|
1
|
Shahid Z, Jain T, Dioverti V, Pennisi M, Mikkilineni L, Thiruvengadam SK, Shah NN, Dadwal S, Papanicolaou G, Hamadani M, Carpenter PA, Alfaro GM, Seo SK, Hill JA. Best Practice Considerations by The American Society of Transplant and Cellular Therapy: Infection Prevention and Management After Chimeric Antigen Receptor T Cell Therapy for Hematological Malignancies. Transplant Cell Ther 2024; 30:955-969. [PMID: 39084261 DOI: 10.1016/j.jtct.2024.07.018] [Citation(s) in RCA: 14] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2024] [Accepted: 07/24/2024] [Indexed: 08/02/2024]
Abstract
Chimeric antigen receptor (CAR) T-cell therapy is rapidly advancing, offering promising treatments for patients with hematological malignancy. However, associated infectious complications remain a significant concern because of their contribution to patient morbidity and non-relapse mortality. Recent epidemiological insights shed light on risk factors for infections after CAR T-cell therapy. However, the available evidence is predominantly retrospective, highlighting a need for further prospective studies. Institutions are challenged with managing infections after CAR T-cell therapy but variations in the approaches taken underscore the importance of standardizing infection prevention and management protocols across different healthcare settings. Therefore, the Infectious Diseases Special Interest Group of the American Society of Transplantation and Cellular Therapy assembled an expert panel to develop best practice considerations. The aim was to guide healthcare professionals in optimizing infection prevention and management for CAR T-cell therapy recipients and advocates for early consultation of Infectious Diseases during treatment planning phases given the complexities involved. By synthesizing current evidence and expert opinion these best practice considerations provide the basis for understanding infection risk after CAR T-cell therapies and propose risk-mitigating strategies in children, adolescents, and adults. Continued research and collaboration will be essential to refining and effectively implementing these recommendations.
Collapse
Affiliation(s)
- Zainab Shahid
- Infectious Diseases Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
| | - Tania Jain
- Division of Hematological Malignancies and Bone Marrow Transplantation, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland
| | - Veronica Dioverti
- Division of Infectious Disease, Department of Medicine, John Hopkins School of Medicine, Baltimore, Maryland
| | - Martini Pennisi
- Division of Hematology and Stem Cell Transplantation, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy
| | - Lekha Mikkilineni
- Division of Bone and Marrow Transplant & Cellular Therapies, Stanford School of Medicine, Palo Alto, California
| | - Swetha Kambhampati Thiruvengadam
- Division of Lymphoma, Department of Hematology & Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, California
| | - Nirali N Shah
- Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland
| | - Sanjeet Dadwal
- Division of Infectious Disease, Department of Medicine, City of Hope National Medical Center, Duarte, California
| | - Genovefa Papanicolaou
- Infectious Diseases Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Mehdi Hamadani
- Bone Marrow Transplant & Cellular Therapy Program, Medical College of Wisconsin, Milwaukee, Wisconsin; Center for International Blood and Marrow Transplant Research, Milwaukee, Wisconsin
| | - Paul A Carpenter
- Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, Washington
| | - Gabriela Maron Alfaro
- Department of Infectious Diseases, St. Jude Children's Research Hospital and Department of Pediatrics, University of Tennessee Health Science Center, Memphis, Tennessee
| | - Susan K Seo
- Infectious Diseases Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Joshua A Hill
- Vaccine and Infectious Disease Division, Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, Washington
| |
Collapse
|
|
2
|
Kucharzik T, Dignass A, Atreya R, Bokemeyer B, Esters P, Herrlinger K, Kannengiesser K, Kienle P, Langhorst J, Lügering A, Schreiber S, Stallmach A, Stein J, Sturm A, Teich N, Siegmund B. Aktualisierte S3-Leitlinie Colitis ulcerosa (Version 6.2). ZEITSCHRIFT FUR GASTROENTEROLOGIE 2024; 62:769-858. [PMID: 38718808 DOI: 10.1055/a-2271-0994] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/02/2024]
Affiliation(s)
- T Kucharzik
- Klinik für Allgemeine Innere Medizin und Gastroenterologie, Städtisches Klinikum Lüneburg, Lüneburg, Deutschland
| | - A Dignass
- Medizinische Klinik I, Agaplesion Markus Krankenhaus, Frankfurt, Deutschland
| | - R Atreya
- Medizinische Klinik 1 Gastroent., Pneumologie, Endokrin., Universitätsklinikum Erlangen, Erlangen, Deutschland
| | - B Bokemeyer
- Interdisziplinäres Crohn Colitis Centrum Minden - ICCCM, Minden, Deutschland
| | - P Esters
- Medizinische Klinik I, Agaplesion Markus Krankenhaus, Frankfurt, Deutschland
| | - K Herrlinger
- Innere Medizin I, Asklepios Klinik Nord, Hamburg, Deutschland
| | - K Kannengiesser
- Klinik für Allgemeine Innere Medizin und Gastroenterologie, Städtisches Klinikum Lüneburg, Lüneburg, Deutschland
| | - P Kienle
- Abteilung für Allgemein- und Viszeralchirurgie, Theresienkrankenhaus, Mannheim, Deutschland
| | - J Langhorst
- Klinik für Integrative Medizin und Naturheilkunde, Sozialstiftung Bamberg Klinikum am Bruderwald, Bamberg, Deutschland
| | - A Lügering
- Medizinisches Versorgungszentrum Portal 10, Münster, Deutschland
| | - S Schreiber
- Klinik für Innere Medizin I, Universitätsklinikum Schleswig Holstein, Kiel, Deutschland
| | - A Stallmach
- Klinik für Innere Medizin IV Gastroenterologie, Hepatologie, Infektiologie, Universitätsklinikum Jena, Jena, Deutschland
| | - J Stein
- Abteilung Innere Medizin mit Schwerpunkt Gastroenterologie, Krankenhaus Sachsenhausen, Frankfurt, Deutschland
| | - A Sturm
- Klinik für Innere Medizin mit Schwerpunkt Gastroenterologie, DRK Kliniken Berlin Westend, Berlin, Deutschland
| | - N Teich
- Internistische Gemeinschaftspraxis, Leipzig, Deutschland
| | - B Siegmund
- Medizinische Klinik für Gastroenterologie, Infektiologie und Rheumatologie, Charité Campus Benjamin Franklin - Universitätsmedizin Berlin, Berlin, Deutschland
| |
Collapse
|
|
3
|
Kucharzik T, Dignass A, Atreya R, Bokemeyer B, Esters P, Herrlinger K, Kannengiesser K, Kienle P, Langhorst J, Lügering A, Schreiber S, Stallmach A, Stein J, Sturm A, Teich N, Siegmund B. [Not Available]. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2023; 61:1046-1134. [PMID: 37579791 DOI: 10.1055/a-2060-0935] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 08/16/2023]
Affiliation(s)
- T Kucharzik
- Klinik für Allgemeine Innere Medizin und Gastroenterologie, Städtisches Klinikum Lüneburg, Lüneburg, Deutschland
| | - A Dignass
- Medizinische Klinik I, Agaplesion Markus Krankenhaus, Frankfurt, Deutschland
| | - R Atreya
- Medizinische Klinik 1 Gastroent., Pneumologie, Endokrin., Universitätsklinikum Erlangen, Erlangen, Deutschland
| | - B Bokemeyer
- Interdisziplinäres Crohn Colitis Centrum Minden - ICCCM, Minden, Deutschland
| | - P Esters
- Medizinische Klinik I, Agaplesion Markus Krankenhaus, Frankfurt, Deutschland
| | - K Herrlinger
- Innere Medizin I, Asklepios Klinik Nord, Hamburg, Deutschland
| | - K Kannengiesser
- Klinik für Allgemeine Innere Medizin und Gastroenterologie, Städtisches Klinikum Lüneburg, Lüneburg, Deutschland
| | - P Kienle
- Abteilung für Allgemein- und Viszeralchirurgie, Theresienkrankenhaus, Mannheim, Deutschland
| | - J Langhorst
- Klinik für Integrative Medizin und Naturheilkunde, Sozialstiftung Bamberg Klinikum am Bruderwald, Bamberg, Deutschland
| | - A Lügering
- Medizinisches Versorgungszentrum Portal 10, Münster, Deutschland
| | - S Schreiber
- Klinik für Innere Medizin I, Universitätsklinikum Schleswig Holstein, Kiel, Deutschland
| | - A Stallmach
- Klinik für Innere Medizin IV Gastroenterologie, Hepatologie, Infektiologie, Universitätsklinikum Jena, Jena, Deutschland
| | - J Stein
- Abteilung Innere Medizin mit Schwerpunkt Gastroenterologie, Krankenhaus Sachsenhausen, Frankfurt, Deutschland
| | - A Sturm
- Klinik für Innere Medizin mit Schwerpunkt Gastroenterologie, DRK Kliniken Berlin Westend, Berlin, Deutschland
| | - N Teich
- Internistische Gemeinschaftspraxis, Leipzig, Deutschland
| | - B Siegmund
- Medizinische Klinik für Gastroenterologie, Infektiologie und Rheumatologie, Charité Campus Benjamin Franklin - Universitätsmedizin Berlin, Berlin, Deutschland
| |
Collapse
|
|
4
|
Nayak SP, Bagchi B, Roy S. Effects of immunosuppressants on T-cell dynamics: Understanding from a generic coarse-grained immune network model. J Biosci 2022; 47:70. [PMID: 36503907 PMCID: PMC9734612 DOI: 10.1007/s12038-022-00312-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Long-term immunosuppressive therapy is a drug regimen often used to lower aggressive immune responses in various chronic inflammatory diseases. However, such long-term therapy leading to immune suppression may trigger other adverse reactions in the immune system. The rising concern regarding the optimal dose and duration of such treatment has motivated us to understand non-classical immunomodulatory responses induced by various immunosuppressive steroid and secosteroid drugs such as glucocorticoid and vitamin D supplements. The immunomodulatory actions of such immunosuppressants (that govern the adaptive immune response) are often mediated through their characteristic control over CD4+ T-cells involving pro- and antiinflammatory T-cells. Several early studies attempted to decode temporal and dose-dependent behaviors of such pro- and anti-inflammatory T-cells using the chemical dynamics approach. We first summarize these early works. Then, we develop a minimal coarse-grained kinetic network model to capture the commonality in their immunomodulatory functions. This generic model successfully reproduces the characteristic dynamical features, including the clinical latency period in long-term T-cell dynamics. The temporal behavior of T-cells is found to be sensitive to specific rate parameters and doses of immunosuppressants. The steady-state analysis reflects the transition from an early classified weakly regulated (autoimmune-prone) immune state to a strongly regulated state (immunocompromised state), separated by an intervening state of moderate/balanced regulation. An optimal dose and duration are essential in rescuing balanced immune regulation. This review elucidates how developing a simple generic coarse-grained immune network model may provide immense information that helps diagnose inefficacy in adaptive immune function before and after administering immunosuppressants such as glucocorticoid or vitamin D.
Collapse
Affiliation(s)
- Sonali Priyadarshini Nayak
- Department of Systems and Computational Biology, School of Life Sciences, University of Hyderabad, Hyderabad, 500046 India
- Max Planck School Matter to Life, University of Göttingen, Friedrich-Hund-Platz 1, 37077 Göttingen, Germany
| | - Biman Bagchi
- Solid State and Structural Chemistry Unit, Indian Institute of Science, Bengaluru, 560012 India
| | - Susmita Roy
- Department of Chemical Sciences, Indian Institute of Science Education and Research, Kolkata, 741246 India
| |
Collapse
|
|
5
|
Inada K, Kaneko S, Kurosaki M, Yamashita K, Kirino S, Osawa L, Hayakawa Y, Sekiguchi S, Higuchi M, Takaura K, Maeyashiki C, Tamaki N, Yasui Y, Itakura J, Takahashi Y, Tsuchiya K, Nakanishi H, Okamoto R, Izumi N. Tenofovir alafenamide for prevention and treatment of hepatitis B virus reactivation and de novo hepatitis. JGH Open 2021; 5:1085-1091. [PMID: 34584979 PMCID: PMC8454476 DOI: 10.1002/jgh3.12636] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2021] [Revised: 07/25/2021] [Accepted: 07/25/2021] [Indexed: 12/14/2022]
Abstract
Background and Aim Administration of tenofovir alafenamide (TAF) as prevention or treatment of hepatitis B virus (HBV) reactivation is not well known. The aim of this study is to reveal the efficacy and safety of TAF against HBV reactivation. Methods Entecavir (ETV) and TAF were given to 66 and 11 patients, respectively, as prophylaxis against or treatment of HBV reactivation during chemotherapy or immune suppression therapy from January 2010 to June 2020. The antiviral effects and safety were assessed. Results At week 24, the antiviral effects on patients receiving ETV and TAF were similar in terms of reduction of HBV DNA (-2.83 ± 1.45log IU/mL vs -3.05 ± 2.47log IU/mL; P = 0.857) and achieving undetectable levels of HBV DNA (78.8 vs 90.9%; P = 0.681). There was no significant difference in the decrease in the estimated glomerular filtration rate (eGFR) between the two groups (-0.62 ± 11.2 mL/min/1.73 m2 vs -3.67 ± 13.2 mL/min/1.73 m2; P = 0.291). Conclusion TAF is safe and effective against HBV reactivation.
