|
1
|
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: 78] [Impact Index Per Article: 15.6] [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.
Collapse
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
| |
Collapse
|
|
2
|
|
|
3
|
Yu F, Huang Y, Wang Y, Yu Z, Li X, Dong J. Very late onset post-transplant diffuse large B cell lymphoma in a liver transplant recipient with hepatitis B: A case report. Medicine (Baltimore) 2018; 97:e13063. [PMID: 30383683 PMCID: PMC6221709 DOI: 10.1097/md.0000000000013063] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
RATIONALE Post transplantation lymphoproliferative disorder (PTLD) is a rare but severe complication. Epstein-Barr virus (EBV) is considered an important pathogen for PTLD and EBV deoxyribonucleic acid (DNA) load is widely monitored to detect PTLD early. Hepatitis B virus (HBV) infection is rarely reported to be related with PTLD. We report a case of EBV negative (EBV), HBV positive (HBV) diffuse large B cell lymphoma in a patient 12 years after liver transplantation. PATIENT CONCERNS AND DIAGNOSIS A 52-year-old man complained of worsening appetite, abdominal distension, and pruritus. Abdominal computed tomography (CT) detected a huge retroperitoneal mass and pathology of the fine needle biopsy established the diagnosis of diffuse large B cell lymphoma. Virology showed active hepatitis B viral duplication and EBV DNA was negative. INTERVENTION Treatment modalities for this patient included: reduction and subsequent cessation of immunosuppression; antiviral therapy for HBV with entecavir and adefovir; conventional chemotherapy consisting of cyclophosphamide, epirubicin, vindesine, and prednisone, followed by radiotherapy. He achieved complete remission (CR) and was kept on entecavir treatment afterwards. OUTCOMES He has been in remission for 2 years. LESSONS HBV infection might have played some role in this very late onset EBV PTLD patient. Therefore, HBV serology and HBV load should be monitored during the follow-up of HBV surface antigen positive (HBsAg) transplant recipients and life-long antiviral therapy is required.
Collapse
Affiliation(s)
- Fan Yu
- Department of Hematology and Oncology
| | | | | | - Zhuo Yu
- Department of Hematology and Oncology
| | | | - Jiahong Dong
- Department of Hepatobiliary and Pancreatic Surgery, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China
| |
Collapse
|
|
4
|
Ozoya OO, Chavez J, Sokol L, Dalia S. Optimizing antiviral agents for hepatitis B management in malignant lymphomas. ANNALS OF TRANSLATIONAL MEDICINE 2017; 5:39. [PMID: 28251118 DOI: 10.21037/atm.2016.12.25] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
The global scale of hepatitis B infection is well known but its impact is still being understood. Missed hepatitis B infection impacts lymphoma therapy especially increased risk of hepatitis B virus (HBV) reactivation and poor treatment outcomes. The presence of undiagnosed chronic hepatitis also undermines chronic HBV screening methods that are based on a positive HBsAg alone. The goal of this review is to evaluate the literature for optimizing antiviral therapy for lymphoma patients with HBV infection or at risk of HBV reactivation. Relevant articles for this review were identified by searching PubMed, Embase, Ovid Medline, and Scopus using the following terms, alone and in combination: "chronic hepatitis B", "occult hepatitis B", "special groups", "malignant lymphoma", "non-Hodgkin's lymphoma", "Hodgkin's lymphoma", "immunocompromised host", "immunosuppressive agents", "antiviral", "HBV reactivation". The period of the search was restricted to a 15-year period to limit the search to optimizing antiviral agents for HBV infection in malignant lymphomas [2001-2016]. Several clinical practice guidelines recommend nucleos(t)ide analogues-entecavir, tenofovir and lamivudine among others. These agents are best initiated along with or prior to immunosuppressive therapy. Additional methods recommended for optimizing antiviral therapy include laboratory modalities such as HBV genotyping, timed measurements of HBsAg and HBV DNA levels to measure and predict antiviral treatment response. In conclusion, optimizing antiviral agents for these patients require consideration of geographic prevalence of HBV, cost of antiviral therapy or testing, screening modality, hepatitis experts, type of immunosuppressive therapy and planned duration of therapy.
Collapse
Affiliation(s)
| | - Julio Chavez
- Department of Hematological Malignancies, H. Lee Moffitt Cancer Center, Tampa, FL, USA
| | - Lubomir Sokol
- Department of Hematological Malignancies, H. Lee Moffitt Cancer Center, Tampa, FL, USA
| | - Samir Dalia
- Oncology and Hematology, Mercy Clinic Joplin, Joplin, MO, USA
| |
Collapse
|
|
5
|
Ozoya OO, Sokol L, Dalia S. Hepatitis B Reactivation with Novel Agents in Non-Hodgkin's Lymphoma and Prevention Strategies. J Clin Transl Hepatol 2016; 4:143-50. [PMID: 27350944 PMCID: PMC4913070 DOI: 10.14218/jcth.2016.00005] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/13/2016] [Revised: 04/25/2016] [Accepted: 04/26/2016] [Indexed: 12/12/2022] Open
Abstract
Hepatitis B virus (HBV) infection remains an endemic disease in most parts of the world despite available prophylactic vaccines. Non-Hodgkin's lymphoma is the most common hematological malignancy, and certain patients undergoing therapy are at increased risk of HBV reactivation. Rituximab, a monoclonal antibody, is well studied in HBV reactivation, but newer agents have been implicated as well. Here, we review novel agents suspected in HBV reactivation and effective strategies to prevent HBV reactivation. Fifteen years of literature were reviewed in order to better understand the reactivation rates of hepatitis B in patients with non-Hodgkin's lymphoma. Anti-CD20 antibodies continue to be the main medications that can lead to HBV reactivation, and HBV reactivation rates have decreased with increased awareness. HBV reactivation is uncommon when using other novel agents. Entecavir and lamivudine remain the agents of choice to prevent HBV reactivation in high risk patients. In conclusion, the immunosuppressive effect of NHL and its therapy provide a pathway for HBV reactivation, especially in patients treated with anti-CD20 antibody. Since many HBV positive patients are often excluded from clinical trials of novel agents in NHL, more aggressive post-market surveillance of new agents, well-designed best practice advisories, and timely case reports are needed to reduce the incidence of HBV reactivation. Lastly, large prospective investigations coupled with well-utilized best practice advisories need to be conducted to understand the impact of more potent novel NHL therapy on HBV reactivation.
