|
1
|
Balsa A, Díaz Del Campo Fontecha P, Silva Fernández L, Valencia Martín J, Nistal Martínez V, León Vázquez F, Hernández Hernández MV, Corominas H, Cáliz Cáliz R, Aguado García JM, Candelas Rodríguez G, Ibargoyen Roteta N, Martí Carvajal A, Plana Farras MN, Puñal Riobóo J, Park HS, Triñanes Pego Y, Villaverde García V. Recommendations by the Spanish Society of Rheumatology on risk management of biological treatment and JAK inhibitors in patients with rheumatoid arthritis. REUMATOLOGIA CLINICA 2023; 19:533-548. [PMID: 38008602 DOI: 10.1016/j.reumae.2023.07.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/26/2023] [Accepted: 07/06/2023] [Indexed: 11/28/2023]
Abstract
OBJECTIVE To present recommendations based on the available evidence and the consensus of experts, for risk management of biological treatment and JAK inhibitors in patients with rheumatoid arthritis. METHODS Clinical research questions relevant to the purpose of the document were identified. These questions were reformulated in PICO format (patient, intervention, comparison, outcome or outcome) by a panel of experts, selected based on their experience in the area. A systematic review of the evidence was carried out, grading according to the GRADE criteria (Grading of Recommendations Assessment, Development, and Evaluation). Specific recommendations were then formulated. RESULTS 6 PICO questions were proposed by the panel of experts based on their clinical relevance and the existence of recent information regarding the risk of occurrence of serious infections, the risk of reactivation of the hepatitis B virus, the risk of reactivation of the virus varicella-zoster, the risk of appearance of skin (melanoma and non-melanoma) or haematological cancer, the risk of appearance of thromboembolic disease and the risk of progression of the human papilloma virus. A total of 28 recommendations were formulated, structured by question, based on the evidence found and the consensus of the experts. CONCLUSIONS The SER recommendations on risk management of treatment with biologic therapies and JAK inhibitors in rheumatoid arthritis are presented.
Collapse
Affiliation(s)
- Alejandro Balsa
- Servicio de Reumatología, Hospital Universitario La Paz, Madrid, Spain
| | | | - Lucía Silva Fernández
- Servicio de Reumatología, Complexo Hospitalario Universitario de A Coruña, A Coruña, Spain
| | - José Valencia Martín
- Unidad de Medicina Preventiva y Salud Pública, Hospital Universitario Virgen del Rocío, Sevilla, Spain
| | | | - Fernando León Vázquez
- Medicina de Familia, Centro de Salud San Juan de la Cruz, Pozuelo de Alarcón, Madrid, Spain
| | - M Vanesa Hernández Hernández
- Servicio de Reumatología, Complejo Hospitalario Universitario de Canarias, San Cristóbal de la Laguna, Santa Cruz de Tenerife, Spain
| | - Héctor Corominas
- Servicio de Reumatología, Hospital Universitari de la Santa Creu i Sant Pau & Hospital Dos de Maig, Barcelona, Spain
| | | | - José María Aguado García
- Unidad de Enfermedades Infecciosas, Hospital Universitario 12 de Octubre. CIBERINFEC, ISCIII. Departamento de Medicina, UCM, Madrid, Spain
| | | | - Nora Ibargoyen Roteta
- Servicio de Evaluación de Tecnologías Sanitarias del País Vasco (Osteba). BIOEF, Barakaldo, Vizcaya, Spain
| | - Arturo Martí Carvajal
- Cátedra Rectoral de Medicina basada en la Evidencia, Universidad de Carabobo, Venezuela; Facultad de Ciencias de la Salud Eugenio Espejo, Universidad UTE, Quito, Ecuador
| | - M Nieves Plana Farras
- Unidad de Evaluación de Tecnologías Sanitarias, Hospital Ramón y Cajal, IRYCIS. CIBER de Epidemiología y Salud Pública (CIBERESP), Spain
| | - Janet Puñal Riobóo
- Unidad de Asesoramiento Científico-técnico, Avalia-t, Agencia Gallega para la Gestión del Conocimiento en Salud, ACIS, Santiago de Compostela, A Coruña, Spain
| | - Hye Sang Park
- Servicio de Reumatología, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
| | - Yolanda Triñanes Pego
- Unidad de Asesoramiento Científico-técnico, Avalia-t, Agencia Gallega para la Gestión del Conocimiento en Salud, ACIS, Santiago de Compostela, A Coruña, Spain
| | | |
Collapse
|
|
2
|
Onorato L, Pisaturo M, Camaioni C, Grimaldi P, Codella AV, Calò F, Coppola N. Risk and Prevention of Hepatitis B Virus Reactivation during Immunosuppression for Non-Oncological Diseases. J Clin Med 2021; 10:5201. [PMID: 34768721 PMCID: PMC8584565 DOI: 10.3390/jcm10215201] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2021] [Revised: 10/30/2021] [Accepted: 11/03/2021] [Indexed: 12/31/2022] Open
Abstract
Reactivation of overt or occult HBV infection (HBVr) is a well-known, potentially life-threatening event which can occur during the course of immunosuppressive treatments. Although it has been described mainly in subjects receiving therapy for oncological or hematological diseases, the increasing use of immunosuppressant agents in non-oncological patients observed in recent years has raised concerns about the risk of reactivation in several other settings. However, few data can be found in the literature on the occurrence of HBVr in these populations, and few clear recommendations on its management have been defined. The present paper was written to provide an overview of the risk of HBV reactivation in non-neoplastic patients treated with immunosuppressive drugs, particularly for rheumatological, gastrointestinal, dermatological and neurological diseases, and for COVID-19 patients receiving immunomodulating agents; and to discuss the potential strategies for prevention and treatment of HBVr in these settings.
Collapse
Affiliation(s)
- Lorenzo Onorato
- Department of Mental Health and Public Medicine, Faculty of Medicine, University of Campania Luigi Vanvitelli, Via L. Armanni 5, 80138 Naples, Italy; (L.O.); (M.P.); (C.C.); (P.G.)
- Infectious Diseases Unit, Azienda Ospedaliera Universitaria Luigi Vanvitelli, Via Pansini 5, 80138 Naples, Italy; (A.V.C.); (F.C.)
| | - Mariantonietta Pisaturo
- Department of Mental Health and Public Medicine, Faculty of Medicine, University of Campania Luigi Vanvitelli, Via L. Armanni 5, 80138 Naples, Italy; (L.O.); (M.P.); (C.C.); (P.G.)
| | - Clarissa Camaioni
- Department of Mental Health and Public Medicine, Faculty of Medicine, University of Campania Luigi Vanvitelli, Via L. Armanni 5, 80138 Naples, Italy; (L.O.); (M.P.); (C.C.); (P.G.)
| | - Pierantonio Grimaldi
- Department of Mental Health and Public Medicine, Faculty of Medicine, University of Campania Luigi Vanvitelli, Via L. Armanni 5, 80138 Naples, Italy; (L.O.); (M.P.); (C.C.); (P.G.)
| | - Alessio Vinicio Codella
- Infectious Diseases Unit, Azienda Ospedaliera Universitaria Luigi Vanvitelli, Via Pansini 5, 80138 Naples, Italy; (A.V.C.); (F.C.)
| | - Federica Calò
- Infectious Diseases Unit, Azienda Ospedaliera Universitaria Luigi Vanvitelli, Via Pansini 5, 80138 Naples, Italy; (A.V.C.); (F.C.)
| | - Nicola Coppola
- Department of Mental Health and Public Medicine, Faculty of Medicine, University of Campania Luigi Vanvitelli, Via L. Armanni 5, 80138 Naples, Italy; (L.O.); (M.P.); (C.C.); (P.G.)
