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Tobaiqy M, Helmi N, MacLure K, Saade S. The prevalence of hepatic and thyroid toxicity associated with imatinib treatment of chronic myeloid leukaemia: a systematic review. Int J Clin Pharm 2024; 46:368-381. [PMID: 38147280 DOI: 10.1007/s11096-023-01671-0] [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: 11/10/2023] [Accepted: 11/13/2023] [Indexed: 12/27/2023]
Abstract
BACKGROUND Imatinib, a potent inhibitor of targeted protein tyrosine kinases, treats chronic myeloid leukaemia (CML). Data on imatinib-associated changes in hepatic and thyroid functions are limited and conflicting. AIM To report the prevalence of hepatic and thyroid toxicity associated with the use of imatinib in CML patients. METHOD Articles for the systematic review were selected from electronic databases (PubMed, CINALH, Web of Science). Readily accessible peer-reviewed full articles in English published 1st January 2000 to 18th July 2023 were included. The search terms included combinations of: imatinib, CML, liver toxicity, hepatic toxicity, thyroid toxicity. Screening of titles, abstracts, full text articles was conducted independently by two reviewers. Inclusions and exclusions were recorded following PRISMA guidelines. Detailed reasons for exclusion were recorded. Included articles were critically appraised. RESULTS Ten thousand one hundred and twenty-three CML patients were reported in the 82 included studies corresponding to 21 case reports, 2 case series, 39 clinical trials and 20 observational studies were selected. Excluding case studies/reports, 1268 (12.6%; n = 1268/10046) hepatotoxicity adverse events were reported, of which 64.7% were rated as mild grade I & II adverse events, 363 (28.6%) as severe, grade III and IV adverse events; some led to treatment discontinuation, liver transplantation and fatal consequences. Twenty (35.1%) studies reported discontinuation of imatinib treatment due to the severity of hepatic toxicity. Fourteen (8.4%, n = 14/167) thyroid dysfunction adverse events were reported. CONCLUSION High frequency of mild and severe hepatotoxicity, associated with imatinib in CML patients, was reported in the published literature. Low numbers of mild and manageable thyroid toxicity events were reported.
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Affiliation(s)
- Mansour Tobaiqy
- Department of Pharmacology, College of Medicine, University of Jeddah, Jeddah, Saudi Arabia.
| | - Nawal Helmi
- Department of Biochemistry, College of Sciences, University of Jeddah, Jeddah, Saudi Arabia
| | | | - Sylvia Saade
- Health and Sciences Department, American University of Science and Technology, Beirut, Lebanon
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2
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Cheng J, Pan J, Zhao D, Ma X, Sun Q, Li J. HCV Reactivation in a Patient with Hepatocellular Carcinoma Due to Sorafenib: A Case Report. Int Med Case Rep J 2024; 17:121-124. [PMID: 38370606 PMCID: PMC10870992 DOI: 10.2147/imcrj.s444521] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2023] [Accepted: 02/01/2024] [Indexed: 02/20/2024] Open
Abstract
The global prevalence of hepatitis C virus (HCV) infection is approximately 3%, with a post-infection chronicity rate of up to 50%-85%. HCV reactivation can occur when anti-HCV positive individuals receive antineoplastic therapy. In this study, we report a case of an anti-HCV positive patient with negative HCV RNA after 12 weeks of direct antiviral therapy. Two months later, sorafenib was used to treat hepatocellular carcinoma, and HCV reactivation occurred after 8 months of the treatment. HCV RNA was negative after 12 weeks of antiviral treatment with Sofosbuvir-velpatasvir. We also discussed the mechanism of HCV reactivation caused by sorafenib and the antiviral treatment regimen after HCV reactivation with the relevant literature.
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Affiliation(s)
- Jun Cheng
- Department of Infectious Disease, The First Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China
| | - Jinjin Pan
- Department of Infectious Disease, The First Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China
| | - Dongmei Zhao
- Department of Infectious Disease, The First Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China
| | - Xuejiao Ma
- Department of Infectious Disease, The First Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China
| | - Qiulin Sun
- Department of Infectious Disease, The First Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China
| | - Jiabin Li
- Department of Infectious Disease, The First Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China
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3
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Wang LY, Chu SC, Chang IY, Chan KA. Sex-specific incidence of hepatitis B virus flares among Bcr-Abl tyrosine kinase inhibitor users in Taiwan. Pharmacoepidemiol Drug Saf 2023; 32:1368-1377. [PMID: 37463800 DOI: 10.1002/pds.5667] [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: 11/14/2022] [Revised: 06/13/2023] [Accepted: 07/04/2023] [Indexed: 07/20/2023]
Abstract
BACKGROUND The use of Bcr-Abl TKI was found to be associated with hepatitis B (HBV) flares, with a more profound risk observed in females. This study was conducted to characterize the clinical features of patients with HBV flare among Bcr-Abl TKI users, to estimate sex-specific incidence rates of HBV flare, and to evaluate potential cumulative effect of Bcr-Abl TKI. METHODS Bcr-Abl TKI users with chronic HBV infection were identified from Taiwan's National Health Insurance database. The HBV flare cases were identified within the cohort. Incidence rates of HBV flare between men and women were assessed. Nested case-control analysis was used to evaluate the cumulative effect of Bcr-Abl TKI use on HBV flare. RESULTS Among 415 patients with chronic HBV infection treated with Bcr-Abl TKI from 2005 through 2018, 45 flare cases (28 males and 17 females) were identified. Days between Bcr-Abl TKI initiation and HBV flare was 319 days in women compared to 610 days in men. 66.7% of the flares occurred during TKI therapy. Twelve of the 45 patients died, half of them died around 6 months after hepatitis B flare. Incidence rates of HBV flare were 2.34 and 3.33 per 100 person-years in males and females, respectively. Higher incidence was observed among patients with chronic myeloid leukemia. Cumulative effect of Bcr-Abl TKI on HBV flare was not observed. CONCLUSION Approximately 10% of HBV carriers who used Bcr-Abl TKI experienced HBV flare in Taiwan. The risk was higher in women and among patients with chronic myeloid leukemia.
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Affiliation(s)
- Ling-Yi Wang
- Department of Pharmacy, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan
- Graduate Institute of Clinical Pharmacy, Tzu Chi University, Hualien, Taiwan
| | - Sung-Chao Chu
- Division of Hematology and Oncology, Department of Internal Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan
- School of Medicine, Tzu Chi University, Hualien, Taiwan
| | - I-Yun Chang
- National Taiwan University Health Data Research Center, Taipei City, Taiwan
| | - K Arnold Chan
- National Taiwan University Health Data Research Center, Taipei City, Taiwan
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4
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Aldapt MB, Al-Mashdali AF, Obeidat K, Chandra P, Yassin M. Viral Infections and Incidence of Reactivations in Chronic Myeloid Leukemia Patients. Oncology 2023; 102:380-388. [PMID: 37848004 PMCID: PMC10994575 DOI: 10.1159/000534266] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2023] [Accepted: 09/15/2023] [Indexed: 10/19/2023]
Abstract
BACKGROUND Viral infections remain a significant problem for patients with chronic myeloid leukemia (CML) who undergo stem cell transplants (SCTs). These infections often result from the reactivation of latent viruses. However, our understanding of the risk of viral reactivation in CML patients who have not undergone SCT is limited, and there is a scarcity of data on this topic. Tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of CML as it is highly successful and has transformed the prognosis of patients with CML. However, TKI may be associated with an increased risk of infections. SUMMARY We have performed a literature search for publications related to viral infections and their reactivations in patients with CML using PubMed, Scopus, and Google Scholar for the period 2001-2022. The population consisted of patients over 18 years old with a diagnosis of CML and no history of bone marrow transplantation. In an analysis of 41 patients, with 25 males and 16 females, M:F ratio of 1.56:1, and a median age of 50. Age ranged from 22 to 79 years. Most patients with reported viral infections or reactivations were in the chronic phase (CP) of CML, with 22 patients (76%) in the CP, 6 patients (21%) in the accelerated phase, and 1 patient (3%) in the blast phase. Most cases with reported outcomes responded to treatment for CML; only one had refractory disease and 8 cases (32%) had major molecular response. Imatinib was the most used TKI in 31 patients (77%). The most reported viral reactivations were herpes zoster in 17 cases (41%), followed by hepatitis B reactivation in 15 cases (37%). KEY MESSAGES This review sheds light on the importance of having a hepatitis B serology checked before starting TKI therapy and close monitoring for viral infections and reactivations in patients with CML.
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Affiliation(s)
- Mahmood B. Aldapt
- Department of Medicine, Unity Hospital, Rochester Regional Health, New York, NY, USA
| | - Abdulrahman F. Al-Mashdali
- Department of Medical Oncology/Hematology, National Center for Cancer Care and Research, Hamad Medical Corporation, Doha, Qatar
| | - Khaldun Obeidat
- Department of Medicine, John H. Stroger, Jr. Hospital of Cook County, Chicago, IL, USA
| | - Prem Chandra
- Medical Research Center, Hamad Medical Corporation, Doha, Qatar
| | - Mohamed Yassin
- Department of Medical Oncology/Hematology, National Center for Cancer Care and Research, Hamad Medical Corporation, Doha, Qatar
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Yu T, Li W, Yu T. Management of chronic myelogenous leukemia with COVID-19 and hepatitis B. Front Oncol 2023; 13:1217023. [PMID: 37601670 PMCID: PMC10438954 DOI: 10.3389/fonc.2023.1217023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2023] [Accepted: 07/13/2023] [Indexed: 08/22/2023] Open
Abstract
The application of immunosuppressive agents and targeted drugs has opened a novel approach for the treatment of hematological tumors, and the application of tyrosine kinase inhibitors for the treatment of chronic myeloid leukemia is one of the landmark breakthroughs that has considerably improved the prognosis of CML patients. However, with the extensive use of TKI, the co-infection of CML patients has become increasingly apparent, especially regarding infectious diseases such as hepatitis B and COVID-19. The underlying mechanism may be related to the inhibition of the immune function by TKI. Poor management, including disease progression due to the infectious disease or TKI dose reduction or discontinuation, may lead to adverse clinical outcomes and can even be life-threatening. Therefore, this review principally provides an overview of the pathogenesis and standardized management principles of CML patients with comorbid COVID-19 or hepatitis B in order to improve clinicians' awareness of the risks so as to more effectively diagnose and treat CML and improve the survival rate and quality of life of patients. In the past two decades, owing to the advent of imatinib, chronic myeloid leukemia (CML) has transformed into a chronic controllable disease, and even treatment-free remission can be anticipated. Earlier studies have indicated that tyrosine kinase inhibitor (TKI) exerts a peculiar inhibitory effect on the body's immune function. Therefore, with the widespread application of TKI, more and more attention has been paid to the comorbidity of infectious diseases in CML patients, especially in patients with progressive disease or non-remission. Despite some studies revealing that the proportion and severity of SARS-CoV-2 infection in CML patients receiving TKI treatment are lower than in patients with other hematological malignancies, CML patients with stable disease are still recommended to be vaccinated against SARS-CoV-2, while TKI may or may not be discontinued. Meanwhile, the management of CML patients during the epidemic of coronavirus disease 2019 (COVID-19) still necessitates further discussion. This article also provides an overview of TKI-related hepatitis B reactivation. If not managed, patients may face adverse consequences such as hepatitis B reactivation-related hepatitis, liver failure, and progression of CML after forced withdrawal of medication. Therefore, this review aimed to comprehensively describe the management of CML patients with comorbid COVID-19, the pathogenesis of hepatitis B reactivation, the indicated population for prophylactic antiviral therapy, the time of antiviral drug discontinuation, and drug selection.
