect on disease progression or resolution, which makes the immune system a critical target for new therapies. In the current therapeutic scenario enriched by chemo-free regimens, it is important to establish the effect of various drugs on the disease, as well as on the restoration of immune functions. In fact, treatment of B-cell lymphoma with passive immunotherapy that targets tumor cells or targets the tumor microenvironment, together with adoptive immunotherapy, is becoming more frequent. The aim of this review is to report relevant data on the evolution of the immune system during and after treatment with targeted therapy of B-cell lymphomas.
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Barone M, Venerito V, Paolillo R, Emmi G, Fornaro M, Cacciapaglia F, Cantarini L, Di Leo A, Iannone F, Lopalco G. Long-term safety of rituximab in rheumatic patients with previously resolved hepatitis B virus infection. Intern Emerg Med 2022; 17:475-480. [PMID: 34476737 DOI: 10.1007/s11739-021-02836-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2021] [Accepted: 08/20/2021] [Indexed: 02/07/2023]
Abstract
Conflicting results can be found in the literature on the frequency of hepatitis B virus (HBV) reactivation (HBVr) on rituximab (RTX) in rheumatic patients with previously resolved HBV (prHBV) infection. Here, we report the frequency of HBVr in a large historical cohort of caucasian rheumatic patients with prHBV receiving RTX. Registry data of rheumatic patients treated with RTX were retrospectively analysed. Demographic and clinical characteristics including evaluation of anti-HCV and HBV markers, annual HBV-DNA determination and aminotransferase levels assessed every three months, were recorded. Kaplan-Meier estimate was used to compare the risk of being still under therapy at different time points in patients with or without prHBV infection. Cox regression analysis was used to determine the association between recorded variables and treatment discontinuation. A total of 311 patients treated with RTX, 44 (14.1%) with and 267 (85.9%) without prHBV were analysed. No significant difference between the two groups regarding demographic and clinical characteristics was observed. During RTX treatment, detectable HBV-DNA and reappearance of HBsAg in patients with prHBV (seroreversion) were never observed. Kaplan-Meier functions were similar in patients with or without prHBV infection which was not associated with RTX discontinuation neither at univariate nor at multivariate analysis. These data are in favor of the concept that patients with rheumatologic diseases have a very low risk of reactivation of the HBV infection under RTX treatment. However, future prospective studies, including a larger number of patients, are still necessary to draw definitive conclusions.
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Affiliation(s)
- Michele Barone
- Gastroenterology Unit, Department of Emergency and Organ Transplantation (D.E.T.O.), University of Bari, Bari, Italy
| | - Vincenzo Venerito
- Rheumatology Unit, Department of Emergency and Organ Transplantation (D.E.T.O.), University of Bari, Bari, Italy
| | - Rosa Paolillo
- Gastroenterology Unit, Department of Emergency and Organ Transplantation (D.E.T.O.), University of Bari, Bari, Italy
| | - Giacomo Emmi
- Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - Marco Fornaro
- Rheumatology Unit, Department of Emergency and Organ Transplantation (D.E.T.O.), University of Bari, Bari, Italy
| | - Fabio Cacciapaglia
- Rheumatology Unit, Department of Emergency and Organ Transplantation (D.E.T.O.), University of Bari, Bari, Italy
| | - Luca Cantarini
- Rheumatology Unit, Department Research Center of Systemic Autoimmune and Autoinflammatory Diseases, University of Siena, Siena, Italy
| | - Alfredo Di Leo
- Gastroenterology Unit, Department of Emergency and Organ Transplantation (D.E.T.O.), University of Bari, Bari, Italy
| | - Florenzo Iannone
- Rheumatology Unit, Department of Emergency and Organ Transplantation (D.E.T.O.), University of Bari, Bari, Italy
| | - Giuseppe Lopalco
- Rheumatology Unit, Department of Emergency and Organ Transplantation (D.E.T.O.), University of Bari, Bari, Italy.
