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Alkhdir AAM, Mohamedsharif AA, Mohammed IBS, Abbas AM. Seroprevalence and Risk Factors of Hepatitis B Virus Among Newly Diagnosed Cancer Patients in Khartoum State: Implications for Chemotherapy Management and Screening Protocols. JGH Open 2025; 9:e70171. [PMID: 40314027 PMCID: PMC12041132 DOI: 10.1002/jgh3.70171] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2024] [Revised: 04/11/2025] [Accepted: 04/19/2025] [Indexed: 05/03/2025]
Abstract
Aims This study aimed to determine the seroprevalence of hepatitis B virus (HBV) among newly diagnosed cancer patients in Khartoum State, Sudan, prior to chemotherapy initiation and to identify associated risk factors. Methods and Results A cross-sectional study was conducted from October 2022 to April 2023 at various oncology centers in Khartoum State. A total of 300 newly diagnosed cancer patients, aged 18 years and older, were included. Blood samples were screened for Hepatitis B surface antigen (HBsAg) using a rapid immunochromatographic test (ICT) and confirmed by enzyme-linked immunosorbent assay (ELISA). The study found that 31 patients (10.3%) were HBsAg positive. A significant association was observed between HBV positivity and patients' history of blood transfusions (41.9% of positive cases), as well as geographic origin, with higher rates among those from Western Sudan (44.7%) and Central Sudan (40.6%). Patients diagnosed with hematological malignancies exhibited the highest HBV prevalence. Statistical analysis revealed significant correlations between HBV positivity and factors such as age, gender, residence, and transfusion history, indicating these as key risk factors. Conclusion The study reveals a notable HBV seroprevalence among cancer patients in Khartoum, particularly linked to blood transfusion history and specific regions. These findings emphasize the need for routine HBV screening in oncology patients before chemotherapy to prevent reactivation and improve clinical outcomes.
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Kampouri E, Reynolds G, Teh BW, Hill JA. Chimeric antigen receptor-T-cell therapies going viral: latent and incidental viral infections. Curr Opin Infect Dis 2024; 37:526-535. [PMID: 39361275 PMCID: PMC11932447 DOI: 10.1097/qco.0000000000001066] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/01/2024]
Abstract
PURPOSE OF REVIEW Infections are the leading cause of non-relapse mortality following chimeric antigen receptor (CAR)-T-cell therapy, with viral infections being frequent both in the early and late phases post-infusion. We review the epidemiology of viral infections and discuss critical approaches to prevention and management strategies in this setting. RECENT FINDINGS Herpesviruses dominate the early period. herpes simplex virus and varicella zoster virus infections are rare due to widespread antiviral prophylaxis, but cytomegalovirus (CMV) reactivation is increasingly observed, particularly in high-risk groups including B cell maturation antigen (BCMA)-CAR-T-cell therapy recipients and patients receiving corticosteroids. While CMV end-organ disease is rare, CMV is associated with increased mortality, emphasizing the need to evaluate the broader impact of CMV on long-term hematological, infection, and survival outcomes. Human herpesvirus-6 (HHV-6) has also emerged as a concern, with its diagnosis complicated by overlapping symptoms with neurotoxicity, underscoring the importance of considering viral encephalitis in differential diagnoses. Respiratory viruses are the most common late infections with a higher incidence after BCMA CAR-T-cell therapy. Vaccination remains a critical preventive measure against respiratory viruses but may be less immunogenic following CAR-T-cell therapy. The optimal timing, type of vaccine, and dosing schedule require further investigation. SUMMARY A better understanding of viral epidemiology and preventive trials are needed to improve infection prevention practices and outcomes following CAR-T-cell therapies.
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Affiliation(s)
- Eleftheria Kampouri
- Infectious Diseases Service, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
| | - Gemma Reynolds
- Department of Infectious Diseases, Peter MacCallum Cancer Centre, Melbourne
| | - Benjamin W. Teh
- Department of Infectious Diseases, Peter MacCallum Cancer Centre, Melbourne
- Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville
- National Centre for Infections in Cancer, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
| | - Joshua A. Hill
- Vaccine and Infectious Disease Division
- Clinical Research Division, Fred Hutchinson Cancer Center
- Department of Medicine, University of Washington, Seattle, Washington, USA
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Celsa C, Rizzo GEM, Di Maria G, Enea M, Vaccaro M, Rancatore G, Graceffa P, Falco G, Petta S, Cabibbo G, Calvaruso V, Craxì A, Cammà C, Di Marco V. What is the benefit of prophylaxis to prevent HBV reactivation in HBsAg-negative anti-HBc-positive patients? Meta-analysis and decision curve analysis. Liver Int 2024; 44:2890-2903. [PMID: 39206573 DOI: 10.1111/liv.16064] [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: 12/04/2023] [Revised: 07/04/2024] [Accepted: 07/29/2024] [Indexed: 09/04/2024]
Abstract
BACKGROUND AND AIMS Patients with overt or occult hepatitis B virus (HBV) infection receiving immunosuppressive treatments have a wide risk of HBV reactivation (HBVr). We performed meta-analysis with decision curve analyses (DCA) to estimate the risk of HBVr in HBsAg-negative anti-HBc-positive patients naïve to nucleos(t)ide analogues (NAs) receiving immunosuppressive treatments. APPROACH AND RESULTS Studies were identified through literature search until October 2022. Pooled estimates were obtained using random-effects model. Subgroup analyses were performed according to underlying disease and immunosuppressive treatments. DCA was used to identify the threshold probability associated with the net benefit of antiviral prophylaxis in HBsAg-negative anti-HBc-positive patients. We selected 68 studies (40 retrospective and 28 prospective), including 8034 patients with HBsAg negative anti-HBc positive. HBVr was 4% (95% CI 3%-6%) in HBsAg-negative anti-HBc-positive patients, with a significantly high heterogeneity (I2 69%; p < .01). The number-needed-to-treat (NNT) by DCA ranged from 8 to 24 for chemotherapy plus rituximab, from 12 to 24 for targeted therapies in cancer patients and from 13 to 39 for immune-mediated diseases. Net benefit was small for monoclonal antibodies. CONCLUSIONS Our DCA in HBsAg-negative anti-HBc-positive patients provided evidence that NA prophylaxis is strongly recommended in patients treated with chemotherapy combined with rituximab and could be appropriate in patients with cancer treated with targeted therapies and in patients with immune-mediated diseases. Finally, in patients with cancer treated with monoclonal antibodies or with chemotherapy without rituximab, the net benefit is even lower.
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Affiliation(s)
- Ciro Celsa
- Department of Health Promotion, Section of Gastroenterology and Hepatology, Mother and Child Care, Internal Medicine and Medical Specialties, PROMISE, University of Palermo, Palermo, Italy
- Department of Surgery & Cancer, Imperial College London, London, UK
| | - Giacomo E M Rizzo
- Department of Health Promotion, Section of Gastroenterology and Hepatology, Mother and Child Care, Internal Medicine and Medical Specialties, PROMISE, University of Palermo, Palermo, Italy
- Department of Precision Medicine in Medical, Surgical and Critical Care (Me.Pre.C.C.), University of Palermo, Palermo, Italy
- Department of Diagnostic and Therapeutic Services, The Mediterranean Institute for Transplantation and Highly Specialized Therapies (ISMETT), Palermo, Italy
| | - Gabriele Di Maria
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, PROMISE, University of Palermo, Palermo, Italy
| | - Marco Enea
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, PROMISE, University of Palermo, Palermo, Italy
| | - Marco Vaccaro
- Department of Economic, Business and Statistical Sciences, University of Palermo, Palermo, Italy
| | - Gabriele Rancatore
- Department of Health Promotion, Section of Gastroenterology and Hepatology, Mother and Child Care, Internal Medicine and Medical Specialties, PROMISE, University of Palermo, Palermo, Italy
- Department of Diagnostic and Therapeutic Services, The Mediterranean Institute for Transplantation and Highly Specialized Therapies (ISMETT), Palermo, Italy
| | - Pietro Graceffa
- Department of Health Promotion, Section of Gastroenterology and Hepatology, Mother and Child Care, Internal Medicine and Medical Specialties, PROMISE, University of Palermo, Palermo, Italy
| | - Giuseppe Falco
- Department of Health Promotion, Section of Gastroenterology and Hepatology, Mother and Child Care, Internal Medicine and Medical Specialties, PROMISE, University of Palermo, Palermo, Italy
| | - Salvatore Petta
- Department of Health Promotion, Section of Gastroenterology and Hepatology, Mother and Child Care, Internal Medicine and Medical Specialties, PROMISE, University of Palermo, Palermo, Italy
| | - Giuseppe Cabibbo
- Department of Health Promotion, Section of Gastroenterology and Hepatology, Mother and Child Care, Internal Medicine and Medical Specialties, PROMISE, University of Palermo, Palermo, Italy
| | - Vincenza Calvaruso
- Department of Health Promotion, Section of Gastroenterology and Hepatology, Mother and Child Care, Internal Medicine and Medical Specialties, PROMISE, University of Palermo, Palermo, Italy
| | - Antonio Craxì
- Department of Health Promotion, Section of Gastroenterology and Hepatology, Mother and Child Care, Internal Medicine and Medical Specialties, PROMISE, University of Palermo, Palermo, Italy
| | - Calogero Cammà
- Department of Health Promotion, Section of Gastroenterology and Hepatology, Mother and Child Care, Internal Medicine and Medical Specialties, PROMISE, University of Palermo, Palermo, Italy
| | - Vito Di Marco
- Department of Health Promotion, Section of Gastroenterology and Hepatology, Mother and Child Care, Internal Medicine and Medical Specialties, PROMISE, University of Palermo, Palermo, Italy
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Marty C, Adam JP, Martel-Laferrière V, Doucet S, Martel D. Impact of universal hepatitis B virus (HBV) screening using chemotherapy orders on the HBV reactivation in cancer patients. Support Care Cancer 2024; 32:541. [PMID: 39046551 DOI: 10.1007/s00520-024-08750-6] [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: 01/29/2024] [Accepted: 07/18/2024] [Indexed: 07/25/2024]
Abstract
INTRODUCTION Hepatitis B virus (HBV) reactivation (HBVr) induced by chemotherapy in patients with resolved or chronic infection can lead to severe consequences. Despite recommendations, rates of HBV screening before chemotherapy are low due to poor recognition of risk factors by clinicians. The aim of the study is to assess whether routine HBV screening using universal HBV screening on chemotherapy orders (CO) could reduce HBVr incidence. METHODS This is a 1-year retrospective single-center observational study of patients who received intravenous chemotherapy post implementation of CO. We compared the incidence of HBVr in three groups of patients: those screened through CO (group 1), those screened by the medical team (group 2), and those not screened (group 3). RESULTS On a total of 1374 patients, 179 of 206 patients were screened as requested on CO (group 1) and 421 by the medical team (group 2), whereas 747 patients were not screened (group 3). Only one HBVr occurred, and no difference was seen on the incidence of HBVr between group 1 and group 3 (0% vs 0.1%; p = 1.00), probably because of a lack of follow-up after chemotherapy. Follow-up for HBVr was imperfect in group 1 and group 2 (16.7% vs 5.6%; p = 0.32). Screening was done for 92% of patients on anti-CD20 therapy. In group 3, 89 patients had ALT elevation during chemotherapy but only 17 (19%) were tested for HBVr. CONCLUSION Systematic HBV detection requested on CO is an effective way to obtain a high percentage of patients with adequate screening, particularly when chemotherapy is at high risk of HBVr. Nevertheless, this screening method do not guarantee optimal follow-up and requires improvements.
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Affiliation(s)
- Céline Marty
- Faculty of Pharmacy, Aix-Marseille Université, Marseille, France
| | - Jean-Philippe Adam
- Department of Pharmacy, Centre Hospitalier de L'Université de Montréal (CHUM), 1050 Sanguinet St, Montréal, QC, Canada.
- Centre de Recherche du Centre Hospitalier de L'Université de Montréal (CRCHUM), Montréal, QC, H2X 0C1, Canada.
| | - Valérie Martel-Laferrière
- Centre de Recherche du Centre Hospitalier de L'Université de Montréal (CRCHUM), Montréal, QC, H2X 0C1, Canada
- Division of Microbiology and Infectious Diseases, Centre Hospitalier de L'Université de Montréal, Montréal, QC, Canada
- Department of Microbiology, Infectious Diseases and Immunology, Université de Montréal, Montréal, QC, Canada
| | - Stéphane Doucet
- Centre de Recherche du Centre Hospitalier de L'Université de Montréal (CRCHUM), Montréal, QC, H2X 0C1, Canada
- Division of Medicine-Medical Oncology/Hematology, Centre Hospitalier de L'Université de Montréal, Montréal, QC, Canada
| | - Dominic Martel
- Department of Pharmacy, Centre Hospitalier de L'Université de Montréal (CHUM), 1050 Sanguinet St, Montréal, QC, Canada
- Centre de Recherche du Centre Hospitalier de L'Université de Montréal (CRCHUM), Montréal, QC, H2X 0C1, Canada
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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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Qin Y, Zhou W, Zhou X, Li H. Case report: Recombinant human type II tumour necrosis factor receptor-antibody fusion protein induced occult hepatitis B virus reactivation leading to liver failure. J Int Med Res 2024; 52:3000605241252580. [PMID: 38760056 PMCID: PMC11107333 DOI: 10.1177/03000605241252580] [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: 10/18/2023] [Accepted: 04/15/2024] [Indexed: 05/19/2024] Open
Abstract
Recombinant human type II tumour necrosis factor receptor-antibody fusion protein (rh TNFR:Fc) is an immunosuppressant approved for treating rheumatoid arthritis (RA). This case report describes a case of hepatitis B reactivation in a patient with drug-induced acute-on-chronic liver failure. A 58-year-old woman with a history of RA was treated with rh TNFR:Fc; and then subsequently received 25 mg rh TNFR:Fc, twice a week, as maintenance therapy. No anti-hepatitis B virus (HBV) preventive treatment was administered. Six months later, she was hospitalized with acute jaundice. HBV reactivation was observed, leading to acute-on-chronic liver failure. After active treatment, the patient's condition improved and she recovered well. Following careful diagnosis and treatment protocols are essential when treating RA with rh TNFR:Fc, especially in anti-hepatitis B core antigen antibody-positive patients, even when the HBV surface antigen and the HBV DNA are negative. In the case of HBV reactivation, liver function parameters, HBV surface antigen and HBV DNA should be closely monitored during treatment, and antiviral drugs should be used prophylactically when necessary, as fatal hepatitis B reactivation may occur in rare cases. A comprehensive evaluation and medication should be administered in a timely manner after evaluating the patient's physical condition and closely monitoring the patient.