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Affiliation(s)
- Tian Yu
- Department of Hematology, Affiliated Renhe Hospital of China Three Gorges University, Yichang, China
- College of Basic Medical Sciences, China Three Gorges University, Yichang, China
| | - Weiming Li
- Department of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Tao Yu
- Department of Hematology, Affiliated Renhe Hospital of China Three Gorges University, Yichang, China
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Kong JH, Jang JY, Ko TH, Kang SH, Kim Y. High rate of hepatitis B reactivation during tyrosine kinase inhibitor treatment among patients with chronic myeloid leukemia in Korea. Blood Res 2022; 57:290-293. [PMID: 36419239 PMCID: PMC9812728 DOI: 10.5045/br.2022.2022099] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2022] [Revised: 10/07/2022] [Accepted: 11/14/2022] [Indexed: 11/26/2022] Open
Affiliation(s)
- Jee Hyun Kong
- Department of Hematology-Oncology, Division of Internal Medicine, Wonju Severance Christian Hospital, Yonsei University Wonju College of Medicine, Wonju, Korea,Center of Evidence-Based Medicine, Institute of Convergence Science, Yonsei University, Seoul, Korea,Correspondence to: Jee Hyun Kong Department of Hematology-Oncology, Wonju Severance Christian Hospital, 20, Ilsan-ro, Wonju 26426, Korea, E-mail:
| | - Jae Yeon Jang
- Department of Hematology-Oncology, Division of Internal Medicine, Wonju Severance Christian Hospital, Yonsei University Wonju College of Medicine, Wonju, Korea
| | - Tae Hwa Ko
- Center of Biomedical Data Science, Yonsei University Wonju College of Medicine, Wonju, Korea
| | - Seong Hee Kang
- Department of Gastroenterology and Hepatology, Division of Internal Medicine, Wonju Severance Christian Hospital, Yonsei University Wonju College of Medicine, Wonju, Korea
| | - Yundeok Kim
- Department of Hematology-Oncology, Division of Internal Medicine, Wonju Severance Christian Hospital, Yonsei University Wonju College of Medicine, Wonju, Korea
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Chang Y, Jeong SW, Jang JY. Hepatitis B Virus Reactivation Associated With Therapeutic Interventions. Front Med (Lausanne) 2022; 8:770124. [PMID: 35096867 PMCID: PMC8795508 DOI: 10.3389/fmed.2021.770124] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2021] [Accepted: 12/20/2021] [Indexed: 12/14/2022] Open
Abstract
Hepatitis B virus (HBV) reactivation associated with various therapeutic interventions is an important cause of morbidity and mortality in patients with current or resolved HBV infection. Because no curative treatment for HBV infection is yet available, there are many individuals at risk for HBV reactivation in the general population. Populations at risk for HBV reactivation include patients who are currently infected with HBV or who have been exposed to HBV in the past. HBV reactivation and its potential consequences is a concern when these populations are exposed to anti-cancer chemotherapy, immunosuppressive or immunomodulatory therapies for the management of various malignancies, rheumatologic diseases, inflammatory bowel disease, or solid-organ or hematologic stem cell transplantation. Accordingly, it has become important to understand the basics of HBV reactivation and the mechanisms by which certain therapies are more susceptible to HBV reactivation. This review aims to raise the awareness of HBV reactivation and to understand the mechanisms and the risks of HBV reactivation in various clinical settings.
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Affiliation(s)
- Young Chang
- Department of Internal Medicine, Institute for Digestive Research, Digestive Disease Center, Soonchunhyang University College of Medicine, Seoul, South Korea
| | - Soung Won Jeong
- Department of Internal Medicine, Institute for Digestive Research, Digestive Disease Center, Soonchunhyang University College of Medicine, Seoul, South Korea
| | - Jae Young Jang
- Department of Internal Medicine, Institute for Digestive Research, Digestive Disease Center, Soonchunhyang University College of Medicine, Seoul, South Korea
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8
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Caviglia GP, Zorzi A, Rizzetto M, Mirandola M, Olivero A, Carolo G. Hepatitis B Virus Reactivation upon Immunosuppression: Is There a Role for Hepatitis B Core-Related Antigen in Patients with Immune-Escape Mutants? A Case Report. Diagnostics (Basel) 2021; 11:2185. [PMID: 34943420 PMCID: PMC8700299 DOI: 10.3390/diagnostics11122185] [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] [Received: 10/22/2021] [Revised: 11/21/2021] [Accepted: 11/23/2021] [Indexed: 01/06/2023] Open
Abstract
The reactivation of hepatitis B virus (HBVr) in patients undergoing pharmacological immunosuppression is a potentially fatal clinical event that may occur in patients with overt or occult HBV infection. The risk of HBVr is mainly determined by the type of immunosuppressive therapy and the HBV serologic profile, with a higher risk in patients positive for the hepatitis B surface antigen (HBsAg), and a lower risk in HBsAg-negative/antibodies to core antigen-positive subjects. Notably, a considerable proportion of patients experiencing HBVr showed a high degree of variability of the HBV S gene, possibly leading to immune escape mutants. These mutations, usually in the "a-determinant" of the HBsAg, can cause diagnostic problems and consequently hamper the appropriate management strategy of patients at risk of HBVr. Here, we describe a case of HBVr in a patient with a diagnosis of chronic myeloid leukemia and a previous history of kidney transplant, providing evidence of the potential usefulness of hepatitis B core-related antigen measurement in patients with HBV immune-escape mutants at risk of viral reactivation.
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Affiliation(s)
| | - Antonella Zorzi
- Virology and Microbiology Unit, Department of Pathology and Diagnostics, Verona University Hospital, 37126 Verona, Italy;
| | - Mario Rizzetto
- Department of Medical Sciences, University of Turin, 10126 Turin, Italy;
| | - Massimo Mirandola
- Infectious Diseases Section, Department of Diagnostics and Public Health, University of Verona, 37134 Verona, Italy; (M.M.); (G.C.)
| | - Antonella Olivero
- Department of Medical Sciences, University of Turin, 10126 Turin, Italy;
| | - Giada Carolo
- Infectious Diseases Section, Department of Diagnostics and Public Health, University of Verona, 37134 Verona, Italy; (M.M.); (G.C.)
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9
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Konopleva MV, Belenikin MS, Shanko AV, Bazhenov AI, Kiryanov SA, Tupoleva TA, Sokolova MV, Pronin AV, Semenenko TA, Suslov AP. Detection of S-HBsAg Mutations in Patients with Hematologic Malignancies. Diagnostics (Basel) 2021; 11:diagnostics11060969. [PMID: 34072185 PMCID: PMC8228241 DOI: 10.3390/diagnostics11060969] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2021] [Revised: 05/21/2021] [Accepted: 05/24/2021] [Indexed: 01/04/2023] Open
Abstract
Multiple studies of hepatitis B virus (HBV) genetic variability and its relationship with the disease pathogenesis are currently ongoing, stemming from growing evidence of the clinical significance of HBV mutations. It is becoming increasingly evident that patients with hematologic malignancies may be particularly prone to a higher frequency of such mutations. The present report is the first extensive study of the prevalence of escape mutations in S-HBsAg, performed using isolates from 59 patients from hospital hematology departments with diagnoses of leukemia (n = 32), lymphoma (n = 20), multiple myeloma (n = 3), and non-tumor blood diseases (n = 4). The isolates were serologically examined for the presence of HBV markers and sequenced using either next-generation sequencing (NGS) or Sanger sequencing. Occult hepatitis B was found in 5.1% of cases. Genetic analysis of the region corresponding to S-HBsAg demonstrated an exceptionally high mutation frequency in patients with leukemias (93.4%) and lymphomas (85.0%), along with the prominent mutation heterogeneity. Additionally, more than 15 mutations in one sample were found in patients with leukemias (6.3% of cases) and lymphomas (5.0% of cases). Most of the mutations were clinically significant. The study analyzes the mutation profile of HBV in different oncohematological diseases and the frequency of individual mutations. The data strongly suggest that the NGS method, capable of detecting minor populations of HBV mutations, provides a diagnostic advantage, lays the foundation for the development of screening methods, and allows for the study of the virological and pathogenetic aspects of hepatitis B.
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Affiliation(s)
- Maria V. Konopleva
- Federal State Budget Institution “National Research Centre for Epidemiology and Microbiology Named After Honorary Academician N.F. Gamaleya” of the Ministry of Health of the Russian Federation, 123098 Moscow, Russia; (M.V.K.); (A.V.S.); (S.A.K.); (M.V.S.); (A.V.P.); (T.A.S.)
| | - Maxim S. Belenikin
- Laboratory of Molecular Medical Diagnostics, Moscow Institute of Physics and Technology, State University, 141701 Dolgoprudny, Russia;
| | - Andrei V. Shanko
- Federal State Budget Institution “National Research Centre for Epidemiology and Microbiology Named After Honorary Academician N.F. Gamaleya” of the Ministry of Health of the Russian Federation, 123098 Moscow, Russia; (M.V.K.); (A.V.S.); (S.A.K.); (M.V.S.); (A.V.P.); (T.A.S.)
| | - Alexey I. Bazhenov
- State Budget Institution “Research Institute of Emergency Medicine Named After N.V. Sklifosovsky” of the Moscow Department of Healthcare, 129010 Moscow, Russia;
| | - Sergei A. Kiryanov
- Federal State Budget Institution “National Research Centre for Epidemiology and Microbiology Named After Honorary Academician N.F. Gamaleya” of the Ministry of Health of the Russian Federation, 123098 Moscow, Russia; (M.V.K.); (A.V.S.); (S.A.K.); (M.V.S.); (A.V.P.); (T.A.S.)
| | | | - Maria V. Sokolova
- Federal State Budget Institution “National Research Centre for Epidemiology and Microbiology Named After Honorary Academician N.F. Gamaleya” of the Ministry of Health of the Russian Federation, 123098 Moscow, Russia; (M.V.K.); (A.V.S.); (S.A.K.); (M.V.S.); (A.V.P.); (T.A.S.)
| | - Alexander V. Pronin
- Federal State Budget Institution “National Research Centre for Epidemiology and Microbiology Named After Honorary Academician N.F. Gamaleya” of the Ministry of Health of the Russian Federation, 123098 Moscow, Russia; (M.V.K.); (A.V.S.); (S.A.K.); (M.V.S.); (A.V.P.); (T.A.S.)
| | - Tatyana A. Semenenko
- Federal State Budget Institution “National Research Centre for Epidemiology and Microbiology Named After Honorary Academician N.F. Gamaleya” of the Ministry of Health of the Russian Federation, 123098 Moscow, Russia; (M.V.K.); (A.V.S.); (S.A.K.); (M.V.S.); (A.V.P.); (T.A.S.)
| | - Anatoly P. Suslov
- Federal State Budget Institution “National Research Centre for Epidemiology and Microbiology Named After Honorary Academician N.F. Gamaleya” of the Ministry of Health of the Russian Federation, 123098 Moscow, Russia; (M.V.K.); (A.V.S.); (S.A.K.); (M.V.S.); (A.V.P.); (T.A.S.)
- Correspondence:
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10
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Mutation accumulation in cancer genes relates to nonoptimal outcome in chronic myeloid leukemia. Blood Adv 2021; 4:546-559. [PMID: 32045476 DOI: 10.1182/bloodadvances.2019000943] [Citation(s) in RCA: 42] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2019] [Accepted: 12/18/2019] [Indexed: 12/24/2022] Open
Abstract
Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm accounting for ∼15% of all leukemia. Progress of the disease from an indolent chronic phase to the more aggressive accelerated phase or blast phase (BP) occurs in a minority of cases and is associated with an accumulation of somatic mutations. We performed genetic profiling of 85 samples and transcriptome profiling of 12 samples from 59 CML patients. We identified recurrent somatic mutations in ABL1 (37%), ASXL1 (26%), RUNX1 (16%), and BCOR (16%) in the BP and observed that mutation signatures in the BP resembled those of acute myeloid leukemia (AML). We found that mutation load differed between the indolent and aggressive phases and that nonoptimal responders had more nonsilent mutations than did optimal responders at the time of diagnosis, as well as in follow-up. Using RNA sequencing, we identified other than BCR-ABL1 cancer-associated hybrid genes in 6 of the 7 BP samples. Uncovered expression alterations were in turn associated with mechanisms and pathways that could be targeted in CML management and by which somatic alterations may emerge in CML. Last, we showed the value of genetic data in CML management in a personalized medicine setting.
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11
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Ali Hailan YM, Mudawi D, Yassin MA. Chronic Myeloid Leukemia in a Patient with Hepatitis B Virus Infection: A Case Report. Case Rep Oncol 2021; 14:1004-1009. [PMID: 34326735 PMCID: PMC8299369 DOI: 10.1159/000516747] [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] [Received: 04/02/2021] [Accepted: 04/12/2021] [Indexed: 11/19/2022] Open
Abstract
Chronic myeloid leukemia (CML) is a myeloproliferative disorder diagnosed by demonstrating the Philadelphia chromosome (Ph) or the BCR-ABL fusion gene. Tyrosine kinase inhibitors (TKIs) are the standard of therapy. There are increasing reports of hepatitis B virus reactivation (HBVr) in patients on this treatment. We report a case of a 46-year-old male patient diagnosed to have CML in the chronic phase and resolved hepatitis B infection. He was treated with imatinib as upfront therapy for CML and with lamivudine as prophylaxis against HBVr. The patient tolerated both treatments well with no adverse effects. The aim is to address the deficiencies in the literature in regard to managing these patients, prevention, and follow-up.