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Clerico M, Dogliotti I, Ghione P, Zilioli VR, Merli F, Botto B, Al Essa W, Battaglini M, Grimaldi D, Cervi L, Ragaini S, Ferrero S, Peri V, De Luca G, Marzano A, Cavallo F. HBV Reactivation in Patients with Past Infection Affected by Non-Hodgkin Lymphoma and Treated with Anti-CD20 Antibody Based Immuno-Chemotherapy: A Multicenter Experience. J Pers Med 2022; 12:jpm12020285. [PMID: 35207774 PMCID: PMC8875663 DOI: 10.3390/jpm12020285] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2021] [Revised: 02/07/2022] [Accepted: 02/11/2022] [Indexed: 11/16/2022] Open
Abstract
Hepatitis B virus reactivation (HBVr) can develop in HBV surface antigen (HBsAg) positive or HBsAg-negative and anti-hepatitis B core antigen antibodies (anti-HBc) positive (past HBV infection) patients receiving immuno-chemotherapy for hematological malignancies. A higher rate of HBVr is associated with the use of rituximab (R) in patients with past HBV infection, thus justifying an antiviral prophylaxis. In this study we evaluated the incidence of HBVr in a real-life cohort of 362 anti-HBc-positive subjects affected by non-Hodgkin lymphoma (NHL), mainly receiving lamivudine (LAM) prophylaxis (93%) and all undergoing a R-containing regimen. A retrospective, multicenter, observational study was conducted in 4 Italian Hematology Departments. The primary endpoint was the incidence of virologic (HBV DNA-positive), serologic (HBsAg-positive) and clinical (ALT increase > 3 × upper limit of normal) HBVr, which occurred in five, four and one patients, respectively, with a total HBVr rate of 1.4%. None of them had to discontinue the chemotherapy program, while two patients required a delay. Treatment-related adverse events (AEs) were reported during LAM prophylaxis in three patients (0.9%). In conclusion, this study confirms the efficacy and safety of LAM prophylaxis in anti-HBc-positive patients undergoing R-containing regimens.
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Affiliation(s)
- Michele Clerico
- Division of Hematology, Department of Molecular Biotechnology and Health Sciences, University of Torino, A.O.U. Città della Salute e della Scienza di Torino, 10126 Turin, Italy; (M.C.); (S.R.); (S.F.); (V.P.); (G.D.L.)
| | - Irene Dogliotti
- Stem Cell Transplant Unit, A.O.U. Città della Salute e della Scienza di Torino, 10126 Turin, Italy;
| | - Paola Ghione
- Lymphoma Program, Department of Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA;
| | | | - Francesco Merli
- Division of Hematology, Azienda Unità Sanitaria Locale—IRCCS, 42123 Reggio Emilia, Italy;
| | - Barbara Botto
- Division of Hematology, A.O.U. Città della Salute e della Scienza di Torino, 10126 Turin, Italy;
| | - Wael Al Essa
- Division of Hematology, Department of Translational Medicine, University of Eastern Piedmont, 28100 Novara, Italy;
| | - Marcella Battaglini
- DDINOGMI, Department University of Genoa, IRCCS Istituto Giannina Gaslini, 16147 Genoa, Italy;
| | - Daniele Grimaldi
- Division of Hematology, A.O.S. Croce e Carle, 12100 Cuneo, Italy;
| | - Loretta Cervi
- Division of Pharmacy, ASST Grande Ospedale Metropolitano Niguarda, 20162 Milan, Italy;
| | - Simone Ragaini
- Division of Hematology, Department of Molecular Biotechnology and Health Sciences, University of Torino, A.O.U. Città della Salute e della Scienza di Torino, 10126 Turin, Italy; (M.C.); (S.R.); (S.F.); (V.P.); (G.D.L.)
| | - Simone Ferrero
- Division of Hematology, Department of Molecular Biotechnology and Health Sciences, University of Torino, A.O.U. Città della Salute e della Scienza di Torino, 10126 Turin, Italy; (M.C.); (S.R.); (S.F.); (V.P.); (G.D.L.)
| | - Veronica Peri
- Division of Hematology, Department of Molecular Biotechnology and Health Sciences, University of Torino, A.O.U. Città della Salute e della Scienza di Torino, 10126 Turin, Italy; (M.C.); (S.R.); (S.F.); (V.P.); (G.D.L.)
| | - Gabriele De Luca
- Division of Hematology, Department of Molecular Biotechnology and Health Sciences, University of Torino, A.O.U. Città della Salute e della Scienza di Torino, 10126 Turin, Italy; (M.C.); (S.R.); (S.F.); (V.P.); (G.D.L.)
| | - Alfredo Marzano
- Division of Gastroenterology and Hepatology, San Giovanni Battista Hospital, 10126 Turin, Italy;
| | - Federica Cavallo
- Division of Hematology, Department of Molecular Biotechnology and Health Sciences, University of Torino, A.O.U. Città della Salute e della Scienza di Torino, 10126 Turin, Italy; (M.C.); (S.R.); (S.F.); (V.P.); (G.D.L.)