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Affiliation(s)
- Yujie Qin
- Department of Infectious Diseases, Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou Province, China
| | - Wenxiu Zhou
- Department of Infectious Diseases, Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou Province, China
| | - Xingnian Zhou
- Department of Infectious Diseases, Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou Province, China
| | - Hong Li
- Department of Infectious Diseases, Guizhou Provincial People’s Hospital, Guiyang, Guizhou Province, China
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Unver Ulusoy T, Tıglıoglu P, Demirköse H, Albayrak M, Şencan İ. Change in Hepatitis B Surface Antibody Titers After Chemotherapy in Patients With Hematological Malignancies. Cureus 2024; 16:e51572. [PMID: 38314000 PMCID: PMC10836041 DOI: 10.7759/cureus.51572] [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: 01/02/2024] [Indexed: 02/06/2024] Open
Abstract
Background The change in hepatitis B surface antibody (anti-HBs) titers after chemotherapy (CT) in patients with hematological malignancy, affecting factors, and its clinical implications have not been sufficiently understood. Therefore, we aim to evaluate the change in anti-HBs titers and hepatitis B virus reactivation (HBVr) after CT. Methods This retrospective study enrolled patients with hematological malignancies who received CT between 2013 and 2021. All patients were followed up for HBVr and a change in anti-HBs titers for one year. Results Overall, 192 patients were included. In total, 33.9% of the patients were anti-HBs (+) and 26% of the patients were anti-HBc (+) ± anti-HBs (+). Hepatitis B virus (HBV) prophylaxis was given to 35 (70%) of 50 Anti-HBc (+) patients. Tenofovir disoproxil fumarate and entecavir prophylaxis were initiated in 25 (71.4%) and 10 (28.6%) patients, respectively. A significant decrease was found in anti-HBs titers of all patients (p=0.017). A significant decrease was also found in anti-HBs titers of HBc IgG (+) patients and those who received four or more courses of CT (p=0.025; p=0.041). HBVr was not diagnosed in any of the patients. Conclusion Chemotherapeutic agents administered for hematological malignancy have serious immunosuppression effects. In these patients, anti-HBs titers may decrease or become negative one year after CT. Anti-HBs titer before CT or its change after CT may not constitute a risk for HBVr patients who received HBV prophylaxis in line with current guidelines and these recommendations.
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Affiliation(s)
- Tülay Unver Ulusoy
- Department of Infectious Diseases and Clinical Microbiology, Ankara Etlik City Hospital, Ankara, TUR
- Department of Infectious Diseases and Clinical Microbiology, Dışkapı Yildirim Beyazit Training and Research Hospital, University of Health Sciences, Ankara, TUR
| | - Pınar Tıglıoglu
- Department of Hematology, Dr. Ersin Arslan Training and Research Hospital, Gaziantep, TUR
| | - Hacer Demirköse
- Department of Public Health, Pursaklar District Health Directorate, Ankara, TUR
| | - Murat Albayrak
- Department of Haematology, Ankara Etlik City Hospital, Ankara, TUR
| | - İrfan Şencan
- Department of Infectious Diseases and Clinical Microbiology, Dışkapı Yildirim Beyazit Training and Research Hospital, University of Health Sciences, Ankara, TUR
- Department of Infectious Diseases and Clinical Microbiology, Ankara Etlik City Hospital, Ankara, TUR
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Wang YM, Luo SD, Wu CN, Wu SC, Chen WC, Yang YH, Chiu TJ. The Impact of Clinical Prognosis of Viral Hepatitis in Head and Neck Cancer Patients Receiving Concurrent Chemoradiotherapy. Biomedicines 2023; 11:2946. [PMID: 38001947 PMCID: PMC10669880 DOI: 10.3390/biomedicines11112946] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2023] [Revised: 10/25/2023] [Accepted: 10/29/2023] [Indexed: 11/26/2023] Open
Abstract
This study evaluated the clinical characteristics of head and neck cancer (HNC) patients with hepatitis B (HBV) or hepatitis C (HCV) who underwent concurrent chemoradiotherapy (CCRT) and examined the prognostic impact of antiviral therapies. In a 19-year retrospective analysis of 8224 HNC patients treated with CCRT, 29.8% (2452) were diagnosed with HBV or HCV, of whom 714 received antiviral therapy. For non-metastatic HNC patients on CCRT, factors such as gender, Charlson Comorbidity Index (CCI), liver cirrhosis markers (Fibrosis-4, APRI), and initial tumor stage were significant determinants of their overall survival. However, the presence of HBV or HCV and the administration of antiviral treatments did not yield distinct survival outcomes. In summary, antiviral therapy for HBV or HCV did not affect the 5-year survival rates of non-metastatic HNC patients undergoing CCRT, while gender, tumor stage, CCI, and liver cirrhosis were notable prognostic indicators.
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Affiliation(s)
- Yu-Ming Wang
- Department of Radiation Oncology & Proton and Radiation Therapy Center, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 833, Taiwan;
- School of Traditional Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan; (S.-D.L.); (Y.-H.Y.)
| | - Sheng-Dean Luo
- Department of Otolaryngology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 833, Taiwan; (C.-N.W.); (W.-C.C.)
- Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, No. 259, Wenhua 1st Rd., Guishan District, Taoyuan 333, Taiwan;
| | - Ching-Nung Wu
- Department of Otolaryngology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 833, Taiwan; (C.-N.W.); (W.-C.C.)
| | - Shao-Chun Wu
- Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, No. 259, Wenhua 1st Rd., Guishan District, Taoyuan 333, Taiwan;
- Department of Anesthesiology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 833, Taiwan
| | - Wei-Chih Chen
- Department of Otolaryngology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 833, Taiwan; (C.-N.W.); (W.-C.C.)
| | - Yao-Hsu Yang
- School of Traditional Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan; (S.-D.L.); (Y.-H.Y.)
- Department of Traditional Chinese Medicine, Chang Gung Memorial Hospital, Chiayi 613, Taiwan
- Health Information and Epidemiology Laboratory of Chang Gung Memorial Hospital, Chiayi 613, Taiwan
| | - Tai-Jan Chiu
- Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, No. 259, Wenhua 1st Rd., Guishan District, Taoyuan 333, Taiwan;
- Division of Hematology-Oncology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 833, Taiwan
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Kampouri E, Little JS, Rejeski K, Manuel O, Hammond SP, Hill JA. Infections after chimeric antigen receptor (CAR)-T-cell therapy for hematologic malignancies. Transpl Infect Dis 2023; 25 Suppl 1:e14157. [PMID: 37787373 DOI: 10.1111/tid.14157] [Citation(s) in RCA: 45] [Impact Index Per Article: 22.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2023] [Revised: 08/30/2023] [Accepted: 09/10/2023] [Indexed: 10/04/2023]
Abstract
BACKGROUND Chimeric antigen receptor (CAR)-T-cell therapies have revolutionized the management of acute lymphoblastic leukemia, non-Hodgkin lymphoma, and multiple myeloma but come at the price of unique toxicities, including cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, and long-term "on-target off-tumor" effects. METHODS All of these factors increase infection risk in an already highly immunocompromised patient population. Indeed, infectious complications represent the key determinant of non-relapse mortality after CAR-T cells. The temporal distribution of these risk factors shapes different infection patterns early versus late post-CAR-T-cell infusion. Furthermore, due to the expression of their targets on B lineage cells at different stages of differentiation, CD19, and B-cell maturation antigen (BCMA) CAR-T cells induce distinct immune deficits that could require different prevention strategies. Infection incidence is the highest during the first month post-infusion and subsequently decreases thereafter. However, infections remain relatively common even a year after infusion. RESULTS Bacterial infections predominate early after CD19, while a more equal distribution between bacterial and viral causes is seen after BCMA CAR-T-cell therapy, and fungal infections are universally rare. Cytomegalovirus (CMV) and other herpesviruses are increasingly breported, but whether routine monitoring is warranted for all, or a subgroup of patients, remains to be determined. Clinical practices vary substantially between centers, and many areas of uncertainty remain, including CMV monitoring, antibacterial and antifungal prophylaxis and duration, use of immunoglobulin replacement therapy, and timing of vaccination. CONCLUSION Risk stratification tools are available and may help distinguish between infectious and non-infectious causes of fever post-infusion and predict severe infections. These tools need prospective validation, and their integration in clinical practice needs to be systematically studied.
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Affiliation(s)
- Eleftheria Kampouri
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, Washington, USA
- Infectious Diseases Service, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
| | - Jessica S Little
- Division of Infectious Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA
- Division of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA
| | - Kai Rejeski
- Department of Medicine III-Hematology/Oncology, LMU University Hospital, LMU Munich, Munich, Germany
- German Cancer Consortium (DKTK), Munich site, and German Cancer Research Center, Heidelberg, Germany
| | - Oriol Manuel
- Infectious Diseases Service, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
| | - Sarah P Hammond
- Division of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA
- Divisions of Hematology/Oncology and Infectious Diseases, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Joshua A Hill
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, Washington, USA
- Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, Washington, USA
- Department of Medicine, University of Washington, Seattle, Washington, USA
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10
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Nardo M, Yilmaz B, Nelson BE, Torres HA, Wang LS, Granwehr BP, Song J, Dalla Pria HRF, Trinh VA, Glitza Oliva IC, Patel SP, Tannir NM, Kaseb AO, Altan M, Lee SS, Miller E, Zhang H, Stephen BA, Naing A. Safety and Efficacy of Immune Checkpoint Inhibitors in Patients with Cancer and Viral Hepatitis: The MD Anderson Cancer Center Experience. Oncologist 2023; 28:714-721. [PMID: 36952233 PMCID: PMC10400154 DOI: 10.1093/oncolo/oyad039] [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: 10/16/2022] [Accepted: 01/24/2023] [Indexed: 03/24/2023] Open
Abstract
BACKGROUND Despite the clinical benefit of immune checkpoint inhibitors (ICIs), patients with a viral hepatitis have been excluded from clinical trials because of safety concerns. The purpose of this study was to determine the incidence rate of adverse events (AEs) in patients with viral hepatitis who received ICIs for cancer treatment. MATERIALS AND METHODS We conducted a retrospective study in patients with cancer and concurrent hepatitis B or C, who had undergone treatment with ICI at MD Anderson Cancer Center from January 1, 2010 to December 31, 2019. RESULTS Of the 1076 patients screened, we identified 33 with concurrent hepatitis. All 10 patients with HBV underwent concomitant antiviral therapy during ICI treatment. Sixteen of the 23 patients with HCV received it before the initiation of ICI. The median follow-up time was 33 months (95% CI, 23-45) and the median duration of ICI therapy was 3 months (IQR, 1.9-6.6). Of the 33 patients, 12 (39%) experienced irAEs (immune-related adverse events) of any grade, with 2 (6%) having grade 3 or higher. None of the patients developed hepatitis toxicities. CONCLUSION ICIs may be a therapeutic option with an acceptable safety profile in patients with cancer and advanced liver disease.
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Affiliation(s)
- Mirella Nardo
- Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Bulent Yilmaz
- Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Blessie Elizabeth Nelson
- Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Harrys A Torres
- Department of Infectious Diseases Infection Control and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Lan Sun Wang
- Department of Genitourinary Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Bruno Palma Granwehr
- Department of Infectious Diseases Infection Control and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Juhee Song
- Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Hanna R F Dalla Pria
- Department of Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Van A Trinh
- Department of Melanoma Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Isabella C Glitza Oliva
- Department of Melanoma Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Sapna P Patel
- Department of Melanoma Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Nizar M Tannir
- Department of Genitourinary Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Ahmed Omar Kaseb
- Department of Genitourinary Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Mehmet Altan
- Department of Genitourinary Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
- Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston TX, USA
| | - Sunyoung S Lee
- Department of Gastrointestinal Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Ethan Miller
- Department of Gastrointestinal Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Hao Zhang
- Department of Gastrointestinal Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Bettzy A Stephen
- Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Aung Naing
- Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
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11
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[Chinese expert consensus on prevention of hepatitis B virus reactivation after allogeneic hematopoietic stem cell transplantation (2023)]. ZHONGHUA XUE YE XUE ZA ZHI = ZHONGHUA XUEYEXUE ZAZHI 2023; 44:441-448. [PMID: 37550198 PMCID: PMC10450558 DOI: 10.3760/cma.j.issn.0253-2727.2023.06.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Subscribe] [Scholar Register] [Received: 05/01/2023] [Indexed: 08/09/2023]
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12
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Ludwig H, Kumar S. Prevention of infections including vaccination strategies in multiple myeloma. Am J Hematol 2023; 98 Suppl 2:S46-S62. [PMID: 36251367 DOI: 10.1002/ajh.26766] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2022] [Revised: 10/07/2022] [Accepted: 10/10/2022] [Indexed: 11/12/2022]
Abstract
Infections are a major cause of morbidity and mortality in multiple myeloma. The increased risk for bacterial and viral infections results mainly from the disease-inherent and treatment-induced immunosuppression. Additional risk factors are older age with immune senescence, T cell depletion, polymorbidity, and male gender. Hence, every effort should be taken to reduce the risk for infections by identifying patients at higher risk for these complications and by implementing prophylactic measures, including chemoprophylaxis and immunization against various relevant pathogens. Here, we review the available evidence and provide recommendations for medical prophylaxis and vaccination in clinical practice.