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Affiliation(s)
| | - Deena Mudawi
- National Center for Cancer Care and Research, Hamad Medical Corporation, Doha, Qatar
| | - Mohamed A. Yassin
- National Center for Cancer Care and Research, Hamad Medical Corporation, Doha, Qatar
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12
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Wang LY, Chu SC, Lo Y, Yang YY, Chan KA. Association of Bcr-Abl Tyrosine Kinase Inhibitors With Hepatitis B Virus Reactivation Requiring Antiviral Treatment in Taiwan. JAMA Netw Open 2021; 4:e214132. [PMID: 33822067 PMCID: PMC8025118 DOI: 10.1001/jamanetworkopen.2021.4132] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
IMPORTANCE The US Food and Drug Administration (FDA) highlighted the potential risk of hepatitis B reactivation that was associated with Bcr-Abl tyrosine kinase inhibitor (TKI) treatment and has required updated product labels. OBJECTIVE To examine the association between hepatitis B flare and exposure to Bcr-Abl TKIs compared with non-Bcr-Abl TKIs. DESIGN, SETTING, AND PARTICIPANTS This nested case-control study included patients who entered a hepatitis B carrier cohort in Taiwan after January 1, 2005. Patients who received their first antiviral agents for hepatitis B flare for more than 28 days after the cohort entry date were included as case patients. For each case, a corresponding risk set was formed that included all eligible patients in the study cohort who had the same age (within 1 year), same sex, and were at risk of developing hepatitis B flare at the case date. As many as 10 control patients were randomly selected from the risk set for each case patient. TKIs were evaluated before the hepatitis B flare for case patients and before the corresponding index date for control patients. Data were collected from the Taiwan National Health Insurance research database from January 2000 to 2015. Data analysis was conducted from January to June 2019. EXPOSURE Use of Bcr-AbL TKIs. MAIN OUTCOMES AND MEASURES Conditional logistic regression was used to estimate the rate ratio for the association between hepatitis B flare and exposure to Bcr-Abl TKIs compared with non-Bcr-Abl TKIs. RESULTS Among 698 342 patients who carried incident hepatitis B virus, 66 702 patients with hepatitis B flare that required antiviral treatment (47 492 [71.2%] men; mean [SD] age at index date, 50.2 [13.8] years) were included as case patients, and 666 989 age and sex-matched patients (474 903 [71.2%] men; mean [SD] age, 50.2 [13.8] years) were included as control patients. Analysis revealed that Bcr-Abl TKI use during the previous 90 days was independently associated with a 56% higher risk of hepatitis B flare (adjusted rate ratio [aRR], 1.56; 95% CI, 1.11-2.20), and the aRR increased to 1.66 (95% CI, 1.20-2.28) for Bcr-Abl TKI use during the previous 365 days. Use of Bcr-AbL TKIs during the previous 60 days was associated with a significantly increased risk of flare among women (aRR, 3.20; 95% CI, 1.70-6.03) but not among men (aRR, 1.14; 95% CI, 0.72-1.81). CONCLUSIONS AND RELEVANCE These findings suggest that sex-specific strategies may be needed to monitor for hepatitis B reactivation among patients receiving Bcr-Abl TKIs.
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Affiliation(s)
- Ling-Yi Wang
- Epidemiology and Biostatistics Consulting Center, Department of Medical Research, Buddhist Tzu Chi General Hospital, Hualien, Taiwan
- Department of Pharmacology, School of Medicine, College of Medicine, Tzu Chi University, Hualien, Taiwan
- Department of Pharmacy, Buddhist Tzu Chi General Hospital, Hualien, Taiwan
| | - Sung-Chao Chu
- Department of Hematology and Oncology, Buddhist Tzu Chi General Hospital, Hualien, Taiwan
| | - Yin Lo
- Department of Pharmacy, National Taiwan University Hospital
| | - Yen-Yun Yang
- Health Data Research Center, National Taiwan University
| | - K. Arnold Chan
- Health Data Research Center, National Taiwan University
- Department of Medical Research, National Taiwan University Hospital
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Cheng X, Uchida T, Xia Y, Umarova R, Liu CJ, Chen PJ, Gaggar A, Suri V, Mücke MM, Vermehren J, Zeuzem S, Teraoka Y, Osawa M, Aikata H, Tsuji K, Mori N, Hige S, Karino Y, Imamura M, Chayama K, Liang TJ. Diminished hepatic IFN response following HCV clearance triggers HBV reactivation in coinfection. J Clin Invest 2021; 130:3205-3220. [PMID: 32163375 DOI: 10.1172/jci135616] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2019] [Accepted: 03/05/2020] [Indexed: 12/12/2022] Open
Abstract
In patients with HBV and HCV coinfection, HBV reactivation leading to severe hepatitis has been reported with the use of direct-acting antivirals (DAAs) to treat HCV infection. Here we studied the molecular mechanisms behind this viral interaction. In coinfected cell culture and humanized mice, HBV replication was suppressed by HCV coinfection. In vitro, HBV suppression was attenuated when interferon (IFN) signaling was blocked. In vivo, HBV viremia, after initial suppression by HCV superinfection, rebounded following HCV clearance by DAA treatment that was accompanied by a reduced hepatic IFN response. Using blood samples of coinfected patients, IFN-stimulated gene products including C-X-C motif chemokine 10 (CXCL10), C-C motif chemokine ligand 5 (CCL5), and alanine aminotransferase (ALT) were identified to have predictive value for HBV reactivation after HCV clearance. Taken together, our data suggest that HBV reactivation is a result of diminished hepatic IFN response following HCV clearance and identify serologic markers that can predict HBV reactivation in DAA-treated HBV-HCV-coinfected persons.
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Affiliation(s)
- Xiaoming Cheng
- Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, Maryland, USA
| | - Takuro Uchida
- Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, Maryland, USA.,Department of Gastroenterology and Metabolism, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Yuchen Xia
- Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, Maryland, USA
| | - Regina Umarova
- Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, Maryland, USA
| | - Chun-Jen Liu
- Graduate Institute of Clinical Medicine, Hepatitis Research Center and Department of Internal Medicine, National Taiwan University College of Medicine and Hospital, Taipei, Taiwan
| | - Pei-Jer Chen
- Graduate Institute of Clinical Medicine, Hepatitis Research Center and Department of Internal Medicine, National Taiwan University College of Medicine and Hospital, Taipei, Taiwan
| | - Anuj Gaggar
- Gilead Sciences, Foster City, California, USA
| | | | - Marcus M Mücke
- Department of Internal Medicine 1, University Hospital Frankfurt, Frankfurt, Germany
| | - Johannes Vermehren
- Department of Internal Medicine 1, University Hospital Frankfurt, Frankfurt, Germany
| | - Stefan Zeuzem
- Department of Internal Medicine 1, University Hospital Frankfurt, Frankfurt, Germany
| | - Yuji Teraoka
- Department of Gastroenterology and Metabolism, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Mitsutaka Osawa
- Department of Gastroenterology and Metabolism, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Hiroshi Aikata
- Department of Gastroenterology and Metabolism, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Keiji Tsuji
- Department of Gastroenterology, Hiroshima Red Cross Hospital and Atomic-bomb Survivors Hospital, Hiroshima, Japan
| | - Nami Mori
- Department of Gastroenterology, Hiroshima Red Cross Hospital and Atomic-bomb Survivors Hospital, Hiroshima, Japan
| | - Shuhei Hige
- Department of Hepatology, Sapporo Kosei General Hospital, Sapporo, Japan
| | - Yoshiyasu Karino
- Department of Hepatology, Sapporo Kosei General Hospital, Sapporo, Japan
| | - Michio Imamura
- Department of Gastroenterology and Metabolism, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Kazuaki Chayama
- Department of Gastroenterology and Metabolism, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - T Jake Liang
- Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, Maryland, USA
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14
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Tan BK, Chua SS, Chen LC, Chang KM, Balashanker S, Bee PC. Acceptability of pharmacist-led interventions to resolve drug-related problems in patients with chronic myeloid leukaemia. J Oncol Pharm Pract 2020; 27:1644-1656. [PMID: 33040675 DOI: 10.1177/1078155220964539] [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: 11/16/2022]
Abstract
PURPOSE Chronic myeloid leukaemia (CML) patients on long-term tyrosine kinase inhibitor (TKI) therapy are susceptible to drug-related problems (DRPs). This study aimed to evaluate the acceptability and outcomes of pharmacist-led interventions on DRPs encountered by CML patients. METHODS This study included participants from the intervention arm of a randomised controlled trial which was conducted to evaluate the effects of pharmacist-led interventions on CML patients treated with TKIs. Participants were recruited and followed up in the haematology clinics of two hospitals in Malaysia from March 2017 to January 2019. A pharmacist identified DRPs and helped to resolve them. Patients were followed-up for six months, and their DRPs were assessed based on the Pharmaceutical Care Network Europe Classification for DRP v7.0. The identified DRPs, the pharmacist's interventions, and the acceptance and outcomes of the interventions were recorded. A Poisson multivariable regression model was used to analyse factors associated with the number of identified DRPs per participant. RESULTS A total of 198 DRPs were identified from 65 CML patients. The median number of DRPs per participants was 3 (interquartile range: 2, 4). Most participants (97%) had at least one DRP, which included adverse drug events (45.5%), treatment ineffectiveness (31.5%) and patients' treatment concerns or dissatisfaction (23%). The 228 causes of DRPs identified comprised the following: lack of disease or treatment information, or outcome monitoring (47.8%), inappropriate drug use processes (23.2%), inappropriate patient behaviour (19.9%), suboptimal drug selection (6.1%), suboptimal dose selection (2.6%) and logistic issues in dispensing (0.4%). The number of concomitant medications was significantly associated with the number of DRPs (adjusted Odds Ratio: 1.100; 95% CI: 1.005, 1.205; p = 0.040). Overall, 233 interventions were made. These included providing patient education on disease states or TKI-related side effects (75.1%) and recommending appropriate instructions for taking medications (7.7%). Of the 233 interventions, 94.4% were accepted and 83.7% were implemented by the prescriber or patient. A total of 154 DRPs (77.3%) were resolved. CONCLUSIONS The pharmacist-led interventions among CML patients managed to identify various DRPs, were well accepted by both TKI prescribers and patients, and had a high success rate of resolving the DRPs.
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Affiliation(s)
- Bee Kim Tan
- School of Pharmacy, Faculty of Health and Medical Sciences, Taylor's University, Subang Jaya, Malaysia.,Department of Medicine, Faculty of Medicine, 37447University of Malaya, Kuala Lumpur, Malaysia
| | - Siew Siang Chua
- School of Pharmacy, Faculty of Health and Medical Sciences, Taylor's University, Subang Jaya, Malaysia
| | - Li-Chia Chen
- Centre for Pharmacoepidemiology and Drug Safety, Division of Pharmacy and Optometry, School of Health Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK
| | - Kian Meng Chang
- Department of Hematology, 26691Ministry of Health Malaysia, Ampang Hospital, Ampang Jaya, Malaysia
| | - Sharmini Balashanker
- School of Pharmacy, University of Nottingham Malaysia Campus, Semenyih, Malaysia
| | - Ping Chong Bee
- Department of Medicine, Faculty of Medicine, 37447University of Malaya, Kuala Lumpur, Malaysia
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15
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Ekpanyapong S, Reddy KR. Hepatitis B Virus Reactivation: What Is the Issue, and How Should It Be Managed? Clin Liver Dis 2020; 24:317-333. [PMID: 32620274 DOI: 10.1016/j.cld.2020.04.002] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Hepatitis B virus (HBV) reactivation, in the background of cleared and overt chronic HBV infection, can be seen in patients receiving immunosuppressive agents. Risk of reactivation is variably associated with HBV serologic status and types of immunosuppressive therapy. Prevention of HBV reactivation by antiviral prophylaxis is an effective strategy to reduce morbidity and mortality in those with immunocompromised states. This article defines HBV reactivation, discusses risk stratification and common medications that can induce HBV reactivation as well as guideline recommendations for prevention of HBV reactivation, and describes the prognosis and management of patients who experience HBV reactivation.
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Affiliation(s)
- Sirina Ekpanyapong
- Department of Medicine, Division of Gastroenterology and Hepatology, Vejthani Hospital, 1 Soi Lat Phrao 111, Khlong Chan, Bang Kapi District, Bangkok 10240, Thailand
| | - K Rajender Reddy
- Department of Medicine, Division of Gastroenterology and Hepatology, University of Pennsylvania, 3400 Spruce Street, 2 Dulles HUP, Philadelphia, PA 19104, USA.