- Correspondence: ; Tel.: +39-011-633-4556; Fax: +39-011-633-6507
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Perry C. Be on guard: longer monitoring for very-late onset hepatitis B virus reactivation after chemo-immunotherapy? Leuk Lymphoma 2022; 63:771-773. [PMID: 35142574 DOI: 10.1080/10428194.2022.2034162] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Affiliation(s)
- Chava Perry
- Department of Hematology, Tel Aviv Sourasky Medical Center, Tel-Aviv, Israel.,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
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Recent Advances in the Development of Noble Metal NPs for Cancer Therapy. Bioinorg Chem Appl 2022; 2022:2444516. [PMID: 35126483 PMCID: PMC8816609 DOI: 10.1155/2022/2444516] [Citation(s) in RCA: 29] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2021] [Accepted: 01/08/2022] [Indexed: 12/14/2022] Open
Abstract
With the development of nanotechnology, noble metal nanoparticles are widely used in the treatment of cancer due to their unique optical properties, excellent biocompatibility, surface effects, and small size effects. In recent years, researchers have designed and synthesized a large number of nanomedicines that can be used for cancer treatment based on the morphology, physical and chemical properties, mechanism of action, and toxicological studies of noble metal nanoparticles. Furthermore, the integration of diagnosis and treatment, hyperthermia, cytotoxicity research, and drug delivery system based on the study of noble metal nanoparticles can be used as effective means for cancer treatment. This article focuses on the analysis of noble metal nanoparticles that are widely used in the treatment of cancer, such as gold nanoparticles, silver nanoparticles, platinum nanoparticles, and palladium nanoparticles. The various methods and mechanisms of action of noble metal nanoparticles in the treatment of cancer are objectively summarized in detail. Based on the research on the therapeutic safety and toxicity of noble metal nanoparticles, the development prospect of noble metal nanoparticles in the future clinical application is prospected.
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Law MF, Chan HN, Kong SY, Lai HK, Ha CY, Ng C, Yeung YM, Yip SF. Clinical outcomes of patients with acute lymphoblastic leukemia receiving the hyper-CVAD regimen and assessment of the risk of hepatitis flares due to hepatitis B virus reactivation after chemotherapy. Arch Med Sci 2022; 18:121-128. [PMID: 35251415 PMCID: PMC8886409 DOI: 10.5114/aoms/103606] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/13/2018] [Accepted: 02/02/2019] [Indexed: 11/17/2022] Open
Abstract
INTRODUCTION Hyper-CVAD (hyperfractionated cyclophosphamide, vincristine, doxorubicin and dexamethasone) has become a popular regimen for adults with acute lymphoblastic leukemia (ALL). We assessed the efficacy and tolerability of hyper-CVAD in the treatment of adult ALL. MATERIAL AND METHODS We retrospectively reviewed ALL patients aged 18 or above receiving the hyper-CVAD regimen. We assessed complete remission rate and overall survival, as well as hepatitis B carrier rate and hepatitis flare due to hepatitis B virus (HBV) reactivation. RESULTS Fifty-two patients were treated with the hyper-CVAD regimen. The median age at diagnosis was 42 years; 27% of patients were Philadelphia (Ph) chromosome positive. The complete remission (CR) rate was 90.4% after the first cycle of chemotherapy. The induction mortality rate was 1.9%. Three patients required two cycles of hyper-CVAD to achieve CR. The median overall survival was 39.6 months and the 5-year overall survival was 50%. Age over 30 years and white blood cell count of more than 30 × 109/l were found to be prognostic for poor overall survival in multivariate analysis. The hepatitis B carrier rate was 17% in our cohort, and the rate of hepatitis flare due to HBV reactivation was 11% in patients with current infection. CONCLUSIONS Hyper-CVAD is feasible and tolerable with a good CR rate in the treatment of adult ALL patients. It is an option for the treatment of ALL. Antiviral prophylaxis should be considered in ALL patients with HBV infection to reduce the risk of HBV reactivation.