Collapse
Affiliation(s)
- Kento Inada
- Department of Gastroenterology and Hepatology Musashino Red Cross Hospital Tokyo Japan
| | - Shun Kaneko
- Department of Gastroenterology and Hepatology Musashino Red Cross Hospital Tokyo Japan
| | - Masayuki Kurosaki
- Department of Gastroenterology and Hepatology Musashino Red Cross Hospital Tokyo Japan
| | - Koji Yamashita
- Department of Gastroenterology and Hepatology Musashino Red Cross Hospital Tokyo Japan
| | - Sakura Kirino
- Department of Gastroenterology and Hepatology Musashino Red Cross Hospital Tokyo Japan
| | - Leona Osawa
- Department of Gastroenterology and Hepatology Musashino Red Cross Hospital Tokyo Japan
| | - Yuka Hayakawa
- Department of Gastroenterology and Hepatology Musashino Red Cross Hospital Tokyo Japan
| | - Shuhei Sekiguchi
- Department of Gastroenterology and Hepatology Musashino Red Cross Hospital Tokyo Japan
| | - Mayu Higuchi
- Department of Gastroenterology and Hepatology Musashino Red Cross Hospital Tokyo Japan
| | - Kenta Takaura
- Department of Gastroenterology and Hepatology Musashino Red Cross Hospital Tokyo Japan
| | - Chiaki Maeyashiki
- Department of Gastroenterology and Hepatology Musashino Red Cross Hospital Tokyo Japan
| | - Nobuharu Tamaki
- Department of Gastroenterology and Hepatology Musashino Red Cross Hospital Tokyo Japan
| | - Yutaka Yasui
- Department of Gastroenterology and Hepatology Musashino Red Cross Hospital Tokyo Japan
| | - Jun Itakura
- Department of Gastroenterology and Hepatology Musashino Red Cross Hospital Tokyo Japan
| | - Yuka Takahashi
- Department of Gastroenterology and Hepatology Musashino Red Cross Hospital Tokyo Japan
| | - Kaoru Tsuchiya
- Department of Gastroenterology and Hepatology Musashino Red Cross Hospital Tokyo Japan
| | - Hiroyuki Nakanishi
- Department of Gastroenterology and Hepatology Musashino Red Cross Hospital Tokyo Japan
| | - Ryuichi Okamoto
- Department of Gastroenterology and Hepatology Tokyo Medical and Dental University Tokyo Japan
| | - Namiki Izumi
- Department of Gastroenterology and Hepatology Musashino Red Cross Hospital Tokyo Japan
| |
Collapse
|
|
6
|
Tamori A, Kimura K, Kioka K, Enomoto H, Odagiri N, Kozuka R, Uchida-Kobayashi S, Enomoto M, Kawada N, Mizokami M. Outcome of nucleos(t)ide analog intervention in patients with preventive or on-demand therapy for hepatitis B virus reactivation. J Med Virol 2021; 93:3679-3687. [PMID: 32940921 DOI: 10.1002/jmv.26526] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2020] [Revised: 08/24/2020] [Accepted: 08/26/2020] [Indexed: 01/05/2023]
Abstract
Preventive or on-demand nucleos(t)ide analog (NA) therapy can prevent severe hepatitis related to hepatitis B virus reactivation (HBV-R). However, it is unclear if NA can be safely stopped in such patients after cytotoxic therapies or during immunosuppressive therapies. We retrospectively evaluated 133 patients who initiated NA therapy between 2007 and 2018. A total of 103 patients were positive for HBV surface antigen (HBsAg) at baseline, and NA therapy was started before cytotoxic or immunosuppressive therapy (preventive group). Thirty patients with resolved HBV infection were treated with NA therapy after HBV reactivation (on-demand group). Virological relapse was defined as a serum HBV DNA level >20 IU/ml. NA therapy was stopped in 12 (12%) patients (preventive group), and in 16 (53%) patients (on-demand group). After the cessation of NA therapy, the cumulative rates of relapse were 36% and 39% at 12 and 24 months, respectively. High levels of HBsAg both at baseline and at the cessation of NA therapy were related to the occurrence of relapse. Relapse did not occur in patients with HBsAg levels <20 IU/ml (preventive group). HBV relapse occurred in five (33%) patients in the on-demand group. Relapse occurred only in anti-HBs-negative patients at the cessation of NA therapy. There were no cases of hepatitis flare after the cessation of NA therapy. HBsAg predicted HBV relapse after the cessation of NA therapy in HBsAg-positive patients. Anti-HBs could be a predictive marker for NA therapy cessation in patients with resolved HBV.
Collapse
Affiliation(s)
- Akihiro Tamori
- Department of Hepatology, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Kiminori Kimura
- Department of Hepatology, Tokyo Metropolitan Komagome Hospital, Tokyo, Japan
| | - Kiyohide Kioka
- Department of Hepatology, Osaka City General Hospital, Osaka, Japan
| | - Hirayuki Enomoto
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Hyogo College of Medicine, Nishinomiya, Japan
| | - Naoshi Odagiri
- Department of Hepatology, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Ritsuzo Kozuka
- Department of Hepatology, Osaka City University Graduate School of Medicine, Osaka, Japan
| | | | - Masaru Enomoto
- Department of Hepatology, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Norifumi Kawada
- Department of Hepatology, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Masashi Mizokami
- Genome Medical Sciences Project, National Center for Global Health and Medicine, Tokyo, Japan
| |
Collapse
|
|
7
|
Boumaza A, Mezouar S, Bardou M, Raoult D, Mège JL, Desnues B. Tumor Necrosis Factor Inhibitors Exacerbate Whipple's Disease by Reprogramming Macrophage and Inducing Apoptosis. Front Immunol 2021; 12:667357. [PMID: 34093562 PMCID: PMC8173622 DOI: 10.3389/fimmu.2021.667357] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2021] [Accepted: 05/05/2021] [Indexed: 12/23/2022] Open
Abstract
Tropheryma whipplei is the agent of Whipple’s disease, a rare systemic disease characterized by macrophage infiltration of the intestinal mucosa. The disease first manifests as arthralgia and/or arthropathy that usually precede the diagnosis by years, and which may push clinicians to prescribe Tumor necrosis factor inhibitors (TNFI) to treat unexplained arthralgia. However, such therapies have been associated with exacerbation of subclinical undiagnosed Whipple’s disease. The objective of this study was to delineate the biological basis of disease exacerbation. We found that etanercept, adalimumab or certolizumab treatment of monocyte-derived macrophages from healthy subjects significantly increased bacterial replication in vitro without affecting uptake. Interestingly, this effect was associated with macrophage repolarization and increased rate of apoptosis. Further analysis revealed that in patients for whom Whipple’s disease diagnosis was made while under TNFI therapy, apoptosis was increased in duodenal tissue specimens as compared with control Whipple’s disease patients who never received TNFI prior diagnosis. In addition, IFN-γ expression was increased in duodenal biopsy specimen and circulating levels of IFN-γ were higher in patients for whom Whipple’s disease diagnosis was made while under TNFI therapy. Taken together, our findings establish that TNFI aggravate/exacerbate latent or subclinical undiagnosed Whipple’s disease by promoting a strong inflammatory response and apoptosis and confirm that patients may be screened for T. whipplei prior to introduction of TNFI therapy.
Collapse
Affiliation(s)
- Asma Boumaza
- Aix Marseille Univ, IRD, APHM, MEPHI, Marseille, France.,IHU-Méditerranée Infection, Marseille, France
| | - Soraya Mezouar
- Aix Marseille Univ, IRD, APHM, MEPHI, Marseille, France.,IHU-Méditerranée Infection, Marseille, France
| | - Matthieu Bardou
- Aix Marseille Univ, IRD, APHM, MEPHI, Marseille, France.,IHU-Méditerranée Infection, Marseille, France
| | - Didier Raoult
- Aix Marseille Univ, IRD, APHM, MEPHI, Marseille, France.,IHU-Méditerranée Infection, Marseille, France
| | - Jean-Louis Mège
- Aix Marseille Univ, IRD, APHM, MEPHI, Marseille, France.,IHU-Méditerranée Infection, Marseille, France
| | - Benoit Desnues
- Aix Marseille Univ, IRD, APHM, MEPHI, Marseille, France.,IHU-Méditerranée Infection, Marseille, France
| |
Collapse
|
|
8
|
Kucharzik T, Dignass AU, Atreya R, Bokemeyer B, Esters P, Herrlinger K, Kannengießer K, Kienle P, Langhorst J, Lügering A, Schreiber S, Stallmach A, Stein J, Sturm A, Teich N, Siegmund B. [Not Available]. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2020; 58:e241-e326. [PMID: 33260237 DOI: 10.1055/a-1296-3444] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Affiliation(s)
- Torsten Kucharzik
- Klinik für Allgemeine Innere Medizin und Gastroenterologie, Klinikum Lüneburg, Lüneburg, Deutschland
| | - Axel U Dignass
- Medizinische Klinik I, Agaplesion Markus Krankenhaus, Frankfurt am Main, Deutschland
| | - Raja Atreya
- Medizinische Klinik 1, Universitätsklinikum Erlangen, Deutschland
| | - Bernd Bokemeyer
- Gastroenterologische Gemeinschaftspraxis Minden, Deutschland
| | - Philip Esters
- Medizinische Klinik I, Agaplesion Markus Krankenhaus, Frankfurt am Main, Deutschland
| | | | - Klaus Kannengießer
- Klinik für Allgemeine Innere Medizin und Gastroenterologie, Klinikum Lüneburg, Lüneburg, Deutschland
| | - Peter Kienle
- Allgemein- und Viszeralchirurgie, Theresienkrankenhaus und Sankt Hedwig-Klinik GmbH, Mannheim, Deutschland
| | - Jost Langhorst
- Klinik für Integrative Medizin und Naturheilkunde, Klinikum am Bruderwald, Bamberg, Deutschland
| | - Andreas Lügering
- Medizinisches Versorgungszentrum Portal 10, Münster, Deutschland
| | | | - Andreas Stallmach
- Gastroenterologie, Hepatologie und Infektiologie, Friedrich Schiller Universität, Jena, Deutschland
| | - Jürgen Stein
- Innere Medizin mit Schwerpunkt Gastroenterologie, Krankenhaus Sachsenhausen, Frankfurt/Main, Deutschland
| | - Andreas Sturm
- Klinik für Innere Medizin mit Schwerpunkt Gastroenterologie, DRK Kliniken Berlin Westend, Berlin, Deutschland
| | - Niels Teich
- Internistische Gemeinschaftspraxis für Verdauungs- und Stoffwechselkrankheiten, Leipzig, Deutschland
| | - Britta Siegmund
- Medizinische Klinik I, Charité Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Deutschland
| |
Collapse
|
|
9
|
Li YR, Chen WC, Tsai WL, Cheng JS, Tsay FW, Kao SS, Chen HC, Hsu PI. Severe acute exacerbation of HCV infection in cancer patients who undergo chemotherapy without antiviral prophylaxis. J Viral Hepat 2020; 27:873-879. [PMID: 32301253 DOI: 10.1111/jvh.13302] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2020] [Accepted: 03/23/2020] [Indexed: 12/21/2022]
Abstract
No guidelines have been developed for the management of HCV-infected cancer patients receiving chemotherapy. The current study aimed to investigate the incidence of severe acute exacerbation of HCV infection in cancer patients receiving chemotherapy and to search for risk factors predicting severe acute exacerbation of HCV infection. This retrospective cohort study reviewed the clinical data of the cancer patients receiving chemotherapy in our institute from August 2012 to December 2017. Incidences of severe acute exacerbation of HCV infection in different kinds of cancers were assessed, and risk factors were analysed. Cancer patients with HCV infection (n = 306) had a higher frequency of severe acute liver injury (2.3% vs 0.7%; P = .003) than those without HCV infection (n = 4419). The incidence of severe acute exacerbation in HCV-infected haematological cancer patients was higher than that in those with HCC and non-HCC solid tumours (9.4% vs 1.9% and 1.1%). Rituximab-containing chemotherapy and haematological malignancy were the risk factors related to the acute exacerbation (P < .001 and P = .004, respectively). None of the patients with severe acute HCV flares developed hepatic decompensation or mortality. However, 57.1% of them discontinued chemotherapy due to liver dysfunction. In conclusion, HCV infection increases the risk of acute severe liver injury in cancer patients undergoing chemotherapy. Rituximab-containing chemotherapy and haematological malignancy are the risk factors related to severe acute exacerbation of HCV infection in cancer patients undergoing chemotherapy. Pre-chemotherapy HCV testing is therefore mandatory before rituximab-containing chemotherapy for the treatment of haematological malignancy.
Collapse
Affiliation(s)
- Yuan-Rung Li
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Veterans General Hospital and National Yang-Ming University, Kaohsiung, Taiwan
| | - Wen-Chi Chen
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Veterans General Hospital and National Yang-Ming University, Kaohsiung, Taiwan
| | - Wei-Lun Tsai
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Veterans General Hospital and National Yang-Ming University, Kaohsiung, Taiwan
| | - Jin-Shiung Cheng
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Veterans General Hospital and National Yang-Ming University, Kaohsiung, Taiwan
| | - Feng-Woei Tsay
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Veterans General Hospital and National Yang-Ming University, Kaohsiung, Taiwan
| | - Sung-Shuo Kao
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Veterans General Hospital and National Yang-Ming University, Kaohsiung, Taiwan
| | - Hui-Chun Chen
- Department of Radiation Oncology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung City, Taiwan
| | - Ping-I Hsu
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Veterans General Hospital and National Yang-Ming University, Kaohsiung, Taiwan
| |
Collapse
|
|
10
|
Lazarevic I, Banko A, Miljanovic D, Cupic M. Biological features of hepatitis B virus strains associated with fulminant hepatitis. Future Virol 2020. [DOI: 10.2217/fvl-2020-0011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
Accumulating evidence suggests that hepatitis B virus (HBV) biological features may influence the course and clinical manifestations of infection and possibly the development of fulminant hepatitis (FH). Since HBV is not a cytocidal virus, virus-induced liver damage results from an interplay between the virus replication and the host's defense. Therefore, viral factors contributing to enhanced replication, induction of a stronger immune attack or apoptosis of hepatocytes could be crucial in development of FH. Numerous mutations in basal core promoter, pre-C, C and S regions of the HBV genome contribute to development of FH by different mechanisms, including enhanced viral replication, the loss of a decoy for immune response, unbalanced expression of viral proteins and retention of unprocessed cytotoxic proteins in hepatocytes.