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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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17
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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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18
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Management of Hepatitis B Virus Infection and Prevention of Hepatitis B Virus Reactivation in Children With Acquired Immunodeficiencies or Undergoing Immune Suppressive, Cytotoxic, or Biological Modifier Therapies. J Pediatr Gastroenterol Nutr 2020; 70:527-538. [PMID: 31977956 DOI: 10.1097/mpg.0000000000002628] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Reactivation of hepatitis B virus (HBV) is a known complication of immune-suppressive, cytotoxic, and biological modifier therapies in patients currently infected with HBV or who have had past exposure to HBV. Nowadays, newer and emerging forms of targeted biologic therapies are available for the management of rheumatologic conditions, malignancies, inflammatory bowel disease, dermatologic conditions and solid-organ, bone marrow, or haematologic stem cell transplant but there is currently a lack of a systematic approach to the care of patients with or at risk of HBV reactivation. The Hepatology Committee of the European Society of Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) together with a working group of ESPGHAN members with clinical and research expertise in viral hepatitis developed an evidence-based position paper on reactivation of HBV infection in children identifying pertinent issues addressing the diagnosis, prevention, and treatment of this condition. Relevant clinical questions were formulated and agreed upon by all the members of the working group. Questions were answered and positions were based on evidence resulting from a systematic literature search on PubMed and Embase from their inception to July 1, 2019. A document was produced and the working group and ESPGHAN Hepatology Committee members voted on each recommendation, using a formal voting technique. A recommendation was accepted provided upon agreement by at least 75% of the working group members. This position paper provides a comprehensive update on the diagnosis, prevention and treatment of HBV reactivation in children.
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19
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Panagopoulos A, Taraviras S, Nishitani H, Lygerou Z. CRL4Cdt2: Coupling Genome Stability to Ubiquitination. Trends Cell Biol 2020; 30:290-302. [DOI: 10.1016/j.tcb.2020.01.005] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2019] [Revised: 01/12/2020] [Accepted: 01/14/2020] [Indexed: 12/20/2022]
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20
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High hepatitis B virus screening rate among patients receiving systemic anticancer treatment in Japan. Int J Clin Oncol 2020; 25:1327-1333. [PMID: 32200482 DOI: 10.1007/s10147-020-01655-4] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2019] [Accepted: 03/08/2020] [Indexed: 10/24/2022]
Abstract
BACKGROUND Patients with hepatitis B virus (HBV) infection have a risk of reactivation after chemotherapy. All patients undergoing chemotherapy should be screened for HBV infection. No large-scale studies have been conducted to examine HBV screening practice in Japan. METHODS We analyzed health insurance claims equivalent data linked with a nationwide hospital-based cancer registry. Patients diagnosed with cancer in 2014, who were aged 20 years and older and those who underwent systemic anticancer treatment in 2014-15 were included. We assessed the HBV screening rates by the HBsAg or anti-HBc tests, HBV-DNA tests, and entecavir prescriptions. Multiple logistic regression models were used to identify factors related to the receipt of screening. RESULTS Of 177,597 patients (mean [SD] age, 65.6 [12.2] years), 82.6% and 12.9% patients had a solid tumor and hematologic malignancy, respectively. Among them, 88.1%, 6.3%, and 5.5% received cytotoxic chemotherapy, targeted therapy, and anti-CD20 antibodies, respectively. Overall, 70.6% of patients were screened. The positive predictor of HBV screening was receiving anti-CD20 antibodies [odds ratio (OR); 2.23, 95% confidence interval (CI) 2.06-2.41, p < 0.001] and negative predictors were age ≥ 85 (OR 0.76, 95% CI 0.71-0.81), age 75-84 (OR 0.77, 95% CI 0.75-0.79) and targeted therapy (OR 0.69, 95% CI 0.67-0.72). Among the screened patients, 13.2% were tested for HBV-DNA, and 1.49% were prescribed entecavir. CONCLUSIONS The HBV screening rate in Japan is higher than in other countries. Further improvement of the HBV screening rate is needed to prevent reactivation and avoidable deaths of patients with HBV infection.
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21
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Riveiro-Barciela M, Gubern P, Roade L, Abrisqueta P, Carreras MJ, Farriols A, Bosch F, Esteban R, Buti M. An electronic alert system increases screening for hepatitis B and C and improves management of patients with haematological disorders. Sci Rep 2020; 10:3038. [PMID: 32080253 PMCID: PMC7033156 DOI: 10.1038/s41598-020-59476-4] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2019] [Accepted: 01/15/2020] [Indexed: 01/18/2023] Open
Abstract
Treatment of haematological disorders in patients with chronic hepatitis B or resolved infection (anti-HBc-positive) is associated with a risk of hepatitis B reactivation. Moreover, patients with chronic hepatitis C have a higher risk of haematological malignancies than general population. An electronic alert system was developed to promote screening of hepatitis B (HBV) and C (HCV) in patients starting haematological therapies. The system included screening and linkage to care and a request for testing in those without data. From March, 2017 to March, 2018 data from 420 consecutive patients with haematological diseases were included. At first prescription before the alerts, the HCV and HBV screening rate was 60.5%. Following the alerts, an additional 115 were screened, increasing the overall screening rate to 87.9%. Anti-HBc alone was detected in 57, anti-HCV in 13, and HBsAg in 2 patients. Overall, 68% of patients with any viral hepatitis markers were previously not know, and the impact was particularly important for anti-HBc detection (47/57 unknown). Nucleoside analogues were prescribed in 28 (49.1%) anti-HBc-positive and the 2 HBsAg-positive patients. Prospective follow-up with HBV DNA and HBsAg testing showed no cases of HBV reactivation. An estimated 1.2 HBV reactivations were avoided as consequence of the alert system. In summary, an electronic alert system increased viral hepatitis screening in patients receiving haematological treatment and led to improvements in the management of these patients, including avoided HBV reactivation.
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Affiliation(s)
- Mar Riveiro-Barciela
- Liver Unit, Internal Medicine Department, Vall d'Hebron Hospital, Barcelona, Spain.,Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain
| | - Paula Gubern
- Liver Unit, Internal Medicine Department, Vall d'Hebron Hospital, Barcelona, Spain
| | - Luisa Roade
- Liver Unit, Internal Medicine Department, Vall d'Hebron Hospital, Barcelona, Spain
| | - Pau Abrisqueta
- Department of Hematology, Vall d'Hebron Hospital, Barcelona, Spain
| | | | - Anna Farriols
- Pharmacy Department, Vall d'Hebron Hospital, Barcelona, Spain
| | - Francesc Bosch
- Department of Hematology, Vall d'Hebron Hospital, Barcelona, Spain
| | - Rafael Esteban
- Liver Unit, Internal Medicine Department, Vall d'Hebron Hospital, Barcelona, Spain.,Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain
| | - María Buti
- Liver Unit, Internal Medicine Department, Vall d'Hebron Hospital, Barcelona, Spain. .,Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain.
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22
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Atteya A, Ahmad A, Daghstani D, Mushtaq K, Yassin MA. Evaluation of Hepatitis B Reactivation Among Patients With Chronic Myeloid Leukemia Treated With Tyrosine Kinase Inhibitors. Cancer Control 2020; 27:1073274820976594. [PMID: 33297765 PMCID: PMC8480343 DOI: 10.1177/1073274820976594] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2020] [Revised: 11/04/2020] [Accepted: 11/05/2020] [Indexed: 02/06/2023] Open
Abstract
Hepatitis B reactivation (HBVr) in cancer patients is a well-established complication due to chemotherapy-induced immunosuppression. Studies have reported HBVr associated with immunosuppressive medications, such as rituximab, methotrexate, and high dose steroids. There are different risks for different types of chemotherapy with rituximab carrying one of the highest risks for hepatitis B reactivation. Tyrosine kinase inhibitors (TKIs) are the standard of care in patients with chronic myeloid leukemia (CML). The risk of HBVr in chronic myeloid leukemia has been reported in many studies, but to this date, there are no clear guidelines or recommendations regarding screening and monitoring of HBV in CML patients receiving TKIs. We conducted this review to identify the risk of HBVr in patients with CML who are treated with tyrosine kinase inhibitors. We recommend testing for HBV status in patients who are to be treated with TKIs and to consider giving prophylaxis in those who are positive for HBsAg at baseline. More studies are needed to assess the risk of reactivation in patients with Hepatitis B core antibody positive receiving TKIs. Currently, monitoring such patients for reactivation may be the best strategy.
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MESH Headings
- Antibiotic Prophylaxis/methods
- Antibiotic Prophylaxis/standards
- Antiviral Agents/therapeutic use
- Drug Monitoring/standards
- Hepatitis B Surface Antigens/immunology
- Hepatitis B Surface Antigens/isolation & purification
- Hepatitis B virus/isolation & purification
- Hepatitis B virus/physiology
- Hepatitis B, Chronic/diagnosis
- Hepatitis B, Chronic/immunology
- Hepatitis B, Chronic/prevention & control
- Hepatitis B, Chronic/virology
- Humans
- Immunocompromised Host
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive/immunology
- Mass Screening/standards
- Mass Screening/statistics & numerical data
- Practice Guidelines as Topic
- Protein Kinase Inhibitors/adverse effects
- Virus Activation/drug effects
- Virus Activation/immunology
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Affiliation(s)
- Asmaa Atteya
- National Center for Cancer Care and Research, Doha, Qatar
| | - Aiman Ahmad
- National Center for Cancer Care and Research, Doha, Qatar
| | - Dima Daghstani
- Department of Pharmacy, National Center for Cancer Care and Research, Doha, Qatar
| | - Kamran Mushtaq
- Gastroenterology Department, Hamad Medical Corporation, Doha, Qatar
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23
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Su J, Lim JK. Hepatitis B Virus Reactivation in the Setting of Immunosuppressive Drug Therapy. Gastroenterol Hepatol (N Y) 2019; 15:585-592. [PMID: 31802984 PMCID: PMC6883727] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/10/2023]
Abstract
Chronic hepatitis B virus (HBV) infection remains a global health burden, affecting an estimated 257 million people, and is associated with substantial morbidity and mortality due to cirrhosis and hepatocellular carcinoma. Reactivation of HBV infection among individuals with resolved and/or chronic HBV infection may result in clinical hepatitis with a rise in serum HBV DNA and serum alanine aminotransferase, and delayed identification may result in fulminant hepatitis and fatal liver failure. Routine screening for HBV is recommended in patients undergoing immunosuppressive drug regimens known to be associated with HBV reactivation (HBVr). A subset of patients identified to have positive hepatitis B surface antigen and/or hepatitis B core antibody may require preemptive antiviral therapy to reduce the risk of HBVr. This article summarizes the current evidence and society guidelines governing the evaluation and management of HBVr in the context of cancer chemotherapy and immunosuppressive drug therapy.
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Affiliation(s)
- Jessica Su
- Dr Su is an internal medicine resident in the Department of Internal Medicine at Yale School of Medicine in New Haven, Connecticut
- Dr Lim is a professor of medicine and director of the Viral Hepatitis Program in the Section of Digestive Diseases and Yale Liver Center at Yale School of Medicine
| | - Joseph K Lim
- Dr Su is an internal medicine resident in the Department of Internal Medicine at Yale School of Medicine in New Haven, Connecticut
- Dr Lim is a professor of medicine and director of the Viral Hepatitis Program in the Section of Digestive Diseases and Yale Liver Center at Yale School of Medicine
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Hepatitis B reactivation during treatment of tyrosine kinase inhibitors—Experience in 142 adult patients with chronic myeloid leukemia. Leuk Res 2019; 81:95-97. [DOI: 10.1016/j.leukres.2019.05.001] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2019] [Revised: 04/25/2019] [Accepted: 05/01/2019] [Indexed: 12/28/2022]
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Wu CCH, Kumar R. Hepatitis B reactivation in patients with hepatitis B core antibody positive and surface antigen negative on immunosuppressants. World J Meta-Anal 2019; 7:209-217. [DOI: 10.13105/wjma.v7.i5.209] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2019] [Revised: 05/20/2019] [Accepted: 05/22/2019] [Indexed: 02/06/2023] Open
Abstract
Hepatitis B viral (HBV) reactivation in the immunosuppressed is a significant problem even in patients who have achieved serological clearance due to the persistence of HBV as cccDNA. HBV reactivation will continue to pose a significant healthcare burden given the high prevalence of HBV and increasing use of immunosuppressants. Screening of hepatitis B surface antigen, antibody to Hepatitis B core antigen antibody and HBV DNA levels should be done routinely in all patients planned for significant immunosuppressant use. We aimed to examine the factors affecting reactivation risk. This depended on HBV disease status, the underlying disease requiring immunosuppression, and the specific immunosuppressive regime. While antiviral prophylaxis can prevent reactivation, it increases cost and still has risk of delayed reactivation after stopping antivirals and close follow-up and on-demand treatment is a good alternative for patients at risk of reactivation.