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Affiliation(s)
- Man Fai Law
- Department of Medicine, Tuen Mun Hospital, Hong Kong, Hong Kong
- Department of Medicine and Therapeutics, Prince of Wales Hospital, Hong Kong, Hong Kong
| | - Hay Nun Chan
- Department of Medicine, Tuen Mun Hospital, Hong Kong, Hong Kong
| | - Shun Yin Kong
- Department of Medicine, Tuen Mun Hospital, Hong Kong, Hong Kong
| | - Ho Kei Lai
- Department of Medicine, Tuen Mun Hospital, Hong Kong, Hong Kong
| | - Chung Yin Ha
- Department of Medicine, Tuen Mun Hospital, Hong Kong, Hong Kong
| | - Celia Ng
- Department of Medicine, Tuen Mun Hospital, Hong Kong, Hong Kong
| | - Yiu Ming Yeung
- Department of Medicine, Tuen Mun Hospital, Hong Kong, Hong Kong
| | - Sze Fai Yip
- Department of Medicine, Tuen Mun Hospital, Hong Kong, Hong Kong
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Detection of the hepatitis B surface antigen in patients with occult hepatitis B using an assay with enhanced sensitivity. J Clin Microbiol 2021; 60:e0220421. [PMID: 34936478 DOI: 10.1128/jcm.02204-21] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
Patients with occult hepatitis B infection (OBI) have undetectable hepatitis B surface antigen (HBsAg) by conventional assays but detectable hepatitis B virus (HBV) DNA in blood/liver. We evaluated the key performance characteristics of a sensitive HBsAg assay (ARCHITECT HBsAg Next Qualitative Assay, referred as NEXT) with respect to HBsAg detection. Assay precision, sample carryover and seroconversion sensitivity of NEXT were evaluated. HBsAg was measured by NEXT in 1,138 individuals, including 1,038 patients who attended liver clinics in a tertiary hospital (200 HBV DNA-positive blood donors whose HBsAg was undetectable by conventional assays, and 38 patients receiving immunosuppressive therapy, 800 chronic hepatitis B patients with HBsAg seroclearance) and 100 HBsAg-negative subjects recruited from a community project. The within-run and within-laboratory coefficients of variation were <6% for the positive sample pools. In 9 seroconversion panels tested, NEXT allowed an earlier HBsAg detection than conventional assays. NEXT detected HBsAg in 10/200 (5%) HBsAg-negative blood donors, 1/20 (5%) and 0/18 HBsAg-negative patients with and without HBV reactivation respectively, and 59/800 (7.3%) patients with HBsAg seroclearance. HBsAg was detectable by NEXT in 27.8%, 8.2%, 6.9%, 3.8% and 1.9% samples at <3, 3-5, >5-8, >8-11, and >11 years after HBsAg seroclearance, respectively. Seven out of 100 HBsAg-negative community identified subjects was tested positive by NEXT. Comparing with conventional HBsAg assays, NEXT demonstrated a higher sensitivity and conferred an increment of 5-7% detection rate in patients with OBI, thereby helping in identifying HBV carriers and prevention of OBI-associated HBV transmission and reactivation.
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Kłujszo EH, Zarębska-Michaluk D, Kręcisz B, Witkowska A. Safety of therapies using ustekinumab in patients with psoriasis who have had hepatitis B virus infection. Dermatol Ther 2021; 35:e15274. [PMID: 34921578 DOI: 10.1111/dth.15274] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2021] [Accepted: 12/10/2021] [Indexed: 12/22/2022]
Abstract
Biological therapies used in psoriasis treatment pose a risk of reactivation of hepatitis B virus (HBV) infection. This risk occurs not only in patients with HB surface antigen (HBsAg) (+) but also in patients with past or occult HBV infection (with negative HBsAg, positive HB core antibodies (HBcAb), and positive HBV deoxyribonucleic acid [DNA]). Ustekinumab (UST) is a biologic agent acts by blocking the IL-12/23 pathway. Thus, hindering this response may lead to HBV reactivation. UST therapy is associated with mild HBV-r risk; however, there is insufficient data to confirm that hypothesis. Herein, we present observations on the safety of UST therapy in patients with psoriasis and serologically proved past HBV infection. One-hundred and six consecutive patients with moderate to severe psoriasis treated with biological therapy between May 2013 and January 2020 were retrospectively analyzed. Out of 106 patients, there were five who reported having past HBV. Those five patients were tested for the presence of HBsAg, HBcAb, HBsAb as well as HBV DNA at baseline and at the end of the follow-up period. HBV reactivation was defined as changing of "undetectable" to "detectable" viremia. All five patients were treated with UST. Five patients in our cohort group were found to have resolved HBV infection: HBsAg (-), HBcAb (+), and HBV DNA (-); 4/5 were HBsAb (+) and 1/5 HBsAb (-). None of the patients experienced an increase in their liver function tests values and no signs of hepatitis or HBV reactivation were observed at any point during the study. All the patients were HBsAg and HBV DNA negative at the end of the follow-up period. The average treatment time was 82.4 (28, 96) weeks. The average follow-up time was 75.2 (31, 176) weeks. Based on the available literature and the results from our observations, UST therapy seems to be a safe option for patients with resolved HBV infection.