Collapse
Affiliation(s)
| | - Lubomir Sokol
- Department of Hematological Malignancies, H. Lee Moffitt Cancer Center, Tampa, FL, USA
| | - Samir Dalia
- Oncology and Hematology, Mercy Clinic Joplin, Joplin, MO, USA
- *Correspondence to: Samir Dalia, Oncology and Hematology, Mercy Clinic Joplin, 100 Mercy Way, Joplin, MO 64804, USA. Tel: +1-417-782-7722, Fax: +1-417-556-3063, E-mail: or
| |
Collapse
|
|
6
|
Pattullo V. Prevention of Hepatitis B reactivation in the setting of immunosuppression. Clin Mol Hepatol 2016; 22:219-37. [PMID: 27291888 PMCID: PMC4946398 DOI: 10.3350/cmh.2016.0024] [Citation(s) in RCA: 85] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2016] [Accepted: 04/27/2016] [Indexed: 12/13/2022] Open
Abstract
Advances in the treatment of malignant and inflammatory diseases have developed over time, with increasing use of chemotherapeutic and immunosuppressive agents of a range of drug classes with varying mechanism and potency in their effects on the immune system. These advances have been met with the challenge of increased risk of hepatitis B virus (HBV) reactivation in susceptible individuals. The magnitude of risk of HBV reactivation is associated with the individual’s HBV serological status and the potency and duration of immunosuppression. Individuals with chronic hepatitis B (CHB) and previously infected but serologically cleared HBV infection are both susceptible to HBV reactivation. HBV reactivation in the setting of immunosuppression is a potentially life threatening condition leading to liver failure and death in extreme cases. It is important to recognize that HBV reactivation in the setting of immunosuppression is potentially preventable. Therefore, identification of patients at risk of HBV reactivation and institution of prophylactic antiviral therapy prior to initiation of immunosuppression is essential.
Collapse
Affiliation(s)
- Venessa Pattullo
- Department of Gastroenterology, Royal North Shore Hospital, Sydney, Australia
| |
Collapse
|
|
7
|
Tsutsumi Y, Yamamoto Y, Ito S, Ohigashi H, Shiratori S, Naruse H, Teshima T. Hepatitis B virus reactivation with a rituximab-containing regimen. World J Hepatol 2015; 7:2344-2351. [PMID: 26413224 PMCID: PMC4577642 DOI: 10.4254/wjh.v7.i21.2344] [Citation(s) in RCA: 57] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/20/2015] [Revised: 07/27/2015] [Accepted: 09/08/2015] [Indexed: 02/06/2023] Open
Abstract
Rituximab is currently used not only in the treatment of B-cell lymphoma but also for various other diseases, including autoimmune diseases, post-transplant graft vs host disease, and rejection following kidney transplants. Due to rituximab’s widespread use, great progress has been made regarding research into complications that arise from its use, one of the most serious being the reactivation of hepatitis B virus (HBV), and efforts continue to establish guidelines for preventive treatment against this occurrence. This report discusses preventive measures against rituximab-induced HBV reactivation and future objectives.
Collapse
|
|
8
|
Pattullo V. Hepatitis B reactivation in the setting of chemotherapy and immunosuppression - prevention is better than cure. World J Hepatol 2015; 7:954-967. [PMID: 25954478 PMCID: PMC4419099 DOI: 10.4254/wjh.v7.i7.954] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/02/2014] [Revised: 01/16/2015] [Accepted: 02/12/2015] [Indexed: 02/06/2023] Open
Abstract
Due to the inherent relationship between the immune system and the hepatitis B virus (HBV) in exposed and infected individuals, immunomodulation associated with the treatment of solid tumours, haematological malignancies and inflammatory disorders has been linked to HBV reactivation (HBVr). Reactivation of HBV infection in the setting of chemotherapy and immunosuppression may lead to fulminant liver failure and death, but there is a cumulative body of evidence that these are potentially preventable adverse outcomes. As chronic hepatitis B is largely asymptomatic but also endemic worldwide, clinicians caring for patients requiring chemotherapy or immunosuppression need to be vigilant of the potential for HBVr in susceptible individuals. Serological screening and prophylactic and pre-emptive antiviral treatment with a nucleos(t)ide analogue should be considered in appropriate settings. Hepatitis B prevalence is examined in this review article, as are the risks of HBVr in patients receiving chemo- and immunosuppressive therapy. Recommendations regarding screening, monitoring and the role of antiviral prophylaxis are outlined with reference to current international associations’ guidelines and the best available evidence to date.
Collapse
|
|
9
|
Feld JJ. HBV treatment in a patient who will be receiving immunosuppressive therapy. Clin Liver Dis (Hoboken) 2013; 2:34-37. [PMID: 30992818 PMCID: PMC6448607 DOI: 10.1002/cld.157] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Affiliation(s)
- Jordan J. Feld
- From the Toronto Western Hospital Liver Center, Sandra Rotman Centre for Global Health, University of Toronto, Toronto, Ontario, Canada
| |
Collapse
|