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Affiliation(s)
- Clement Chun-Ho Wu
- Department of Gastroenterology and Hepatology, Singapore General Hospital, Singapore 169608, Singapore
- Duke-NUS Medical School, Singapore 169608, Singapore
| | - Rajneesh Kumar
- Department of Gastroenterology and Hepatology, Singapore General Hospital, Singapore 169608, Singapore
- Duke-NUS Medical School, Singapore 169608, Singapore
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Lopina N, Dmytrenko I, Hamov D, Lopin D, Dyagil I. Novel Score-based Decision Approach in Chronic Myeloid Leukemia Patients After Acute Toxic Imatinib-induced Liver Injury. Cureus 2019; 11:e4411. [PMID: 31245199 PMCID: PMC6559390 DOI: 10.7759/cureus.4411] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023] Open
Abstract
The tyrosine kinase inhibitor (TKI) imatinib in rare cases can cause acute toxic hepatitis, hepatic failure, and death. Currently, the choice of further chronic myeloid leukemia (CML) therapy in patients after acute hepatotoxicity is still a difficult question, which requires a complex individual approach based on the clinical guidelines of adverse event management. Data about the further follow-up strategy approach in patients with CML after acute toxic imatinib-induced liver injury are of concern, and at times controversial. In addition, one of the questions is about the necessity and safety of the imatinib therapy resumption after acute hepatotoxicity. In some publications, imatinib resumption without the recurrence of hepatotoxicity has been discussed; in others, imatinib resumption with the recurrence of imatinib hepatotoxicity has been mentioned. There are a few publications about the experience of administration of the second-line TKIs after acute imatinib hepatotoxicity. There are no clear data on which factors the physician's decision should be based on in patients with CML after acute toxic imatinib-induced liver injury. Imatinib should be restarted or withdrawn, when and for whom second-line therapy should be started. The physician's decision is usually based on the published data of similar cases, personal experience, and the severity of hepatotoxicity. We have discussed the clinical guidelines devoted to the peculiarities of the patient's management after acute toxic imatinib-induced hepatitis and main strategy approaches. A complex score-based decision algorithm for choosing the further strategy approach after acute toxic imatinib-induced hepatitis in patients with CML has been presented. The following parameters should be assessed: the grade of hepatotoxicity reaction, the presence of liver transplantation or imatinib-induced liver cirrhosis and its possible pathogenetic mechanism, the presence of early molecular response (EMR) to imatinib therapy defined as three-month BCR-ABL1 ≤10% according to the international scale (BCR-ABL1IS ) or/and six-month BCR-ABL1 IS <1%; and the presence of the offender concomitant drug that probably caused the drug interaction with imatinib and the presence of viral hepatitis reactivation identified by polymerase chain reaction (PCR).
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Affiliation(s)
- Nataliia Lopina
- Internal Medicine and Endocrinology, Kharkiv National Medical University, Kharkiv, UKR
| | - Iryna Dmytrenko
- Hematology and Transplantology, National Research Center for Radiation Medicine of the National Academy of Medical Sciences of Ukraine, Kyiv, UKR
| | - Dmytro Hamov
- Hematology, Cherkasy Regional Oncology Dispensary of Cherkasy Regional Council, Cherkassy, UKR
| | - Dmytro Lopin
- Internal Medicine, SI Zaitsev V.t Institute of General and Urgent Surgery of National Academy of Medical Science of Ukraine, Kharkiv, UKR
| | - Iryna Dyagil
- Radiation Oncohematology and Stem Cell Transplantation, National Research Center for Radiation Medicine of the National Academy of Medical Sciences of Ukraine, Kyiv, UKR
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Atkins S, He F. Chemotherapy and Beyond: Infections in the Era of Old and New Treatments for Hematologic Malignancies. Infect Dis Clin North Am 2019; 33:289-309. [PMID: 30935703 DOI: 10.1016/j.idc.2019.01.001] [Citation(s) in RCA: 30] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Treatment options for hematologic malignancies have been rapidly expanding in the past decade, resulting in better survival outcomes for many patients. Infection is an important cause of morbidity and mortality in this patient population. Cytotoxic chemotherapy has well-studied infectious risks related to the degree and duration of myelosuppression. Targeted therapies and immunotherapies have less clearly predictable infectious risk and diverse effects on immune function. This review discusses contemporary management of hematologic malignancies, followed by special discussion of novel agents, including signaling/small molecule inhibitors, monoclonal antibodies, immunomodulators, and immunotherapies, for treatment of hematologic malignancies with focus on infectious risk.
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Affiliation(s)
- Sarah Atkins
- Department of Internal Medicine, University of Minnesota, 420 Delaware Street Southeast, MMC 284, Minneapolis, MN 55455, USA
| | - Fiona He
- Division of Hematology, Oncology, and Transplantation, University of Minnesota, 420 Delaware Street Southeast, MMC 480, Minneapolis, MN 55455, USA.
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28
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Wang B, Mufti G, Agarwal K. Reactivation of hepatitis B virus infection in patients with hematologic disorders. Haematologica 2019; 104:435-443. [PMID: 30733266 PMCID: PMC6395346 DOI: 10.3324/haematol.2018.210252] [Citation(s) in RCA: 37] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2018] [Accepted: 01/18/2019] [Indexed: 12/16/2022] Open
Abstract
Hepatitis B reactivation is the reappearance or rise of hepatitis B virus (HBV) DNA in patients with past or chronic HBV infection, usually occurring in the context of immunosuppression. HBV reactivation has been most commonly reported in patients with hematologic disorders, with potentially serious and life-threatening consequences. In this review, we discuss the basis and presentation of HBV reactivation, and risk factors in terms of the host, the virus and the immunosuppression regimen, including newer agents used to manage hematologic malignancies. We overview the management of HBV reactivation, highlighting an up-dated recommendation on the use of newer nucleoside and nucleotide analogs, such as tenofovir and entecavir, for antiviral prophylaxis.
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Affiliation(s)
| | - Ghulam Mufti
- Department of Hematology, King's College Hospital, London, UK
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Hou L, Zhao J, Gao S, Ji T, Song T, Li Y, Wang J, Geng C, Long M, Chen J, Lin H, Cai X, Cang Y. Restriction of hepatitis B virus replication by c-Abl-induced proteasomal degradation of the viral polymerase. SCIENCE ADVANCES 2019; 5:eaau7130. [PMID: 30775435 PMCID: PMC6365112 DOI: 10.1126/sciadv.aau7130] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/16/2018] [Accepted: 12/19/2018] [Indexed: 05/13/2023]
Abstract
About 257 million people with chronic infection of hepatitis B virus (HBV) worldwide are at high risk of developing terminal liver diseases. Reactivation of virus replication has been frequently reported in those patient populations receiving imatinib (an Abl kinase inhibitor) or bortezomib (a proteasome inhibitor) to treat concurrent diseases, but the underlying mechanism for this reactivation is unknown. We report that the HBV polymerase protein is recruited by Cdt2 to the cullin-RING ligase 4 (CRL4) for ubiquitination and proteasome degradation and that this process is stimulated by the c-Abl nonreceptor tyrosine kinase. Genetic ablation of the Abl-CRL4Cdt2 axis or pharmaceutical inhibition of this process stabilizes HBV polymerase protein and increases viral loads in HBV-infected liver cancer cell lines. Our study reveals a kinase-dependent activation of CRL4 ubiquitin ligase that can be targeted for blocking HBV replication.
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Affiliation(s)
- Lidan Hou
- Life Sciences Institute, Zhejiang University, Hangzhou, Zhejiang 310058, China
- School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China
| | - Jie Zhao
- Department of General Surgery, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310058, China
| | - Shaobing Gao
- Life Sciences Institute, Zhejiang University, Hangzhou, Zhejiang 310058, China
- Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan 450008, China
| | - Tong Ji
- Department of General Surgery, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310058, China
| | - Tianyu Song
- Life Sciences Institute, Zhejiang University, Hangzhou, Zhejiang 310058, China
- School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China
| | - Yining Li
- Life Sciences Institute, Zhejiang University, Hangzhou, Zhejiang 310058, China
| | - Jingjie Wang
- Life Sciences Institute, Zhejiang University, Hangzhou, Zhejiang 310058, China
| | - Chenlu Geng
- Life Sciences Institute, Zhejiang University, Hangzhou, Zhejiang 310058, China
| | - Min Long
- Life Sciences Institute, Zhejiang University, Hangzhou, Zhejiang 310058, China
| | - Jiang Chen
- Department of General Surgery, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310058, China
| | - Hui Lin
- Department of General Surgery, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310058, China
| | - Xiujun Cai
- Department of General Surgery, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310058, China
| | - Yong Cang
- School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China
- Corresponding author.
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Li J, Wang M, Zhang B, Wu X, Lin TL, Liu XF, Zhou Y, Zhang XH, Xu H, Shen LJ, Zou J, Lu P, Zhang D, Gu WJ, Zhang MX, Pan J, Cao H, Chinese Society of Surgeons for Gastrointestinal Stromal Tumor of the Chinese Medical Doctor Association. Chinese consensus on management of tyrosine kinase inhibitor-associated side effects in gastrointestinal stromal tumors. World J Gastroenterol 2018; 24:5189-5202. [PMID: 30581268 PMCID: PMC6295840 DOI: 10.3748/wjg.v24.i46.5189] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/23/2018] [Revised: 11/04/2018] [Accepted: 11/07/2018] [Indexed: 02/06/2023] Open
Abstract
Tyrosine kinase inhibitors (TKIs) have improved the overall survival of patients with gastrointestinal stromal tumors (GISTs), but their side effects can impact dose intensity and, consequently, the clinical benefit. To date, no guideline or consensus has been published on the TKI-associated adverse reactions. Therefore, the Chinese Society of Surgeons for Gastrointestinal Stromal Tumor of the Chinese Medical Doctor Association organized an expert panel discussion involving representatives from gastrointestinal surgery, medical oncology, cardiology, dermatology, nephrology, endocrinology, and ophthalmology to consider the systemic clinical symptoms, molecular and cellular mechanisms, and treatment recommendations of GISTs. Here, we present the resultant evidence- and experience-based consensus to guide the management of TKI-associated side events in clinical practice.
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Affiliation(s)
- Jian Li
- Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing 100142, China
| | - Ming Wang
- Department of Gastrointestinal Surgery, Reiji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200127, China
| | - Bo Zhang
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Xin Wu
- Department of General Surgery, the General Hospital of the People’s Liberation Army, Beijing 100853, China
| | - Tian-Long Lin
- Department of Gastrointestinal Surgery, Reiji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200127, China
| | - Xiu-Feng Liu
- Department of Oncology, The Chinese People’s Liberation Army 81st Hospital, Nanjing 210031, Jiangsu Province, China
| | - Ye Zhou
- Department of Gastric Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China
| | - Xin-Hua Zhang
- Department of Gastrointestinal Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, Guangdong Province, China
| | - Hao Xu
- Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing 320100, Jiangsu Province, China
| | - Li-Jing Shen
- Department of Hematology, Ren Ji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200240, China
| | - Jing Zou
- Department of Respirology, Ren Ji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200240, China
| | - Ping Lu
- Department of Dermatology, Ren Ji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200240, China
| | - Dong Zhang
- Department of Nephrology, The General Hospital of the People’s Liberation Army, Beijing 100853, China
| | - Wei-Jun Gu
- Department of Endocrinology, The General Hospital of the People’s Liberation Army, Beijing 100853, China
| | - Mei-Xia Zhang
- Department of Ophthalmology, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Jian Pan
- Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Hui Cao
- Department of Gastrointestinal Surgery, Reiji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200127, China
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Noreña I, Fernández-Ruiz M, Aguado JM. Viral infections in the biologic therapy era. Expert Rev Anti Infect Ther 2018; 16:781-791. [PMID: 30198355 DOI: 10.1080/14787210.2018.1521270] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
INTRODUCTION The development of biologic therapies for treating patients with rheumatic, hematologic, or oncological diseases has increased in the last few years, spreading their use in clinical practice. Areas covered: Clinical experience has evidenced substantial risks for some viral infections and/or reactivations such as viral hepatitis, herpetic infections, and other viruses, as a consequence of specific immune pathway blockages. Biological therapies produce a variable risk of reactivation of viral infections, which is particularly uncertain in the case of the most recently introduced agents. Here we make an extensive review of the viral infections associated with the use of biological drugs and provide a series of recommendations for its prevention and management. Expert commentary: To prevent these infections/reactivations, the practitioner must be aware of the infection-risk profile, performing accurate screening during and after the use of any biologic agent. In some instances, expert recommendations are made for some therapies, while in other scenarios recommendations have not yet been defined making experimental and clinical research an essential approach to elucidate multiple issues yet not resolved in this field.