Collapse
Affiliation(s)
- Ivana Lazarevic
- Institute of Microbiology & Immunology, Faculty of Medicine, University of Belgrade, Dr Subotica 1, 11000 Belgrade, Serbia
| | - Ana Banko
- Institute of Microbiology & Immunology, Faculty of Medicine, University of Belgrade, Dr Subotica 1, 11000 Belgrade, Serbia
| | - Danijela Miljanovic
- Institute of Microbiology & Immunology, Faculty of Medicine, University of Belgrade, Dr Subotica 1, 11000 Belgrade, Serbia
| | - Maja Cupic
- Institute of Microbiology & Immunology, Faculty of Medicine, University of Belgrade, Dr Subotica 1, 11000 Belgrade, Serbia
| |
Collapse
|
|
11
|
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.
Collapse
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
| |
Collapse
|
|
12
|
Yamauchi R, Takeyama Y, Takata K, Fukunaga A, Sakurai K, Tanaka T, Fukuda H, Fukuda S, Kunimoto H, Umeda K, Morihara D, Yokoyama K, Irie M, Shakado S, Sakisaka S, Hirai F. Hepatitis B Virus Reactivation after Receiving Cancer Chemotherapy under Administration of Leuprorelin Acetate. Intern Med 2020; 59:1163-1166. [PMID: 31956202 PMCID: PMC7270765 DOI: 10.2169/internalmedicine.3805-19] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/30/2022] Open
Abstract
An 88-year-old man was admitted for elevated liver enzyme levels. Nine years earlier, the patient had been diagnosed with diffuse large B-cell lymphoma (DLBCL) and undergone rituximab, cyclophosphamide, doxorubicin hydrochloride, oncovin, prednisone (R-CHOP) therapy. This patient previously had had a hepatitis B virus (HBV) infection before chemotherapy. After the chemotherapy, he was administered an luteinizing hormone-releasing hormone (LHRH) agonist for prostate cancer. We diagnosed him with HBV reactivation because of positive serum HBV-DNA. HBV reactivation can occur a long time after chemotherapy, particularly if another treatment with immunity-altering drugs is added. In such cases, additional surveillance may be required to detect HBV reactivation.
Collapse
Affiliation(s)
- Ryo Yamauchi
- Department of Gastroenterology and Medicine, Fukuoka University Faculty of Medicine, Japan
| | - Yasuaki Takeyama
- Department of Gastroenterology and Medicine, Fukuoka University Faculty of Medicine, Japan
| | - Kazuhide Takata
- Department of Gastroenterology and Medicine, Fukuoka University Faculty of Medicine, Japan
| | | | | | - Takashi Tanaka
- Department of Gastroenterology and Medicine, Fukuoka University Faculty of Medicine, Japan
| | - Hiromi Fukuda
- Department of Gastroenterology and Medicine, Fukuoka University Faculty of Medicine, Japan
| | - Sho Fukuda
- Department of Gastroenterology and Medicine, Fukuoka University Faculty of Medicine, Japan
| | - Hideo Kunimoto
- Department of Gastroenterology and Medicine, Fukuoka University Faculty of Medicine, Japan
| | - Kaoru Umeda
- Department of Gastroenterology and Medicine, Fukuoka University Faculty of Medicine, Japan
| | - Daisuke Morihara
- Department of Gastroenterology and Medicine, Fukuoka University Faculty of Medicine, Japan
| | - Keiji Yokoyama
- Department of Gastroenterology and Medicine, Fukuoka University Faculty of Medicine, Japan
| | - Makoto Irie
- Department of Gastroenterology, Fukuoka University Nishijn Hospital, Japan
| | - Satoshi Shakado
- Department of Gastroenterology and Medicine, Fukuoka University Faculty of Medicine, Japan
| | - Shotaro Sakisaka
- Department of Gastroenterology and Medicine, Fukuoka University Faculty of Medicine, Japan
- General Medical Research Center, Fukuoka University Faculty of Medicine, Japan
| | - Fumihito Hirai
- Department of Gastroenterology and Medicine, Fukuoka University Faculty of Medicine, Japan
| |
Collapse
|
|
13
|
Gentile G, Antonelli G. HBV Reactivation in Patients Undergoing Hematopoietic Stem Cell Transplantation: A Narrative Review. Viruses 2019; 11:v11111049. [PMID: 31717647 PMCID: PMC6893755 DOI: 10.3390/v11111049] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2019] [Revised: 10/30/2019] [Accepted: 11/07/2019] [Indexed: 02/06/2023] Open
Abstract
HBV reactivation (HBVr) can occur due to the ability of HBV to remain latent in the liver as covalently closed circular DNA and by the capacity of HBV to alter the immune system of the infected individuals. HBVr can occur in patients undergoing hematopoietic stem cell transplantation (HSCT) with a clinical spectrum that ranges from asymptomatic infection to fulminant hepatic failure. The risk of HBVr is determined by a complex interplay between host immunity, virus factors, and immunosuppression related to HSCT. All individuals who undergo HSCT should be screened for HBV. HSCT patients positive for HBsAg and also those HBcAb-positive/HBsAg-negative are at high risk of HBV reactivation (HBVr) due to profound and prolonged immunosuppression. Antiviral prophylaxis prevents HBVr, decreases HBVr-related morbidity and mortality in patients with chronic or previous HBV. The optimal duration of antiviral prophylaxis remains to be elucidated. The vaccination of HBV-naïve recipients and their donors against HBV prior to HSCT has an important role in the prevention of acquired HBV infection. This narrative review provides a comprehensive update on the current concepts, risk factors, molecular mechanisms, prevention, and management of HBVr in HSCT.
Collapse
Affiliation(s)
- Giuseppe Gentile
- Dept. Translational and Precision Medicine, Sapienza University of Rome, 00161 Rome, Italy
- Correspondence: or
| | - Guido Antonelli
- Dept. Molecular Medicine, Sapienza University of Rome, 00161 Rome, Italy
| |
Collapse
|
|
14
|
2018 Korean Liver Cancer Association-National Cancer Center Korea Practice Guidelines for the Management of Hepatocellular Carcinoma. Korean J Radiol 2019; 20:1042-1113. [PMID: 31270974 PMCID: PMC6609431 DOI: 10.3348/kjr.2019.0140] [Citation(s) in RCA: 191] [Impact Index Per Article: 31.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2019] [Accepted: 02/24/2019] [Indexed: 01/10/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the fifth most common cancer globally and the fourth most common cancer in men in Korea, where the prevalence of chronic hepatitis B infection is high in middle-aged and elderly patients. These practice guidelines will provide useful and constructive advice for the clinical management of patients with HCC. A total of 44 experts in hepatology, oncology, surgery, radiology, and radiation oncology in the Korean Liver Cancer Association-National Cancer Center Korea Practice Guideline Revision Committee revised the 2014 Korean guidelines and developed new recommendations that integrate the most up-to-date research findings and expert opinions.
Collapse
|
|
15
|
Pratt PK, Nunes D, Long MT, Farraye FA. Improved Antibody Response to Three Additional Hepatitis B Vaccine Doses Following Primary Vaccination Failure in Patients with Inflammatory Bowel Disease. Dig Dis Sci 2019; 64:2031-2038. [PMID: 30945037 PMCID: PMC6764090 DOI: 10.1007/s10620-019-05595-6] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/11/2018] [Accepted: 03/18/2019] [Indexed: 12/13/2022]
Abstract
BACKGROUND Studies have shown the efficacy of hepatitis B (HBV) vaccination in patients with inflammatory bowel disease (IBD) is impaired, but few data exist regarding the effectiveness of revaccination strategies following primary vaccination failure. Our aim was to analyze the association between administration of additional vaccine doses and hepatitis B surface antibody (HBsAb) seroconversion. METHODS This is a retrospective cohort study. Inclusion criteria are as follows: age ≥ 18, diagnosis of Crohn's disease (CD) or ulcerative colitis (UC), inadequate HBsAb < 10 IU/L following initial HBV vaccination series, subsequent administration of 1-3 additional doses of HBV vaccine with follow-up serum HBsAb measurements. Patients were stratified into groups of ≤ 2 or 3 doses received. Primary outcome was achieving HBsAb > 10 IU/L. Outcomes were stratified by age ≥ or < 40 years. We performed logistic and linear multivariable regression analyses for categorical and continuous data. RESULTS The study cohort consists of (n = 149) 54.4% women; 77.9% white; 72.6% with CD, with mean age: 46.2. Patients of all ages and age ≥ 40 years, who received 3 additional doses of vaccine, were more likely to achieve seroprotective HBsAb levels than patients who received 1 or 2 doses (OR 1.77, P = 0.01; OR 1.9, P = 0.03, respectively, after adjusting for age, sex, race, immunosuppressive medication exposure, time between vaccine/titer). CONCLUSIONS Following initial HBV vaccination failure, patients with IBD of all ages are more likely to develop seroprotective levels of HBsAb following 3 additional vaccine doses, rather than 1 or 2 alone. In patients who fail primary HBV vaccination, providers should consider a more aggressive revaccination strategy with an additional 3-dose series.
Collapse
Affiliation(s)
- Perry K. Pratt
- Present Address: Division of Gastroenterology and Hepatology, University of Connecticut Health, Farmington, CT, USA
| | - David Nunes
- Section of Gastroenterology, Boston University Medical Center, 85 East Concord Street, Boston, MA 02118, USA
| | - Michelle T. Long
- Section of Gastroenterology, Boston University Medical Center, 85 East Concord Street, Boston, MA 02118, USA
| | - Francis A. Farraye
- Section of Gastroenterology, Boston University Medical Center, 85 East Concord Street, Boston, MA 02118, USA
| |
Collapse
|
|
16
|
2018 Korean Liver Cancer Association-National Cancer Center Korea Practice Guidelines for the Management of Hepatocellular Carcinoma. Gut Liver 2019; 13:227-299. [PMID: 31060120 PMCID: PMC6529163 DOI: 10.5009/gnl19024] [Citation(s) in RCA: 241] [Impact Index Per Article: 40.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2019] [Accepted: 01/24/2019] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the fifth most common cancer globally and the fourth most common cancer in men in Korea, where the prevalence of chronic hepatitis B infection is high in middle-aged and elderly patients. These practice guidelines will provide useful and constructive advice for the clinical management of patients with HCC. A total of 44 experts in hepatology, oncology, surgery, radiology and radiation oncology in the Korean Liver Cancer Association-National Cancer Center Korea Practice Guideline Revision Committee revised the 2014 Korean guidelines and developed new recommendations that integrate the most up-to-date research findings and expert opinions.
Collapse
|
|
17
|
Kim HY, Yoo JJ, Oh S, Yu SJ, Kim YJ, Yoon JH, Kim W, Jung YJ, Kim BH, Kim CM, Park JW, Lee JH. Scoring system for risk stratification of viral reactivation during prophylactic antiviral treatment in Korean patients with hepatitis B undergoing anticancer chemotherapy: A multicenter study. J Med Virol 2018; 90:1593-1603. [PMID: 29900560 DOI: 10.1002/jmv.25241] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2018] [Accepted: 05/26/2018] [Indexed: 12/26/2022]
Abstract
Prophylactic antiviral therapy is recommended for hepatitis B virus (HBV)-infected patients with malignancies who are undergoing systemic chemotherapy. In the current study, we aimed to develop a risk scoring system to guide the selection of prophylactic antiviral agents. In this retrospective analysis, we included consecutive chronic hepatitis B patients who received antiviral prophylaxis for chemotherapy of solid or hematologic malignancies at three large-volume hospitals in Korea. The primary endpoint was HBV reactivation. The inverse probability treatment weighting method was used to minimize selection bias in terms of antiviral assignments. A total of 419 patients were enrolled: 129 patients received lamivudine (LAM), 216 received telbivudine (LdT), and 74 received entecavir (ETV), respectively. Of these, 36 patients developed on-treatment HBV reactivation (LAM, 17; LdT, 18; ETV, 1). Multivariate analysis identified three independent predictors for reactivation: hepatitis B e-antigen positivity, HBV DNA level, and type of malignancy. Accordingly, a risk scoring system was developed wherein one point was assigned for each of the risk factors. HBV reactivation occurred more frequently in the high-risk group (score ≥ 2) than in the low-risk group (hazards ratio, 14.17; P < 0.001). ETV exhibited superior prophylactic efficacy over LdT or LAM in the high-risk group, whereas no significant difference was noted in the low-risk group. The prognostic scoring system was useful for risk stratification of chemotherapy-related HBV reactivation. High genetic barrier agents appear to be vital for high-risk patients, whereas cost-effectiveness may be more relevant for low-risk patients.