- Infectious Diseases Unit, Azienda Ospedaliera Universitaria Luigi Vanvitelli, Via Pansini 5, 80138 Naples, Italy; (A.V.C.); (F.C.)
| |
Collapse
|
|
3
|
Udompap P, Kim WR. Hepatitis B Virus Reactivation and Management of Patients Undergoing Immunosuppression. HEPATITIS B VIRUS AND LIVER DISEASE 2021:427-454. [DOI: 10.1007/978-981-16-3615-8_18] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
|
|
4
|
Chularojanamontri L, Nimanong S, Wongpraparut C, Silpa-Archa N, Chaiyabutr C, Charoenpipatsin N. Impact of long-term systemic treatment for psoriasis on liver disease in psoriasis patients with coexisting hepatitis B virus infection. Dermatol Ther 2020; 33:e14008. [PMID: 32654402 DOI: 10.1111/dth.14008] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2020] [Revised: 07/06/2020] [Accepted: 07/08/2020] [Indexed: 01/11/2023]
Abstract
Continuously updated information is helpful for evaluating the safety of long-term systemic drug use in psoriasis patients with concomitant hepatitis B virus (HBV) infection. To investigate the impact of long-term systemic treatment for psoriasis on liver disease in psoriasis patients with HBV infection. Data of patients during 10-year period were recorded and analyzed. Sixty-six patients (46 males and 20 females) with a mean age of 58.5 ± 13.1 years were recruited. Our study estimated that the 5-year cumulative risks of developing cirrhosis and HCC were 30% and 5%, respectively, in patients receiving systemic treatments for psoriasis. Risks of cirrhosis and HCC were not significantly different between systemic and topical treatment groups. Thirty patients were prescribed systemic treatments (acitretin, methotrexate, ciclosporin, and anti-tumor necrosis factors). Three HBsAg+ patients developed viral reactivation (two patients with methotrexate and one patient with ciclosporin). The effects of systemic treatments for psoriasis on liver outcome in patients with coexisting HBV infection are needed to be determined. HBsAg+ patients are more likely to develop viral reactivation during systemic treatment for psoriasis than HBsAg- patients. Monitoring of liver enzymes and HBV DNA every 3 months is recommended during treatment and for 6 to 12 months after drug discontinuation.
Collapse
Affiliation(s)
- Leena Chularojanamontri
- Department of Dermatology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Supot Nimanong
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Chanisada Wongpraparut
- Department of Dermatology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Narumol Silpa-Archa
- Department of Dermatology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Chayada Chaiyabutr
- Department of Dermatology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Norramon Charoenpipatsin
- Department of Dermatology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| |
Collapse
|
|
5
|
Chiu YM, Chen DY. Infection risk in patients undergoing treatment for inflammatory arthritis: non-biologics versus biologics. Expert Rev Clin Immunol 2020; 16:207-228. [PMID: 31852268 DOI: 10.1080/1744666x.2019.1705785] [Citation(s) in RCA: 60] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Introduction: Despite the therapeutic effectiveness of biologics targeting immune cells or cytokines in patients with inflammatory arthritis, which reflects their pathogenic roles, an increased infection risk is observed in those undergoing biological treatment. However, there are limited data regarding the comparison of infection risks in inflammatory arthritis patients treated with non-biologics (csDMARDs), biologics (bDMARDs), including tumor necrosis factor (TNF) inhibitors and non-TNF inhibitors, or targeted synthetic (ts)DMARDs.Areas covered: Through a review of English-language literature as of 30 June 2019, we focus on the existing evidence on the risk of infections caused by bacteria, Mycobacterium tuberculosis, and hepatitis virus in inflammatory arthritis patients undergoing treatment with csDMARDs, bDMARDs, or tsDMARDs.Expert opinion: While the risks of bacterial and mycobacterial infection are increased in arthritis patients treated with csDMARDs, the risks are further higher in those receiving bDMARDs therapy, particularly TNF inhibitors. Regarding HBV infection, antiviral therapy may effectively prevent HBV reactivation in patients receiving bDMARDs, especially rituximab. However, more data are needed to establish effective preventive strategies for HBsAg-negative/HBcAb-positive patients. It seems safe to use cyclosporine and TNF inhibitors in patients with HCV infection, while those undergoing rituximab therapies should be frequently monitored for HCV activity.Abbreviations: ABT: abatacept; ADA: adalimumab; AS: ankylosing spondylitis; bDMARDs: biologic disease-modifying anti-rheumatic drugs; CKD: chronic kidney disease; COPD: chronic obstructive pulmonary disease; CS: corticosteroids; CsA: cyclosporine A; csDMARDs: conventional synthetic disease-modifying anti-rheumatic drugs; CZP: certolizumab; DAAs: direct-acting antiviral agents; DM: diabetes mellitus; DOT: directly observed therapy; EIN: Emerging Infections Network; ETN: etanercept; GOL: golimumab; GPRD: General Practice Research Database; HBV: hepatitis B virus; HBVr: HBV reactivation; HBsAg+: HBsAg-positive; HBsAg-/anti-HBc+: HBsAg-negative anti-HBc antibodies-positive; HCV: hepatitis C virus; HCQ: hydroxychloroquine: IFX: infliximab; IL-6: interleukin-6; JAK: Janus kinase; LEF: leflunomide; LTBI: latent tuberculosis infection; mAb: monoclonal antibody; MTX: methotrexate; OR: odds ratio; PsA: psoriatic arthritis; PMS: post-marketing surveillance; RA: rheumatoid arthritis; TNF: tumor necrosis factor; TNFi: tumor necrosis factor inhibitor; SCK: secukinumab; SSZ: sulfasalazine; TOZ: tocilizumab; RCT: randomized controlled trial; RR: relative risk; RTX: rituximab; 3HP: 3-month once-weekly isoniazid plus rifapentine; TB: tuberculosis; tsDMARDs: targeted synthetic disease-modifying anti-rheumatic drugs; UTK: ustekinumab; WHO: World Health Organization.