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Affiliation(s)
- Heinz Ludwig
- Department of Medicine I, Center for Medical Oncology and Hematology with Outpatient Department and Palliative Care, Wilhelminen Cancer Research Institute, Vienna, Austria
| | - Shaji Kumar
- Division of Hematology, Mayo Clinic, Rochester, Minnesota, USA
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13
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Hwang JP, Arnold KB, Unger JM, Chugh R, Tincopa MA, Loomba R, Hershman D, Ramsey SD. Antiviral therapy use and related outcomes in patients with cancer and viral infections: results from SWOG S1204. Support Care Cancer 2022; 31:93. [PMID: 36585488 PMCID: PMC9803880 DOI: 10.1007/s00520-022-07525-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2022] [Accepted: 11/16/2022] [Indexed: 01/01/2023]
Abstract
PURPOSE Information is limited about adherence to practice guidelines in patients with hepatitis B virus (HBV), hepatitis C virus (HCV), or HIV infection receiving anticancer treatment. METHODS Newly diagnosed adult cancer patients were enrolled in a multicenter, prospective cohort study (SWOG S1204) during 2013-2017 to evaluate the prevalence of HBV, HCV, or HIV in patients initiating anticancer treatment. At 6 months, records of virus-positive patients were reviewed for antiviral therapy use; anticancer treatment dose reduction; and HBV reactivation (elevated viral load). Categorical variables were compared using chi-square or Fisher's exact test. RESULTS Of 3055 enrolled patients with viral testing, 230 had chronic or past HBV, HCV, or HIV with 6-month follow-up data (chronic HBV, 15 patients; past HBV, 158; HCV, 49; HIV, 30). Twenty percent (3/15) of chronic HBV and 11% (17/158) of past HBV patients were co-infected with HCV and/or HIV. Rates of antiviral therapy use by 6 months were as follows: chronic HBV, 85% (11/13); past HBV receiving anti-B cell therapy, 60% (3/5); past HBV receiving systemic anticancer therapy without anti-B cell therapy, 8% (8/105); HCV, 6% (2/35); and HIV, 90% (19/21). Among patients with available data, anticancer treatment dose was reduced in 1 of 145 patients with past HBV and 1 of 42 with HCV. HBV reactivation occurred in 1 of 15 patients with chronic HBV; this patient was not receiving antiviral therapy. CONCLUSION Many patients with cancer and viral infections either do not receive guideline-recommended antiviral treatment or receive antiviral treatment that is not recommended in guidelines. Further education is needed to improve adherence to guidelines.
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Affiliation(s)
- Jessica P Hwang
- Department of General Internal Medicine, Unit 1465, The University of Texas MD Anderson Cancer Center, P.O. Box 301402, Houston, TX, 77230-1402, USA.
| | - Kathryn B Arnold
- SWOG Statistics and Data Management Center, Seattle, WA, USA
- Fred Hutchinson Cancer Center, Seattle, WA, USA
| | - Joseph M Unger
- SWOG Statistics and Data Management Center, Seattle, WA, USA
- Fred Hutchinson Cancer Center, Seattle, WA, USA
| | | | | | - Rohit Loomba
- Division of Gastroenterology, Department of Medicine, and Wertheim School of Public Health, University of California at San Diego, La Jolla, CA, USA
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14
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DURAK S, COŞAR AM. Evaluation of the safety and antiviral efficacy of the tenofovir alafenamide fumarate molecule in immunosuppressed patients. JOURNAL OF HEALTH SCIENCES AND MEDICINE 2022. [DOI: 10.32322/jhsm.1179106] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Abstract
Aim: Patients with chronic or prior hepatitis B virus (HBV) infection may experience HBV reactivation during immunosuppressive therapy. The objective of this study was to evaluate the safety and antiviral efficacy of tenofovir alafenamide fumarate (TAF) for prophylaxis of HBV reactivation in patients on immunosuppressive therapy.
Material and Method: This study included patients who were started on immunosuppressive treatment due to hematologic/solid malignancy, autoimmune disease, or inflammatory disease and were treated with TAF for at least six months due to HBsAg and/or total anti-HBc positivity at Karadeniz Technical University Farabi Hospital between January 2018 and February 2021. Electronic medical records were retrospectively reviewed and the adverse event profile was analyzed.
Results: Of the 94 patients enrolled in the study, 70.2% (n=66) were male. The mean age of the patients was 60.37±14.56 years. The reasons for initiation of immunosuppressive drug treatment were hematologic malignancies in 48.9% (n=46), solid tumors in 27.7% (n=26), and other causes (autoimmune/inflammatory) in 23.4% (n=22). There was no statistically significant difference in creatinine, phosphorus, glucose, and LDL profile between baseline and 6-12 months of TAF treatment (p=0.861, p=0.136, p=0.323, p=0.304, respectively). All patients in whom HBV DNA was detectable at baseline became negative at the last follow-up visit. None of the patients developed HBV reactivation and there was no need to discontinue antiviral/immunosuppressive treatment due to side effects.
Conclusion: TAF is a safe and effective short-term option to prevent HBV reactivation in patients receiving immunosuppressive therapy.
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Affiliation(s)
- Serdar DURAK
- Kanuni Training and Research Hospital, Department of Gastroenterology
| | - Arif Mansur COŞAR
- KARADENIZ TECHNICAL UNIVERSITY, SCHOOL OF MEDICINE, DEPARTMENT OF INTERNAL MEDICINE, DEPARTMENT OF INTERNAL MEDICINE, GASTROENTEROLOGY
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15
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Hwang JP, Artz AS, Shah P, Symington B, Feld JJ, Hammond SP, Ludwig E, Pai A, Ramsey SD, Schlam I, Suga JM, Wang SH, Somerfield MR. Practical Implementation of Universal Hepatitis B Virus Screening for Patients With Cancer. JCO Oncol Pract 2022; 18:636-644. [DOI: 10.1200/op.22.00074] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Affiliation(s)
| | - Andy S. Artz
- City of Hope Comprehensive Cancer Center, Duarte, CA
| | - Parth Shah
- Fred Hutchinson Cancer Research Center, Seattle, WA
| | - Banu Symington
- Memorial Hospital of Sweetwater County, Rock Springs, WY
| | - Jordan J. Feld
- Toronto Centre for Liver Disease, University Health Network, University of Toronto, Toronto, Ontario, Canada
| | - Sarah P. Hammond
- Massachusetts General Hospital and Dana-Farber Cancer Institute, Boston, MA
| | - Emmy Ludwig
- Memorial Sloan Kettering Cancer Center, New York, NY
| | - Amy Pai
- The University of Texas MD Anderson Cancer Center, Houston, TX
| | | | | | | | - Su H. Wang
- Saint Barnabas Medical Center, Florham Park, NJ
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16
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Sagnelli C, Sica A, Creta M, Borsetti A, Ciccozzi M, Sagnelli E. Prevention of HBV Reactivation in Hemato-Oncologic Setting during COVID-19. Pathogens 2022; 11:567. [PMID: 35631088 PMCID: PMC9144674 DOI: 10.3390/pathogens11050567] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2022] [Revised: 05/06/2022] [Accepted: 05/10/2022] [Indexed: 02/04/2023] Open
Abstract
Onco-hematologic patients are highly susceptible to SARS-CoV-2 infection and, once infected, frequently develop COVID-19 due to the immunosuppression caused by tumor growth, chemotherapy and immunosuppressive therapy. In addition, COVID-19 has also been recognized as a further cause of HBV reactivation, since its treatment includes the administration of corticosteroids and some immunosuppressive drugs. Consequently, onco-hematologic patients should undergo SARS-CoV-2 vaccination and comply with the rules imposed by lockdowns or other forms of social distancing. Furthermore, onco-hematologic facilities should be adapted to new needs and provided with numerically adequate health personnel vaccinated against SARS-CoV-2 infection. Onco-hematologic patients, both HBsAg-positive and HBsAg-negative/HBcAb-positive, may develop HBV reactivation, made possible by the support of the covalently closed circular DNA (cccDNA) persisting in the hepatocytic nuclei of patients with an ongoing or past HBV infection. This occurrence must be prevented by administering high genetic barrier HBV nucleo(t)side analogues before and throughout the antineoplastic treatment, and then during a long-term post-treatment follow up. The prevention of HBV reactivation during the SARS-CoV-2 pandemic is the topic of this narrative review.
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Affiliation(s)
- Caterina Sagnelli
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, University of Campania “Luigi Vanvitelli”, 80131 Naples, Italy;
| | - Antonello Sica
- Department of Precision Medicine, University of Campania “Luigi Vanvitelli”, 80131 Naples, Italy;
| | - Massimiliano Creta
- Department of Neurosciences, Reproductive Sciences and Odontostomatology, University of Naples Federico II, 80131 Naples, Italy;
| | - Alessandra Borsetti
- National HIV/AIDS Research Center, Istituto Superiore di Sanità, 00161 Rome, Italy;
| | - Massimo Ciccozzi
- Medical Statistics and Molecular Epidemiology Unit, Campus Bio-Medico University, 00128 Rome, Italy;
| | - Evangelista Sagnelli
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, University of Campania “Luigi Vanvitelli”, 80131 Naples, Italy;
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17
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Fujita M, Kusumoto S, Ishii I, Iwata T, Fujisawa T, Sugiyama M, Hata A, Mizokami M. Cost-effectiveness of managing HBV reactivation in patients with resolved HBV infection treated with anti-CD20 antibody for B-cell non-Hodgkin lymphoma. Sci Rep 2022; 12:7365. [PMID: 35513395 PMCID: PMC9072369 DOI: 10.1038/s41598-022-10665-3] [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: 10/06/2021] [Accepted: 04/11/2022] [Indexed: 11/24/2022] Open
Abstract
There is no universal recommendation for managing the reactivation of HBV in patients with resolved HBV infection treated with anti-CD20 monoclonal antibodies for B-cell non-Hodgkin lymphoma. This study compared the cost-effectiveness of two commonly used strategies: prophylactic anti-HBV nucleos(t)ide analog therapy (Pro NAT), and HBV DNA monitoring followed by on-demand antiviral therapy (HBV DNA monitoring). Using a decision tree model, the incremental cost-effectiveness ratio (ICER) expressed as cost per quality-adjusted life-year (QALY) gained was calculated. The threshold for cost-effectiveness was set at 5,000,000 JPY, equivalent to 45,662 USD. In a base–case analysis, HBV DNA monitoring was found to be more cost-effective based on the calculation of ICER as 132,048 USD per QALY, a value that far exceeds 45,662 USD. The same results were consistently obtained by a one-way deterministic sensitivity analysis, even after changing each parameter value within the predetermined range. A probabilistic sensitivity analysis with 10,000 simulations also revealed that HBV DNA monitoring is more cost-effective than Pro NAT in 96.8% of cases. Therefore, this study suggests that HBV DNA monitoring is an appropriate managing measure in Japan from a cost-effectiveness perspective.
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Affiliation(s)
- Misuzu Fujita
- Department of Health Research, Chiba Foundation for Health Promotion and Disease Prevention, 32-14, Shinminato, Mihama-ku, Chiba, Chiba, 261-0002, Japan. .,Genome Medical Science Project, National Center for Global Health and Medicine, 1-7-1, Kounodai, Ichikawa, Chiba, 272-8516, Japan. .,Department of Public Health, Chiba University Graduate School of Medicine, Chiba, Chiba, Japan.
| | - Shigeru Kusumoto
- Department of Hematology and Oncology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, Japan
| | - Itsuko Ishii
- Division of Pharmacy, Chiba University Hospital, Chiba, Chiba, Japan
| | - Tadashi Iwata
- Department of Medical Practice, The University of Tokyo Hospital, Bunkyo-ku, Tokyo, Japan
| | - Takehiko Fujisawa
- Department of Health Research, Chiba Foundation for Health Promotion and Disease Prevention, 32-14, Shinminato, Mihama-ku, Chiba, Chiba, 261-0002, Japan
| | - Masaya Sugiyama
- Genome Medical Science Project, National Center for Global Health and Medicine, 1-7-1, Kounodai, Ichikawa, Chiba, 272-8516, Japan
| | - Akira Hata
- Department of Health Research, Chiba Foundation for Health Promotion and Disease Prevention, 32-14, Shinminato, Mihama-ku, Chiba, Chiba, 261-0002, Japan.
| | - Masashi Mizokami
- Genome Medical Science Project, National Center for Global Health and Medicine, 1-7-1, Kounodai, Ichikawa, Chiba, 272-8516, Japan.
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18
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The Korean Association for the Study of the Liver (KASL). KASL clinical practice guidelines for management of chronic hepatitis B. Clin Mol Hepatol 2022; 28:276-331. [PMID: 35430783 PMCID: PMC9013624 DOI: 10.3350/cmh.2022.0084] [Citation(s) in RCA: 69] [Impact Index Per Article: 23.0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2022] [Accepted: 04/01/2022] [Indexed: 01/10/2023] Open
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19
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Crosby J, Smith F, Ganti SS, Moka N, Bailey S. Hepatitis B Virus Reactivation Following Treatment of HNSCC With Cisplatin. J Investig Med High Impact Case Rep 2022; 10:23247096221090842. [PMID: 35426319 PMCID: PMC9016584 DOI: 10.1177/23247096221090842] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
Hepatitis B Virus (HBV) reactivation is a known complication of intense immunosuppression
with B-cell depleting monoclonal antibody therapy and transplantation immunosuppression.