Collapse
Affiliation(s)
- Hwi Young Kim
- Department of Internal Medicine, College of Medicine, Ewha Womans University, Seoul, Republic of Korea
| | - Jeong-Ju Yoo
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Republic of Korea
| | - Sohee Oh
- Department of Biostatistics, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, Republic of Korea
| | - Su Jong Yu
- Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Yoon Jun Kim
- Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Jung-Hwan Yoon
- Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Won Kim
- Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, Republic of Korea
| | - Yong Jin Jung
- Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, Republic of Korea
| | - Bo Hyun Kim
- Center for Liver Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Republic of Korea
| | - Chang-Min Kim
- Center for Liver Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Republic of Korea
| | - Joong-Won Park
- Center for Liver Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Republic of Korea
| | - Jeong-Hoon Lee
- Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea
| |
Collapse
|
|
18
|
Seto WK, Chan TSY, Hwang YY, Wong DKH, Fung J, Liu KSH, Gill H, Lam YF, Lau EHY, Cheung KS, Lie AKW, Lai CL, Kwong YL, Yuen MF. Hepatitis B reactivation in occult viral carriers undergoing hematopoietic stem cell transplantation: A prospective study. Hepatology 2017; 65:1451-1461. [PMID: 28027590 DOI: 10.1002/hep.29022] [Citation(s) in RCA: 79] [Impact Index Per Article: 9.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2016] [Revised: 10/10/2016] [Accepted: 12/22/2016] [Indexed: 12/15/2022]
Abstract
UNLABELLED Hepatitis B virus (HBV) reactivation in hepatitis B surface antigen (HBsAg)-negative, antibody to hepatitis B core antigen (anti-HBc)-positive patients after allogeneic hematopoietic stem cell transplantation (HSCT) has not been prospectively studied. HBsAg-negative, anti-HBc-positive patients with undetectable HBV DNA undergoing allogeneic HSCT were prospectively monitored every 4 weeks. The primary endpoint was HBV reactivation, defined as detectable HBV DNA (≥10 IU/mL). Secondary endpoints included overall survival, HBsAg positivity, and changes in liver biochemistry and antibody to HBsAg levels. Among 297 allogeneic HSCT recipients, 85 (28.7%) were HBsAg-negative, anti-HBc-positive, of whom 62 were recruited and monitored for a median of 48 (4-104) weeks. The 2-year cumulative HBV DNA detectability rate was 40.8%, occurring at a median of 44 (8-100) weeks. Multivariate analysis showed that age ≥50 years (P = 0.004, hazard ratio = 8.2) and chronic graft-versus-host disease (P = 0.010, hazard ratio = 5.3) were significantly associated with HBV reactivation. Other clinical parameters, including baseline antibody to HBsAg status, serial changes in antibody to HBsAg levels, and donor serology, were not associated with HBV reactivation. Patients <50 years old and without chronic graft-versus-host disease, compared with the remaining patient cohort, had a significantly lower 2-year cumulative HBV reactivation rate (5.6% versus 65.0%, P = 0.004). Entecavir successfully suppressed HBV DNA to undetectable levels, with no cases developing biochemical hepatitis. CONCLUSION HBsAg-negative, anti-HBc-positive patients had a high rate of HBV reactivation after allogeneic HSCT, with determinants of HBV reactivation including age ≥50 years and chronic graft-versus-host disease; treatment strategies based on these parameters may prevent HBV reactivation and subsequent complications. (ClinicalTrials.gov identifier NCT01481649.) (Hepatology 2017;65:1451-1461).
Collapse
Affiliation(s)
- Wai-Kay Seto
- Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong.,State Key Laboratory for Liver Research, The University of Hong Kong, Queen Mary Hospital, Hong Kong
| | - Thomas Sau-Yan Chan
- Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong
| | - Yu-Yan Hwang
- Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong
| | - Danny Ka-Ho Wong
- Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong.,State Key Laboratory for Liver Research, The University of Hong Kong, Queen Mary Hospital, Hong Kong
| | - James Fung
- Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong.,State Key Laboratory for Liver Research, The University of Hong Kong, Queen Mary Hospital, Hong Kong
| | - Kevin Sze-Hang Liu
- Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong
| | - Harinder Gill
- Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong
| | - Yuk-Fai Lam
- Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong
| | - Eric H Y Lau
- School of Public Health, The University of Hong Kong, Hong Kong
| | - Ka-Shing Cheung
- Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong
| | - Albert K W Lie
- Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong
| | - Ching-Lung Lai
- Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong.,State Key Laboratory for Liver Research, The University of Hong Kong, Queen Mary Hospital, Hong Kong
| | - Yok-Lam Kwong
- Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong
| | - Man-Fung Yuen
- Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong.,State Key Laboratory for Liver Research, The University of Hong Kong, Queen Mary Hospital, Hong Kong
| |
Collapse
|
|
19
|
Lin XJ, Lao XM, Shi M, Li SP. Changes of HBV DNA After Chemoembolization for Hepatocellular Carcinoma and the Efficacy of Antiviral Treatment. Dig Dis Sci 2016; 61:2465-76. [PMID: 27105647 DOI: 10.1007/s10620-016-4167-5] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2015] [Accepted: 04/13/2016] [Indexed: 02/07/2023]
Abstract
Unlike systemic chemotherapy for hematological malignancies with hepatitis B virus (HBV) infection, transarterial chemoembolization (TACE) for HBV-related hepatocellular carcinoma (HCC) has only recently been reported to cause HBV reactivation and subsequent hepatitis. Most patients with HBV-related HCC have an underlying disease with liver fibrosis or cirrhosis, and TACE may potentially induce HBV reactivation and liver decompensation. Currently, there are no clinical guidelines for managing TACE-caused HBV reactivation. In this review, we summarize the changes of HBV status and liver function after TACE and the effect of antiviral treatment before, during, or after TACE.
Collapse
Affiliation(s)
- Xiao-Jun Lin
- Department of Hepatobiliary Oncology, Sun Yat-sen University Cancer Center, 651, Dongfeng Road East, Guangzhou, 510060, Guangdong, People's Republic of China
- State Key Laboratory of Southern China, Guangzhou, 510060, Guangdong, People's Republic of China
- Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong, People's Republic of China
| | - Xiang-Ming Lao
- Department of Hepatobiliary Oncology, Sun Yat-sen University Cancer Center, 651, Dongfeng Road East, Guangzhou, 510060, Guangdong, People's Republic of China.
- State Key Laboratory of Southern China, Guangzhou, 510060, Guangdong, People's Republic of China.
- Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong, People's Republic of China.
| | - Ming Shi
- Department of Hepatobiliary Oncology, Sun Yat-sen University Cancer Center, 651, Dongfeng Road East, Guangzhou, 510060, Guangdong, People's Republic of China
- State Key Laboratory of Southern China, Guangzhou, 510060, Guangdong, People's Republic of China
- Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong, People's Republic of China
| | - Sheng-Ping Li
- Department of Hepatobiliary Oncology, Sun Yat-sen University Cancer Center, 651, Dongfeng Road East, Guangzhou, 510060, Guangdong, People's Republic of China
- State Key Laboratory of Southern China, Guangzhou, 510060, Guangdong, People's Republic of China
- Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong, People's Republic of China
| |
Collapse
|
|
20
|
An J, Shim JH, Kim SO, Choi J, Kim SW, Lee D, Kim KM, Lim YS, Lee HC, Chung YH, Lee YS, Suh DJ. Comprehensive outcomes of on- and off-antiviral prophylaxis in hepatitis B patients undergoing cancer chemotherapy: A competing risks analysis. J Med Virol 2016; 88:1576-86. [PMID: 26945543 DOI: 10.1002/jmv.24512] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/01/2016] [Indexed: 12/20/2022]
Abstract
Although antiviral prophylaxis is essential in hepatitis B patients in the context of cancer chemotherapy, there is little evidence-based consensus regarding the appropriate prevention strategy depending on the underlying type of cancer and viral status. This retrospective study included a comprehensive cohort of 302 hepatitis B surface antigen-positive patients with various cancers undergoing chemotherapy and antiviral prophylaxis. The rates of hepatitis B virus (HBV) reactivation during antiviral therapy (>1 log10 IU/mL increase or positive conversion of serum HBV DNA) and relapse when off antivirals ([re]appearance of HBV DNA >2,000 IU/ml with related alanine aminotransferase elevation) were evaluated, together with the associated risk factors, in a competing risks analysis where cancer death was considered as the competing event. During antiviral prophylaxis, HBV was reactivated in six patients (1.9%), who had leukemia (n = 4) or lymphoma (n = 2) and were treated with lamivudine (n = 4) or entecavir (n = 2). The incidence rate of HBV relapse in 127 off-prophylaxis patients was 21.3% during a median post-antiviral period of 11.7 months. Lymphoma, pre-prophylactic HBV DNA ≥2,000 IU/ml, and age ≥50 years were independent predictors of off-treatment HBV relapse (adjusted hazard ratios 5.25, 3.07, and 0.34, respectively; Ps < 0.05). Antiviral and anticancer drugs, duration of consolidation on antiviral prophylaxis, and HBeAg positivity were not independent predictors. In conclusion, hepatitis B flare-ups are not rare in patients receiving cancer chemotherapy during and after anti-HBV prophylaxis, even when potent antivirals are used. Patients with hematopoietic or lymphoid neoplasms or high viral burdens should receive prolonged and powerful HBV prophylaxis. J. Med. Virol. 88:1576-1586, 2016. © 2016 Wiley Periodicals, Inc.
Collapse
Affiliation(s)
- Jihyun An
- Department of Gastroenterology, Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Ju Hyun Shim
- Department of Gastroenterology, Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Seon-Ok Kim
- Department of Biostatistics and Clinical Epidemiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Jonggi Choi
- Department of Gastroenterology, Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Sang-We Kim
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Danbi Lee
- Department of Gastroenterology, Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Kang Mo Kim
- Department of Gastroenterology, Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Young-Suk Lim
- Department of Gastroenterology, Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Han Chu Lee
- Department of Gastroenterology, Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Young-Hwa Chung
- Department of Gastroenterology, Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Yung Sang Lee
- Department of Gastroenterology, Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Dong Jin Suh
- Department of Internal Medicine, Vievisnamuh Hospital, Seoul, Republic of Korea
| |
Collapse
|
|
21
|
Manka P, Verheyen J, Gerken G, Canbay A. Liver Failure due to Acute Viral Hepatitis (A-E). Visc Med 2016; 32:80-5. [PMID: 27413724 PMCID: PMC4926881 DOI: 10.1159/000444915] [Citation(s) in RCA: 55] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Viral hepatitis is still one of the key causes of acute liver failure (ALF) in the world. METHODS A selective literature search of the PubMed database was conducted, including current studies, reviews, meta-analyses, and guidelines. We obtained an overview of ALF due to viral hepatitis in terms of epidemiology, course, and treatment options. RESULTS Most fulminant viral courses are reported after infection with hepatitis A, B, and B/D, but not with hepatitis C. Hepatitis E is also known to cause ALF but has not gained much attention in recent years. However, more and more autochthonous hepatitis E virus infections have been recently observed in Europe. Reactivation of hepatitis B virus (HBV) under immunosuppressive conditions, such as after intensive chemotherapy, is also an increasing problem. For most viral-induced cases of ALF, liver transplantation represented the only therapeutic option in the past. Today, immediate treatment of HBV-induced ALF with nucleotide or nucleoside analogs is well tolerated and beneficially affects the course of the disease. CONCLUSION Although numbers in Western European countries are decreasing rapidly, reliable diagnostic screening for hepatitis A-E is necessary to identify the etiology and to determine those most at risk of developing ALF.
Collapse
Affiliation(s)
- Paul Manka
- Department of Gastroenterology and Hepatology, University Hospital Essen, Essen, Germany
- Regeneration and Repair Group, The Institute of Hepatology, Foundation for Liver Research, London, UK
- Division of Transplantation Immunology and Mucosal Biology, King's College, London, UK
| | - Jens Verheyen
- Institute of Virology, University Hospital, University Duisburg-Essen, Essen, Germany
| | - Guido Gerken
- Department of Gastroenterology and Hepatology, University Hospital Essen, Essen, Germany
| | - Ali Canbay
- Department of Gastroenterology and Hepatology, University Hospital Essen, Essen, Germany
| |
Collapse
|
|
22
|
Pinter M, Trauner M, Peck-Radosavljevic M, Sieghart W. Cancer and liver cirrhosis: implications on prognosis and management. ESMO Open 2016; 1:e000042. [PMID: 27843598 PMCID: PMC5070280 DOI: 10.1136/esmoopen-2016-000042] [Citation(s) in RCA: 195] [Impact Index Per Article: 21.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2016] [Accepted: 02/06/2016] [Indexed: 12/11/2022] Open
Abstract
Liver cirrhosis, the end-stage of every chronic liver disease, is not only the major risk factor for the development of hepatocellular carcinoma but also a limiting factor for anticancer therapy of liver and non-hepatic malignancies. Liver cirrhosis may limit surgical and interventional approaches to cancer treatment, influence pharmacokinetics of anticancer drugs, increase side effects of chemotherapy, render patients susceptible for hepatotoxicity, and ultimately result in a competitive risk for morbidity and mortality. In this review, we provide a concise overview about the impact of liver cirrhosis on the management and prognosis of patients with primary liver cancer or non-hepatic malignancies.
Collapse
Affiliation(s)
- Matthias Pinter
- Division of Gastroenterology & Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; Edwin L. Steele Laboratories for Tumor Biology, Department of Radiation Oncology, Harvard Medical School & Massachusetts General Hospital, Boston, USA
| | - Michael Trauner
- Division of Gastroenterology & Hepatology, Department of Internal Medicine III , Medical University of Vienna , Vienna , Austria
| | - Markus Peck-Radosavljevic
- Division of Gastroenterology & Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; Department of Gastroenterology & Hepatology, Endocrinology and Nephrology, Klinikum Klagenfurt am Wörthersee, Klagenfurt, Austria
| | - Wolfgang Sieghart
- Division of Gastroenterology & Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; Austrian Society of Gastroenterology & Hepatology, Working Group GI-Oncology
| |
Collapse
|
|
23
|
Kumar R, Pérez-Del-Pulgar S, Testoni B, Lebossé F, Zoulim F. Clinical relevance of the study of hepatitis B virus covalently closed circular DNA. Liver Int 2016; 36 Suppl 1:72-7. [PMID: 26725901 DOI: 10.1111/liv.13001] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/20/2015] [Accepted: 10/22/2015] [Indexed: 12/14/2022]
Abstract
Hepatitis B virus (HBV) remains a public health concern with 240 million people affected worldwide. HBV is an hepadnavirus that replicates its genome in hepatocytes. One of the key steps of the viral life cycle is the formation of cccDNA - covalently closed circular DNA - in the nucleus, the equivalent of a viral mini-chromosome that acts as a template for subsequent virus replication. Current antiviral medications are not effective in eradicating cccDNA, which can persist in the infected liver even in the absence of detectable HBV DNA or HBsAg in the blood. cccDNA cannot be measured in serum, and few surrogate markers have been proposed. Persistent cccDNA has been associated with various clinical events, including viral reactivation induced by immunosuppressive therapies, HBV recurrence after liver transplantation and hepatocellular carcinoma (HCC). cccDNA remains the main target to achieve a cure of HBV infection, thus extensive efforts are being made to develop new antiviral concepts to degrade or silence cccDNA.