Collapse
Affiliation(s)
- Ying-Ming Chiu
- Rheumatology and Immunology Center, China Medical University Hospital, Taichung, Taiwan.,College of Medicine, China Medical University, Taichung, Taiwan
| | - Der-Yuan Chen
- Rheumatology and Immunology Center, China Medical University Hospital, Taichung, Taiwan.,College of Medicine, China Medical University, Taichung, Taiwan.,Translational Medicine Laboratory, Rheumatic Diseases Research Center, China Medical University Hospital, Taichung, Taiwan.,Program in Translational Medicine and Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taichung, Taiwan.,Institute of Biochemistry, Microbiology and Immunology, Chung Shan Medical University, Taichung, Taiwan
| |
Collapse
|
|
6
|
Piaserico S, Messina F, Russo FP. Managing Psoriasis in Patients with HBV or HCV Infection: Practical Considerations. Am J Clin Dermatol 2019; 20:829-845. [PMID: 31222626 DOI: 10.1007/s40257-019-00457-3] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Considered more efficacious and safer than traditional systemic drugs, biologic therapies have dramatically improved the quality of life of patients with psoriasis. Recently, there has been a proliferation of new targeted treatment options, including anti-interleukin-17, anti-interleukin-12/23, as well as small-molecule drugs such as apremilast. There are nevertheless some concerns regarding their use, especially in patients with chronic infections such as hepatitis B virus (HBV) and hepatitis C virus (HCV). It has been estimated that two billion individuals are infected with HBV worldwide and approximately 240 million have chronic HBV infection. Moreover, there are approximately 71 million individuals with chronic HCV infection worldwide, with a high percentage of them unaware of being infected. As patients with HBV and HCV infections are excluded from controlled clinical trials investigating new drugs, data regarding their safety in patients with psoriasis are based almost exclusively on case reports and small retrospective cohort studies and need to be constantly updated. The risk of HBV reactivation can be defined as: high risk (≥ 10%), moderate risk (1-10%), and low risk (< 1%) depending on the type of immunosuppressive therapy stratified by the presence or absence of hepatitis B surface antigen but positivity to anti-hepatitis B core antigen. Hepatitis B surface antigen-positive patients treated with tumor necrosis factor-α inhibitors, ustekinumab, or cyclosporine carry a high or moderate risk of HBV reactivation and should be considered candidates for prophylactic anti-HBV therapy. Once therapy is commenced, it is important to check HBV DNA levels every 3 months. Hepatitis B virus reactivation typically occurs with immune reconstitution and therefore antiviral therapy should continue for 6-12 months after stopping immunosuppression. Hepatitis B surface antigen-positive patients who are prescribed methotrexate, acitretin, or apremilast have a low risk and need to be monitored for viral reactivation by determining alanine aminotransferase and HBV DNA levels every 3 months. No conclusive data are available for interleukin-17 and interleukin-23 inhibitors. Anti-hepatitis B core antigen-positive patients treated with tumor necrosis factor-α inhibitors, ustekinumab, and cyclosporine are linked to a moderate risk of reactivation, and they should preferably undergo HBV DNA or hepatitis B surface antigen and alanine aminotransferase testing rather than be subjected to routine pre-emptive therapy. Anti-hepatitis B core antigen-positive patients receiving methotrexate, acitretin, or apremilast have a low risk of reactivation and do not require anti-HBV therapy, nor should monitoring be considered mandatory. No conclusive data are available for interleukin-17 and interleukin-23 inhibitors.
Collapse
Affiliation(s)
- Stefano Piaserico
- Dermatology Unit, Department of Medicine, University of Padova, Via Cesare Battisti 206, 35128, Padua, Italy.
| | - Francesco Messina
- Dermatology Unit, Department of Medicine, University of Padova, Via Cesare Battisti 206, 35128, Padua, Italy
| | - Francesco Paolo Russo
- Gastroenterology Unit, Department of Surgical, Oncological and Gastroenterological Sciences, University of Padua, Padua, Italy
| |
Collapse
|
|
7
|
Hematological Malignancies and HBV Reactivation Risk: Suggestions for Clinical Management. Viruses 2019; 11:v11090858. [PMID: 31540124 PMCID: PMC6784078 DOI: 10.3390/v11090858] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2019] [Revised: 09/10/2019] [Accepted: 09/12/2019] [Indexed: 12/12/2022] Open
Abstract
It is well known that hepatitis B virus reactivation (HBVr) can occur among patients undergoing treatment for hematological malignancies (HM). The evaluation of HBVr risk in patients undergoing immunosuppressive treatments is a multidimensional process, which includes conducting an accurate clinical history and physical examination, consideration of the virological categories, of the medication chosen to treat these hematological malignancies and the degree of immunosuppression induced. Once the risk of reactivation has been defined, it is crucial to adopt adequate management strategies (should reactivation occur). The purpose of treatment is to prevent dire clinical consequences of HBVr such as acute/fulminant hepatitis, and liver failure. Treatment will be instituted according to the indications and evidence provided by current international recommendations and to prevent interruption of lifesaving anti-neoplastic treatments. In this paper, we will present the available data regarding the risk of HBVr in this special population of immunosuppressed patients and explore the relevance of effective prevention and management of this potentially life-threatening event. A computerized literature search was performed using appropriate terms to discover relevant articles. Current evidence supports the policy of universal HBV testing of patients scheduled to undergo treatment for hematological malignancies, and clinicians should be aware of the inherent risk of viral reactivation among the different virological categories and classes of immunosuppressive drugs.
Collapse
|
|
8
|
Pisaturo M, Di Caprio G, Calò F, Portunato F, Martini S, Coppola N. Management of HBV reactivation in non-oncological patients. Expert Rev Anti Infect Ther 2019; 16:611-624. [PMID: 30058401 DOI: 10.1080/14787210.2018.1505501] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
INTRODUCTION HBV reactivation (HBVr) in patients undergoing immunosuppressive therapy is a well-known event. While there are clear directives on the management of current or resolved HBV infection in onco-hematological diseases, there are few data regarding patients with non-oncological diseases. Thus, the aim of the present review is to evaluate HBVr in patients with non-oncological diseases, and identify the management of these patients to prevent HBVr. Areas covered: Original papers, case reports and meta-analyses reporting data on HBVr of current or resolved infection in gastrointestinal, dermatological, rheumatologic and neurological diseases were evaluated. Expert commentary: In HBsAg-positive subjects, those with HBV-related hepatitis (both HBeAg-positive or negative) should be treated with a high genetic barrier nucleos(t)ide analog. The patients with HBV-infection (both HBeAg-positive and negative) an antiviral prophylaxis should be used, with lamivudine in those HBeAg-negative without signs of advanced liver disease, and with ETV, TDF or TAF in all the HBeAg-positive or in those HBeAg-negative with signs of advanced liver disease. In HBsAg-negative/anti-HBc positive subjects, when the risk of HBV reactivation is moderate (use of B-cell depleting agents), a prophylaxis-strategy may be considered; instead, in those with low risk of HBVr, a pre-emptive therapy strategy may be used.