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Affiliation(s)
| | | | - Beata Kręcisz
- Faculty of Medicine and Health Science, Jan Kochanowski University in Kielce, Kielce, Poland
| | - Anna Witkowska
- Department of Rheumatology, Mater Misericordiae University Hospital, Dublin, Ireland
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Cliff ERS, Sasadeusz J, Visvanathan K, Grigg A. Very late-onset hepatitis B reactivation following chemoimmunotherapy. Leuk Lymphoma 2021; 63:991-995. [PMID: 34852722 DOI: 10.1080/10428194.2021.2010066] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Affiliation(s)
| | - Joe Sasadeusz
- Victorian Infectious Diseases Service, Royal Melbourne Hospital, Melbourne, Australia.,Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, Australia
| | - Kumar Visvanathan
- Department of Medicine, St Vincent's Hospital, The University of Melbourne, Melbourne, Australia.,Immunology Research Centre, St Vincent's Hospital, Melbourne, Australia
| | - Andrew Grigg
- Department of Clinical Haematology, Austin Health, Heidelberg, Australia.,Olivia Newton-John Cancer Research Institute, Austin Health, Heidelberg, Australia
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Abstract
Hepatitis B virus (HBV) can hide in the liver in the form of covalently closed circular DNA. When the body’s immunity changes, HBV reactivation (HBV-R) can occur. The risk of HBV-R is determined by the complex interaction among virological factors, medication factors and host factors. However, many patients do not know that they are infected with HBV, and doctors often do not invest enough time to systematically evaluate the patient’s HBV-R risk factors before immunosuppressive treatment. Therefore, HBV clinical screening should be vigorously promoted to achieve early detection and early prevention for patients with high risk of HBV-R. The mechanism, clinical features, risk factors, HBV-R under different disease etiologies, prevention and treatment of HBV-R were summarized to improve the in-depth understanding and awareness.
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Affiliation(s)
- Wei Huang
- Center of Infectious Diseases, West China Hospital of Sichuan University, Chengdu, 610041, China
- Division of Infectious Diseases, State Key Laboratory of Biotherapy & Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Lingyao Du
- Center of Infectious Diseases, West China Hospital of Sichuan University, Chengdu, 610041, China
- Division of Infectious Diseases, State Key Laboratory of Biotherapy & Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Hong Tang
- Center of Infectious Diseases, West China Hospital of Sichuan University, Chengdu, 610041, China
- Division of Infectious Diseases, State Key Laboratory of Biotherapy & Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, 610041, China
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Abstract
BACKGROUND Multiple sclerosis (MS) is the most common neurological cause of disability in young adults. Off-label rituximab for MS is used in most countries surveyed by the International Federation of MS, including high-income countries where on-label disease-modifying treatments (DMTs) are available. OBJECTIVES: To assess beneficial and adverse effects of rituximab as 'first choice' and as 'switching' for adults with MS. SEARCH METHODS We searched CENTRAL, MEDLINE, Embase, CINAHL, and trial registers for completed and ongoing studies on 31 January 2021. SELECTION CRITERIA We included randomised controlled trials (RCTs) and controlled non-randomised studies of interventions (NRSIs) comparing rituximab with placebo or another DMT for adults with MS. DATA COLLECTION AND ANALYSIS We followed standard Cochrane methodology. We used the Cochrane Collaboration's tool for assessing risk of bias. We rated the certainty of evidence using GRADE for: disability worsening, relapse, serious adverse events (SAEs), health-related quality of life (HRQoL), common infections, cancer, and mortality. We conducted separate analyses for rituximab as 'first choice' or as 'switching', relapsing or progressive MS, comparison versus placebo or another DMT, and RCTs or NRSIs. MAIN RESULTS We included 15 studies (5 RCTs, 10 NRSIs) with 16,429 participants