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Affiliation(s)
- Ivan Noreña
- a Infectious Diseases Unit , Fundación Cardioinfantil-Instituto de Cardiología , Bogotá , Colombia.,b Infectious Diseases Unit , Clínica los Nogales , Bogotá , Colombia
| | - Mario Fernández-Ruiz
- c Infectious Diseases Unit , Hospital Universitario 12 de Octubre , Madrid , Spain.,d Instituto de Investigación Hospital "12 de Octubre" (i+12), School of Medicine , Universidad Complutense , Madrid , Spain
| | - José María Aguado
- c Infectious Diseases Unit , Hospital Universitario 12 de Octubre , Madrid , Spain.,d Instituto de Investigación Hospital "12 de Octubre" (i+12), School of Medicine , Universidad Complutense , Madrid , Spain
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32
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Inayat F, Song F, Ali NS, Aslam MH, Aloma A, Hachem H, Saif MW. Hepatitis B virus reactivation following imatinib therapy: A comparative review of 9 cases. J Oncol Pharm Pract 2018; 25:1500-1508. [PMID: 30079802 DOI: 10.1177/1078155218790337] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Patients undergoing cytotoxic or immunosuppressive therapy for cancer have an established predilection for hepatitis B virus reactivation; however, the risk associated with newer molecularly targeted agents has not been well investigated. Imatinib, a small molecule tyrosine kinase inhibitor, induces rapid and sustained clinical benefit by inhibiting a number of signaling pathways, including BCR-ABL and c-KIT. We report the case of a patient who developed hepatitis B virus reactivation while receiving imatinib therapy for gastrointestinal stromal tumor. Furthermore, a structured literature search of the medical databases consisting of MEDLINE and PubMed was performed using the terms "hepatitis B", "reactivation", and "imatinib". The search identified nine case reports only. The data on patients' characteristics, epidemiology, clinical features, comorbid conditions, diagnosis, and management are summarized. Imatinib-associated hepatitis B virus reactivation was reported in seven patients with chronic myeloid leukemia, one with desmoid tumor, and one with gastrointestinal stromal tumor. This review serves to outline our current understanding of the epidemiology, risk factors, and pathophysiology of chronic hepatitis B virus reactivation secondary to imatinib therapy as well as the current approaches to diagnosis and management of this condition. We aim to increase awareness about this possible association and advocate for hepatitis B virus screening prior to imatinib therapy, especially in patients who are at increased risk for chronic hepatitis B virus infection.
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Affiliation(s)
| | - Fei Song
- 2 Tufts Medical Center, Boston, USA
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Kaya M, Akdogan R, Uçmak F, O Ayyildiz M, Karakus A, A Kaplan M. The Incidence and Predictive Factors in the Development of Acute Hepatitis in Patients with Leukemia. Euroasian J Hepatogastroenterol 2018; 8:31-37. [PMID: 29963458 PMCID: PMC6024041 DOI: 10.5005/jp-journals-10018-1254] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2017] [Accepted: 01/24/2018] [Indexed: 11/23/2022] Open
Abstract
Introduction Liver involvement is common in hematological malignancies, but the incidence and pattern of liver injury vary among the different types. The aims of our study were to determine the incidence and clinical course of acute hepatitis and the important factors for its development in patients with leukemia after chemotherapy. Materials and methods All patients with the diagnosis of leukemia who were treated at the Department of Hematology between January 2008 and January 2013 were included in the study. A detailed medical history, clinical and laboratory findings, treatment modalities, complications, and clinical course were recorded retrospectively. Results A total of 124 patients (64 females) with the diagnosis of leukemia were included in the study. The mean age was 45.2 years (16-89 years) and mean follow-up time was 29.7 months (0.25-192 months). A total of 43 (34.6%) patients had acute hepatitis after chemotherapy. Pattern of liver injury was hepatocellular in 31 patients, cholestasis in 2, and mix in 10 patients. Age (p = 0.001), hepatitis B surface antigen (HBsAg, p = 0.007), acute leukemia (p < 0.001), positive blood culture (p = 0.004), the amount of transfused red blood cell (p = 0.001), and amount of transfused platelets (p = 0.002) were significantly different under univariate analysis between the acute hepatitis group and the nonacute hepatitis group. Under multivariate analysis, only acute lymphoblastic leukemia (ALL) was identified as independent predictive factor for development of acute hepatitis after starting chemotherapy. Conclusion Acute and self-limited hepatitis develops in the substantial proportion of patients with leukemia. The most important factor for development of acute hepatitis is the type of leukemia. How to cite this article: Kaya M, Akdogan R, Uçmak F, Ayyildiz MO, Karakus A, Kaplan MA. The Incidence and Predictive Factors in the Development of Acute Hepatitis in Patients with Leukemia. Euroasian J Hepato-Gastroenterol 2018;8(1):31-37.
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Affiliation(s)
- Muhsin Kaya
- Department of Gastroenterology, Dicle University School of Medicine, Diyarbakir, Turkey
| | - Recai Akdogan
- Department of Internal Medicine, Dicle University School of Medicine, Diyarbakir, Turkey
| | - Feyzullah Uçmak
- Department of Gastroenterology, Dicle University School of Medicine, Diyarbakir, Turkey
| | - Mehmet O Ayyildiz
- Department of Hematology, Dicle University School of Medicine, Diyarbakir, Turkey
| | - Abdullah Karakus
- Department of Hematology, Dicle University School of Medicine, Diyarbakir, Turkey
| | - Muhammet A Kaplan
- Department of Oncology, Dicle University School of Medicine, Diyarbakir, Turkey
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Sanagawa A, Hotta Y, Kataoka T, Maeda Y, Kondo M, Kawade Y, Ogawa Y, Nishikawa R, Tohkin M, Kimura K. Hepatitis B infection reported with cancer chemotherapy: analyzing the US FDA Adverse Event Reporting System. Cancer Med 2018; 7:2269-2279. [PMID: 29663729 PMCID: PMC6010750 DOI: 10.1002/cam4.1429] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2017] [Revised: 01/14/2018] [Accepted: 02/09/2018] [Indexed: 02/06/2023] Open
Abstract
We conducted data mining using the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database on spontaneously reported adverse events to evaluate the association between anticancer drug therapy and hepatitis B infection. Reports of hepatitis B infection were retrieved from the FAERS database. The reporting odds ratio (ROR) was used to estimate the association between hepatitis B infection and various anticancer agents and drug combinations. We detected statistically significant risk signals of hepatitis B for 33 of 64 anticancer agents by ROR (26 cytotoxicity drugs and seven molecular-targeted drugs). We focused on molecular-targeted drugs and assessed the risk of hepatitis B from specific anticancer drug combinations. The frequency of hepatitis B infection was significantly high for drugs such as rituximab, bortezomib, imatinib, and everolimus. The addition of cyclophosphamide, doxorubicin, and fludarabine to drug combinations additively enhanced the frequency of hepatitis B infection. There were no reports on hepatitis B infection associated with trastuzumab or azacitidine monotherapy. However, trastuzumab-containing regimens (e.g., combinations with docetaxel or paclitaxel) were correlated with the incidence of hepatitis B infection, similar to azacitidine monotherapy. Our findings suggest that the concomitant use of anticancer drugs, such as trastuzumab, taxane, and azacitidine, may contribute to the risk of hepatitis B infection. The unique signals detected from the public database might provide clues to eliminate the threat of HBV in oncology.
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Affiliation(s)
- Akimasa Sanagawa
- Department of PharmacyNagoya City University HospitalNagoyaJapan
- Department of Hospital PharmacyGraduate School of Pharmaceutical SciencesNagoya City UniversityNagoyaJapan
| | - Yuji Hotta
- Department of Hospital PharmacyGraduate School of Pharmaceutical SciencesNagoya City UniversityNagoyaJapan
| | - Tomoya Kataoka
- Department of Clinical PharmaceuticsGraduate School of Medical SciencesNagoya City UniversityNagoyaJapan
| | - Yasuhiro Maeda
- Department of Hospital PharmacyGraduate School of Pharmaceutical SciencesNagoya City UniversityNagoyaJapan
| | - Masahiro Kondo
- Department of PharmacyNagoya City University HospitalNagoyaJapan
| | - Yoshihiro Kawade
- Department of Hospital PharmacyGraduate School of Pharmaceutical SciencesNagoya City UniversityNagoyaJapan
| | - Yoshihiro Ogawa
- Department of Regulatory ScienceGraduate School of Pharmaceutical SciencesNagoya City UniversityNagoyaJapan
| | - Ryohei Nishikawa
- Department of Regulatory ScienceGraduate School of Pharmaceutical SciencesNagoya City UniversityNagoyaJapan
| | - Masahiro Tohkin
- Department of Regulatory ScienceGraduate School of Pharmaceutical SciencesNagoya City UniversityNagoyaJapan
| | - Kazunori Kimura
- Department of PharmacyNagoya City University HospitalNagoyaJapan
- Department of Hospital PharmacyGraduate School of Pharmaceutical SciencesNagoya City UniversityNagoyaJapan
- Department of Clinical PharmaceuticsGraduate School of Medical SciencesNagoya City UniversityNagoyaJapan
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Reinwald M, Silva JT, Mueller NJ, Fortún J, Garzoni C, de Fijter JW, Fernández-Ruiz M, Grossi P, Aguado JM. ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biological therapies: an infectious diseases perspective (Intracellular signaling pathways: tyrosine kinase and mTOR inhibitors). Clin Microbiol Infect 2018; 24 Suppl 2:S53-S70. [PMID: 29454849 DOI: 10.1016/j.cmi.2018.02.009] [Citation(s) in RCA: 128] [Impact Index Per Article: 18.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2017] [Revised: 02/08/2018] [Accepted: 02/11/2018] [Indexed: 12/11/2022]
Abstract
BACKGROUND The present review is part of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biologic therapies. AIMS To review, from an infectious diseases perspective, the safety profile of therapies targeting different intracellular signaling pathways and to suggest preventive recommendations. SOURCES Computer-based Medline searches with MeSH terms pertaining to each agent or therapeutic family. CONTENT Although BCR-ABL tyrosine kinase inhibitors modestly increase the overall risk of infection, dasatinib has been associated with cytomegalovirus and hepatitis B virus reactivation. BRAF/MEK kinase inhibitors do not significantly affect infection susceptibility. The effect of Bruton tyrosine kinase inhibitors (ibrutinib) among patients with B-cell malignancies is difficult to distinguish from that of previous immunosuppression. However, cases of Pneumocystis jirovecii pneumonia (PCP), invasive fungal infection and progressive multifocal leukoencephalopathy have been occasionally reported. Because phosphatidylinositol-3-kinase inhibitors (idelalisib) may predispose to opportunistic infections, anti-Pneumocystis prophylaxis and prevention strategies for cytomegalovirus are recommended. No increased rates of infection have been observed with venetoclax (antiapoptotic protein Bcl-2 inhibitor). Therapy with Janus kinase inhibitors markedly increases the incidence of infection. Pretreatment screening for chronic hepatitis B virus and latent tuberculosis infection must be performed, and anti-Pneumocystis prophylaxis should be considered for patients with additional risk factors. Cancer patients receiving mTOR inhibitors face an increased incidence of overall infection, especially those with additional risk factors (prior therapies or delayed wound healing). IMPLICATIONS Specific preventive approaches are warranted in view of the increased risk of infection associated with some of the reviewed agents.