Collapse
Affiliation(s)
- Mariantonietta Pisaturo
- a Department of Mental Health and Public Medicine, Section of Infectious Diseases , University of Campania , Naples , Italy
| | - Giovanni Di Caprio
- a Department of Mental Health and Public Medicine, Section of Infectious Diseases , University of Campania , Naples , Italy
| | - Federica Calò
- a Department of Mental Health and Public Medicine, Section of Infectious Diseases , University of Campania , Naples , Italy
| | - Federica Portunato
- a Department of Mental Health and Public Medicine, Section of Infectious Diseases , University of Campania , Naples , Italy
| | - Salvatore Martini
- a Department of Mental Health and Public Medicine, Section of Infectious Diseases , University of Campania , Naples , Italy.,b Section of Infectio us Diseases , A.O.R.N. Dei Colli, Cotugno Hospital , Napoli , Italy
| | - Nicola Coppola
- a Department of Mental Health and Public Medicine, Section of Infectious Diseases , University of Campania , Naples , Italy.,c Section of Infectious Diseases , A.O.R.N S.Anna S. Sebastiano Caserta , Caserta , Italy
| |
Collapse
|
|
9
|
|
|
10
|
Pattullo V. Prevention of Hepatitis B reactivation in the setting of immunosuppression. Clin Mol Hepatol 2016; 22:219-37. [PMID: 27291888 PMCID: PMC4946398 DOI: 10.3350/cmh.2016.0024] [Citation(s) in RCA: 88] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2016] [Accepted: 04/27/2016] [Indexed: 12/13/2022] Open
Abstract
Advances in the treatment of malignant and inflammatory diseases have developed over time, with increasing use of chemotherapeutic and immunosuppressive agents of a range of drug classes with varying mechanism and potency in their effects on the immune system. These advances have been met with the challenge of increased risk of hepatitis B virus (HBV) reactivation in susceptible individuals. The magnitude of risk of HBV reactivation is associated with the individual’s HBV serological status and the potency and duration of immunosuppression. Individuals with chronic hepatitis B (CHB) and previously infected but serologically cleared HBV infection are both susceptible to HBV reactivation. HBV reactivation in the setting of immunosuppression is a potentially life threatening condition leading to liver failure and death in extreme cases. It is important to recognize that HBV reactivation in the setting of immunosuppression is potentially preventable. Therefore, identification of patients at risk of HBV reactivation and institution of prophylactic antiviral therapy prior to initiation of immunosuppression is essential.
Collapse
Affiliation(s)
- Venessa Pattullo
- Department of Gastroenterology, Royal North Shore Hospital, Sydney, Australia
| |
Collapse
|
|
11
|
Cheung KS, Seto WK, Lai CL, Yuen MF. Prevention and management of hepatitis B virus reactivation in cancer patients. Hepatol Int 2016; 10:407-14. [PMID: 26739135 DOI: 10.1007/s12072-015-9692-3] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/19/2015] [Accepted: 11/24/2015] [Indexed: 12/19/2022]
Abstract
Hepatitis B virus (HBV) reactivation during immunosuppressive therapy is common in patients with solid tumor or hematological malignancies. It is associated with significant morbidity and mortality due to hepatitis flare and/or hepatic decompensation. These consequences arising from HBV reactivation are, however, largely preventable. Routine screening for HBV serologic status is recommended for all cancer patients undergoing chemotherapy or biologics. By recognizing different serological patterns (which represent either overt or occult HBV infection) and the types of immunosuppressive therapies prescribed, a risk-adapted approach can be established. Prophylactic therapy with nucleos(t)ide analogues (prior to or concomitantly with the commencement of immunosuppressive therapies) is more effective than pre-emptive therapy (starting antiviral when HBV DNA level is rising) in high-risk individuals. Entecavir has been proven to be more effective than lamivudine according to recent studies. Close monitoring of serum HBV level is the preferred strategy in low-risk patients. However, the optimal interval of DNA monitoring and the duration of therapy remain unknown.
Collapse
Affiliation(s)
- Ka-Shing Cheung
- Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Pokfulam Road, Hong Kong, China
| | - Wai-Kay Seto
- Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Pokfulam Road, Hong Kong, China.,State Key Laboratory for Liver Research, The University of Hong Kong, Hong Kong, China
| | - Ching-Lung Lai
- Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Pokfulam Road, Hong Kong, China.,State Key Laboratory for Liver Research, The University of Hong Kong, Hong Kong, China
| | - Man-Fung Yuen
- Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Pokfulam Road, Hong Kong, China. .,State Key Laboratory for Liver Research, The University of Hong Kong, Hong Kong, China.
| |
Collapse
|
|
12
|
Kato M, Atsumi T. Reactivation of occult hepatitis B virus infection in patients with rheumatic diseases: pathogenesis, risk assessment and prevention. Rheumatol Int 2015; 36:635-41. [PMID: 26573663 DOI: 10.1007/s00296-015-3395-x] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2015] [Accepted: 11/06/2015] [Indexed: 12/20/2022]
Abstract
Over the past decade, reactivation of occult hepatitis B virus (HBV) infection has garnered much attention from rheumatologists owing to a number of reports which have indicated the potential risk of biologics in causing this previously ignored infectious complication. Hepatitis due to reactivation of occult HBV infection occurs only occasionally but with high mortality upon occurrence, placing us in a clinical dilemma "to address or not to address?" In this review, we discuss how biological and other immunosuppressive therapies increase the risk of developing reactivation of occult HBV infection and attempt to solve this clinical quandary.
Collapse
Affiliation(s)
- Masaru Kato
- Division of Rheumatology, Endocrinology and Nephrology, Graduate School of Medicine, Hokkaido University, N15W7, Kita-Ku, Sapporo, 060-8638, Japan.
| | - Tatsuya Atsumi
- Division of Rheumatology, Endocrinology and Nephrology, Graduate School of Medicine, Hokkaido University, N15W7, Kita-Ku, Sapporo, 060-8638, Japan
| |
Collapse
|
|
13
|
Mori S, Fujiyama S. Hepatitis B virus reactivation associated with antirheumatic therapy: Risk and prophylaxis recommendations. World J Gastroenterol 2015; 21:10274-10289. [PMID: 26420955 PMCID: PMC4579875 DOI: 10.3748/wjg.v21.i36.10274] [Citation(s) in RCA: 66] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/01/2015] [Revised: 06/20/2015] [Accepted: 08/25/2015] [Indexed: 02/06/2023] Open
Abstract
Accompanying the increased use of biological and non-biological antirheumatic drugs, a greater number of cases of hepatitis B virus (HBV) reactivation have been reported in inactive hepatitis B surface antigen (HBsAg) carriers and also in HBsAg-negative patients who have resolved HBV infection. The prevalence of resolved infection varies in rheumatic disease patients, ranging from 7.3% to 66%. Through an electronic search of the PubMed database, we found that among 712 patients with resolved infection in 17 observational cohort studies, 12 experienced HBV reactivation (1.7%) during biological antirheumatic therapy. Reactivation rates were 2.4% for etanercept therapy, 0.6% for adalimumab, 0% for infliximab, 8.6% for tocilizumab, and 3.3% for rituximab. Regarding non-biological antirheumatic drugs, HBV reactivation was observed in 10 out of 327 patients with resolved infection from five cohort studies (3.2%). Most of these patients received steroids concomitantly. Outcomes were favorable in rheumatic disease patients. A number of recommendations have been established, but most of the supporting evidence was derived from the oncology and transplantation fields. Compared with patients in these fields, rheumatic disease patients continue treatment with multiple immunosuppressants for longer periods. Optimal frequency and duration of HBV-DNA monitoring and reliable markers for discontinuation of nucleoside analogues should be clarified for rheumatic disease patients with resolved HBV infection.