of whom 13,143 were relapsing MS and 3286 progressive MS. The studies were one to two years long and compared rituximab as 'first choice' with placebo (1 RCT) or other DMTs (1 NRSI), rituximab as 'switching' against placebo (2 RCTs) or other DMTs (2 RCTs, 9 NRSIs). The studies were conducted worldwide; most originated from high-income countries, six from the Swedish MS register. Pharmaceutical companies funded two studies. We identified 14 ongoing studies. Rituximab as 'first choice' for relapsing MS Rituximab versus placebo: no studies met eligibility criteria for this comparison. Rituximab versus other DMTs: one NRSI compared rituximab with interferon beta or glatiramer acetate, dimethyl fumarate, natalizumab, or fingolimod in active relapsing MS at 24 months' follow-up. Rituximab likely results in a large reduction in relapses compared with interferon beta or glatiramer acetate (hazard ratio (HR) 0.14, 95% confidence interval (CI) 0.05 to 0.39; 335 participants; moderate-certainty evidence). Rituximab may reduce relapses compared with dimethyl fumarate (HR 0.29, 95% CI 0.08 to 1.00; 206 participants; low-certainty evidence) and natalizumab (HR 0.24, 95% CI 0.06 to 1.00; 170 participants; low-certainty evidence). It may make little or no difference on relapse compared with fingolimod (HR 0.26, 95% CI 0.04 to 1.69; 137 participants; very low-certainty evidence). The study reported no deaths over 24 months. The study did not measure disability worsening, SAEs, HRQoL, and common infections. Rituximab as 'first choice' for progressive MS One RCT compared rituximab with placebo in primary progressive MS at 24 months' follow-up. Rituximab likely results in little to no difference in the number of participants who have disability worsening compared with placebo (odds ratio (OR) 0.71, 95% CI 0.45 to 1.11; 439 participants; moderate-certainty evidence). Rituximab may result in little to no difference in recurrence of relapses (OR 0.60, 95% CI 0.18 to 1.99; 439 participants; low-certainty evidence), SAEs (OR 1.25, 95% CI 0.71 to 2.20; 439 participants; low-certainty evidence), common infections (OR 1.14, 95% CI 0.75 to 1.73; 439 participants; low-certainty evidence), cancer (OR 0.50, 95% CI 0.07 to 3.59; 439 participants; low-certainty evidence), and mortality (OR 0.25, 95% CI 0.02 to 2.77; 439 participants; low-certainty evidence). The study did not measure HRQoL. Rituximab versus other DMTs: no studies met eligibility criteria for this comparison. Rituximab as 'switching' for relapsing MS One RCT compared rituximab with placebo in relapsing MS at 12 months' follow-up. Rituximab may decrease recurrence of relapses compared with placebo (OR 0.38, 95% CI 0.16 to 0.93; 104 participants; low-certainty evidence). The data did not confirm or exclude a beneficial or detrimental effect of rituximab relative to placebo on SAEs (OR 0.90, 95% CI 0.28 to 2.92; 104 participants; very low-certainty evidence), common infections (OR 0.91, 95% CI 0.37 to 2.24; 104 participants; very low-certainty evidence), cancer (OR 1.55, 95% CI 0.06 to 39.15; 104 participants; very low-certainty evidence), and mortality (OR 1.55, 95% CI 0.06 to 39.15; 104 participants; very low-certainty evidence). The study did not measure disability worsening and HRQoL. Five NRSIs compared rituximab with other DMTs in relapsing MS at 24 months' follow-up. The data did not confirm or exclude a beneficial or detrimental effect of rituximab relative to interferon beta or glatiramer acetate on disability worsening (HR 0.86, 95% CI 0.52 to 1.42; 1 NRSI, 853 participants; very low-certainty evidence). Rituximab likely results in a large reduction in relapses compared with interferon beta or glatiramer acetate (HR 0.18, 95% CI 0.07 to 0.49; 1 NRSI, 1383 participants; moderate-certainty evidence); and fingolimod (HR 0.08, 95% CI 0.02 to 0.32; 1 NRSI, 256 participants; moderate-certainty evidence). The data did not confirm or exclude a beneficial or detrimental effect of rituximab relative to natalizumab on relapses (HR 1.0, 95% CI 0.2 to 5.0; 1 NRSI, 153 participants; very low-certainty evidence). Rituximab likely increases slightly common infections compared with interferon beta or glatiramer acetate (OR 1.71, 95% CI 1.11 to 2.62; 1 