HBV reactivation has occurred following treatment with chemotherapy regimens for
hematologic malignancies and solid tumors. There are 2 prior case reports of HBV
reactivation following cisplatin monotherapy for head and neck squamous cell carcinoma
(HNSCC). Here, we present a case of a 49-year-old Caucasian male with a past medical
history of laryngeal squamous cell carcinoma (SCC). There are no consensus guidelines on
how to define hepatitis B reactivation. There are guidelines on when to initiate
prophylaxis with Entecavir while on immunosuppressive therapy with risk according to
medication category and hepatitis B surface antigen/hepatitis B core antibody IgG
serology. CDC recommends screening everyone. American Society of Clinical Oncology (ASCO)
now with a recent update in 2020 recommends screening everyone. There is a definite role
of immunosuppression in HBV reactivation, however, there is also direct enhancement by
cisplatin of viral replication by creating endoplasmic reticulum stress which increases
HBV DNA indirectly. Finally, cytotoxicity enhances HBV reactivation and immune
reconstitution post withdrawing immunosuppressive treatment. Because of the effects of
chemotherapy, aka cisplatin goes beyond immunosuppression-related reactivation of HBV, our
recommendations are in line with CDC and ASCO to screen all patients for HBV before onset
of chemotherapy and start Entecavir/Tenofovir Disoproxil Fumarate before the onset of
chemotherapy for HBV-positive patients.
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Affiliation(s)
- James Crosby
- Appalachian Regional Healthcare, Whitesburg, KY, USA
| | - Forrest Smith
- Appalachian Regional Healthcare, Whitesburg, KY, USA
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20
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Infection risk and prophylaxis in patients with lymphoid cancer. Blood 2021; 139:1517-1528. [PMID: 34748625 DOI: 10.1182/blood.2019003687] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2020] [Accepted: 05/05/2021] [Indexed: 11/20/2022] Open
Abstract
Infections are a common cause of morbidity and mortality in patients with lymphoid cancer. With evolving cancer therapeutics, including new targeted and immunotherapies, clinicians need to be aware of additional risk factors and infections that may arise in patients treated with these agents. This "How I Treat" article will highlight fundamental issues including risk factors for infection, infectious diseases screenings and antimicrobial prophylaxis recommendations in patients with lymphoid cancers. We present 4 scenarios of patients with lymphoid cancers with varied infections and describe a treatment approach based on a combination of evidence-based data and experience, as there are limitations in objective infection data especially with newer agents. The goal of this discussion is to provide a framework for institutions and health care providers to develop their own approach in preventing and treating infections in patients with lymphoid cancer.
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21
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Leber K, Otten HJMMB, Brandjes DPM, Claassen MAA, Lauw FN. Clinical practice of hepatitis B screening in patients starting with chemotherapy: A survey among Dutch oncologists. Eur J Cancer Care (Engl) 2021; 30:e13495. [PMID: 34310787 PMCID: PMC9285452 DOI: 10.1111/ecc.13495] [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: 02/03/2021] [Revised: 06/10/2021] [Accepted: 07/08/2021] [Indexed: 11/30/2022]
Abstract
OBJECTIVE Screening for hepatitis B virus (HBV) before chemotherapy is recommended by international guidelines; still, the HBV screening rate is low, and patients remain at risk for HBV reactivation (HBVr). Because HBVr is a serious and preventable condition, we conducted a survey to evaluate the screening behaviour of oncologists in the Netherlands. METHODS We conducted an anonymous digital survey by email to all practicing medical oncologists. The surveys were sent in two session, the first one in 2017 and the second one in 2019. Questions included HBV screening procedures, reasons for screening and experience with HBVr. RESULTS Among the 110 respondents, 29 (27%) followed a standardised protocol. Overall, 13 (12%) oncologists screened all patients, 76 (70%) only screened patients they considered as high risk and 19 (18%) did not screen anyone. Fourteen percent of the respondents experienced a HBVr in one of their patients. CONCLUSION This survey suggests that universal HBV screening is not common practice and usually patients considered as at risk for HBVr are screened, while this group is not always properly identified. Introduction of a national protocol for HBV screening and adjustment of the Dutch oncology guidelines might contribute to a reduction of HBVr during chemotherapy.
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Affiliation(s)
- Karin Leber
- Department of Internal MedicineAmsterdam UMC, location AMCAmsterdamThe Netherlands
- Department of Internal MedicineZaans Medisch CentrumZaandamThe Netherlands
| | | | - Dees P. M. Brandjes
- Department of Internal/Vascular MedicineAmsterdam UMC, location AMCAmsterdamThe Netherlands
| | - Mark A. A. Claassen
- Department of Internal Medicine/Infectious DiseasesRijnstate HospitalArnhemThe Netherlands
| | - Fanny N. Lauw
- Department of Internal Medicine/Infectious DiseasesMedical Center Jan van GoyenAmsterdamThe Netherlands
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22
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Hepatitis B Virus Infection in Patients Receiving Allogeneic Hematopoietic Stem Cell Transplantation. J Pers Med 2021; 11:jpm11111108. [PMID: 34834460 PMCID: PMC8619006 DOI: 10.3390/jpm11111108] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2021] [Revised: 10/20/2021] [Accepted: 10/25/2021] [Indexed: 01/12/2023] Open
Abstract
Considering a steady increase in the number of allogeneic hematopoietic stem cell transplantations (allo-HSCT) worldwide and the significant proportion of the world’s population that has been exposed to hepatitis B virus (HBV) infection, HBV reactivation following allo-HSCT remains an important issue for post-transplant morbidity and mortality. Antiviral prophylaxis can reduce HBV replication, severity of HBV-related hepatitis, and mortality; therefore, identification of patients at risk is crucial. It is recommended that all recipients and donors should be screened for active or prior HBV infection, including HBsAg, antiHBc, and antiHBs. Adoptive immunity transfer from the donor seems to have protective effects against HBV reactivation. Antiviral prophylaxis should be initiated in all HBsAg-positive patients. HBsAg-negative, antiHBc-positive patients remain at risk; therefore, antiviral prophylaxis should be considered if baseline serum HBV DNA is detectable. In HBsAg-negative, antiHBc-positive patients without detectable HBV DNA, close monitoring of viral load with an on-demand therapy is necessary. Entecavir or tenofovir rather than lamivudine are more appropriate for the emergence of lamivudine resistance. The treatment duration remains unclear, with 6- to 12-month therapy after cessation of immunosuppressive therapy commonly recommended. Here we review the updated evidence and recent recommendations regarding HBV reactivation in patients undergoing allo-HSCT for individualized therapy.
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23
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Lee PC, Chao Y, Chen MH, Lan KH, Lee IC, Hou MC, Huang YH. Risk of HBV reactivation in patients with immune checkpoint inhibitor-treated unresectable hepatocellular carcinoma. J Immunother Cancer 2021; 8:jitc-2020-001072. [PMID: 32863270 PMCID: PMC7462159 DOI: 10.1136/jitc-2020-001072] [Citation(s) in RCA: 50] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/01/2020] [Indexed: 12/15/2022] Open
Abstract
Background Immunotherapy with immune checkpoint inhibitor (ICI) is a promising treatment for unresectable hepatocellular carcinoma (HCC). However, whether ICIs would have the risk of hepatitis B virus (HBV) reactivation and the necessary of nucleos(t)ide analogs (NUCs) prophylaxis are still unclear. We aimed to investigate the role of NUCs prophylaxis in HBV-infected patients who underwent ICIs treatment. Methods The study was a retrospective prospective design to review and follow-up consecutive 62 patients with chronic hepatitis B or resolved HBV infection who had received ICIs treatment for the unresectable HCC. Of them, 60 patients with documented baseline serum HBV DNA value were classified into three categories according to the baseline HBV viral load and the status of antiviral therapy before ICI treatment. The clinical status, including tumor response, viral kinetics and liver function, was recorded and investigated. Results No HBV reactivation occurred in the 35 patients with HBV DNA ≤100 IU/mL on NUCs therapy. Of the 19 patients with HBV DNA >100 IU/mL who started NUCs simultaneously with ICI treatment, none encountered HBV reactivation during the immunotherapy. Of the six HBV patients without NUCs treatment, three had a greater than 1 log decrease in HBV viral load, and one maintained his serum HBV DNA in undetectable status during ICI treatment. Eventually, one out of six experienced HBV reactivation after 9 weeks of ICI treatment. Conclusion No patients on antiviral therapy developed HBV reactivation, and one out of six not receiving antiviral therapy had HBV reactivation. HBV viral load higher than 100 IU/mL is safe and not a contraindication for ICI treatment for HCC, if NUCs can be coadministrated.
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Affiliation(s)
- Pei-Chang Lee
- Division of Gastroenterology and Hepatology, Taipei Veterans General Hospital, Taipei, Taiwan.,Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan.,Institute of Pharmacology, National Yang-Ming University School of Medicine, Taipei, Taiwan
| | - Yee Chao
- Department of Oncology, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Ming-Huang Chen
- Department of Oncology, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Keng-Hsin Lan
- Division of Gastroenterology and Hepatology, Taipei Veterans General Hospital, Taipei, Taiwan.,Institute of Pharmacology, National Yang-Ming University School of Medicine, Taipei, Taiwan
| | - I-Cheng Lee
- Division of Gastroenterology and Hepatology, Taipei Veterans General Hospital, Taipei, Taiwan.,Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
| | - Ming-Chih Hou
- Division of Gastroenterology and Hepatology, Taipei Veterans General Hospital, Taipei, Taiwan.,Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
| | - Yi-Hsiang Huang
- Division of Gastroenterology and Hepatology, Taipei Veterans General Hospital, Taipei, Taiwan .,Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan.,Institute of Clinical Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
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24
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Chi CT, Lee IC, Lee RC, Hung YW, Su CW, Hou MC, Chao Y, Huang YH. Effect of Transarterial Chemoembolization on ALBI Grade in Intermediate-Stage Hepatocellular Carcinoma: Criteria for Unsuitable Cases Selection. Cancers (Basel) 2021; 13:4325. [PMID: 34503135 PMCID: PMC8431519 DOI: 10.3390/cancers13174325] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2021] [Revised: 08/21/2021] [Accepted: 08/24/2021] [Indexed: 02/08/2023] Open
Abstract
Transarterial chemoembolization (TACE) is the standard of care for intermediate stage hepatocellular carcinoma (HCC). We aimed to identify unsuitable cases who were at risk of ALBI-grade migration by TACE. Consecutive 531 BCLC-B HCC patients undergoing TACE were reviewed, and factors associated with ALBI-grade migration were analyzed. There were 129 (24.3%) patients experienced acute ALBI-grade migration after TACE, and 85 (65.9%) out of the 129 patients had chronic ALBI-grade migration. Incidences of acute ALBI-grade migration were 13.9%, 29.0% for patients within or beyond up-to-7 criteria (p < 0.001) and 20.0%, 36.2% for patients within or beyond up-to-11 criteria (p < 0.001), respectively. HBV infection, tumor size plus tumor number criteria were risk factors associated with acute ALBI-grade migration. Bilobar tumor involvement was the risk factor of chronic ALBI-grade migration in patients with acute ALBI-grade migration. Up-to-eleven (p = 0.007) performed better than up-to-seven (p = 0.146) to differentiate risk of dynamic ALBI score changes. Moreover, ALBI-grade migration to grade 3 has adverse effect on survival. In conclusion, tumor burden beyond up-to-eleven was associated with ALBI-grade migration after TACE, indicating that up-to-eleven can select TACE-unsuitable HCC patients who are at risk of liver function deterioration.
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Affiliation(s)
- Chen-Ta Chi
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei 11217, Taiwan; (C.-T.C.); (I.-C.L.); (Y.-W.H.); (C.-W.S.); (M.-C.H.)
- Institute of Clinical Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei 11221, Taiwan
| | - I-Cheng Lee
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei 11217, Taiwan; (C.-T.C.); (I.-C.L.); (Y.-W.H.); (C.-W.S.); (M.-C.H.)
| | - Rheun-Chuan Lee
- Department of Radiology, Taipei Veterans General Hospital, Taipei 11217, Taiwan;
| | - Ya-Wen Hung
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei 11217, Taiwan; (C.-T.C.); (I.-C.L.); (Y.-W.H.); (C.-W.S.); (M.-C.H.)
| | - Chien-Wei Su
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei 11217, Taiwan; (C.-T.C.); (I.-C.L.); (Y.-W.H.); (C.-W.S.); (M.-C.H.)
| | - Ming-Chih Hou
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei 11217, Taiwan; (C.-T.C.); (I.-C.L.); (Y.-W.H.); (C.-W.S.); (M.-C.H.)
| | - Yee Chao
- Department of Oncology, Taipei Veterans General Hospital, Taipei 11217, Taiwan;
| | - Yi-Hsiang Huang
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei 11217, Taiwan; (C.-T.C.); (I.-C.L.); (Y.-W.H.); (C.-W.S.); (M.-C.H.)
- Institute of Clinical Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei 11221, Taiwan
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25
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Chen MH, Wu CS, Chen MH, Tsai CY, Lee FY, Huang YH. High Risk of Viral Reactivation in Hepatitis B Patients with Systemic Lupus Erythematosus. Int J Mol Sci 2021; 22:9116. [PMID: 34502025 PMCID: PMC8430791 DOI: 10.3390/ijms22179116] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2021] [Revised: 07/13/2021] [Accepted: 08/23/2021] [Indexed: 12/12/2022] Open
Abstract
HBV reactivation (HBVr) can occur in hepatitis B surface antigen (HBsAg)-positive and negative patients. Here, we determined the incidence of HBVr and its related hepatitis in patients with systemic lupus erythematosus (SLE). From 2000 to 2017, 3307 SLE cases were retrospectively reviewed for episodes of hepatitis. The incidence, long-term outcomes and risk factors associated with HBVr, including HBsAg reverse seroconversion (RS) were analyzed. Among them, 607 had available HBsAg status. Fifty-five (9.1%) patients were positive for HBsAg and 63 (11.4%) were HBsAg-negative/antibody to hepatitis B core antigen (anti-HBc)-positive (resolved hepatitis B infection, RHB). None of them received antiviral prophylaxis before immunosuppressive treatment. During a mean 15.4 years of follow-up, 30 (54.5%) HBsAg-positive patients developed HBVr and seven (23.3%) died of liver failure, whereas only two (3.2%) RHB cases experienced HBsAg reverse seroconversion (RS). Multivariate logistic regression analysis showed that age ≥ 40 years at diagnosis of SLE (HR 5.30, p < 0.001), receiving glucocorticoid-containing immunosuppressive therapy (HR 4.78, p = 0.003), and receiving glucocorticoid ≥ 10 mg prednisolone equivalents (HR 3.68, p = 0.003) were independent risk factors for HBVr in HBsAg-positive patients. Peak level of total bilirubin ≥ 5 mg/dL during HBVr was an independent factor of mortality (p = 0.002). In conclusion, the risk of HBVr was associated with glucocorticoid daily dose. Antiviral prophylaxis is mandatory for SLE patients diagnosed at age of ≥40 years who receive ≥ 10 mg daily dose of oral prednisone or equivalent.