Collapse
|
|
14
|
Pattullo V. Hepatitis B reactivation in the setting of chemotherapy and immunosuppression - prevention is better than cure. World J Hepatol 2015; 7:954-967. [PMID: 25954478 PMCID: PMC4419099 DOI: 10.4254/wjh.v7.i7.954] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/02/2014] [Revised: 01/16/2015] [Accepted: 02/12/2015] [Indexed: 02/06/2023] Open
Abstract
Due to the inherent relationship between the immune system and the hepatitis B virus (HBV) in exposed and infected individuals, immunomodulation associated with the treatment of solid tumours, haematological malignancies and inflammatory disorders has been linked to HBV reactivation (HBVr). Reactivation of HBV infection in the setting of chemotherapy and immunosuppression may lead to fulminant liver failure and death, but there is a cumulative body of evidence that these are potentially preventable adverse outcomes. As chronic hepatitis B is largely asymptomatic but also endemic worldwide, clinicians caring for patients requiring chemotherapy or immunosuppression need to be vigilant of the potential for HBVr in susceptible individuals. Serological screening and prophylactic and pre-emptive antiviral treatment with a nucleos(t)ide analogue should be considered in appropriate settings. Hepatitis B prevalence is examined in this review article, as are the risks of HBVr in patients receiving chemo- and immunosuppressive therapy. Recommendations regarding screening, monitoring and the role of antiviral prophylaxis are outlined with reference to current international associations’ guidelines and the best available evidence to date.
Collapse
|
|
15
|
López-Serrano P, de la Fuente Briongos E, Alonso EC, Pérez-Calle JL, Rodríguez CF. Hepatitis B and immunosuppressive therapies for chronic inflammatory diseases: When and how to apply prophylaxis, with a special focus on corticosteroid therapy. World J Hepatol 2015; 7:539-547. [PMID: 25848477 PMCID: PMC4381176 DOI: 10.4254/wjh.v7.i3.539] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2014] [Revised: 12/28/2014] [Accepted: 01/09/2015] [Indexed: 02/06/2023] Open
Abstract
Currently immunosuppressive and biological agents are used in a more extensive and earlier way in patients with inflammatory bowel disease, rheumatic or dermatologic diseases. Although these drugs have shown a significant clinical benefit, the safety of these treatments is a challenge. Hepatitis B virus (HBV) reactivations have been reported widely, even including liver failure and death, and it represents a deep concern in these patients. Current guidelines recommend to pre-emptive therapy in patients with immunosuppressants in general, but preventive measures focused in patients with corticosteroids and inflammatory diseases are scarce. Screening for HBV infection should be done at diagnosis. The patients who test positive for hepatitis B surface antigen, but do not meet criteria for antiviral treatment must receive prophylaxis before undergoing immunosuppression, including corticosteroids at higher doses than prednisone 20 mg/d during more than two weeks. Tenofovir and entecavir are preferred than lamivudine because of their better resistance profile in long-term immunosuppressant treatments. There is not a strong evidence, to make a general recommendation on the necessity of prophylaxis therapy in patients with inflammatory diseases that are taking low doses of corticosteroids in short term basis or low systemic bioavailability corticosteroids such as budesonide or beclomethasone dipropionate. In these cases regularly HBV DNA monitoring is recommended, starting early antiviral therapy if DNA levels begin to rise. In patients with occult or resolved hepatitis the risk of reactivation is much lower, and excepting for Rituximab treatment, the prophylaxis is not necessary.
Collapse
Affiliation(s)
- Pilar López-Serrano
- Pilar López-Serrano, Elsa de la Fuente Briongos, Jose Lázaro Pérez-Calle, Conrado Fernández Rodríguez, Department of Gastroenterology, University Hospital Fundación Alcorcón, 28922 Madrid, Spain
| | - Elsa de la Fuente Briongos
- Pilar López-Serrano, Elsa de la Fuente Briongos, Jose Lázaro Pérez-Calle, Conrado Fernández Rodríguez, Department of Gastroenterology, University Hospital Fundación Alcorcón, 28922 Madrid, Spain
| | - Elisa Carrera Alonso
- Pilar López-Serrano, Elsa de la Fuente Briongos, Jose Lázaro Pérez-Calle, Conrado Fernández Rodríguez, Department of Gastroenterology, University Hospital Fundación Alcorcón, 28922 Madrid, Spain
| | - Jose Lázaro Pérez-Calle
- Pilar López-Serrano, Elsa de la Fuente Briongos, Jose Lázaro Pérez-Calle, Conrado Fernández Rodríguez, Department of Gastroenterology, University Hospital Fundación Alcorcón, 28922 Madrid, Spain
| | - Conrado Fernández Rodríguez
- Pilar López-Serrano, Elsa de la Fuente Briongos, Jose Lázaro Pérez-Calle, Conrado Fernández Rodríguez, Department of Gastroenterology, University Hospital Fundación Alcorcón, 28922 Madrid, Spain
| |
Collapse
|
|
16
|
Reynolds JA, Manch RA, Gish RG. Medical interventions associated with HBV reactivation: Common and less common. Clin Liver Dis (Hoboken) 2015; 5:32-34. [PMID: 31040944 PMCID: PMC6490451 DOI: 10.1002/cld.413] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/01/2014] [Revised: 07/07/2014] [Accepted: 07/19/2014] [Indexed: 02/04/2023] Open
Affiliation(s)
- Justin A. Reynolds
- St. Joseph's Hospital and Medical Center, Center for Liver & Hepatobiliary DiseasePhoenixAZ
| | - Richard A. Manch
- St. Joseph's Hospital and Medical Center, Center for Liver & Hepatobiliary DiseasePhoenixAZ
| | - Robert G. Gish
- St. Joseph's Hospital and Medical Center, Center for Liver & Hepatobiliary DiseasePhoenixAZ
| |
Collapse
|
|
17
|
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
|
|
18
|
Perrillo RP, Gish R, Falck-Ytter YT. American Gastroenterological Association Institute technical review on prevention and treatment of hepatitis B virus reactivation during immunosuppressive drug therapy. Gastroenterology 2015; 148:221-244.e3. [PMID: 25447852 DOI: 10.1053/j.gastro.2014.10.038] [Citation(s) in RCA: 389] [Impact Index Per Article: 38.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Affiliation(s)