Collapse
Affiliation(s)
- Rajneesh Kumar
- Cancer Research Center of Lyon (CRCL), INSERM U1052, CNRS 5286, Lyon, France.,Lyon University, F-69100, Villeurbanne, France
| | - Sofía Pérez-Del-Pulgar
- Cancer Research Center of Lyon (CRCL), INSERM U1052, CNRS 5286, Lyon, France.,Liver Unit, Hospital Clínic, IDIBAPS, CIBERehd, Barcelona, Spain
| | - Barbara Testoni
- Cancer Research Center of Lyon (CRCL), INSERM U1052, CNRS 5286, Lyon, France.,Lyon University, F-69100, Villeurbanne, France
| | - Fanny Lebossé
- Cancer Research Center of Lyon (CRCL), INSERM U1052, CNRS 5286, Lyon, France.,Lyon University, F-69100, Villeurbanne, France.,Hepatology Department, Hospices Civils de Lyon, Lyon, France
| | - Fabien Zoulim
- Cancer Research Center of Lyon (CRCL), INSERM U1052, CNRS 5286, Lyon, France.,Lyon University, F-69100, Villeurbanne, France.,Hepatology Department, Hospices Civils de Lyon, Lyon, France
| |
Collapse
|
|
24
|
Abdalla M, Hamad T. Hepatitis B Virus Seroprevalence Among Children With Cancer in Sudan. Pediatr Blood Cancer 2016; 63:124-6. [PMID: 26375506 DOI: 10.1002/pbc.25720] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2015] [Accepted: 07/28/2015] [Indexed: 01/31/2023]
Abstract
BACKGROUND The seroprevalence of hepatitis B among children with cancer in Sudan is unknown. The aim of this study was to detect the seroprevalence of hepatitis B virus (HBV) infection in children with malignancy and its correlation with different risk factors. PROCEDURE This study included 178 children with malignancy presenting to the Radioisotope Center in Khartoum during the period of May-July 2011. Sixty-four healthy children served as controls. Sera from patients and controls were investigated for HBV total anti-core antibody, HBV surface antigen (HBsAg), and HBV e antigen (HBeAg). RESULTS HBV total anti-core antibody was positive in 71/178 (39.9%), HBsAg was positive in 38 (21.3%), and HBeAg was positive in 19 (10.7%). Blood product transfusion, surgical exposure, chemotherapy, malignancy type, and sex did not affect the seroprevalence of HBV in this study. Vaccinated children had reduced rates of exposure compared to non-vaccinated patients. CONCLUSION There is a high seroprevalence of HBV in children with malignancies in Sudan. Vaccination appears to play a major protective role.
Collapse
Affiliation(s)
- Mohammed Abdalla
- Pediatric Department, University of Khartoum Faculty of Medicine, Khartoum, Sudan
| | | |
Collapse
|
|
25
|
Leonard AN, Love BL, Norris LB, Siddiqui SK, Wallam MN, Bennett CL. Screening for viral hepatitis prior to rituximab chemotherapy. Ann Hematol 2015; 95:27-33. [PMID: 26382277 DOI: 10.1007/s00277-015-2502-0] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2015] [Accepted: 09/08/2015] [Indexed: 01/17/2023]
Abstract
In 2008, the CDC published guidelines recommending screening of all persons undergoing treatment with rituximab to identify persons at risk of hepatitis B virus (HBV) reactivation. We evaluated implementation of this recommendation in veterans, who are at increased risk of HBV, and determined characteristics of those screened. We also evaluated a control setting, rates of hepatitis C virus (HCV) screening among the same rituximab-treated patients. There are no guidelines that recommend HCV screening prior to initiation of rituximab. Medical records of patients receiving rituximab between January 2006 and December 2012 were reviewed according to two time periods: 2006-2008 (period 1, pre-guidelines) and 2009-2012 (period 2, post-guidelines). Patient demographics, concomitant chemotherapy regimen (protocol, dose, duration), treatment indication, risk factors for hepatitis infection (substance abuse, homelessness, human immunodeficiency virus (HIV)), and HBV/HCV screening status were documented. During the study period, 102 patients were treated with rituximab (49 in period 1 and 53 in period 2). During periods 1 and 2, 22 and 32 % of rituximab-treated patients were screened for HBV, respectively (p = 0.375). Treatment during 2009 was the only significant predictor of HBV screening in the adjusted model (p = 0.01). For HCV during periods 1 and 2, 22 and 21 % of patients were screened, respectively (p = 1.00). There were no significant predictors of HCV screening. Rates of screening for HBV among rituximab-treated patients were low, both before and after dissemination of guidelines recommending universal HBV screening of rituximab-treated patients.
Collapse
Affiliation(s)
- A N Leonard
- Department of Clinical Pharmacy and Outcomes Sciences, South Carolina College of Pharmacy, 715 Sumter St, CLS 311, Columbia, SC, 29208, USA
| | - B L Love
- Department of Clinical Pharmacy and Outcomes Sciences, South Carolina College of Pharmacy, 715 Sumter St, CLS 311, Columbia, SC, 29208, USA. .,Department of Research, William Jennings Bryan Dorn Veterans Affairs Medical Center, Columbia, SC, 29208, USA.
| | - L B Norris
- Department of Clinical Pharmacy and Outcomes Sciences, South Carolina College of Pharmacy, 715 Sumter St, CLS 311, Columbia, SC, 29208, USA.,Department of Research, William Jennings Bryan Dorn Veterans Affairs Medical Center, Columbia, SC, 29208, USA
| | - S K Siddiqui
- Department of Gastroenterology, William Jennings Bryan Dorn Veterans Affairs Medical Center, Columbia, SC, 29208, USA
| | - M N Wallam
- Department of Oncology, William Jennings Bryan Dorn Veterans Affairs Medical Center, Columbia, SC, 29208, USA
| | - C L Bennett
- Department of Clinical Pharmacy and Outcomes Sciences, South Carolina College of Pharmacy, 715 Sumter St, CLS 311, Columbia, SC, 29208, USA.,Department of Research, William Jennings Bryan Dorn Veterans Affairs Medical Center, Columbia, SC, 29208, USA.,Department of Oncology, William Jennings Bryan Dorn Veterans Affairs Medical Center, Columbia, SC, 29208, USA.,South Carolina Center of Economic Excellence for Medication Safety and Efficacy, Columbia, SC, 29208, USA
| |
Collapse
|
|
26
|
Hsu PI, Lai KH, Cheng JS, Kao SS, Li YR, Sun WC, Chen WC, Lin KH, Shin CA, Chiang PH, Li YD, Ou WT, Chen HC, Yu HC. Prevention of acute exacerbation of chronic hepatitis B infection in cancer patients receiving chemotherapy in a hepatitis B virus endemic area. Hepatology 2015; 62:387-396. [PMID: 26041578 DOI: 10.1002/hep.27843] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2014] [Accepted: 04/07/2015] [Indexed: 12/20/2022]
Abstract
UNLABELLED Reactivation of hepatitis B viral (HBV) infection in cancer patients undergoing chemotherapy may cause interruption of chemotherapy and lead to liver failure and death. In our institute, a computerized order entry-based alert system was introduced in September 2011 to remind healthcare providers of HBV testing when prescribing chemotherapy. Since August 2012, an order entry-based therapeutic control system has been applied to ensure HBV prophylaxis during chemotherapy. This retrospective cohort study included cancer patients receiving chemotherapy in the Kaohsiung Veterans General Hospital from November 2009 to June 2013. The prechemotherapy HBV screening rate, HBV prophylactic rate, and severe HBV acute exacerbation rate were compared between stages with different order systems. Newly diagnosed cancer patients (n = 2512) were included. The HBV testing rate in the screening reminder stage was higher than that in the educational stage (93.5% versus 40.2%, P < 0.001), whereas the adequate HBV prophylactic rates in the two order entry-based stages were comparable (41.1% versus 39.2%). Patients in the order entry-based therapeutic control stage had a higher HBV screening rate (99.3% versus 40.2%, P < 0.001) and a higher HBV prophylactic rate (95.8% versus 39.2%, P < 0.001) than those in the educational stage. Additionally, the severe HBV acute exacerbation rate in the therapeutic control stage was lower than those in the educational and screening reminder stages (0% versus 1.2% and 1.2%, respectively; both P < 0.01). CONCLUSION A computerized order entry-based therapeutic control system can provide excellent prechemotherapy HBV screening for cancer patients undergoing chemotherapy and can effectively prevent severe acute exacerbation of HBV infection in hospitals among HBV endemic areas.
Collapse
Affiliation(s)
- Ping-I Hsu
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Veterans General Hospital and National Yang-Ming University, Kaohsiung, Taiwan
| | - Kwok-Hung Lai
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Veterans General Hospital and National Yang-Ming University, Kaohsiung, Taiwan
| | - Jin-Shiung Cheng
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Veterans General Hospital and National Yang-Ming University, Kaohsiung, Taiwan
| | - Sung-Shuo Kao
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Veterans General Hospital and National Yang-Ming University, Kaohsiung, Taiwan
| | - Yuan-Rung Li
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Veterans General Hospital and National Yang-Ming University, Kaohsiung, Taiwan
| | - Wei-Chih Sun
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Veterans General Hospital and National Yang-Ming University, Kaohsiung, Taiwan
| | - Wen-Chi Chen
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Veterans General Hospital and National Yang-Ming University, Kaohsiung, Taiwan
| | - Kung-Hung Lin
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Veterans General Hospital and National Yang-Ming University, Kaohsiung, Taiwan
| | - Chih-An Shin
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Veterans General Hospital and National Yang-Ming University, Kaohsiung, Taiwan
| | - Po-Hung Chiang
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Veterans General Hospital and National Yang-Ming University, Kaohsiung, Taiwan
| | - Yun-Da Li
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Veterans General Hospital and National Yang-Ming University, Kaohsiung, Taiwan
| | - Wei-Ting Ou
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Veterans General Hospital and National Yang-Ming University, Kaohsiung, Taiwan
| | - Hui-Chun Chen
- Department of Radiation Oncology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung City, Taiwan
| | - Hsien-Chung Yu
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Veterans General Hospital and National Yang-Ming University, Kaohsiung, Taiwan
| |
Collapse
|
|
27
|
Regev A, Seeff LB, Merz M, Ormarsdottir S, Aithal GP, Gallivan J, Watkins PB. Causality assessment for suspected DILI during clinical phases of drug development. Drug Saf 2015; 37 Suppl 1:S47-56. [PMID: 25352327 PMCID: PMC4212150 DOI: 10.1007/s40264-014-0185-4] [Citation(s) in RCA: 46] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Causality assessment is a critical step in establishing the diagnosis of drug induced liver injury (DILI) during drug development. DILI may resemble almost any type of liver disease, and often presents a serious challenge to clinical investigators and drug makers. The diagnosis of DILI is largely based upon a combination of a compatible clinical course, exclusion of all other reasonable causes, resemblance of clinical and pathological features to known features of liver injury due to the drug (i.e., “drug’s signature”), and incidence of liver injury among patients treated with the drug compared to placebo or comparator. Causality assessment for suspected DILI is currently performed using either evaluation by physicians with expertise in liver disorders (i.e., expert opinion) or standardized scoring instruments such as the Roussel Uclaf Causality Assessment Method (RUCAM). Both approaches are widely used in the post marketing setting. Causality assessment based on expert opinion is considered superior to standardized instruments such as RUCAM, in the setting of drug development, and is currently the preferred approach during clinical trials. There is a need for a systematic revision of RUCAM that will render it more suitable for the setting of clinical trials and drug development. Careful monitoring and meticulous data collection during clinical trials are essential in all cases with established liver injury to allow for a proper causality assessment. A workshop was convened to discuss best practices for the assessment of drug-induced liver injury (DILI) in clinical trials. This publication is based on the conclusions of this workshop.
Collapse
Affiliation(s)
- Arie Regev
- Global Patient Safety, Eli Lilly and Company, Lilly Corporate Center, Drop Code 2121, Indianapolis, IN, 46285, USA,
| | | | | | | | | | | | | |
Collapse
|
|
28
|
Mina T, Amini-Bavil-Olyaee S, Tacke F, Maes P, Van Ranst M, Pourkarim MR. Genomic Diversity of Hepatitis B Virus Infection Associated With Fulminant Hepatitis B Development. HEPATITIS MONTHLY 2015; 15:e29477. [PMID: 26288637 PMCID: PMC4533131 DOI: 10.5812/hepatmon.29477v2] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 04/23/2015] [Accepted: 05/25/2015] [Indexed: 12/11/2022]
Abstract
CONTEXT After five decades of Hepatitis B Virus (HBV) vaccine discovery, HBV is still a major public health problem. Due to the high genetic diversity of HBV and selective pressure of the host immune system, intra-host evolution of this virus in different clinical manifestations is a hot topic of research. HBV infection causes a range of clinical manifestations from acute to chronic infection, cirrhosis and hepatocellular carcinoma. Among all forms of HBV infection manifestations, fulminant hepatitis B infection possesses the highest fatality rate. Almost 1% of the acutely infected patients develop fulminant hepatitis B, in which the mortality rate is around 70%. EVIDENCE ACQUISITION All published papers deposited in Genbank, on the topic of fulminant hepatitis were reviewed and their virological aspects were investigated. In this review, we highlight the genomic diversity of HBV reported from patients with fulminant HBV infection. RESULTS The most commonly detected diversities affect regulatory motifs of HBV in the core and S region, indicating that these alterations may convert the virus to an aggressive strain. Moreover, mutations at T-cell and B-cell epitopes located in pre-S1 and pre-S2 proteins may lead to an immune evasion of the virus, likely favoring a more severe clinical course of infection. Furthermore, point and frame shift mutations in the core region increase the viral replication of HBV and help virus to evade from immune system and guarantee its persistence. CONCLUSIONS Fulminant hepatitis B is associated with distinct mutational patterns of HBV, underlining that genomic diversity of the virus is an important factor determining its pathogenicity.