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Affiliation(s)
- Ming-Han Chen
- Division of Allergy-Immunology-Rheumatology, Department of Medicine, Taipei Veterans General Hospital, Taipei 11217, Taiwan;
- Faculty of Medicine, National Yang Ming Chiao Tung University, Taipei 11221, Taiwan;
| | - Chien-Sheng Wu
- Division of Allergy-Immunology-Rheumatology, Department of Medicine, Far Eastern Memorial Hospital, Taipei 220216, Taiwan;
| | - Ming-Huang Chen
- Faculty of Medicine, National Yang Ming Chiao Tung University, Taipei 11221, Taiwan;
| | - Chang-Youh Tsai
- Division of Allergy-Immunology-Rheumatology, Department of Medicine, Taipei Veterans General Hospital, Taipei 11217, Taiwan;
- Faculty of Medicine, National Yang Ming Chiao Tung University, Taipei 11221, Taiwan;
| | - Fa-Yauh Lee
- Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taipei 11217, Taiwan; (F.-Y.L.); (Y.-H.H.)
| | - Yi-Hsiang Huang
- Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taipei 11217, Taiwan; (F.-Y.L.); (Y.-H.H.)
- Institute of Clinical Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei 11221, Taiwan
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26
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Shih CA, Chen WC. Prevention of hepatitis B reactivation in patients requiring chemotherapy and immunosuppressive therapy. World J Clin Cases 2021; 9:5769-5781. [PMID: 34368296 PMCID: PMC8316946 DOI: 10.12998/wjcc.v9.i21.5769] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2021] [Revised: 04/12/2021] [Accepted: 06/02/2021] [Indexed: 02/06/2023] Open
Abstract
Hepatitis B virus (HBV) reactivation can lead to severe acute hepatic failure and death in patients with HBV infection. HBV reactivation (HBVr) most commonly develops in patients undergoing cancer chemotherapy, especially B cell-depleting agent therapy such as rituximab and ofatumumab for hematological or solid organ malignancies and that receiving hematopoietic stem cell transplantation without antiviral prophylaxis. In addition, the potential consequences of HBVr is particularly a concern when patients are exposed to either immunosuppressive or biologic therapies for the management of rheumatologic diseases, inflammatory bowel disease and dermatologic diseases. Thus, screening with HBV serological markers and prophylactic or pre-emptive antiviral treatment with nucleos(t)ide analogues should be considered in these patients to diminish the risk of HBVr. This review discusses the clinical manifestation, prognosis and management of HBVr, risk stratifications of cancer chemotherapy and immunosuppressive therapy and international guideline recommendations for the prevention of HBVr in patients with HBV infection and resolved hepatitis B.
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Affiliation(s)
- Chih-An Shih
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung 813, Taiwan
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Antai Medical Care Corporation, Antai Tian-Sheng Memorial Hospital, Pingtung County 928, Taiwan
- Department of Nursing, Meiho University, Pingtung County 928, Taiwan
| | - Wen-Chi Chen
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung 813, Taiwan
- Faculty of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei 112, Taiwan
- Institute of Biomedical Sciences, College of Science, National Sun Yat-sen University, Kaohsiung 8424, Taiwan
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27
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Borojevic B, Chauhan A, Patterson S. Liver failure from delayed hepatitis B reactivation in anti-HBc-positive patient following rituximab for B-cell lymphoma. BMJ Case Rep 2021; 14:14/7/e243526. [PMID: 34244190 DOI: 10.1136/bcr-2021-243526] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
A 93-year-old man was admitted with 1 week of frank jaundice and abdominal pain. His medical history included diffuse large B-cell lymphoma treated with rituximab and cyclophosphamide, hydroxydaunomycin, oncovin and prednisolone (R-CHOP) chemotherapy 10 months prior. His investigations revealed marked hyperbilirubinemia with a total bilirubin of 355 μmol/L, along with a 17-fold elevation in alanine transaminase and impaired hepatic synthetic function. He tested hepatitis B surface antigen (HBsAg) and hepatitis B surface antibody (HBsAb) negative, hepatitis B core antibody (HBcAb) positive and had elevated hepatitis B virus DNA level at 13 691 IU/L. This was in the setting of radiological evidence of suspected cirrhosis. He was later found to have tested positive for HBcAb and negative for HBsAg and HBsAb prior to chemotherapy, but had not received antiviral prophylaxis. He was diagnosed with fulminant hepatitis secondary to delayed hepatitis B reactivation in the setting of rituximab. Hepatitis B reactivation and the role of screening and antiviral prophylaxis in isolated HBcAb-positive patients is reviewed.
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Affiliation(s)
- Branko Borojevic
- General Medicine, Austin Health, Heidelberg, Victoria, Australia
| | - Ayushi Chauhan
- General Medicine, Eastern Health, Box Hill, Victoria, Australia
| | - Scott Patterson
- Gastroenterology and General Medicine, Austin Health, Heidelberg, Victoria, Australia
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28
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Hwang JP, Yilmaz B. Reactivation of Hepatitis B Virus Among Patients With Cancer Receiving Immunotherapy. JOURNAL OF IMMUNOTHERAPY AND PRECISION ONCOLOGY 2021; 4:53-55. [PMID: 35663533 PMCID: PMC9153263 DOI: 10.36401/jipo-20-19] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/01/2020] [Revised: 07/13/2021] [Accepted: 07/22/2020] [Indexed: 05/14/2023]
Affiliation(s)
- Jessica P. Hwang
- Department of General Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Bulent Yilmaz
- Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
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29
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Pritchard H, Hwang JP, Angelidakis G, Yibirin M, Wang L, Miller E, Torres HA. Hepatitis B virus reactivation in cancer patients receiving direct-acting antivirals for hepatitis C virus infection. J Viral Hepat 2021; 28:844-848. [PMID: 33523503 PMCID: PMC8928572 DOI: 10.1111/jvh.13478] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/13/2021] [Accepted: 01/15/2021] [Indexed: 12/09/2022]
Abstract
Direct-acting antivirals (DAAs) against hepatitis C virus (HCV) infection can cause hepatitis B virus (HBV) reactivation in HBV/HCV co-infected patients. Cancer patients undergoing immunosuppressant treatment or chemotherapy are at risk for HBV reactivation. To our knowledge, no prospective studies have examined the risk of HBV reactivation during DAA treatment for HCV infection in cancer patients with HBV/HCV co-infection. Here, we report the results of one such study. In a prospective observational study, we enrolled HCV-infected cancer patients undergoing DAA treatment at The University of Texas MD Anderson Cancer Center between January 2015 and March 2018. Data regarding demographics, cancer history, and prior HCV treatment history were collected. Patients were assessed for HBV status before DAA treatment and for HBV-related outcomes, including HBV reactivation, hepatitis flare, and HBV-associated hepatitis, during DAA treatment. Demographic and treatment variables were analyzed using descriptive statistics. One hundred sixty-six patients were analyzed. Forty-eight patients received systemic chemotherapy within 6 months before to 6 months after treatment with DAAs. Ledipasvir plus sofosbuvir was the most common DAA regimen, administered to 88 patients (53%). Fifty-one patients (31%) had past HBV infection, and 4 (2.4%) had chronic HBV infection. No patient experienced HBV reactivation, hepatitis flare, or HBV-associated hepatitis induced by DAA treatment. In HCV-infected cancer patients, DAA treatment is safe regardless of whether patients have past or chronic HBV infection. However, HBV screening is still recommended before the initiation of and during DAA treatment, as is anti-HBV prophylactic treatment in selected cases.
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Affiliation(s)
- Haley Pritchard
- Department of Medicine, Section of Infectious Diseases, Baylor College of Medicine, Houston, Texas,Department of Infectious Diseases, Infection Control and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Jessica P. Hwang
- Department of General Internal Medicine, Division of Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Georgios Angelidakis
- Department of Infectious Diseases, Infection Control and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Marcel Yibirin
- Department of Infectious Diseases, Infection Control and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Lan Wang
- Department of Gastroenterology, Hepatology, and Nutrition, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Ethan Miller
- Department of Gastroenterology, Hepatology, and Nutrition, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Harrys A. Torres
- Department of Infectious Diseases, Infection Control and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, Texas,Department of Gastroenterology, Hepatology, and Nutrition, The University of Texas MD Anderson Cancer Center, Houston, Texas
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30
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Management of Hepatitis B Virus Reactivation in Malignant Lymphoma Prior to Immunosuppressive Treatment. J Pers Med 2021; 11:jpm11040267. [PMID: 33918206 PMCID: PMC8066124 DOI: 10.3390/jpm11040267] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2021] [Revised: 03/29/2021] [Accepted: 03/30/2021] [Indexed: 12/25/2022] Open
Abstract
Hepatitis B reactivation is a common complication in lymphoma patients under immunosuppressive treatment with potentially serious and life-threating consequences. In this review, we discuss the basis of chronic Hepatitis B virus (HBV) infection, the definition and risk factors for HBV reactivation. We overview the management of HBV reactivation based on virological status and immunosuppressive regimen risk stratification. We also highlight and update information about the HBV reactivation in lymphoma patients under novel agent treatment, including newer monoclonal antibodies, small molecule inhibitors, and even chimeric antigen receptor T-cell immunotherapy.
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31
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Chang SC, Tsai CY, Liu KH, Wang SY, Hsu JT, Yeh TS, Yeh CN. Everolimus Related Fulminant Hepatitis in Pancreatic Neuroendocrine Tumor With Liver Metastases: A Case Report and Literature Review. Front Endocrinol (Lausanne) 2021; 12:639967. [PMID: 33868173 PMCID: PMC8047461 DOI: 10.3389/fendo.2021.639967] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/24/2020] [Accepted: 03/03/2021] [Indexed: 12/30/2022] Open
Abstract
BACKGROUND Everolimus, an immunosuppressant, is approved for the treatment of advanced renal cell carcinoma, metastatic hormone receptor-positive breast cancer, and pancreatic neuroendocrine tumors (P-NETs) but has been reported to be related to hepatitis B reactivation. Here, we present the first case of fatal fulminant hepatitis B reactivation in a man with P-NET accompanied by multiple liver metastases who received everolimus and octreotide long-acting repeatable (LAR). CASE PRESENTATION A 45-year-old male had a history of chronic hepatitis B infection. He was found to have a complicated liver cyst incidentally, and then he underwent biopsy, which disclosed a grade 2 neuroendocrine tumor (NET). Subsequent MRI of the abdomen and PET revealed a solid mass at the pancreatic tail with numerous liver tumors favoring metastases and peripancreatic lymph node metastases. Transarterial chemoembolization (TACE) of the right lobe of the liver was performed, and he started to take 5 mg everolimus twice a day and 20 mg octreotide LAR every month 8 days after the 1st TACE. No hepatitis B virus (HBV) prophylaxis treatment was administered. He then underwent laparoscopic distal pancreatectomy and splenectomy three and half months after the initial treatment of everolimus. He continued everolimus 5 mg twice a day and octreotide 20 mg every month after the operation. Three months later, hepatic failure occurred due to acute hepatitis B flare-up-related fulminant hepatic failure since other possible causes of hepatic failure were excluded. Five days after hepatic failure presented, hepatic failure was apparent, and pulseless ventricular tachycardia occurred. The patient expired after failed resuscitation. CONCLUSION A literature review of everolimus-related hepatitis B reactivation was conducted. In P-NET patients with chronic hepatitis B who will undergo everolimus treatment, HBV prophylaxis should be considered since fatal hepatitis B reactivation might occur under rare conditions.
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Affiliation(s)
| | | | | | | | | | | | - Chun-Nan Yeh
- Department of General Surgery, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan
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Sundaram S, Patil P, Sengar M, Rathod R, Mehta S. A survey of clinical practices among oncologists regarding hepatitis B screening in patients with cancer. Indian J Med Res 2021; 151:604-608. [PMID: 32719235 PMCID: PMC7602929 DOI: 10.4103/ijmr.ijmr_2327_18] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022] Open
Abstract
Background & objectives: Screening for hepatitis B prior to the initiation of chemotherapy in patients with cancer is recommended by all major hepatology and oncology societies. This study was aimed to determine the screening practices for hepatitis B among oncologists from India and their experience with hepatitis B reactivation. Methods: A questionnaire-based survey was conducted among oncologists attending the Evidence-Based Medicine Conference at Tata Memorial Centre, Mumbai, India. The questionnaire was developed in keeping with the recent guidelines for hepatitis B reactivation on chemotherapy, with questions regarding demographics, years in practice and hepatitis B screening practices and management. There was 78 per cent response rate to the questionnaire. Results: Most respondents were <35 yr of age (69%), with <five years of experience (39%), practicing in an academic institution (81%). Seventy four per cent respondents always screened their patients with cancer for hepatitis prior to chemotherapy, whereas 19 per cent in special settings and seven per cent never screened; 96 per cent respondents used hepatitis B surface antigen (HBsAg) as a screening test, while 17 per cent also used antibody to hepatitis B core antigen. Sixty one per cent respondents used entecavir or tenofovir for prophylaxis; 70 per cent continued prophylaxis till 6-12 months after completion of chemotherapy, while 21 per cent continued only till the end of chemotherapy. Interpretation & conclusions: More than 25 per cent of the oncologists were not screening their patients with cancer for viral hepatitis prior to cancer-directed therapy, and only 17 per cent of the oncologists used the recommended tests for screening. Better training of oncologists regarding viral hepatitis screening and management is needed.