- Robert P Perrillo
- Hepatology Division, Baylor University Medical Center, Department of Medicine, University of Texas Southwestern, Dallas, Texas
| | - Robert Gish
- Division of Gastroenterology and Hepatology, Department of Medicine,Stanford University, Palo Alto, California; Hepatitis B Foundation, Doylestown, Pennsylvania
| | - Yngve T Falck-Ytter
- Division of Gastroenterology and Hepatology, Department of Medicine, Case and VA Medical Center, Case Western Reserve University, Cleveland, Ohio
| |
Collapse
|
|
19
|
Keith P, Wetter D, Wilson J, Lehman J. Evidence-based guidelines for laboratory screening for infectious diseases before initiation of systemic immunosuppressive agents in patients with autoimmune bullous dermatoses. Br J Dermatol 2014; 171:1307-17. [DOI: 10.1111/bjd.13355] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/13/2014] [Indexed: 12/12/2022]
Affiliation(s)
- P.J. Keith
- Department of Dermatology; Mayo Clinic; 200 First St SW Rochester MN 55905 U.S.A
| | - D.A. Wetter
- Department of Dermatology; Mayo Clinic; 200 First St SW Rochester MN 55905 U.S.A
| | - J.W. Wilson
- Division of Infectious Diseases; Mayo Clinic; 200 First St SW Rochester MN 55905 U.S.A
| | - J.S. Lehman
- Department of Dermatology; Mayo Clinic; 200 First St SW Rochester MN 55905 U.S.A
- Division of Anatomic Pathology; Mayo Clinic; 200 First St SW Rochester MN 55905 U.S.A
| |
Collapse
|
|
20
|
Riveiro-Barciela M, Buti M. [Hepatitis B virus infection in pregnancy and the immunosuppressed patient]. GASTROENTEROLOGIA Y HEPATOLOGIA 2014; 38:31-9. [PMID: 25066320 DOI: 10.1016/j.gastrohep.2014.05.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/01/2014] [Revised: 05/15/2014] [Accepted: 05/20/2014] [Indexed: 10/25/2022]
Abstract
Hepatitis B virus (HBV) infection continues to be a major public health problem worldwide. Although treatment indications are well established in clinical practice guidelines, there are some risk groups, such as pregnant women and immunosuppressed patients, who require different and specific management of HBV infection. In pregnant women, treatment indication should be individualized and the risk of HBV transmission to the newborn evaluated because cases of vertical transmission continue to be reported, despite active and passive immunoprophylaxis. In patients receiving immunosuppressive therapy, HBV reactivation is associated with high morbidity and mortality, even in patients with past HBV infection, highlighting the importance of screening and the need to evaluate prophylactic therapy in some cases.
Collapse
Affiliation(s)
- Mar Riveiro-Barciela
- Servicio de Hepatología, Medicina Interna, Hospital Universitario Vall d'Hebron, Barcelona, España
| | - María Buti
- Servicio de Hepatología, Medicina Interna, Hospital Universitario Vall d'Hebron, Barcelona, España.
| |
Collapse
|
|
21
|
Abstract
After hepatitis B virus (HBV) infection, HBV DNA persists in minute amounts in hepatocyte nuclei even in individuals with “resolved” infection. Viral replication and development of liver disease depend on the balance between viral mechanisms promoting persistence and host immune control. Patients with active or inactive disease or resolved HBV infection are at risk for reactivation with immunosuppressive therapy use. HBV reactivation varies from a clinically asymptomatic condition to one associated with acute liver failure and death. We review recent studies on HBV reactivation during immunomodulatory therapies for oncologic, gastroenterological, rheumatic, and dermatologic disorders. Risk calculation should be determined through HBV screening and assessment of immunosuppressive therapy potency. We also discuss monitoring for reactivation, prophylactic antiviral therapy, and treatment of reactivation. Prophylactic antiviral treatment is needed for all HBsAg carriers and selected patients who have anti-HBc without HBsAg and is critical for preventing viral reactivation and improving outcomes.
Collapse
Affiliation(s)
- Anil Seetharam
- Banner Transplant and Advanced Liver Disease Center, Phoenix, AZ USA ; University of Arizona College of Medicine, Phoenix, AZ USA
| | - Robert Perrillo
- Hepatology Division, Baylor University Medical Center, Dallas, TX USA ; Department of Internal Medicine, University of Texas Southwestern Medical School, Dallas, TX USA
| | - Robert Gish
- St. Joseph's Hospital Medical Center/Liver Center, Phoenix, AZ USA ; 6022 La Jolla Mesa Drive, San Diego, CA 92037 USA
| |
Collapse
|
|
22
|
Abstract
Patients with chronic HBV infection are at risk of reactivation of HBV should they require immunosuppressive therapies for a variety of clinical settings, including chemotherapy for patients with cancer, immunosuppression for solid organ and stem cell transplant recipients, and use of anti-CD20 antibodies, TNF inhibitors, or corticosteroids in patients with oncological, gastrointestinal, rheumatological or dermatological conditions. The key to preventing HBV reactivation is the identification of patients with HBV infection prior to immunosuppressive therapy, initiation of prophylactic antiviral therapy in patients at moderate or high risk of HBV reactivation, and close monitoring of other patients so that antiviral therapy can be initiated at the first sign of HBV reactivation. Unfortunately, many patients infected with HBV are unaware of their infection or risk factors, and physicians often do not have sufficient time to systematically assess patients for risk factors for HBV prior to starting immunosuppressive therapy. In this article, we review the incidence, risk factors and outcomes of HBV reactivation, and the efficacy of antiviral therapy in preventing its occurrence. We also propose an algorithm for managing patients with HBV infection who require immunosuppressive therapy.