NRSI, 5477 participants; moderate-certainty evidence); and compared with natalizumab (OR 1.58, 95% CI 1.08 to 2.32; 2 NRSIs, 5001 participants; moderate-certainty evidence). Rituximab may increase slightly common infections compared with fingolimod (OR 1.26, 95% CI 0.90 to 1.77; 3 NRSIs, 5187 participants; low-certainty evidence). It may make little or no difference compared with ocrelizumab (OR 0.02, 95% CI 0.00 to 0.40; 1 NRSI, 472 participants; very low-certainty evidence). The data did not confirm or exclude a beneficial or detrimental effect of rituximab on mortality compared with fingolimod (OR 5.59, 95% CI 0.22 to 139.89; 1 NRSI, 136 participants; very low-certainty evidence) and natalizumab (OR 6.66, 95% CI 0.27 to 166.58; 1 NRSI, 153 participants; very low-certainty evidence). The included studies did not measure SAEs, HRQoL, and cancer. AUTHORS' CONCLUSIONS For preventing relapses in relapsing MS, rituximab as 'first choice' and as 'switching' may compare favourably with a wide range of approved DMTs. A protective effect of rituximab against disability worsening is uncertain. There is limited information to determine the effect of rituximab for progressive MS. The evidence is uncertain about the effect of rituximab on SAEs. They are relatively rare in people with MS, thus difficult to study, and they were not well reported in studies. There is an increased risk of common infections with rituximab, but absolute risk is small. Rituximab is widely used as off-label treatment in people with MS; however, randomised evidence is weak. In the absence of randomised evidence, remaining uncertainties on beneficial and adverse effects of rituximab for MS might be clarified by making real-world data available.
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Affiliation(s)
- Graziella Filippini
- Scientific Director's Office, Carlo Besta Foundation and Neurological Institute, Milan, Italy
| | - Jera Kruja
- Neurology, UHC Mother Theresa, University of Medicine, Tirana, Albania
| | - Cinzia Del Giovane
- Institute of Primary Health Care (BIHAM), University of Bern, Bern, Switzerland
- Population Health Laboratory (#PopHealthLab), University of Fribourg, Fribourg, Switzerland
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de Almeida NAA, de Paula VS. Occult Hepatitis B virus (HBV) infection and challenges for hepatitis elimination: A literature review. J Appl Microbiol 2021; 132:1616-1635. [PMID: 34724308 DOI: 10.1111/jam.15351] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2021] [Revised: 09/08/2021] [Accepted: 10/11/2021] [Indexed: 12/15/2022]
Abstract
Occult hepatitis B infection (OBI) is characterized by the detection of hepatitis B virus (HBV) DNA in serum or liver but negativity for hepatitis B surface antigen. OBI, which is thought to be maintained by host, immunological, viral and/or epigenetic factors, is one of the most challenging clinical features in the study of viral hepatitis. Currently, there is no validated detection test for OBI. It is believed that OBI is widely distributed throughout the world, with a higher prevalence in populations at high-risk HBV, but the detailed worldwide prevalence patterns are unknown. We conducted a survey of recently published studies on OBI rates across all continents. High prevalence rates of OBI are observed in some specific groups, including patients with hepatitis C virus, human immunodeficiency virus co-infection or hepatocellular carcinoma. In 2016, the World Health Organization adopted strategies to eliminate viral hepatitis by 2030, but the difficulties in detecting and treating OBI currently challenge this goal. Subjects with OBI can transmit HBV, and episodes of reactivation can occur. Further studies to understanding the mechanisms that drive the development of OBI are needed and can contribute to efforts at eliminating viral hepatitis.
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The compliance of our practice of hepatitis B virus screening with the current guidelines in patients undergoing chemotherapy for hematological malignancies. JOURNAL OF SURGERY AND MEDICINE 2021. [DOI: 10.28982/josam.981625] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
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