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Affiliation(s)
- Sridhar Sundaram
- Department of Digestive Diseases & Clinical Nutrition, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Prachi Patil
- Department of Digestive Diseases & Clinical Nutrition, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Manju Sengar
- Department of Medical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Raosaheb Rathod
- Department of Digestive Diseases & Clinical Nutrition, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Shaesta Mehta
- Department of Digestive Diseases & Clinical Nutrition, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, Maharashtra, India
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33
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Reynolds G, Haeusler G, Slavin MA, Teh B, Thursky K. Latent infection screening and prevalence in cancer patients born outside of Australia: a universal versus risk-based approach? Support Care Cancer 2021; 29:6193-6200. [PMID: 33763725 DOI: 10.1007/s00520-021-06116-w] [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: 12/01/2020] [Accepted: 02/26/2021] [Indexed: 11/26/2022]
Abstract
PURPOSE Contention surrounds how best to screen patients for latent and undiagnosed infection prior to cancer treatment. Early treatment and prophylaxis against reactivation may improve infection-associated morbidity. This study sought to examine rates of screening and prevalence of latent infection in overseas-born patients receiving cancer therapies. METHODS A single-centre retrospective audit of 952 overseas-born patients receiving chemotherapy, targeted agents and immunotherapy between January 1 and December 31 2019 was undertaken at Peter MacCallum Cancer Centre. Pre-treatment screening for hepatitis B (HBV), hepatitis C (HCV), human immunodeficiency virus (HIV), latent tuberculosis (LTBI), toxoplasmosis and strongyloidiasis was audited. RESULTS Approximately half of our overseas-born patients were screened for HBV (58.9%) and HCV (50.7%). Fewer patients were screened for HIV (30.5%), LTBI (18.3%), strongyloidiasis (8.6%) or toxoplasmosis (8.1%). Although 59.7% of our patients were born in countries with high epidemiological risk for latent infection, according to World Health Organization data, 35% were not screened for any infection prior to commencement of therapy. CONCLUSION The prevalence of latent infections amongst overseas-born patients with cancer, and complexities associated with risk-based screening, likely supports universal latent infection screening amongst this higher-risk cohort.
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Affiliation(s)
- Gemma Reynolds
- Department of Infectious Diseases, Peter MacCallum Cancer Centre, 305 Grattan Street, Melbourne, Victoria, 3000, Australia.
| | - Gabrielle Haeusler
- Department of Infectious Diseases, Peter MacCallum Cancer Centre, 305 Grattan Street, Melbourne, Victoria, 3000, Australia
- Department of Infectious Diseases, Royal Children's Hospital, Melbourne, Victoria, Australia
- National Centre for Infections in Cancer, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
- Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Victoria, Australia
- Murdoch Children's Research Institute, Parkville, Victoria, Australia
| | - Monica A Slavin
- Department of Infectious Diseases, Peter MacCallum Cancer Centre, 305 Grattan Street, Melbourne, Victoria, 3000, Australia
- National Centre for Infections in Cancer, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
- Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Victoria, Australia
| | - Benjamin Teh
- Department of Infectious Diseases, Peter MacCallum Cancer Centre, 305 Grattan Street, Melbourne, Victoria, 3000, Australia
- National Centre for Infections in Cancer, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
- Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Victoria, Australia
| | - Karin Thursky
- Department of Infectious Diseases, Peter MacCallum Cancer Centre, 305 Grattan Street, Melbourne, Victoria, 3000, Australia
- National Centre for Infections in Cancer, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
- Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Victoria, Australia
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34
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Reagan PM, Neelapu SS. How I Manage: Pathophysiology and Management of Toxicity of Chimeric Antigen Receptor T-Cell Therapies. J Clin Oncol 2021; 39:456-466. [DOI: 10.1200/jco.20.01616] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Affiliation(s)
- Patrick M. Reagan
- Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY
| | - Sattva S. Neelapu
- Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX
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35
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Wu Y, Huang H, Luo Y. Management of Hepatitis B Virus in Allogeneic Hematopoietic Stem Cell Transplantation. Front Immunol 2021; 11:610500. [PMID: 33613534 PMCID: PMC7890023 DOI: 10.3389/fimmu.2020.610500] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2020] [Accepted: 12/22/2020] [Indexed: 12/16/2022] Open
Abstract
The high morbidity of HBV reactivation following allogeneic hematopoietic stem cell transplantation (allo-HSCT) is partially due to the intense immunologic potency of complex therapeutic regimens, the use of antithymocyte globulin and calcineurin inhibitors to prevent graft versus-host disease (GVHD), prolonged immune reconstitution, and hematological malignancies infected with hepatitis B virus (HBV). Immunosuppression results in the reactivation of HBV replication from covalently closed circular DNA (cccDNA) residing in hepatocytes. However, the role of viral mutations during HBV reactivation needs to be validated. All individuals scheduled to receive allo-HSCT or wish to donate stem cells should be screened for hepatitis B surface antigen (HBsAg), antibodies to hepatitis B core (anti-HBc), and HBV-DNA. HBsAg-positive recipients of allo-HSCT have a high risk of HBV reactivation; thus, they should receive prophylactic antiviral therapy. The high barrier to resistance nucleos(t)-ide analogs (NAs) seems to be superior to the low barrier agents. Resolved-HBV recipients have a lower risk of HBV reactivation than HBsAg-positive recipients. Although prophylactic antiviral therapy remains controversial, regular monitoring of alanine transaminase (ALT) and HBV-DNA combined with preemptive antiviral treatment may be an optimized strategy. However, optimal antiviral therapy duration and time intervals for monitoring remain to be established. Accepting stem cells from HBsAg-positive donors is associated with a risk of developing HBV-related hepatitis. The overall intervention strategy, including donors and recipients, may decrease the risk of HBV-related hepatitis following HSCT from HBsAg positive stem cells. In this review, we summarize the issues of HBV in allo-HSCT, including HBV reactivation mechanism, HBsAg-positive recipients, HBV-resolved infection recipients, and donor-related factors, and discuss their significance.
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Affiliation(s)
- Yibo Wu
- Bone Marrow Transplantation Center, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Institute of Hematology, Zhejiang University, Hangzhou, China
- Zhejiang Laboratory for Systems & Precision Medicine, Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Hangzhou, China
- Zhejiang Laboratory for Systems & Precision Medicine, Zhejiang University Medical Center, Hangzhou, China
| | - He Huang
- Bone Marrow Transplantation Center, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Institute of Hematology, Zhejiang University, Hangzhou, China
- Zhejiang Laboratory for Systems & Precision Medicine, Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Hangzhou, China
- Zhejiang Laboratory for Systems & Precision Medicine, Zhejiang University Medical Center, Hangzhou, China
| | - Yi Luo
- Bone Marrow Transplantation Center, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Institute of Hematology, Zhejiang University, Hangzhou, China
- Zhejiang Laboratory for Systems & Precision Medicine, Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Hangzhou, China
- Zhejiang Laboratory for Systems & Precision Medicine, Zhejiang University Medical Center, Hangzhou, China
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36
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Garcia-Horton A, Smith E, Maze D, McNamara C, Sibai H, Gupta V. Risk of hepatitis B virus reactivation in HBsAg-negative, anti-HBc-positive patients with myeloproliferative neoplasms treated with ruxolitinib. Leuk Lymphoma 2021; 62:495-497. [PMID: 33459565 DOI: 10.1080/10428194.2020.1832671] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Affiliation(s)
- Alejandro Garcia-Horton
- Medical Oncology and Hematology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Canada
| | - Elliot Smith
- Medical Oncology and Hematology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Canada
| | - Dawn Maze
- Medical Oncology and Hematology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Canada
| | - Caroline McNamara
- Medical Oncology and Hematology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Canada
| | - Hassan Sibai
- Medical Oncology and Hematology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Canada
| | - Vikas Gupta
- Medical Oncology and Hematology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Canada
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Udompap P, Kim WR. Hepatitis B Virus Reactivation and Management of Patients Undergoing Immunosuppression. HEPATITIS B VIRUS AND LIVER DISEASE 2021:427-454. [DOI: 10.1007/978-981-16-3615-8_18] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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38
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Hwang JP, Feld JJ, Hammond SP, Wang SH, Alston-Johnson DE, Cryer DR, Hershman DL, Loehrer AP, Sabichi AL, Symington BE, Terrault N, Wong ML, Somerfield MR, Artz AS. Hepatitis B Virus Screening and Management for Patients With Cancer Prior to Therapy: ASCO Provisional Clinical Opinion Update. J Clin Oncol 2020; 38:3698-3715. [PMID: 32716741 PMCID: PMC11828660 DOI: 10.1200/jco.20.01757] [Citation(s) in RCA: 100] [Impact Index Per Article: 20.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/02/2020] [Indexed: 12/13/2022] Open
Abstract
PURPOSE This Provisional Clinical Opinion update presents a clinically pragmatic approach to hepatitis B virus (HBV) screening and management. PROVISIONAL CLINICAL OPINION All patients anticipating systemic anticancer therapy should be tested for HBV by 3 tests-hepatitis B surface antigen (HBsAg), hepatitis B core antibody (anti-HBc) total immunoglobulin (Ig) or IgG, and antibody to hepatitis B surface antigen-but anticancer therapy should not be delayed. Findings of chronic HBV (HBsAg-positive) or past HBV (HBsAg-negative and anti-HBc-positive) infection require HBV reactivation risk assessment.Patients with chronic HBV receiving any systemic anticancer therapy should receive antiviral prophylactic therapy through and for minimum 12 months following anticancer therapy. Hormonal therapy alone should not pose a substantial risk of HBV reactivation in patients with chronic HBV receiving hormonal therapy alone; these patients may follow noncancer HBV monitoring and treatment guidance. Coordination of care with a clinician experienced in HBV management is recommended for patients with chronic HBV to determine HBV monitoring and long-term antiviral therapy after completion of anticancer therapy.Patients with past HBV infection undergoing anticancer therapies associated with a high risk of HBV reactivation, such as anti-CD20 monoclonal antibodies or stem-cell transplantation, should receive antiviral prophylaxis during and for minimum 12 months after anticancer therapy completion, with individualized management thereafter. Careful monitoring may be an alternative if patients and providers can adhere to frequent, consistent follow-up so antiviral therapy may begin at the earliest sign of reactivation. Patients with past HBV undergoing other systemic anticancer therapies not clearly associated with a high risk of HBV reactivation should be monitored with HBsAg and alanine aminotransferase during cancer treatment; antiviral therapy should commence if HBV reactivation occurs.Additional information is available at www.asco.org/supportive-care-guidelines.
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Affiliation(s)
- Jessica P Hwang
- The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Jordan J Feld
- Toronto Centre for Liver Disease, University Health Network, University of Toronto, Toronto, Ontario, Canada
| | | | - Su H Wang
- Saint Barnabas Medical Center, Florham Park, NJ
| | | | | | - Dawn L Hershman
- Herbert Irving Comprehensive Cancer Center at Columbia University, New York, NY
| | | | | | | | - Norah Terrault
- Keck School of Medicine, University of Southern California, Los Angeles, CA
| | - Melisa L Wong
- University of California San Francisco, San Francisco, CA
| | | | - Andrew S Artz
- City of Hope Comprehensive Cancer Center, Duarte, CA
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39
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Ziogas DC, Kostantinou F, Cholongitas E, Anastasopoulou A, Diamantopoulos P, Haanen J, Gogas H. Reconsidering the management of patients with cancer with viral hepatitis in the era of immunotherapy. J Immunother Cancer 2020; 8:jitc-2020-000943. [PMID: 33067316 PMCID: PMC7570225 DOI: 10.1136/jitc-2020-000943] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/10/2020] [Indexed: 12/15/2022] Open
Abstract
In the evolving immune-oncology landscape, numerous patients with cancer are constantly treated with immune checkpoint inhibitors (ICPIs) but among them, only sporadic cases with pre-existing hepatitis B virus (HBV) and hepatitis C virus (HCV) are recorded. Despite the global dissemination of HBV and HCV infections, viral hepatitis-infected patients with cancer were traditionally excluded from ICPIs containing trials and current evidence is particularly limited in case reports, retrospective cohort studies and in few clinical trials on advanced hepatocellular carcinoma. Thus, many concerns still remain about the overall oncological management of this special subpopulation, including questions about the efficacy, toxicity and reactivation risks induced by ICPIs. Here, we examine the natural course of both HBV and HCV in cancer environment, review the latest antiviral guidelines for patients undergoing systematic cancer therapies, estimating treatment-related immunosuppression and relocate immunotherapy in this therapeutic panel. Among the ICPIs-treated cases with prior viral hepatitis, we focus further on those experienced HBV or HCV reactivation and discuss their host, tumor and serological risk factors, their antiviral and immunological management as well as their hepatitis and tumor outcome. Based on a low level of evidence, immunotherapy in these specific cancer cases seems to be associated with no inferior efficacy and with a relevantly low reactivation rate. However, hepatitis reactivation and subsequent irreversible complications appeared to have poor response to deferred antiviral treatment. While, the prophylactic use of modern antiviral drugs could eliminate or diminish up front the viral load in most cases, leading to cure or long-term hepatitis control. Taking together the clinical significance of preventive therapy, the low but existing reactivation risk and the potential immune-related hepatotoxicity, a comprehensive baseline assessment of liver status, including viral hepatitis screening, before the onset of immunotherapy should be suggested as a reasonable and maybe cost-effective strategy but the decision to administer ICPIs and the necessity of prophylaxis should always be weighed at a multidisciplinary level and be individualized in each case, up to be established by future clinical trials.