Collapse
|
|
23
|
Watanabe K, Takase K, Ohno S, Ideguchi H, Nozaki A, Ishigatsubo Y. Reactivation of hepatitis B virus in a hepatitis B surface antigen-negative patient with rheumatoid arthritis treated with methotrexate. Mod Rheumatol 2014. [DOI: 10.3109/s10165-011-0521-9] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
|
|
24
|
Droz N, Gilardin L, Cacoub P, Berenbaum F, Wendling D, Godeau B, Piette AM, Dernis E, Ebbo M, Fautrel B, Le Guenno G, Mekinian A, Bernard-Chabert B, Costedoat-Chalumeau N, Descloux E, Michot JM, Radenne S, Rigolet A, Rivière S, Yvin JL, Thibault V, Thabut D, Pol S, Guillevin L, Mouthon L, Terrier B. Kinetic profiles and management of hepatitis B virus reactivation in patients with immune-mediated inflammatory diseases. Arthritis Care Res (Hoboken) 2013; 65:1504-14. [PMID: 23436730 DOI: 10.1002/acr.21990] [Citation(s) in RCA: 41] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2012] [Accepted: 02/13/2013] [Indexed: 12/13/2022]
Abstract
OBJECTIVE Immunosuppressive therapy may trigger hepatitis B virus (HBV) reactivation for increased morbidity and mortality. We aimed to describe HBV reactivation in patients receiving treatment for immune-mediated inflammatory diseases (IMIDs) and to evaluate a predefined algorithm for its prevention. METHODS Physicians submitted data for patients receiving treatment for IMIDs and exhibiting HBV reactivation, defined as an increase of >1 log10 IU/ml of HBV DNA levels or DNA reappearance. We systematically reviewed cases in the literature. RESULTS The 35 physician-collected patients had rheumatoid arthritis (n = 14), connective tissue disease (n = 7), vasculitis (n = 5), and other diseases (n = 9). At baseline, 65.7% of patients were positive for hepatitis B surface antigen (HBsAg), 31.4% had a history of HBV infection, and 2.9% had occult HBV infection. Reactivation occurred a median of 35 weeks (range 2-397 weeks) after the start of corticosteroid and/or immunosuppressive therapy. In all, 88.6% of patients were clinically asymptomatic, but 25.7% had severe hepatitis; none had fulminant hepatitis. Management was antiviral therapy for 91.4%, with discontinuation or decrease of immunosuppressive therapy for 45.7%. In pooling these 35 cases and 103 patients from the literature, 73.9% of patients were clinically asymptomatic, 33.3% had severe hepatitis, and 12.3% died and/or had fulminant hepatitis. Reactivation occurred early with rituximab or cyclophosphamide therapy and in HBsAg-positive/HBV DNA-positive patients. Using the predefined algorithm, 78% of patients with reactivation would have received preemptive antiviral therapy. CONCLUSION We provide new insights into HBV reactivation in patients receiving treatment for IMIDs. A predefined algorithm may be effective in reducing the risk of HBV reactivation in this population.
Collapse
Affiliation(s)
- Nina Droz
- Université Paris Descartes, AP-HP, Hôpital Cochin, Paris, France
| | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
25
|
Liver abnormalities in the immunosuppressed. Best Pract Res Clin Gastroenterol 2013; 27:597-618. [PMID: 24090945 DOI: 10.1016/j.bpg.2013.06.017] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/04/2013] [Accepted: 06/21/2013] [Indexed: 01/31/2023]
Abstract
The immunosuppressed state may arise due to medical illness or drug therapy, which can result in a diverse array of liver derangements. This article discusses the commonly-encountered immunosuppressed conditions and the associated specific liver diseases. Due to the frequency of blood-borne viral disease globally, viral hepatitis (hepatitis B and C) during chemotherapy, transplantation and the increasingly utilised biological therapies for autoimmune disorders is discussed. An overview of human immunodeficiency virus co-infection with hepatitis B and C is provided. This article aims to highlight the variety of liver diseases which can occur in clinically relevant, particularly iatrogenic, immunosuppressed conditions, and summarise learning and practice points for clinicians. Recognition and prevention of viral liver disease is crucial and early involvement of experts prior to administration of immunosuppressive therapy is advised.
Collapse
|
|
26
|
Shin K, Jang H, Jang WM, Lee JS, Song YW. Treatment of Rheumatoid Arthritis Patients with Chronic Hepatitis B: Analysis of Korean National Health Insurance Claims Data. JOURNAL OF RHEUMATIC DISEASES 2013. [DOI: 10.4078/jrd.2013.20.1.24] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Affiliation(s)
- Kichul Shin
- Department of Internal Medicine, College of Medicine, Seoul National University, Seoul, Korea
| | - Hyeongap Jang
- Department of Health Policy Management, College of Medicine, Seoul National University, Seoul, Korea
| | - Won Mo Jang
- Department of Health Policy Management, College of Medicine, Seoul National University, Seoul, Korea
| | - Jin-Seok Lee
- Department of Health Policy Management, College of Medicine, Seoul National University, Seoul, Korea
| | - Yeong-Wook Song
- Department of Internal Medicine, College of Medicine, Seoul National University, Seoul, Korea
- WCU Department of Molecular Medicine and Biopharmaceutical Sciences, Medical Research Center, College of Medicine, Seoul National University, Seoul, Korea
| |
Collapse
|
|
27
|
Tan J, Zhou J, Zhao P, Wei J. Prospective study of HBV reactivation risk in rheumatoid arthritis patients who received conventional disease-modifying antirheumatic drugs. Clin Rheumatol 2012; 31:1169-75. [PMID: 22544263 DOI: 10.1007/s10067-012-1988-2] [Citation(s) in RCA: 59] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2012] [Revised: 03/18/2012] [Accepted: 04/12/2012] [Indexed: 12/16/2022]
Abstract
Studies that reported hepatitis B virus (HBV) reactivation in rheumatoid arthritis (RA) patients have caused attention of disease-modifying antirheumatic drug (DMARD)-related HBV reactivation. Most of the studies were focused on HBV reactivation risk of biologic DMARDs; insufficient data are available to identify the exact risk of conventional DMARD (c-DMARD)-related HBV reactivation. This prospective study aimed to investigate the risk of HBV reactivation in HBV-infected RA patients who received c-DMARDs. A total of 476 RA patients were screened in this prospective non-randomized, non-controlled study. HBV-infected patients characterized by hepatitis B surface antigen (HBsAg) positive or HBsAg negative/anti-hepatitis B core antigen (anti-HBc) positive were analyzed for HBV DNA, followed with HBV DNA monitoring scheduled every 3 months, serum alanine aminotransferase test at 2-month intervals, or more frequently. Prevalence of HBsAg positive and HBsAg negative/anti-HBc positive was 6.51 and 51.1 %, respectively, among the 476 RA patients. Among 211 patients (23 patients were HBsAg positive and 188 patients were HBsAg negative/anti-HBc positive) who received c-DMARDs without antiviral prophylactic treatment, 4 patients developed HBV reactivation. Both HBsAg positive and HBsAg negative/anti-HBc positive patients have the possibility of developing HBV reactivation. There was no correlation between HBV reactivation and any specific c-DMARD. Glucocorticoid coadministration and negative anti-hepatitis B surface antigen (anti-HBs) at baseline showed correlation with reactivation. In conclusion, it would be rational to initiate antiviral prophylaxis according to risk stratification rather than universal prophylaxis for HBV-infected RA patients. Conventional DMARDs are relatively safe to HBV-infected patients with low reactivation risk (low HBV DNA level, no GCs administration, and anti-HB positive).