Collapse
Affiliation(s)
- Thomas Mina
- Department of Microbiology and Immunology, Laboratory of Clinical and Epidemiological Virology, Rega Institute for Medical Research, KU Leuven, Leuven, Belgium
| | - Samad Amini-Bavil-Olyaee
- Department of Molecular Microbiology and Immunology, Harlyne J. Norris Cancer Research Tower, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
| | - Frank Tacke
- Department of Medicine III, RWTH-University Hospital Aachen, Aachen, Germany
| | - Piet Maes
- Department of Microbiology and Immunology, Laboratory of Clinical and Epidemiological Virology, Rega Institute for Medical Research, KU Leuven, Leuven, Belgium
| | - Marc Van Ranst
- Department of Microbiology and Immunology, Laboratory of Clinical and Epidemiological Virology, Rega Institute for Medical Research, KU Leuven, Leuven, Belgium
| | - Mahmoud Reza Pourkarim
- Department of Microbiology and Immunology, Laboratory of Clinical and Epidemiological Virology, Rega Institute for Medical Research, KU Leuven, Leuven, Belgium
- Blood Transfusion Research Centre, High Institute for Research and Education in Transfusion Medicine, Tehran, IR Iran
- Corresponding Author: Mahmoud Reza Pourkarim, Department of Microbiology and Immunology, Laboratory of Clinical and Epidemiological Virology, Rega Institute for Medical Research, KU Leuven, P. O. Box: BE-3000, Leuven, Belgium. Tel: +32-16332145, Fax: +32-16332141, E-mail:
| |
Collapse
|
|
29
|
Xu L, Gao H, Huang J, Wang H, Zhou Z, Zhang Y, Li S, Chen M. Antiviral therapy in the improvement of survival of patients with hepatitis B virus-related hepatocellular carcinoma treated with sorafenib. J Gastroenterol Hepatol 2015; 30:1032-9. [PMID: 25639513 DOI: 10.1111/jgh.12910] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 01/04/2015] [Indexed: 12/20/2022]
Abstract
BACKGROUND AND AIM To evaluate the role of antiviral therapy with nucleoside analogs (NAs) in sorafenib-treated patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). METHODS A retrospective cohort study was done in 151 HBV-related HCC patients treated with sorafenib at Sun Yat-sen University Cancer Center between 2007 and 2012. Overall survival (OS), progression-free survival and adverse events were compared in patients treated with/without NAs. Subgroup analysis and Cox regression analysis were performed to determine the efficiency of NAs and prognostic factors for OS. RESULTS HBV-related HCC patients (n=151) were identified from our database of HCC patients treated with sorafenib. Patients treated with NAs (antiviral group, n=88) had significantly improved OS compared with the patients who received no NAs (non-antiviral group, n=63; median OS: 16.47 months vs 13.10 months, P=0.03). Patients in the antiviral group had a significant risk reduction of death compared with the non-antiviral group (hazard ratio: 0.67, 95% confidence interval: 0.46-0.98, P=0.04). By subgroup analysis, patients of Barcelona Clinic Liver Cancer (BCLC) stage C and patients with higher presorafenib HBV-DNA level achieved better survival improvement. Antiviral therapy with NAs was one of the independent prognostic factors for OS of HBV-related HCC patients who were treated with sorafenib. CONCLUSION Antiviral therapy with NAs improved OS of HBV-related HCC patients treated with sorafenib, especially in patients with BCLC stage C disease and higher HBV-DNA level.
Collapse
Affiliation(s)
- Li Xu
- Department of Hepatobiliary Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China; State Key Laboratory of Oncology in South China, Guangzhou, China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | | | | | | | | | | | | | | |
Collapse
|
|
30
|
2014 KLCSG-NCC Korea Practice Guideline for the Management of Hepatocellular Carcinoma. Gut Liver 2015; 9:267-317. [PMID: 25918260 PMCID: PMC4413964 DOI: 10.5009/gnl14460] [Citation(s) in RCA: 101] [Impact Index Per Article: 10.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/25/2014] [Accepted: 03/09/2015] [Indexed: 12/23/2022] Open
Abstract
The guideline for the management of hepatocellular carcinoma (HCC) was first developed in 2003 and revised in 2009 by the Korean Liver Cancer Study Group and the National Cancer Center, Korea. Since then, many studies on HCC have been carried out in Korea and other countries. In particular, a substantial body of knowledge has been accumulated on diagnosis, staging, and treatment specific to Asian characteristics, especially Koreans, prompting the proposal of new strategies. Accordingly, the new guideline presented herein was developed on the basis of recent evidence and expert opinions. The primary targets of this guideline are patients with suspicious or newly diagnosed HCC. This guideline provides recommendations for the initial treatment of patients with newly diagnosed HCC.
Collapse
|
|
31
|
2014 Korean Liver Cancer Study Group-National Cancer Center Korea practice guideline for the management of hepatocellular carcinoma. Korean J Radiol 2015; 16:465-522. [PMID: 25995680 PMCID: PMC4435981 DOI: 10.3348/kjr.2015.16.3.465] [Citation(s) in RCA: 143] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2015] [Accepted: 04/02/2015] [Indexed: 02/07/2023] Open
Abstract
The guideline for the management of hepatocellular carcinoma (HCC) was first developed in 2003 and revised in 2009 by the Korean Liver Cancer Study Group and the National Cancer Center, Korea. Since then, many studies on HCC have been carried out in Korea and other countries. In particular, a substantial body of knowledge has been accumulated on diagnosis, staging, and treatment specific to Asian characteristics, especially Koreans, prompting the proposal of new strategies. Accordingly, the new guideline presented herein was developed on the basis of recent evidence and expert opinions. The primary targets of this guideline are patients with suspicious or newly diagnosed HCC. This guideline provides recommendations for the initial treatment of patients with newly diagnosed HCC.
Collapse
|
|
32
|
Preemptive adefovir versus lamivudine for prevention of hepatitis B reactivation in chronic hepatitis B patients undergoing chemotherapy. Hepatol Int 2015; 9:224-30. [PMID: 25788197 DOI: 10.1007/s12072-015-9612-6] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/24/2014] [Accepted: 02/10/2015] [Indexed: 12/19/2022]
Abstract
BACKGROUND This proof-of-concept study compared lamivudine (LAM) with a newer antiviral agent, adefovir dipivoxil (ADF), in preventing hepatitis B virus (HBV) reactivation in chronic HBV patients undergoing chemotherapy. METHODS Hepatitis B surface antigen (HBsAg) positive patients intended to undergo chemotherapy were randomized to receive either LAM 100 mg daily or ADF 10 mg daily. Anti-viral therapy was started 1 week prior to chemotherapy and until 6 months after completing chemotherapy. The primary outcome was HBV reactivation rate. All patients with viral breakthrough were screened for resistance mutations by direct sequencing. RESULTS Seventy treatment-naïve patients were consecutively randomized 1:1 to LAM or ADF. The median baseline HBV DNA levels were similar (LAM 3.36 vs. ADF 3.17 log10 copies/mL, p = 0.860). The median duration was 8.3 months on LAM and 10.6 months on ADF (p = 0.220). HBV reactivation was observed in 13/35 (37.1%) on LAM compared with 10/35 (28.6%) on ADF (p = 0.611). The median time to HBV reactivation was 4.6 and 8.1 months, on LAM and ADF respectively. Among these 13 patients, 8/13 (61.5%) on LAM had developed drug resistance mutations but none on ADF had developed drug resistance mutations to ADF (p = 0.003). Both drugs were well tolerated and no severe drug-related toxicities were reported. CONCLUSION In this randomized clinical study, adefovir and lamivudine demonstrated similar efficacy in preventing hepatitis B reactivation in HBsAg-positive patients undergoing chemotherapy. In patients whose hepatitis B reactivated, adefovir was associated with a lower resistance profile.
Collapse
|
|
33
|
Cholongitas E, Tziomalos K, Pipili C. Management of patients with hepatitis B in special populations. World J Gastroenterol 2015; 21:1738-1748. [PMID: 25684938 PMCID: PMC4323449 DOI: 10.3748/wjg.v21.i6.1738] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/08/2014] [Revised: 10/27/2014] [Accepted: 11/18/2014] [Indexed: 02/06/2023] Open
Abstract
The development of effective nucleos(t)ide analogs (NAs) against hepatitis B virus (HBV) has improved the outcome of patients with chronic hepatitis B (CHB). This review updates issues related to the management of CHB patients included in special populations. Entecavir (ETV) and tenofovir (TDF) represent the currently recommended first-line NAs in patients with HBV decompensated cirrhosis. The combination of HBV immunoglobulin (usually for a finite duration) and NA is considered the standard of care for prophylaxis against HBV recurrence after liver transplantation. TDF is the best choice for hemodialysis patients and in patients with chronic kidney disease with nucleoside resistance. ETV and telbivudine are the preferred options in naïve renal transplant recipients and with low viremia levels, respectively. All hepatitis B surface antigen (HBsAg)-positive candidates should be treated with NAs before renal transplantation to achieve undetectable HBV DNA at the time of transplantation. Conventional interferon or NAs can also be used in children, on the basis of well-established therapeutic indication. Pregnant women at high risk of perinatal transmission could be treated with lamivudine, telbivudine or TDF in the last trimester of pregnancy. HBsAg-positive patients under immunosuppression should receive NA pre-emptively (regardless of HBV DNA levels) up to 12 mo after its cessation. In HBsAg negative, anti-HBc positive patients under immunosuppression, further studies are needed to form a final conclusion; however, it seems that anti-HBV prophylaxis is justified in such patients with hematological diseases and/or for those receiving rituximab-containing regimens, regardless of their anti-HBs or serum HBV DNA status.
Collapse
|
|
34
|
Abstract
Viral hepatitis is a significant disease afflicting hundreds of millions of people. Hepatitis-causing viruses initiate significant morbidity and mortality by establishing both acute and chronic infections, and several of these viruses are specifically associated with the development of hepatocellular carcinoma (HCC). Consequently, intense research efforts are focused on increasing our understanding of virus biology and on improving antiviral therapy. Even though viral hepatitis can be caused by several viruses from a range of virus families, the discovery of components of the hepatitis B virus (HBV) became a catalyst for the development of diagnostic assays that differentiate between these viruses as well as strategies for novel methods of vaccine development. Improvements in both the treatment and prevention of viral hepatitis are advancing rapidly. However, HBV, along with the associated infection by the hepatitis D virus, is still among the most common pathogens afflicting humans.
Collapse
MESH Headings
- Carcinoma, Hepatocellular/epidemiology
- Carcinoma, Hepatocellular/virology
- Genome, Viral
- Hepatitis B virus/genetics
- Hepatitis Delta Virus/genetics
- Hepatitis, Chronic/virology
- Hepatitis, Viral, Human/epidemiology
- Hepatitis, Viral, Human/history
- Hepatitis, Viral, Human/therapy
- History, 19th Century
- History, 20th Century
- History, 21st Century
- Humans
- Liver Neoplasms/epidemiology
Collapse
Affiliation(s)
- Emmanuel Thomas
- Schiff Center for Liver Diseases, University of Miami Miller School of Medicine, Miami, Florida 33136
| | - Masato Yoneda
- Schiff Center for Liver Diseases, University of Miami Miller School of Medicine, Miami, Florida 33136
| | - Eugene R Schiff
- Schiff Center for Liver Diseases, University of Miami Miller School of Medicine, Miami, Florida 33136
| |
Collapse
|
|
35
|
Laohapand C, Arromdee E, Tanwandee T. Long-term use of methotrexate does not result in hepatitis B reactivation in rheumatologic patients. Hepatol Int 2015; 9:202-8. [PMID: 25788188 DOI: 10.1007/s12072-014-9597-6] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/19/2014] [Accepted: 12/01/2014] [Indexed: 12/16/2022]
Abstract
BACKGROUND AND OBJECTIVE Hepatitis B virus (HBV) infection is still prevalent in Asia, including Thailand. HBV can archive in hepatocytes for life and can reactivate after immunosuppression and chemotherapy administration. Use of immunosuppressive agents is recommended in many rheumatologic diseases and reactivation of HBV can occur. Data regarding the effect of methotrexate (MTX) on HBV reactivation is scanty. MTX is a well known cause of hepatic fibrosis but its effect on HBV reactivation is not clearly understood. There is no specific recommendation for HBV prophylaxis for patients using MTX. This study aimed to determine the prevalence of HBV seromarkers in rheumatologic patients who were treated with long-term MTX and to evaluate the hepatitis outcome in the patients with positive HBV markers. METHODS This was a cross-sectional study at the Rheumatology Clinic, Siriraj Hospital, Bangkok, Thailand. Patients aged 15 years or older treated with MTX more than 24 weeks were invited in the study. Review of medical history, MTX prescription and dosage during the last 52 weeks, blood tests for liver function tests, HBV serology, and HBV DNA viral load were performed. The exclusion criteria included patients who were treated with biological DMARDs, drugs active against HBV, known co-infection with HCV or HIV and previous diagnosis of cirrhosis from any causes or presence of hepatocellular carcinoma. RESULTS A total of 173 patients were enrolled (153 females, 20 males, mean age of 52.6 ± 13.6 years). The majority of patients were diagnosed with rheumatoid arthritis (67.0%), SLE (13.9%), spondyloarthopathies (8.7%) and others (10.4%). Thirty percent of them (55/173) had no previous data for HBV seromarkers. Among 118 patients who had baseline data, only one patient (0.8%) had HBsAg positive. Average duration of treatment was 9.9 years and MTX dose prescribed was 571.6 ± 240.4 mg during the last 52 weeks. Out of 173 patients, only two had clinically significant hepatitis (1.16%) and one was HBsAg positive (0.58%). Ninety-six patients (55.5%) were negative for all HBV seromarkers, 67/173 (38.7%) positive for anti-HBs antibody and 65/173 (37.6%) positive for anti-HBc IgG. Only one in 65 patients (1.5%) who had any positive HBV seromarkers had HBV DNA detectable. CONCLUSION Prevalence of HBsAg positive rheumatologic patients treated with MTX in Thailand was only 0.58%, which was lower than the general Thai population. About one-third of the patients had exposure to HBV as demonstrated by presence of anti-HBc IgG (37.6%), but none of them had hepatitis B reactivation during 9.9 years of MTX treatment. Moreover, one case with HBsAg positive had been receiving MTX without HBV prophylaxis for 5 years but had no evidence of HBV flare and evidence of fibrosis. From our study, long-term MTX in patients exposed to HBV was safe and not associated with hepatitis flare. However, more study is needed as to whether HBV prophylaxis is required.