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Affiliation(s)
- M Reinwald
- Department of Hematology and Oncology, Klinikum Brandenburg, Medizinische Hochschule Brandenburg Theodor Fontane, Brandenburg an der Havel, Germany.
| | - J T Silva
- Department of Infectious Diseases, University Hospital of Badajoz, Fundación para la Formación e Investigación de los Profesionales de la Salud (FundeSalud), Badajoz, Spain
| | - N J Mueller
- Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - J Fortún
- Department of Infectious Diseases, Hospital Universitario 'Ramon y Cajal', Madrid, Spain; Spanish Network for Research in Infectious Diseases (REIPI RD16/0016), Instituto de Salud Carlos III, Madrid, Spain
| | - C Garzoni
- Department of Internal Medicine, Clinica Luganese, Lugano, Switzerland; Department of Infectious Disease, Clinica Luganese, Lugano, Switzerland
| | - J W de Fijter
- Department of Medicine, Division of Nephrology, Leiden University Medical Centre, Leiden, The Netherlands
| | - M Fernández-Ruiz
- Unit of Infectious Diseases, Hospital Universitario '12 de Octubre', Instituto de Investigación Hospital '12 de Octubre' (i+12), School of Medicine, Universidad Complutense, Madrid, Spain; Spanish Network for Research in Infectious Diseases (REIPI RD16/0016), Instituto de Salud Carlos III, Madrid, Spain
| | - P Grossi
- Department of Infectious and Tropical Diseases, University of Insubria, Ospedale di Circolo-Fondazioni Macchi, Varese, Italy
| | - J M Aguado
- Unit of Infectious Diseases, Hospital Universitario '12 de Octubre', Instituto de Investigación Hospital '12 de Octubre' (i+12), School of Medicine, Universidad Complutense, Madrid, Spain; Spanish Network for Research in Infectious Diseases (REIPI RD16/0016), Instituto de Salud Carlos III, Madrid, Spain
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Knoll BM, Seiter K. Infections in patients on BCR-ABL tyrosine kinase inhibitor therapy: cases and review of the literature. Infection 2018; 46:409-418. [DOI: 10.1007/s15010-017-1105-1] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2017] [Accepted: 12/03/2017] [Indexed: 01/23/2023]
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Sarmati L, Andreoni M, Antonelli G, Arcese W, Bruno R, Coppola N, Gaeta GB, Galli M, Girmenia C, Mikulska M, Pane F, Perno CF, Picardi M, Puoti M, Rambaldi A, Svicher V, Taliani G, Gentile G. Recommendations for screening, monitoring, prevention, prophylaxis and therapy of hepatitis B virus reactivation in patients with haematologic malignancies and patients who underwent haematologic stem cell transplantation-a position paper. Clin Microbiol Infect 2017; 23:935-940. [PMID: 28668466 DOI: 10.1016/j.cmi.2017.06.023] [Citation(s) in RCA: 60] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2017] [Revised: 06/15/2017] [Accepted: 06/17/2017] [Indexed: 12/18/2022]
Abstract
SCOPE Hepatitis B virus (HBV) infection reactivation is associated with high morbidity and mortality in patients with haematologic malignancy and/or haematopoietic stem cell transplantation (HSCT). However, information on this issue is limited. The scope of this position paper is to provide recommendations on HBV screening, monitoring, prophylaxis, treatment and vaccination in the patients described above. METHODS These recommendations were developed from one meeting of experts attended by different Italian scientific societies as well as from a systematic literature review (of articles published through December 31, 2016) on HBV infection in haematologic patients and in patients who underwent haematopoietic stem cell transplantation published in the same issue of the journal. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was used to assess each recommendation's quality. QUESTIONS ADDRESSED These recommendations provide the answers to the following questions: (a) HBV screening and monitoring: Who should be screened before chemotherapy? Which screening tests should be used? Should HBV-DNA detection be used to monitor HBV reactivation before starting antivirals? What is the best timeline to monitor HBV reactivation? (b) Prophylaxis in HBsAg-positive patients: Which antiviral drugs should be used to treat HBsAg-positive patients? How long should antiviral prophylaxis be provided to HBsAg-positive patients? (c) Prophylaxis in patients with resolved HBV infection: Which patients with resolved HBV infection should receive antiviral prophylaxis? Which antiviral drug should be used? How long should antiviral prophylaxis be provided? (d) HBV infection management strategy in autologous (auto-HSCT) and allogeneic HSCT (allo-HSCT): Which HSCT recipients should receive antiviral prophylaxis? Which antiviral drug should be used? How long should antiviral prophylaxis be provided? (e) Choice of antiviral drugs in the treatment of HBV reactivation: Should third-generation anti-HBV drugs be preferred to first- or second-generation antiviral drugs in the treatment of HBV reactivation with or without hepatitis flare in haematologic patients? (f) Immunization against HBV in patients with haematologic malignancies and/or patients who underwent HSCT: Should these patients be vaccinated? Which HBV vaccination schedule should be adopted? RECOMMENDATIONS Haematologic patients should be screened for hepatitis B surface antigen (HBsAg) plus anti-hepatitis B core protein (HBc), and HBV DNA before chemotherapy. HBV DNA levels should be monitored monthly in all HBV-positive patients who do not receive prophylaxis. HBsAg-positive haematologic patients and those undergoing HSCT should receive third-generation antiviral therapy as prophylaxis. Anti-HBc-positive lymphoma patients and those receiving HSCT should receive antiviral prophylaxis. All HBV-negative haematologic patients should be vaccinated for HBV. The acquisition of data from well-designed studies is desirable in the near future.
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Affiliation(s)
- L Sarmati
- Department of System Medicine, Clinical Infectious Diseases, Tor Vergata University, Rome, Italy.
| | - M Andreoni
- Department of System Medicine, Clinical Infectious Diseases, Tor Vergata University, Rome, Italy
| | - G Antonelli
- Department of Molecular Medicine, 'La Sapienza' University, Rome, Italy
| | - W Arcese
- Department of Hematology, Stem Cell Transplant Unit, Tor Vergata University, Rome, Italy
| | - R Bruno
- Department of Infectious Diseases, Hepatology Outpatients Unit, University of Pavia, IRCCS Policlinico San Matteo, Pavia, Italy
| | - N Coppola
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, Second University of Naples, Naples, Italy
| | - G B Gaeta
- Infectious Diseases and Viral Hepatitis, Department of Mental and Physical Health and Preventive Medicine, Università della Campania, Naples, Italy
| | - M Galli
- Infectious Diseases Unit, University of Milan, L. Sacco Hospital, Milan, Italy
| | - C Girmenia
- Dipartimento di Ematologia, Oncologia, Anatomia Patologica e Medicina Rigenerativa, Azienda Policlinico Umberto I, La Sapienza University, Rome, Italy
| | - M Mikulska
- Division of Infectious Diseases, Department of Health Sciences, University of Genoa, Genoa, Italy; Division of Infectious Diseases, IRCCS San Martino University Hospital-IST, Genoa, Italy
| | - F Pane
- Department of Clinical Medicine and Surgery, Hematology, Federico II University, Naples, Italy
| | - C F Perno
- Department of Experimental Medicine and Surgery, Tor Vergata University, Rome, Italy
| | - M Picardi
- Department of Clinical Medicine and Surgery, Hematology, Federico II University, Naples, Italy
| | - M Puoti
- Infectious Diseases Department, Azienda Ospedaliera Ospedale Niguarda Ca' Granda, Milan, Italy
| | - A Rambaldi
- Dipartimento di Scienze Cliniche e di Comunità, Università degli Studi di Milano, Milan, Italy; Hematology and Bone Marrow Transplant Unit, Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Italy
| | - V Svicher
- Department of Experimental Medicine and Surgery, Tor Vergata University, Rome, Italy
| | - G Taliani
- Clinic of Infectious and Tropical Medicine, Policlinico Umberto I, Rome, Italy
| | - G Gentile
- Department of Cellular Biotechnologies and Hematology, 'La Sapienza' University, Rome, Italy
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Tedeschi A, Frustaci AM, Mazzucchelli M, Cairoli R, Montillo M. Is HBV prophylaxis required during CLL treatment with ibrutinib? Leuk Lymphoma 2017; 58:2966-2968. [DOI: 10.1080/10428194.2017.1317094] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Affiliation(s)
- Alessandra Tedeschi
- Department of Haematology, Niguarda Cancer Center, ASST Grande Ospedale Metropolitano Niguarda, Milano, Italy
| | - Anna Maria Frustaci
- Department of Haematology, Niguarda Cancer Center, ASST Grande Ospedale Metropolitano Niguarda, Milano, Italy
| | - Maddalena Mazzucchelli
- Department of Haematology, Niguarda Cancer Center, ASST Grande Ospedale Metropolitano Niguarda, Milano, Italy
| | - Roberto Cairoli
- Department of Haematology, Niguarda Cancer Center, ASST Grande Ospedale Metropolitano Niguarda, Milano, Italy
| | - Marco Montillo
- Department of Haematology, Niguarda Cancer Center, ASST Grande Ospedale Metropolitano Niguarda, Milano, Italy
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Chang CS, Tsai CY, Yan SL. Hepatitis B reactivation in patients receiving targeted therapies. Hematology 2017; 22:592-598. [DOI: 10.1080/10245332.2017.1321882] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Affiliation(s)
- Cheng-Shyong Chang
- Division of Hematology and Oncology, Department of Internal Medicine, Changhua Christian Hospital, Changhua City, Taiwan
| | - Chien-Yu Tsai
- Division of Hematology and Oncology, Department of Internal Medicine, Changhua Christian Hospital, Changhua City, Taiwan
| | - Sheng-Lei Yan
- Division of Gastroenterology, Department of Internal Medicine, Chang-Bing Show Chwan Memorial Hospital, Lugang Township, Taiwan
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Loomba R, Liang TJ. Hepatitis B Reactivation Associated With Immune Suppressive and Biological Modifier Therapies: Current Concepts, Management Strategies, and Future Directions. Gastroenterology 2017; 152:1297-1309. [PMID: 28219691 PMCID: PMC5501983 DOI: 10.1053/j.gastro.2017.02.009] [Citation(s) in RCA: 436] [Impact Index Per Article: 54.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2016] [Revised: 01/06/2017] [Accepted: 01/13/2017] [Indexed: 02/06/2023]
Abstract
Hepatitis B reactivation associated with immune-suppressive and biological therapies is emerging to be an important cause of morbidity and mortality in patients with current or prior exposure to hepatitis B virus (HBV) infection. The population at risk for HBV reactivation includes those who either currently are infected with HBV or have had past exposure to HBV. Because curative and eradicative therapy for HBV is not currently available, there is a large reservoir of individuals at risk for HBV reactivation in the general population. HBV reactivation with its potential consequences is particularly a concern when these people are exposed to either cancer chemotherapy, immunosuppressive or biologic therapies for the management of rheumatologic conditions, malignancies, inflammatory bowel disease, dermatologic conditions, or solid-organ or bone marrow transplantation. With the advent of newer and emerging forms of targeted biologic therapies, it has become important to understand the mechanisms whereby certain therapies are more prone to HBV reactivation. This review provides a comprehensive update on the current concepts, risk factors, molecular mechanisms, prevention, and management of hepatitis B reactivation. In addition, we provide recommendations for future research in this area.
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Affiliation(s)
- Rohit Loomba
- Division of Gastroenterology, Department of Medicine, University of California at San Diego, La Jolla, California
| | - T Jake Liang
- Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland.
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Itamura H, Kubota Y, Shindo T, Ando T, Kojima K, Kimura S. Elderly Patients With Chronic Myeloid Leukemia Benefit From a Dasatinib Dose as Low as 20 mg. CLINICAL LYMPHOMA MYELOMA & LEUKEMIA 2017; 17:370-374. [PMID: 28396095 DOI: 10.1016/j.clml.2017.02.023] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/08/2017] [Revised: 02/21/2017] [Accepted: 02/28/2017] [Indexed: 01/03/2023]
Abstract
BACKGROUND The clinical outcomes of patients with chronic myeloid leukemia (CML) treated with BCR-ABL tyrosine kinase inhibitors has improved markedly; however, the occurrence of adverse events (AEs) means that elderly patients often cannot be administered the standard dose. Nevertheless, some patients treated with low doses of tyrosine kinase inhibitor have achieved good molecular responses. PATIENTS AND METHODS We retrospectively analyzed the efficacy and safety of low-dose dasatinib treatment of elderly CML patients. The study enrolled 21 patients with newly diagnosed, imatinib-resistant, or imatinib-intolerant chronic phase CML. All the patients were aged ≥ 65 years and received dasatinib at a dose of < 100 mg/day. Of these 21 patients, 77% had newly diagnosed CML. RESULTS Overall, 91% and 72% of patients received a mean dasatinib dose of ≤ 50 mg and ≤ 20 mg, respectively. A molecular response of MR3 (major molecular response, indicating > 3 log reduction in the number of leukemic cells), MR4, and MR4.5 were achieved in 96%, 77%, and 62% of the patients, respectively. Of the 15 patients who received a mean dose of ≤ 20 mg, 94% achieved a major molecular response, and 74% achieved MR4. The most common nonhematologic AE was plural effusion (29%), which was controlled by diuretics and regulating the drug dose. CONCLUSION Low-dose (eg, ≤ 20 mg) dasatinib therapy generates an adequate molecular response in most elderly patients with chronic phase CML without causing severe AEs.