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Affiliation(s)
- Dimitrios C Ziogas
- First Department of Medicine, National and Kapodistrian University of Athens School of Medicine, Athens, Greece
| | - Frosso Kostantinou
- First Department of Medicine, National and Kapodistrian University of Athens School of Medicine, Athens, Greece
| | - Evangelos Cholongitas
- First Department of Medicine, National and Kapodistrian University of Athens School of Medicine, Athens, Greece
| | - Amalia Anastasopoulou
- First Department of Medicine, National and Kapodistrian University of Athens School of Medicine, Athens, Greece
| | - Panagiotis Diamantopoulos
- First Department of Medicine, National and Kapodistrian University of Athens School of Medicine, Athens, Greece
| | - John Haanen
- Division of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Helen Gogas
- First Department of Medicine, National and Kapodistrian University of Athens School of Medicine, Athens, Greece
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40
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Dimond C, Negroiu A, M Hughes D, Patel J. Fatal hepatitis B reactivation in a patient receiving chemoradiation for cervical cancer. J Oncol Pharm Pract 2020; 27:1296-1301. [PMID: 33054690 DOI: 10.1177/1078155220964256] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
INTRODUCTION Hepatitis B virus (HBV) infection remains a global public health threat, with approximately 257 million people suffering from chronic HBV infection worldwide in 2015. HBV reactivation is a known complication of immunosuppressive therapy in people suffering with chronic HBV. Medications commonly associated with HBV reactivation include B-cell depleting agents and anthracycline derivatives. There have been very few documented cases of chemoradiation inducing HBV reactivation among scientific literature. CASE REPORT A 44-year-old woman with chronic HBV infection and [FIGO] stage IIIB cervical cancer developed marked transaminitis and increased HBV viral load after receiving treatment with three doses of cisplatin and one dose of carboplatin with concurrent radiation for cervical cancer.Management and outcome: The patient was admitted for acute liver failure and quickly developed encephalopathy, with treatment complicated by coagulopathy, hypoglycemia, and metabolic acidosis. The patient remained unresponsive to maximal therapeutic efforts and was mechanically ventilated for airway protection. She subsequently died after experiencing ventricular tachycardia followed by asystole. DISCUSSION There are currently no standardized guidelines for the screening of HBV infection or prophylaxis treatment algorithm for patients undergoing chemoradiation. When initiating treatment with immunosuppressive therapy, it is important to screen all patients for chronic HBV infection and to work with an interdisciplinary team of oncologists, hepatologists, and pharmacists to initiate prophylactic antiviral therapy and closely monitor to minimize the risk of HBV reactivation.
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Affiliation(s)
- Colin Dimond
- Department of Pharmacy, Boston Medical Center, Boston, MA, USA.,Department of Pharmacy Practice, University of the Pacific, Stockton, CA, USA
| | - Andreea Negroiu
- Department of Medicine, Boston University School of Medicine and Boston Medical Center, Boston, MA, USA
| | - David M Hughes
- Department of Pharmacy, Boston Medical Center, Boston, MA, USA
| | - Jasmine Patel
- Department of Pharmacy, Boston Medical Center, Boston, MA, USA
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41
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Dutcher J. Management of hepatitis B in the era of checkpoint inhibition. J Immunother Cancer 2020; 8:jitc-2019-000276. [PMID: 32051288 PMCID: PMC7057540 DOI: 10.1136/jitc-2019-000276] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/22/2020] [Indexed: 01/04/2023] Open
Abstract
Hepatitis B virus (HBV) is a major global health concern, affecting more than 350 million people worldwide. Its management in the setting of cancer treatment can be problematic, particularly with the use of immunological treatment modalities, but also with chemotherapy. Immunological perturbations by chemo or immunotherapy have the potential to permit viral hepatitis reactivation and acute hepatic failure. HBV management algorithms have evolved, based on host tumor factors, viral serological factors, and the specific antitumor agents planned. As new agents enter the antitumor armamentarium, their impact on HBV infection needs to be defined. Zhang et al provide data on the utility of antiviral therapy in the management of HBV antigen positive patients receiving checkpoint inhibitors (CPIs) in preventing hepatitis reactivation, and offers guidance for such management in endemic areas, suggesting that prophylaxis is highly effective in preventing reactivation. This is pertinent to Western cancer therapy also, as a recent study has documented the silent existence of positive hepatitis antigenemia among newly diagnosed cancer patients. Whereas antigen and viral DNA screening is standard of care in Asia and Western Pacific oncology practice, evaluation for latent hepatitis may become a necessary part of management worldwide as CPIs continue to expand their role.
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Affiliation(s)
- Janice Dutcher
- Cancer Research Foundation of NY, New York, New York, USA
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42
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Wu Y, Shi J, Tan Y, Zhao Y, Yu J, Lai X, Yang L, Huang H, Luo Y. A Novel Strategy for the Prevention of Hepatitis B Virus-Related Hepatitis Following Allogeneic Hematopoietic Stem Cell Transplantation from Hepatitis B Surface Antigen-Positive Donors. Biol Blood Marrow Transplant 2020; 26:1719-1728. [DOI: 10.1016/j.bbmt.2020.05.004] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2020] [Revised: 04/19/2020] [Accepted: 05/06/2020] [Indexed: 12/17/2022]
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Ludwig H, Boccadoro M, Moreau P, San-Miguel J, Cavo M, Pawlyn C, Zweegman S, Facon T, Driessen C, Hajek R, Dimopoulos MA, Gay F, Avet-Loiseau H, Terpos E, Zojer N, Mohty M, Mateos MV, Einsele H, Delforge M, Caers J, Weisel K, Jackson G, Garderet L, Engelhardt M, van de Donk N, Leleu X, Goldschmidt H, Beksac M, Nijhof I, Abildgaard N, Bringhen S, Sonneveld P. Recommendations for vaccination in multiple myeloma: a consensus of the European Myeloma Network. Leukemia 2020; 35:31-44. [PMID: 32814840 PMCID: PMC7787974 DOI: 10.1038/s41375-020-01016-0] [Citation(s) in RCA: 93] [Impact Index Per Article: 18.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2020] [Revised: 07/24/2020] [Accepted: 08/05/2020] [Indexed: 12/11/2022]
Abstract
Vaccination is one of the most successful medical interventions that has saved the life of millions of people. Vaccination is particularly important in patients with multiple myeloma, who have an increased risk of infections due to the disease-inherent immune suppression, and because of the immune suppressive effects of therapy. Hence, all appropriate measures should be exploited, to elicit an effective immune response to common pathogens like influenza, pneumococci, varicella zoster virus, and to those bacteria and viruses (haemophilus influenzae, meningococci, and hepatitis) that frequently may pose a significant risk to patients with multiple myeloma. Patients after autologous, and specifically after allogeneic transplantation have severely reduced antibody titers, and therefore require a broader spectrum of vaccinations. Response to vaccination in myeloma often is less vigorous than in the general population, mandating either measurement of the postvaccination antibody titers and/or repeating the vaccination. Here, we compile the existing data on vaccination in multiple myeloma and provide recommendations for clinical practice.
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Affiliation(s)
- Heinz Ludwig
- Wilhelminen Cancer Research Institute, c/o 1st Department of Medicine, Center for Oncology, Hematology, and Palliative Care, Clinic Ottakring, Vienna, Austria.
| | - Mario Boccadoro
- Myeloma Unit, Division of Hematology, Azienda Ospedaliero-Universitaria Città della Salute e della Scienza, Torino, Italy
| | - Philippe Moreau
- Service hematologie et thérapie cellulaire, PRC. cic 1402 Inserm, CHU poitiers, Poitiers, France
| | - Jesus San-Miguel
- CIMA, IDISNA, CIBERONC, Clínica Universidad de Navarra, Pamplona, Spain
| | - Michele Cavo
- Seràgnoli Institute of Hematology, Bologna University School of Medicine, Bologna, Italy
| | | | - Sonja Zweegman
- Department of Hematology, Amsterdam UMC, VU University, Amsterdam, The Netherlands
| | - Thierry Facon
- Hôpital Claude Huriez, Lille University Hospital, Lille, France
| | - Christoph Driessen
- Department of Medical Oncology and Hematology, Cantonal Hospital St Gallen, St Gallen, Switzerland
| | - Roman Hajek
- Department of Hematooncology, University Hospital Ostrava and Faculty of Medicine, University of Ostrava, Ostrava, Czech Republic
| | - Melitios A Dimopoulos
- Hematology & Medical Oncology, Department of Clinical Therapeutics, National and Kapodistrian University of Athens, Athens, Greece
| | - Francesca Gay
- Myeloma Unit, Division of Hematology, Azienda Ospedaliero-Universitaria Città della Salute e della Scienza, Torino, Italy
| | | | - Evangelos Terpos
- Hematology & Medical Oncology, Department of Clinical Therapeutics, National and Kapodistrian University of Athens, Athens, Greece
| | - Niklas Zojer
- 1st Department of Medicine, Center for Hematology, Oncology, and Palliatic Care, Clinic Ottakring, Vienna, Austria
| | - Mohamad Mohty
- Department of Clinical Hematology and Cellular Therapy, Hospital Saint-Antoine, Sorbonne University, Paris, France
| | | | - Hermann Einsele
- Department of Internal Medicine II, University Hospital Würzburg, Würzburg, Germany
| | | | - Jo Caers
- Department of Clinical Hematology, CHU of Liège, Liège, Belgium
| | - Katja Weisel
- II. Medizinische Klinik und Poliklinik, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany
| | - Graham Jackson
- NCCC, Newcastle upon Tyne Hospitals Trust, Newcastle upon Tyne, UK
| | - Laurent Garderet
- INSERM, UMR_S 938, Centre de Recherche Saint-Antoine-Team Proliferation and Differentiation of Stem Cells, Assistance Publique-Hôpitaux de Paris, Hôpital Pitié Salpêtrière, Service d'Hématologie, Sorbonne Université, Paris, France
| | - Monika Engelhardt
- Interdisciplinary Tumor Center, Faculty of Freiburg, University of Freiburg, Freiburg, Germany
| | - Niels van de Donk
- Department of Hematology, Amsterdam UMC, VU University, Amsterdam, The Netherlands
| | | | - Hartmut Goldschmidt
- Internal Medicine V and National Center for Tumor Diseases (NCT), University Hospital Heidelberg, Heidelberg, Germany
| | - Meral Beksac
- Department of Hematology, Ankara University, Ankara, Turkey
| | - Inger Nijhof
- Department of Hematology, Amsterdam UMC, VU University, Amsterdam, The Netherlands
| | - Niels Abildgaard
- Department of Hematology, Odense University Hospital, University of Southern Denmark, Odense, Denmark
| | - Sara Bringhen
- Myeloma Unit, Division of Hematology, Azienda Ospedaliero-Universitaria Città della Salute e della Scienza, Torino, Italy
| | - Pieter Sonneveld
- Erasmus MC Cancer Institute, Erasmus University of Rotterdam, Rotterdam, The Netherlands
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Hwang JP, LoConte NK, Rice JP, Foxhall LE, Sturgis EM, Merrill JK, Torres HA, Bailey HH. Oncologic Implications of Chronic Hepatitis C Virus Infection. J Oncol Pract 2020; 15:629-637. [PMID: 31825756 DOI: 10.1200/jop.19.00370] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Chronic hepatitis C virus (HCV) infection increases the risk for several types of cancer, including hepatocellular carcinoma (HCC) and B-cell non-Hodgkin lymphoma, as primary and second primary malignancies. HCV-infected patients with cancer, particularly those undergoing anticancer therapy, are at risk for development of enhanced HCV replication, which can lead to hepatitis flare and progression of liver fibrosis or cirrhosis. Risk factors for HCV infection include injection drug use, blood transfusion, or solid organ transplantation before 1992, receipt of clotting factor concentrates before 1987, long-term hemodialysis, chronic liver disease, HIV positivity, and occupational exposure. Widely available direct-acting antivirals are highly effective against HCV and well tolerated. Identification of HCV-infected individuals is the essential first step in treatment and eradication of the infection. One-time screening is recommended for persons born from 1945 to 1965; screening is also recommended for persons with risk factors. Recently, a public health recommendation has been drafted to screen all adults age 18 to 79 years. Two oncology organizations recommend screening all patients with hematologic malignancies and hematopoietic cell transplant recipients, and a recently published multicenter prospective study supports universal HCV screening for all patients with cancer. HCV screening entails testing for anti-HCV antibodies in serum and, when results are positive, HCV RNA quantitation to confirm infection. Direct-acting antiviral therapy eradicates HCV in almost all cases. Virologic cure of HCV prevents chronic hepatitis and progression to liver fibrosis or cirrhosis. HCV eradication also decreases the risk of developing HCV-associated primary and second primary malignancies, and it may allow HCV-infected patients access to important cancer clinical trials. Patients with HCV-related cirrhosis require lifelong surveillance for HCC, even after viral eradication.
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Affiliation(s)
| | | | - John P Rice
- University of Wisconsin School of Medicine and Public Health, Madison, WI
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Abstract
INTRODUCTION Hepatitis B virus (HBV) reactivation can be induced by treatments that attenuate the immunological control over HBV, leading to increased morbidity and mortality. The risk of HBV reactivation is determined by host immunity, viral factors, and the type and dose of treatments. Nevertheless, the risk of HBV reactivation for a growing number of novel therapies remains uncertain and needs to be carefully examined. Identification of patients at risk and administration of prophylactic antiviral agents are critical to prevent HBV reactivation. Early diagnosis and initiation of antiviral treatment are the keys to avoid devastating outcomes. AREA COVERED We summarized the latest evidence and recommendations for risk stratification, early diagnosis, prophylaxis, and management of HBV reactivation. EXPERT OPINION Universal screening, adequate prophylaxis, and close monitoring are essential for the prevention of HBV reactivation. Risk stratification of patients at risk with appropriate antiviral prophylaxis can prevent HBV reactivation effectively. Several emerging biomarkers have been proved to help determine the risk precisely. Early detection and timely administration of antiviral agents are crucial for management. Further studies on the precision of risk stratification as well as the optimal duration of prophylaxis and treatment are needed to establish an individualized strategy.