Collapse
Affiliation(s)
- Charlie Laohapand
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, 2 Wanglang Road, Bangkoknoi, Bangkok, 10700, Thailand,
| | | | | |
Collapse
|
|
36
|
Lanini S, Ćosić G, Menzo S, Puro V, Đurić P, Garbuglia AR, Milošević V, Karać T, Capobianchi MR, Ippolito G. A Large Epidemic of Hepatitis B in Serbia: An Integrated Model for Outbreak Investigations in Healthcare Settings. Infect Control Hosp Epidemiol 2015. [DOI: 10.1086/599166] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
Abstract
We report a comprehensive approach for outbreak investigations, including cluster analysis (Bernoulli model), an algorithm to build inferential models, and molecular techniques to confirm cases. Our approach may be an interesting tool to best exploit the large amount of unsystematically collected information available during outbreak investigations in healthcare settings.Infect Control Hosp Epidemiol2014;35(6):732–735
Collapse
|
|
37
|
Thio CL, Hawkins C. Hepatitis B Virus and Hepatitis Delta Virus. MANDELL, DOUGLAS, AND BENNETT'S PRINCIPLES AND PRACTICE OF INFECTIOUS DISEASES 2015:1815-1839.e7. [DOI: 10.1016/b978-1-4557-4801-3.00148-x] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
|
|
38
|
Tamori A, Hino M, Kawamura E, Fujii H, Uchida-Kobayashi S, Morikawa H, Nakamae H, Enomoto M, Murakami Y, Kawada N. Prospective long-term study of hepatitis B virus reactivation in patients with hematologic malignancy. J Gastroenterol Hepatol 2014; 29:1715-1721. [PMID: 24730465 DOI: 10.1111/jgh.12604] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 03/16/2014] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND AIM To elucidate the clinical characteristics of hepatitis B virus reactivation (HBV-R), we performed a prospective long-term study of patients with hematologic malignancy, including both hepatitis B virus (HBV) carriers and those with resolved HBV infection. METHODS Twenty-one patients with hematopoietic stem-cell transplants (HSCT) and 36 patients given rituximab-based chemotherapy were enrolled. Entecavir was administered prophylactically to eight patients with HBV surface antigen (HBsAg). HBV-DNA was measured every month in 49 patients with resolved HBV infection, and preemptive therapy was given to eight patients with HBV-R. RESULTS HBV-R developed in five (26%) of 19 patients with HSCT and three (10%) of 30 patients given rituximab-based chemotherapy. HBV-R occurred a median of 3 months (range: 2-10) after the end of rituximab-based chemotherapy and 22 months (range: 9-36) after HSCT. HBV-R did not develop in patients with an antibodies against HBsAg (anti-HBs) titer exceeding 200 mIU/mL at baseline. Mutations in the "a" determinant region with amino acid replacement were detected in four of the eight patients with HBV-R. Preemptive therapy prevented severe hepatitis related to HBV-R. Entecavir treatment was stopped in four patients with HBV-R. Since the withdrawal of entecavir, HBV-DNA has not been detected in two patients persistently positive for anti-HBs. No patient had fatal hepatitis. CONCLUSIONS Proper management of patients with HBsAg or resolved HBV infection prevented fatal hepatitis related to HBV-R in patients who received immunosuppressive or cytotoxic therapy. Entecavir could be safely discontinued in patients with HBV-R who had acquired anti-HBs.
Collapse
Affiliation(s)
- Akihiro Tamori
- Department of Hepatology, Osaka City University Graduate School of Medicine, Osaka, Japan
| | | | | | | | | | | | | | | | | | | |
Collapse
|
|
39
|
Jang JW. Hepatitis B virus reactivation in patients with hepatocellular carcinoma undergoing anti-cancer therapy. World J Gastroenterol 2014; 20:7675-7685. [PMID: 24976705 PMCID: PMC4069296 DOI: 10.3748/wjg.v20.i24.7675] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/01/2013] [Revised: 01/22/2014] [Accepted: 03/12/2014] [Indexed: 02/06/2023] Open
Abstract
Patients with hepatocellular carcinoma (HCC) often experience hepatic morbidity. Hepatitis B virus (HBV) reactivation is well documented as a serious hepatic morbidity during anti-cancer therapy. Reported rates of HBV reactivation in chronic carriers with HCC undergoing chemotherapy range from 4%-67%. Apart from chemotherapy, HBV reactivation has been increasingly identified in settings of hepatectomy and local ablation therapies. The rates of HBV reactivation vary with different levels of immunosuppression and depend on treatment, viral factors, and patient characteristics. The principal concern relating to reactivation is that a substantial proportion of patients with reactivation suffer from liver dysfunction during therapy, which often leads to disruption of planned, potentially life-prolonging treatments, adversely affecting the patients' final outcome. The first step in the management of HBV reactivation is identification of patients at risk of reactivation by testing for HBV serology prior to commencing anti-cancer therapy. Although it is a serious complication, HBV reactivation is preventable with prophylactic anti-HBV drugs. Multiple publications have shown the benefit of prophylactic or preemptive antiviral therapy in this setting and justified such an approach before the start of therapy. Given the tumors and underlying cirrhosis, long-term use of antivirals with high potency and low risk of resistance is recommended in patients with HCC. This topic review will summarize the epidemiology, pathogenesis, and clinical issues related to HBV reactivation in HCC patients, and will discuss proper management against HBV reactivation during anti-cancer therapy for HCC.
Collapse
|
|
40
|
Sansone S, Guarino M, Castiglione F, Rispo A, Auriemma F, Loperto I, Rea M, Caporaso N, Morisco F. Hepatitis B and C virus reactivation in immunosuppressed patients with inflammatory bowel disease. World J Gastroenterol 2014; 20:3516-3524. [PMID: 24707134 PMCID: PMC3974518 DOI: 10.3748/wjg.v20.i13.3516] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2013] [Revised: 12/13/2013] [Accepted: 03/06/2014] [Indexed: 02/06/2023] Open
Abstract
In recent years, a number of case reports and clinical studies have highlighted the risk of hepatitis B and C virus reactivation in patients with inflammatory bowel disease who are treated with immunosuppressive drugs. The cases of viral hepatitis reactivation that have been reported are characterized by a wide range of clinical manifestations, from viremia without clinically relevant manifestations to fulminant life-threatening hepatitis. The development and dissemination of biological immunosuppressive drugs have led to a significant increase in the number of reports of interest to physicians in a variety of clinical settings. On this topic, there have been a number of published guidelines and reviews that have collected the available evidence, providing recommendations on prophylactic and therapeutic strategies and methods for monitoring patients at risk. However, it should be noted that, to date, very few clinical studies have been published, and most of the recommendations have been borrowed from other clinical settings. The published studies are mostly retrospective and are based on very heterogeneous populations, using different therapeutic and prophylactic regimens and obtaining conflicting results. Thus, it seems clear that it is desirable to concentrate our efforts on prospective studies, not conducting further reviews of the literature in the continued absence of new evidence.
Collapse
|
|
41
|
Regev A. How to avoid being surprised by hepatotoxicity at the final stages of drug development and approval. Clin Liver Dis 2013; 17:749-67, xi. [PMID: 24099029 DOI: 10.1016/j.cld.2013.07.014] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Drugs that caused severe drug-induced live injury (DILI) in humans have typically not shown clear hepatotoxic signals in preclinical assessment. However, clinical trial databases may show evidence of a drug's potential for severe DILI if clinical and laboratory data are evaluated for evidence of milder liver injury. The most specific indicator during a clinical trial for a drug's potential to cause severe DILI is occurrence of cases of drug induced hepatocellular injury accompanied by altered liver function (eg, elevated direct bilirubin). Meticulous causality assessment of hepatic cases and strict adherence to hepatic discontinuation rules are critical components of this approach.
Collapse
Affiliation(s)
- Arie Regev
- Global Patient Safety, Eli Lilly and Company, Lilly Corporate Center, Indiana University School of Medicine, Drop Code 2121, Indianapolis, IN 46285, USA.
| |
Collapse
|
|
42
|
Horváth G. New drugs for the treatment of chronic hepatitis B and interdisciplinary aspects of chronic hepatitis B virus infection. Orv Hetil 2013; 154:1142-50. [DOI: 10.1556/oh.2013.29625] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
Hepatitis B virus infection is a significant health problem worldwide. The prevalence of HBsAg positivity is about 0.5–0.7% in Hungary. Liver cirrhosis and/or hepatocellular carcinoma develops in 15–40% of chronic hepatitis B virus infected patients without treatment. The ultimate goal of treatment would be to clear the virus from the infected subject; however, in practice, we can usually achieve long term suppression of viral replicaton with consequent prevention of the progression of liver disease, and reduction of the risk of the development of liver cirrhosis and hepatocellular carcinoma. Currently, there are two different treatment strategies for patients with chronic hepatitis B virus infection: therapy of finite duration with interferon or long-term treatment with nucleot(s)ide analogues. Entecavir and tenofovir are the two most effective nucleot(s)ide analogues with high barrier to resistance, thus, they can be confidently used as first-line treatments. Lamivudine engenders very high rates of resistance; adefovir is less efficacious than entecavir or tenofovir, and also engendering higher rates of resistance, thus none of them are recommended for initiation of a new treatment. Tenofovir is the treatment option in cases with lamivudine resistance, because entecavir has an unfavourable resistance-profile in this group of patients. Interferon is contraindicated during pregnancy. Should treatment of chronic hepatitis B virus infection be necessary during pregnancy, tenofovir, listed by the FDA as pregnancy category B drug, is to be preferred. Nucleot(s)ide analogues may be used to reduce the risk of intra-uterine and perinatal transmission of hepatitis B virus, which may occur in a proportion of newborns from highly viremic mothers, despite active and passive immunization. Similarly, tenofovir is recommended in the last trimester of pregnancy for women with high viremia. The risk of reactivation of chronic hepatitis B virus infection is high in HBsAg positive patients, and in patients with occult hepatitis B virus infection during and after chemotherapy or immunosuppressive treatment, including biological response modifiers (particularly related to rituximab therapy). Therefore, all candidates for these treatments should be screened for HBsAg and anti-HBc. Pre-emptive nucleot(s)ide analogues therapy should be initiated in patients with HBsAg positivity, and patients with occult hepatitis B virus infection. The role of general practitioners and occupational health physicians in the identification and the prevention of hepatitis B virus infection is stressed. Issues of high risk population groups, candidacy for vaccination, and methodology of active and passive immunisation are also reviewed in this paper. Orv. Hetil., 2013, 154, 1142–1150.
Collapse
Affiliation(s)
- Gábor Horváth
- Budai Hepatológiai Centrum Budapest Királyhágó u. 1–3. 1126
- Szent János Kórház és Észak-budai Egyesített Kórházak I. Belgyógyászat – Hepatológiai Szakrendelés Budapest
| |
Collapse
|
|
43
|
Abstract
Acute liver failure (ALF) is a condition wherein the previously healthy liver rapidly deteriorates, resulting in jaundice, encephalopathy, and coagulopathy. There are approximately 2000 cases per year of ALF in the United States. Viral causes (fulminant viral hepatitis [FVH]) are the predominant cause of ALF in developing countries. Given the ease of spread of viral hepatitis and the high morbidity and mortality associated with ALF, a systematic approach to the diagnosis and treatment of FVH is required. In this review, the authors describe the viral causes of ALF and review the intensive care unit management of patients with FVH.