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Affiliation(s)
- Hidekazu Itamura
- Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Faculty of Medicine, Saga University, Saga, Japan
| | - Yasushi Kubota
- Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Faculty of Medicine, Saga University, Saga, Japan.
| | - Takero Shindo
- Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Faculty of Medicine, Saga University, Saga, Japan
| | - Toshihiko Ando
- Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Faculty of Medicine, Saga University, Saga, Japan
| | - Kensuke Kojima
- Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Faculty of Medicine, Saga University, Saga, Japan
| | - Shinya Kimura
- Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Faculty of Medicine, Saga University, Saga, Japan
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Marchetti O, Tissot F, Calandra T. Infections in the Cancer Patient. Infect Dis (Lond) 2017. [DOI: 10.1016/b978-0-7020-6285-8.00079-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
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Voican C, Mir O, Loulergue P, Dhooge M, Brezault C, Dréanic J, Chaussade S, Pol S, Coriat R. Hepatitis B virus reactivation in patients with solid tumors receiving systemic anticancer treatment. Ann Oncol 2016; 27:2172-2184. [DOI: 10.1093/annonc/mdw414] [Citation(s) in RCA: 48] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2014] [Revised: 05/11/2015] [Accepted: 08/23/2016] [Indexed: 02/06/2023] Open
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Orlandi EM, Elena C, Bono E. Risk of hepatitis B reactivation under treatment with tyrosine-kinase inhibitors for chronic myeloid leukemia. Leuk Lymphoma 2016; 58:1764-1766. [DOI: 10.1080/10428194.2016.1260127] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Affiliation(s)
- Ester Maria Orlandi
- Department of Oncology-Hematology, Hematology Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | - Chiara Elena
- Department of Oncology-Hematology, Hematology Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
- Department of Molecular Medicine, University of Pavia, Pavia, Italy
| | - Elisa Bono
- Department of Oncology-Hematology, School of Hematology, University of Pavia, Hematology Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
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45
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Koutsianas C, Thomas K, Vassilopoulos D. Hepatitis B Reactivation in Rheumatic Diseases: Screening and Prevention. Rheum Dis Clin North Am 2016; 43:133-149. [PMID: 27890170 DOI: 10.1016/j.rdc.2016.09.012] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Hepatitis B virus (HBV) reactivation (HBVr) has been an increasingly recognized and appreciated risk of immunosuppressive therapies in rheumatic patients. Despite its potential for significant morbidity and mortality, HBVr is a fully preventable complication with appropriate pretreatment screening and close monitoring of susceptible patients. Better knowledge of the risk for HBVr with the different antirheumatic agents and the establishment of the new-generation oral antivirals in clinical practice has greatly improved the design of screening and therapeutic algorithms. In this review, all available data regarding HBVr in rheumatic patients are critically presented and a screening and therapeutic algorithm is proposed.
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Affiliation(s)
- Christos Koutsianas
- Joint Rheumatology Program, Clinical Immunology-Rheumatology Unit, 2nd Department of Medicine and Laboratory, National and Kapodistrian University of Athens School of Medicine, Hippokration General Hospital, 114 Vass, Sophias Avenue, Athens 115 27, Greece; Department of Rheumatology, The Dudley Group NHS Foundation Trust, Russells Hall Hospital, Pensnett Road, Dudley DY1 2HQ, West Midlands, UK
| | - Konstantinos Thomas
- Joint Rheumatology Program, Clinical Immunology-Rheumatology Unit, 2nd Department of Medicine and Laboratory, National and Kapodistrian University of Athens School of Medicine, Hippokration General Hospital, 114 Vass, Sophias Avenue, Athens 115 27, Greece
| | - Dimitrios Vassilopoulos
- Joint Rheumatology Program, Clinical Immunology-Rheumatology Unit, 2nd Department of Medicine and Laboratory, National and Kapodistrian University of Athens School of Medicine, Hippokration General Hospital, 114 Vass, Sophias Avenue, Athens 115 27, Greece.
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Sorà F, Ponziani FR, Laurenti L, Chiusolo P, Autore F, Gasbarrini A, Sica S, Pompili M. Low risk of hepatitis B virus reactivation in patients with resolved infection and chronic myeloid leukemia treated with tyrosine kinase inhibitors. Leuk Lymphoma 2016; 58:993-995. [DOI: 10.1080/10428194.2016.1219906] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
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Law MF, Ho R, Cheung CKM, Tam LHP, Ma K, So KCY, Ip B, So J, Lai J, Ng J, Tam THC. Prevention and management of hepatitis B virus reactivation in patients with hematological malignancies treated with anticancer therapy. World J Gastroenterol 2016; 22:6484-6500. [PMID: 27605883 PMCID: PMC4968128 DOI: 10.3748/wjg.v22.i28.6484] [Citation(s) in RCA: 66] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/01/2016] [Revised: 05/24/2016] [Accepted: 06/15/2016] [Indexed: 02/06/2023] Open
Abstract
Hepatitis due to hepatitis B virus (HBV) reactivation can be severe and potentially fatal, but is preventable. HBV reactivation is most commonly reported in patients receiving cancer chemotherapy, especially rituximab-containing therapy for hematological malignancies and those receiving stem cell transplantation. All patients with hematological malignancies receiving anticancer therapy should be screened for active or resolved HBV infection by blood tests for hepatitis B surface antigen (HBsAg) and antibody to hepatitis B core antigen (anti-HBc). Patients found to be positive for HBsAg should be given prophylactic antiviral therapy to prevent HBV reactivation. For patients with resolved HBV infection, no standard strategy has yet been established to prevent HBV reactivation. There are usually two options. One is pre-emptive therapy guided by serial HBV DNA monitoring, whereby antiviral therapy is given as soon as HBV DNA becomes detectable. However, there is little evidence regarding the optimal interval and period of monitoring. An alternative approach is prophylactic antiviral therapy, especially for patients receiving high-risk therapy such as rituximab, newer generation of anti-CD20 monoclonal antibody, obinutuzumab or hematopoietic stem cell transplantation. This strategy may effectively prevent HBV reactivation and avoid the inconvenience of repeated HBV DNA monitoring. Entecavir or tenofovir are preferred over lamivudine as prophylactic therapy. Although there is no well-defined guideline on the optimal duration of prophylactic therapy, there is growing evidence to recommend continuing prophylactic antiviral therapy for at least 12 mo after cessation of chemotherapy, and even longer for those who receive rituximab or who had high serum HBV DNA levels before the start of immunosuppressive therapy. Many novel agents have recently become available for the treatment of hematological malignancies, and these agents may be associated with HBV reactivation. Although there is currently limited evidence to guide the optimal preventive measures, we recommend antiviral prophylaxis in HBsAg-positive patients receiving novel treatments, especially the Bruton tyrosine kinase inhibitors and the phosphatidylinositol 3-kinase inhibitors, which are B-cell receptor signaling modulators and reduce proliferation of malignant B-cells. Further studies are needed to clarify the risk of HBV reactivation with these agents and the best prophylactic strategy in the era of targeted therapy for hematological malignancies.
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Temel T, Gunduz E, Sadigova E, Uskudar Teke H, Meric Ozgenel S, Harmanci Ozakyol A. Hepatitis B Virus Reactivation under Treatment with Nilotinib. Euroasian J Hepatogastroenterol 2016; 5:112-114. [PMID: 29201705 PMCID: PMC5578539 DOI: 10.5005/jp-journals-10018-1147] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/13/2015] [Accepted: 04/15/2015] [Indexed: 12/14/2022] Open
Abstract
Hepatitis B virus (HBV) reactivation with imatinib, a tyrosine kinase inhibitor, has been reported in chronic myeloid leukemia. Nilotinib is a more potent second generation tyrosine kinase inhibitor and it inhibits the Src-family kinase LCK and hamper proliferation and function of CD8 (+) T lymphocytes. CD8 (+) T lymphocytes are the main cellular subset responsible for viral clearance in patients with HBV infection. We report a case of HBV reactivation under treatment with nilotinib. Fatal HBV reactivation is not usually related to death in chronic myeloid leukemia patients who have an expectation of longevity with well-tolerated oral drugs. Thus, screening for latent chronic HBV infections including assessment of hepatitis B surface antigen (HBsAg), antibody to hepatitis B core antigen (anti-HBc antibody) and antibody to hepatitis B surface antigen (anti-HBs), especially at countries with intermediate and high prevalence of HBsAg is warranted. Treatment with nucleoside analogs and close monitoring may be life-saving in this context.
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Affiliation(s)
- Tuncer Temel
- Department of Gastroenterology, Eskisehir Osmangazi University, Eskisehir, Turkey
| | - Eren Gunduz
- Department of Hematology, Eskisehir Osmangazi University, Eskisehir, Turkey
| | - Esmira Sadigova
- Department of Internal Medicine, Eskisehir Osmangazi University, Eskisehir, Turkey
| | - Hava Uskudar Teke
- Department of Hematology, Eskisehir Osmangazi University, Eskisehir, Turkey
| | - Safak Meric Ozgenel
- Department of Gastroenterology, Eskisehir Osmangazi University, Eskisehir, Turkey
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Pattullo V. Prevention of Hepatitis B reactivation in the setting of immunosuppression. Clin Mol Hepatol 2016; 22:219-37. [PMID: 27291888 PMCID: PMC4946398 DOI: 10.3350/cmh.2016.0024] [Citation(s) in RCA: 88] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2016] [Accepted: 04/27/2016] [Indexed: 12/13/2022] Open
Abstract
Advances in the treatment of malignant and inflammatory diseases have developed over time, with increasing use of chemotherapeutic and immunosuppressive agents of a range of drug classes with varying mechanism and potency in their effects on the immune system. These advances have been met with the challenge of increased risk of hepatitis B virus (HBV) reactivation in susceptible individuals. The magnitude of risk of HBV reactivation is associated with the individual’s HBV serological status and the potency and duration of immunosuppression. Individuals with chronic hepatitis B (CHB) and previously infected but serologically cleared HBV infection are both susceptible to HBV reactivation. HBV reactivation in the setting of immunosuppression is a potentially life threatening condition leading to liver failure and death in extreme cases. It is important to recognize that HBV reactivation in the setting of immunosuppression is potentially preventable. Therefore, identification of patients at risk of HBV reactivation and institution of prophylactic antiviral therapy prior to initiation of immunosuppression is essential.
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Affiliation(s)
- Venessa Pattullo
- Department of Gastroenterology, Royal North Shore Hospital, Sydney, Australia
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50
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Abstract
INTRODUCTION Understanding the mechanism of DILI with MTA, and how to avoid and manage these toxicities is essential for minimising inferior cancer treatment outcomes. An organised and comprehensive overview of MTA-associated hepatotoxicity is lacking; this review aims to fill the gap. AREAS COVERED A literature review was performed based on published case reports and relevant studies or articles pertaining to the topics on PubMed. Food and Drug Administration drug information documents and search on the US National Library of Medicine LiverTox database was performed for all relevant MTA. EXPERT OPINION MTA-associated hepatotoxicity is common but rarely fatal. The pattern of hepatotoxicity is predominantly idiosyncratic. Pharmacogenomics show potential in predicting patients at risk of poorly metabolising or developing immunoallergic responses to MTA, but prospective data is scant. Preventing reactivation of viral hepatitis using anti-viral drugs, and avoidance of drug combinations at high risk of negative interactions are the most readily preventable measures for DILI.
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Affiliation(s)
- Kirsty Wai-Chung Lee
- a Sir YK Pao Center for Cancer, Department of Clinical Oncology, State Key Laboratory in Oncology in South China , The Chinese University of Hong Kong, Hong Kong Cancer Institute and Prince of Wales Hospital , Shatin , Hong Kong
| | - Stephen Lam Chan
- a Sir YK Pao Center for Cancer, Department of Clinical Oncology, State Key Laboratory in Oncology in South China , The Chinese University of Hong Kong, Hong Kong Cancer Institute and Prince of Wales Hospital , Shatin , Hong Kong.,b Institute of Digestive Disease , The Chinese University of Hong Kong , Shatin , Hong Kong
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