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Affiliation(s)
- Shang-Chin Huang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital , Taipei, Taiwan
| | - Hung-Chih Yang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital , Taipei, Taiwan.,Hepatitis Research Center, National Taiwan University Hospital , Taipei, Taiwan.,Department of Microbiology, National Taiwan University College of Medicine Taipei , Taiwan
| | - Jia-Horng Kao
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital , Taipei, Taiwan.,Hepatitis Research Center, National Taiwan University Hospital , Taipei, Taiwan.,Department of Medical Research, National Taiwan University Hospital , Taipei, Taiwan.,Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine , Taipei, Taiwan
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46
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Shah N, Aiello J, Avigan DE, Berdeja JG, Borrello IM, Chari A, Cohen AD, Ganapathi K, Gray L, Green D, Krishnan A, Lin Y, Manasanch E, Munshi NC, Nooka AK, Rapoport AP, Smith EL, Vij R, Dhodapkar M. The Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of multiple myeloma. J Immunother Cancer 2020; 8:e000734. [PMID: 32661116 PMCID: PMC7359060 DOI: 10.1136/jitc-2020-000734] [Citation(s) in RCA: 30] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/01/2020] [Indexed: 12/24/2022] Open
Abstract
Outcomes in multiple myeloma (MM) have improved dramatically in the last two decades with the advent of novel therapies including immunomodulatory agents (IMiDs), proteasome inhibitors and monoclonal antibodies. In recent years, immunotherapy for the treatment of MM has advanced rapidly, with the approval of new targeted agents and monoclonal antibodies directed against myeloma cell-surface antigens, as well as maturing data from late stage trials of chimeric antigen receptor CAR T cells. Therapies that engage the immune system to treat myeloma offer significant clinical benefits with durable responses and manageable toxicity profiles, however, the appropriate use of these immunotherapy agents can present unique challenges for practicing physicians. Therefore, the Society for Immunotherapy of Cancer convened an expert panel, which met to consider the current role of approved and emerging immunotherapy agents in MM and provide guidance to the oncology community by developing consensus recommendations. As immunotherapy evolves as a therapeutic option for the treatment of MM, these guidelines will be updated.
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Affiliation(s)
- Nina Shah
- Division of Hematology-Oncology, Department of Medicine, University of California San Francisco, San Francisco, California, USA
| | - Jack Aiello
- Patient Empowerment Network, San Jose, California, USA
| | - David E Avigan
- Division of Hematology and Hematologic Malignancies, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA
| | - Jesus G Berdeja
- Department of Medicine, Sarah Cannon Research Institute, Nashville, Tennessee, USA
| | - Ivan M Borrello
- Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center of Johns Hopkins, Baltimore, Maryland, USA
| | - Ajai Chari
- Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Adam D Cohen
- Department of Medicine, Abramson Cancer Center at the University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Karthik Ganapathi
- Department of Laboratory Medicine, University of California San Francisco, San Francisco, California, USA
| | - Lissa Gray
- University of California San Francisco, San Francisco, CA, USA
| | - Damian Green
- Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA
| | - Amrita Krishnan
- Department of Hematology and Hematopoietic Cell Transplantation, Judy and Bernard Briskin Multiple Myeloma Center for Clinical Research, City of Hope Comprehensive Cancer Center, Duarte, California, USA
| | - Yi Lin
- Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota, USA
- Division of Experimental Pathology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA
| | - Elisabet Manasanch
- Department of Lymphoma/Myeloma, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Nikhil C Munshi
- Jerome Lipper Multiple Myeloma Disease Center, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA
| | - Ajay K Nooka
- Department of Hematology/Oncology, Emory University, Atlanta, Georgia, USA
| | - Aaron P Rapoport
- University of Maryland Greenebaum Comprehensive Cancer Center, Baltimore, Maryland, USA
| | - Eric L Smith
- Myeloma Service and Cellular Therapeutics Center, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA
| | - Ravi Vij
- Division of Medical Oncology, Siteman Cancer Center, Washington University in Saint Louis School of Medicine, Saint Louis, Missouri, USA
| | - Madhav Dhodapkar
- School of Medicine, Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia, USA
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47
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Davis JS, Ferreira D, Paige E, Gedye C, Boyle M. Infectious Complications of Biological and Small Molecule Targeted Immunomodulatory Therapies. Clin Microbiol Rev 2020; 33:e00035-19. [PMID: 32522746 PMCID: PMC7289788 DOI: 10.1128/cmr.00035-19] [Citation(s) in RCA: 82] [Impact Index Per Article: 16.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
The past 2 decades have seen a revolution in our approach to therapeutic immunosuppression. We have moved from relying on broadly active traditional medications, such as prednisolone or methotrexate, toward more specific agents that often target a single receptor, cytokine, or cell type, using monoclonal antibodies, fusion proteins, or targeted small molecules. This change has transformed the treatment of many conditions, including rheumatoid arthritis, cancers, asthma, and inflammatory bowel disease, but along with the benefits have come risks. Contrary to the hope that these more specific agents would have minimal and predictable infectious sequelae, infectious complications have emerged as a major stumbling block for many of these agents. Furthermore, the growing number and complexity of available biologic agents makes it difficult for clinicians to maintain current knowledge, and most review articles focus on a particular target disease or class of agent. In this article, we review the current state of knowledge about infectious complications of biologic and small molecule immunomodulatory agents, aiming to create a single resource relevant to a broad range of clinicians and researchers. For each of 19 classes of agent, we discuss the mechanism of action, the risk and types of infectious complications, and recommendations for prevention of infection.
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Affiliation(s)
- Joshua S Davis
- Department of Infectious Diseases and Immunology, John Hunter Hospital, Newcastle, NSW, Australia
- Global and Tropical Health Division, Menzies School of Health Research and Charles Darwin University, Darwin, NT, Australia
- School of Medicine and Public Health, University of Newcastle, Newcastle, NSW, Australia
| | - David Ferreira
- School of Medicine, University of New South Wales, Sydney, NSW, Australia
| | - Emma Paige
- Department of Infectious Diseases, Alfred Hospital, Melbourne, VIC, Australia
| | - Craig Gedye
- School of Medicine, University of New South Wales, Sydney, NSW, Australia
- Department of Oncology, Calvary Mater Hospital, Newcastle, NSW, Australia
| | - Michael Boyle
- Department of Infectious Diseases and Immunology, John Hunter Hospital, Newcastle, NSW, Australia
- School of Medicine and Public Health, University of Newcastle, Newcastle, NSW, Australia
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Hwang JP, Huang D, Vierling JM, Suarez-Almazor ME, Shih YCT, Chavez-MacGregor M, Duan Z, Giordano SH, Hershman DL, Fisch MJ, Cantor SB. Cost-Effectiveness Analysis of Hepatitis B Virus Screening and Management in Patients With Hematologic or Solid Malignancies Anticipating Immunosuppressive Cancer Therapy. JCO Clin Cancer Inform 2020; 3:1-12. [PMID: 30892921 DOI: 10.1200/cci.18.00097] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022] Open
Abstract
PURPOSE National hepatitis B virus (HBV) screening recommendations for patients with cancer anticipating systemic anticancer therapy range from universal screening to screening based on risk of HBV infection, cancer therapy-specific risk of HBV reactivation, or both. We conducted cost-effectiveness analyses to identify optimal HBV screening strategies. PATIENTS AND METHODS We constructed decision-analytic models to analyze three strategies (no screening, universal screening, and selective screening based on use of an HBV infection risk tool) for hypothetic cohorts of patients anticipating anticancer therapy at high or lower risk for HBV reactivation. Model parameters were drawn from previously published studies, the SEER-Medicare database, and other online resources. Outcomes included lifetime expected cost, quality-adjusted life expectancy, and incremental cost-effectiveness ratio, measured in US dollars required to gain an additional quality-adjusted life-year (QALY). RESULTS For patients at high reactivation risk, universal screening dominated (ie, was cheaper and more effective than) the other two strategies. Universal screening was associated with a gain in life expectancy of 0.01 QALY compared with no screening and cost $76.06 less than no screening and $4.34 less than selective screening. For those at lower reactivation risk, universal screening still dominated selective screening; however, the incremental cost-effectiveness ratio of the universal screening strategy compared with no screening was $186,917 per QALY gained. CONCLUSION Universal HBV screening is cost effective and cheaper for patients receiving anticancer therapy associated with a high reactivation risk. For patients receiving anticancer therapy associated with a lower reactivation risk, universal screening is not cost effective.
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Affiliation(s)
| | - Danmeng Huang
- University of Texas MD Anderson Cancer Center, Houston, TX
| | | | | | | | | | - Zhigang Duan
- University of Texas MD Anderson Cancer Center, Houston, TX
| | | | - Dawn L Hershman
- Herbert Irving Comprehensive Cancer Center, Columbia University, New York, NY
| | | | - Scott B Cantor
- University of Texas MD Anderson Cancer Center, Houston, TX
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Konijeti GG, Grandhe S, Tincopa M, Lane JA, Shrime MG, Singh S, Loomba R. Cost-Effectiveness Analysis of Screening for Hepatitis B Virus Infection in Patients With Solid Tumors Before Initiating Chemotherapy. Clin Gastroenterol Hepatol 2020; 18:1600-1608.e4. [PMID: 31678602 DOI: 10.1016/j.cgh.2019.10.039] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/01/2018] [Revised: 10/19/2019] [Accepted: 10/25/2019] [Indexed: 12/12/2022]
Abstract
BACKGROUND & AIMS Patients with solid tumors who undergo chemotherapy have an increased risk of hepatitis B virus (HBV) reactivation, but a low proportion of these patients are screened for HBV infection and guidelines make conflicting recommendations. Further, the cost-effectiveness of newer treatments for HBV prophylaxis has not been examined for this population. We aimed to analyze the cost-effectiveness of HBV screening before chemotherapy for patients with solid tumors. METHODS We compared 3 HBV screening strategies (screen all, screen only high-risk patients, or screen none) using a Markov model of a population of adults in the United States who initiated chemotherapy for a solid tumor. We modeled use of entecavir prophylaxis for HB surface antigen (HBsAg)-positive patients and surveillance for HBsAg-negative patients who are positive for HBV core antibody. The Markov cycle length was 1 year, with model simulation for up to 5 years. RESULTS The screen all strategy was the most cost effective, with an incremental cost-effectiveness ratio of $42,761 compared to screening only high-risk patients. The screen none strategy was less effective and less costly than screening all patients or only high-risk patients. The screen-all strategy was the most cost effective for all estimates of prevalence of HBsAg-positive patients and estimates of HBV reactivation in HBsAg-positive patients. Screening only high-risk patients was the most cost-effective strategy when more than 25% of high-risk patients were screened for HBV infection. CONCLUSIONS In a Markov model analysis, we found screening all patients with solid tumors for HBV infection before chemotherapy to be the most cost-effective strategy. Guidelines should consider recommending HBV tests for patients initiating chemotherapy.
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Affiliation(s)
| | - Sirisha Grandhe
- Division of Gastroenterology, University of California, Davis, Sacramento, California
| | - Monica Tincopa
- Division of Gastroenterology, University of Michigan, Ann Arbor, Michigan
| | - Jill A Lane
- Division of Gastroenterology, Scripps Clinic, La Jolla, California
| | - Mark G Shrime
- Program in Global Surgery and Social Change, Harvard Medical School, Boston, Massachusetts
| | - Siddharth Singh
- Division of Gastroenterology, University of California, San Diego, La Jolla, California
| | - Rohit Loomba
- Division of Gastroenterology, University of California, San Diego, La Jolla, California.
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Immune checkpoint inhibition for non-small cell lung cancer in patients with pulmonary tuberculosis or Hepatitis B: Experience from a single Asian centre. Lung Cancer 2020; 146:145-153. [PMID: 32540557 DOI: 10.1016/j.lungcan.2020.05.020] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2020] [Revised: 05/09/2020] [Accepted: 05/12/2020] [Indexed: 12/20/2022]
Abstract
BACKGROUND The importance of immune-checkpoint inhibitors (ICI) can no longer be understated since its move to front-line treatment in non-small cell lung cancer (NSCLC) in recent years. However, the safety and efficacy of ICI in special populations such as those with infections like tuberculosis (TB) and hepatitis B (HBV) remain unknown as they are routinely excluded from clinical trials. METHODS Records of patients with advanced NSCLC who were treated with ICI from January 2014 to June 2019 at a single Asian centre were reviewed. Those with a history of HBV and/or TB were selected. In this group, safety and treatment outcomes including overall survival (OS), progression-free survival (PFS) and response rate were reported and compared against control. RESULTS 191 patients received ICI, 47 (24.6%) had a history of TB/HBV. The median PFS in those with a history of TB/HBV was 5.7 months (95% CI 3.9-7.6), compared to 3.1 months (95% CI 2.4-3.8) in control (HR 0.61, 95% CI 0.39-0.93, p = 0.021). Median OS was 15.6 months (95% CI 10.2-21.0) compared to 11.1 months (95% CI 7.6-14.7 months) in the control group (HR 0.58, 95% CI 0.34-0.99, p = 0.046). Adverse events of any grade (G) were similar in both groups; slightly more patients with TB/HBV experienced G3 or higher adverse events. Four patients developed TB after initiation of ICI, none with previously documented TB experienced reactivation. Of the 42 patients with a history of HBV, eight had inactive chronic HBV and six had detectable viral load. None of the 34 patients who were previously exposed to HBV had reactivation. CONCLUSION The use of ICI appears to be safe and efficacious in patients with TB/HBV infection. Prospective studies are required to identify those at risk in order to optimise care to these groups of patients.
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