Collapse
MESH Headings
- Acetylcysteine/therapeutic use
- Adult
- Brain Edema/etiology
- Brain Edema/virology
- Developing Countries
- Female
- Hepatectomy
- Hepatitis, Viral, Human/complications
- Hepatitis, Viral, Human/drug therapy
- Hepatitis, Viral, Human/prevention & control
- Herpesviridae/pathogenicity
- Humans
- Hypothermia, Induced/adverse effects
- Hypothermia, Induced/standards
- Immunocompromised Host
- Intensive Care Units
- Intubation, Intratracheal
- Liver Failure, Acute/etiology
- Liver Failure, Acute/therapy
- Liver Failure, Acute/virology
- Liver Transplantation
- Pregnancy
- Pregnancy Complications, Infectious/virology
- Prognosis
- Viral Hepatitis Vaccines/administration & dosage
Collapse
Affiliation(s)
- Saumya Jayakumar
- Faculty of Medicine and Dentistry, Division of Gastroenterology, University of Calgary, TRW Building, 3280 Hospital Drive NW, Calgary, Alberta T2N 4Z6, Canada
| | | | | | | |
Collapse
|
|
44
|
Abstract
Given the high prevalence of the use of medications in daily practice and the large number of people taking antirheumatic agents, the risk of drug-drug interactions and of hepatotoxicity is of concern. Both old and new compounds show such a risk. Nonsteroidal antinflammatory drugs are widely used drugs with potential adverse hepatic reactions. Nonsteroidal antinflammatory drugs are responsible for an important aliquot of transaminase elevation in the general population. Genetic susceptibility to diclofenac hepatotoxicity has promoted the knowledge about drug-specific, class-specific reactions. Some drugs (sulfasalazine, azathioprine, and leflunomide) may cause acute liver injury, whereas other compounds (methotrexate) may cause chronic liver damage as the result of the interaction among drug, host and environmental factors. The tumor necrosis factor-alpha inhibitor, infliximab, is associated with typical drug-induced autoimmune hepatitis. Also, the other biological disease-modifying antirheumatic drugs are not free of potential hepatotoxicity. The diagnosis of drug-induced liver injury follows the exclusion of other causes, involves a temporal relationship between drug exposure and adverse event, and should consider the potential participation of the underlying rheumatic disease to event occurrence. This article also includes data regarding hepatotoxicity from our outclinic patients receiving biological disease-modifying antirheumatic drugs.
Collapse
|
|
45
|
Zheng Y, Zhang S, Tan Grahn HM, Ye C, Gong Z, Zhang Q. Prophylactic Lamivudine to Improve the Outcome of Breast Cancer Patients With HBsAg Positive During Chemotherapy: A Meta-Analysis. HEPATITIS MONTHLY 2013; 13:e6496. [PMID: 23805156 PMCID: PMC3693540 DOI: 10.5812/hepatmon.6496] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/13/2012] [Revised: 11/10/2012] [Accepted: 12/31/2012] [Indexed: 12/11/2022]
Abstract
CONTEXT Raising the chemotherapy-induced HBV reactivation is parallel to the increment of chemotherapy treatments in breast cancer patients. This meta-analysis aims to evaluate the efficacy of prophylactic use of lamivudine in breast cancer patients with HBsAg positive during chemotherapy. EVIDENCE ACQUISITION MEDLINE, Pubmed, Ovid and Embase were used to search for clinical studies comparing with or without prophylactic use of lamivudine for HBV reactivation in breast cancer patients receiving chemotherapy. Outcomes of interest were the rate of HBV reactivation, incidence of hepatitis and incidence of hepatitis attributable to HBV reactivation, severity of hepatitis and severity of hepatitis attributable to HBV reactivation, the rate of chemotherapy disruption, and the rate of chemotherapy disruption attributable to HBV reactivation, overall mortality, and mortality attributable to HBV reactivation. RESULTS Four studies with 285 patients were included in this meta-analysis. The rate of HBV reactivation, incidence of hepatitis and incidence of hepatitis related to HBV reactivation were reduced by use of prophylactic lamivudine compared to control group. Pooled Odds Ratios (ORs) were 0.09 (95% confidence intervals [CI] 0.03-0.26; P < 0.0001), 0.23 (95% CI 0.06-0.92; P = 0.04), and 0.10 (95% CI 0.03-0.32; P < 0.0001) respectively. There was a reduction in chemotherapy disruption related to HBV reactivation by use of prophylactic lamivudine (pooled OR = 0.11; 95% CI 0.02-0.58; P = 0.01). Chemotherapy disruption, overall mortality, and mortality attributable to HBV reactivation were not significantly different between two groups. Pooled ORs were 0.42 (95% CI 0.11-1.58; P = 0.20), 0.37 (95% CI 0.07-2.04; P = 0.25), and 0.25 (95% CI 0.01-6.82; P = 0.41) respectively. Lamivudine was well-tolerated, and no additional toxicity was observed. CONCLUSIONS Use of prophylactic lamivudine may have positive effect on the outcome of breast cancer patients with HBsAg positive during chemotherapy.
Collapse
Affiliation(s)
- Yihu Zheng
- Department of General Surgery, The First Affiliated Hospital, Wenzhou Medical College, Wenzhou, Zhejiang, China
| | - Shengchu Zhang
- Department of General Surgery, The First Affiliated Hospital, Wenzhou Medical College, Wenzhou, Zhejiang, China
- Department of General Surgery, Yichang Central People’s Hospital, The First Clinical Medical College of Three Gorges University, Yichang, China
| | - Hooi Min Tan Grahn
- Metabolism, Obesity/Diabetes, Department of Biochemistry, Boston University School of Medicine, Boston, USA
| | - Chao Ye
- State Key Laboratory for Diagnosis and Treatment of Infectious Disease, The First Affiliated Hospital, Zhejiang University, Hangzhou, China
| | - Zheng Gong
- Department of General Surgery, Yichang Central People’s Hospital, The First Clinical Medical College of Three Gorges University, Yichang, China
| | - Qiyu Zhang
- Department of General Surgery, The First Affiliated Hospital, Wenzhou Medical College, Wenzhou, Zhejiang, China
- Corresponding author: Qiyu Zhang, Department of General Surgery, The First Affiliated Hospital of Wenzhou Medical College, NO. 453 Ward, No. 4 Building, Nan Bai Xiang Street, Ouhai District, Wenzhou, Zhejiang, China. Tel.: +86-57788288181, Fax: 86-57788069555, E-mail:
| |
Collapse
|
|
46
|
López-Serrano P, Pérez-Calle JL, Sánchez-Tembleque MD. Hepatitis B and inflammatory bowel disease: Role of antiviral prophylaxis. World J Gastroenterol 2013; 19:1342-8. [PMID: 23538480 PMCID: PMC3602492 DOI: 10.3748/wjg.v19.i9.1342] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/29/2012] [Revised: 08/22/2012] [Accepted: 08/25/2012] [Indexed: 02/06/2023] Open
Abstract
Hepatitis B virus (HBV) is a very common infection worldwide. Its reactivation in patients receiving immunosuppression has been widely described as being associated with significant morbidity and mortality unless anti-viral prophylaxis is administered. Treatment in inflammatory bowel disease (IBD) patients has changed in recent years and immunosuppression and biological therapies are now used more frequently than before. Although current studies have reported an incidence of hepatitis B in inflammatory bowel disease patients similar to that in the general population, associated liver damage remains an important concern in this setting. Liver dysfunction may manifest in several ways, from a subtle change in serum aminotransferase levels to fulminant liver failure and death. Patients undergoing double immunosuppression are at a higher risk, and reactivation usually occurs after more than one year of treatment. As preventive measures, all IBD patients should be screened for HBV markers at diagnosis and those who are positive for the hepatitis B surface antigen should receive antiviral prophylaxis before undergoing immunosuppression in order to avoid HBV reactivation. Tenofovir/entecavir are preferred to lamivudine as nucleos(t)ide analogues due to their better resistance profile. In patients with occult or resolved HBV, viral reactivation does not appear to be a relevant issue and regular DNA determination is recommended during immunosuppression therapy. Consensus guidelines on this topic have been published in recent years. The prevention and management of HBV infection in IBD patients is addressed in this review in order to address practical recommendations
Collapse
|
|
47
|
Mouler Rechtman M, Burdelova EO, Bar-Yishay I, Ben-Yehoyada M, Fishman S, Halpern Z, Shlomai A. The metabolic regulator PGC-1α links anti-cancer cytotoxic chemotherapy to reactivation of hepatitis B virus. J Viral Hepat 2013; 20:34-41. [PMID: 23231082 DOI: 10.1111/j.1365-2893.2012.01622.x] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
Patients with chronic hepatitis B virus (HBV) infection are at an increased risk for a severe and a potentially fatal viral reactivation following anti-cancer therapy. The molecular mechanism for this induction of HBV expression is still unclear. Here, we show that treating hepatoma cell line expressing HBV with various anti-cancer cytotoxic agents results in a significant up-regulation of HBV expression. This HBV induction is at the transcriptional level and is time dependent. Interestingly, treating hepatoma cells with anti-cancer cytotoxic agents results in a robust induction of peroxisome proliferator-activated receptor-gamma coactivator-1α (PGC-1α), a metabolic and energy regulator that is normally induced in the liver under starvation conditions and that has been previously shown to strongly coactivate HBV transcription. Most importantly, HBV up-regulation following anti-cancer therapy depends on PGC-1α induction, because PGC-1α knock-down abolishes HBV induction. Finally, pretreatment of HBV-expressing cells with the antioxidant agent N-acetylcysteine attenuates the induction of both PGC-1α and HBV in response to anti-cancer treatment, suggesting that chemotherapy-associated PGC-1α induction is mediated by cellular oxidative stress that ultimately leads to HBV up-regulation. We conclude that cytotoxic anti-cancer chemotherapy has a direct and an immune system-independent effect on HBV gene expression, which is mediated by PGC-1α. Our results attribute to this metabolic regulator an unexpected role in linking anti-cancer treatment to HBV reactivation and make PGC-1α a potential target for future anti-HBV therapy, especially under conditions in which it is robustly induced, such as following anti-cancer treatment.
Collapse
Affiliation(s)
- M Mouler Rechtman
- The Research Center for Digestive Tract and Liver Diseases, Tel-Aviv Sourasky Medical Center and Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
| | | | | | | | | | | | | |
Collapse
|
|
48
|
EASL clinical practice guidelines: Management of chronic hepatitis B virus infection. J Hepatol 2012; 57:167-85. [PMID: 22436845 DOI: 10.1016/j.jhep.2012.02.010] [Citation(s) in RCA: 2398] [Impact Index Per Article: 184.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2012] [Accepted: 02/28/2012] [Indexed: 02/06/2023]
|
|
49
|
Gisbert JP, Menchén L, García-Sánchez V, Marín I, Villagrasa JR, Chaparro M. Comparison of the effectiveness of two protocols for vaccination (standard and double dosage) against hepatitis B virus in patients with inflammatory bowel disease. Aliment Pharmacol Ther 2012; 35:1379-85. [PMID: 22530631 DOI: 10.1111/j.1365-2036.2012.05110.x] [Citation(s) in RCA: 50] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2012] [Revised: 03/24/2012] [Accepted: 04/04/2012] [Indexed: 12/15/2022]
Abstract
BACKGROUND The response rate to hepatitis B virus (HBV) vaccination in patients with inflammatory bowel disease (IBD) is low. AIM To compare two vaccination protocols-the standard dose and the double dose-in IBD patients. METHODS Patients diagnosed with IBD from three tertiary hospitals were vaccinated against HBV with two different protocols: the standard protocol (Engerix-B single dose at 0, 1 and 6 months) and the new faster protocol based on a double dose (Engerix B double dose at 0, 1 and 2 months). Anti-HBs titres were measured 1-3 months after the last dose. A multivariate analysis was performed to identify factors that were predictive of response to the vaccine. RESULTS The study sample comprised 148 patients (mean age 40 years, 69% Crohn's disease), 70% of whom were receiving immunosuppressive therapy (22% thiopurines, 23% anti-TNF and 25% both). The standard protocol was followed in 46% of patients and the double dose protocol in 54%. Considering anti-HBs >10 IU/L as a successful response to vaccination, the seroconversion rate was higher among patients vaccinated with the double dose than with the standard dose: 75% (95% CI, 65-85%) vs. 41% (95% CI, 29-54%) (P < 0.001). In the multivariate analysis, vaccination with the double dose was the only factor associated with a better response to the vaccine (OR, 4; 95% CI, 2-8; P < 0.001). CONCLUSIONS The response rate to the HBV vaccination in IBD patients is low. Administration of a double dose was associated with a higher response rate. Therefore, the double dose protocol could be a suitable option in patients with IBD.
Collapse
Affiliation(s)
- J P Gisbert
- Department of Gastroenterology, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa, Madrid, Spain.
| | | | | | | | | | | |
Collapse
|
|
50
|
Marignani M, Gigante E, Begini P, Marzano A, di Fonzo M, Deli I, Gallina S, Cox MC, Delle Fave G. Patients with hematological malignancies and serological signs of prior resolved hepatitis B. World J Gastrointest Oncol 2012; 4:37-45. [PMID: 22468182 PMCID: PMC3312927 DOI: 10.4251/wjgo.v4.i3.37] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/05/2011] [Revised: 10/04/2011] [Accepted: 10/12/2011] [Indexed: 02/05/2023] Open
Abstract
Hepatitis B virus (HBV) infection affects a large part of the world population. Within the different virological HBV categories that have been identified, patients with occult HBV infection represent a peculiar group. These individuals harbor a replication competent virus, inhibited in its replicative function. Accordingly, cases of reactivations have been observed in immunosuppressed individuals who lose immunological control over the infection. Patients with hematological malignancies (HM) are treated with intense myelo- and immunosuppressive chemotherapy regimens which favor HBV reactivation. This event can have severe consequences, such as hepatitis flare, hepatic failure and even death. In addition, it can lead to delays or interruptions of curative treatments, resulting in a decreased disease free and overall survival. In this review, we will examine the event of HBV reactivation in patients with signs of resolved HBV infection undergoing treatment for HM and propose possible management strategies.
Collapse
Affiliation(s)
- Massimo Marignani
- Massimo Marignani, Elia Gigante, Paola Begini, Michela di Fonzo, Ilaria Deli, Sara Gallina, Gianfranco Delle Fave, Digestive and Liver Disease Department, School of Medicine and Psychology University "Sapienza", Azienda Ospedaliera S. Andrea, Via Grottarossa, 1035-1039, 00189 Rome, Italy
| | | | | | | | | | | | | | | | | |
Collapse
|