Collapse
Affiliation(s)
- Jing Tan
- Department of Rheumatology and Hematology, Affiliated Hospital of North Sichuan Medical College, 63 Wenhua Road, Nanchong, Sichuan, People's Republic of China.
| | | | | | | |
Collapse
|
|
28
|
Lan JL, Chen YM, Hsieh TY, Chen YH, Hsieh CW, Chen DY, Yang SS. Kinetics of viral loads and risk of hepatitis B virus reactivation in hepatitis B core antibody-positive rheumatoid arthritis patients undergoing anti-tumour necrosis factor alpha therapy. Ann Rheum Dis 2011; 70:1719-25. [PMID: 21719446 DOI: 10.1136/ard.2010.148783] [Citation(s) in RCA: 142] [Impact Index Per Article: 10.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
OBJECTIVE To investigate the kinetics of hepatitis B virus (HBV) viral loads and HBV reactivation in rheumatoid arthritis (RA) patients undergoing therapy with tumour necrosis factor alpha (TNFα) inhibitors. METHODS The authors investigated the virological, serological and biochemical evidence of HBV reactivation in 88 RA patients receiving anti-TNFα therapy. Levels of HBV surface (HBs) antigen (Ag), anti-HBV core (HBc)-IgG and anti-HBs antibody (Ab) were detected by electrochemiluminescence immunoassay, and viral loads were determined by real-time PCR assay. RESULTS In a total of 88 HBcAb-positive patients, 18 (20.5%) patients were HBsAg-positive, 12 (13.6%) patients were HBsAg-negative/HBsAb-negative and 58 (65.9%) patients were HBsAg-negative/HBsAb-positive before starting anti-TNFα therapy. Among HBsAg-positive patients receiving anti-TNFα therapy, HBV reactivation was documented in none of 10 patients who received lamivudine pre-emptive therapy and serum viral loads significantly decreased (mean ± SEM, 153,860 ± 80,120 IU/ml at baseline vs 313 ± 235 IU/ml after 12 months antiviral therapy, p<0.001), paralleling the decrease in serum aminotransferase levels. In contrast, five (62.5%) of eight patients without antiviral prophylaxis developed HBV reactivation, viral loads significantly increased after anti-TNFα therapy (9375 ± 5924 IU/ml vs 49,710,000 ± 40,535,000 IU/ml, p<0.001), and markedly declined after antiviral therapy (49,710,000 ± 40,535,000 IU/ml vs 6382 ± 2424 IU/ml, p<0.001). Baseline viral loads were detectable in four (33.3%) of 12 patients who had HBsAg-negative/HBsAb-negative status, and one developed HBV reactivation after anti-TNFα therapy. CONCLUSION HBV reactivation can occur in both HBsAg-positive and HBsAg-negative/HBcAb-positive patients with detectable HBV DNA, so-called occult HBV infection, during anti-TNFα therapy. Antiviral prophylaxis may effectively reduce HBV reactivation in HBsAg-positive RA patients undergoing anti-TNFα therapy.
Collapse
MESH Headings
- Adalimumab
- Adult
- Antibodies, Monoclonal/adverse effects
- Antibodies, Monoclonal/pharmacology
- Antibodies, Monoclonal/therapeutic use
- Antibodies, Monoclonal, Humanized
- Antirheumatic Agents/adverse effects
- Antirheumatic Agents/pharmacology
- Antirheumatic Agents/therapeutic use
- Antiviral Agents/therapeutic use
- Arthritis, Rheumatoid/complications
- Arthritis, Rheumatoid/drug therapy
- Arthritis, Rheumatoid/immunology
- Etanercept
- Female
- Hepatitis B Antibodies/blood
- Hepatitis B Surface Antigens/blood
- Hepatitis B virus/isolation & purification
- Hepatitis B virus/physiology
- Hepatitis B, Chronic/complications
- Hepatitis B, Chronic/immunology
- Hepatitis B, Chronic/prevention & control
- Hepatitis B, Chronic/virology
- Humans
- Immunoglobulin G/adverse effects
- Immunoglobulin G/pharmacology
- Immunoglobulin G/therapeutic use
- Immunosuppressive Agents/adverse effects
- Immunosuppressive Agents/pharmacology
- Immunosuppressive Agents/therapeutic use
- Lamivudine/therapeutic use
- Male
- Middle Aged
- Receptors, Tumor Necrosis Factor/therapeutic use
- Retrospective Studies
- Tumor Necrosis Factor-alpha/antagonists & inhibitors
- Viral Load
- Virus Activation/drug effects
Collapse
Affiliation(s)
- Joung-Liang Lan
- Division of Allergy, Immunology and Rheumatology, Taichung Veterans General Hospital, Taichung, Taiwan
| | | | | | | | | | | | | |
Collapse
|
|
29
|
Watanabe K, Takase K, Ohno S, Ideguchi H, Nozaki A, Ishigatsubo Y. Reactivation of hepatitis B virus in a hepatitis B surface antigen-negative patient with rheumatoid arthritis treated with methotrexate. Mod Rheumatol 2011; 22:470-3. [PMID: 21901356 DOI: 10.1007/s10165-011-0521-9] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2011] [Accepted: 08/16/2011] [Indexed: 12/16/2022]
Abstract
Immunosuppressive therapy can induce viral reactivation in patients with chronic hepatitis B virus (HBV) infection and, more rarely, in patients with resolved HBV infection. We report the case of a 57-year-old Japanese woman with rheumatoid arthritis (RA) who developed de-novo hepatitis B virus-related hepatitis after methotrexate (MTX) therapy. Entecavir and oral prednisolone following steroid pulse therapy were administered and her liver function recovered. MTX is widely used for RA for its efficiency and safety. But some cases of HBV reactivation caused by MTX, including de-novo hepatitis, have been reported. Considering these conditions, more attention should be paid when using MTX in patients with RA. And more studies are needed to determine who needs screening of HBV, monitoring of HBV-DNA, and prophylaxis with chemotherapy or immunosuppressive therapy.
Collapse
Affiliation(s)
- Keisuke Watanabe
- Center for Rheumatic Diseases, Yokohama City University Medical Center, 4-57 Urafune-cho, Minami-ku, Yokohama, Kanagawa 232-0024, Japan
| | | | | | | | | | | |
Collapse
|
|
30
|
Cabrera Villalba SR, Victoria Hernández Miguel M, Sanmartí Sala R. ¿Cómo manejar al paciente con artritis reumatoide y serología virus de hepatitis B, hepatitis C, virus de la inmunodeficiencia humana? ACTA ACUST UNITED AC 2011; 7:203-7. [DOI: 10.1016/j.reuma.2010.11.013] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2010] [Revised: 11/24/2010] [Accepted: 11/25/2010] [Indexed: 01/09/2023]
|
|
31
|
Reactivación de hepatitis B en un paciente con espondiloartritis tras suspender metotrexato y eficacia del tratamiento con antivirales en asociación con adalimumab. ACTA ACUST UNITED AC 2011; 7:200-2. [DOI: 10.1016/j.reuma.2010.08.004] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2010] [Revised: 08/05/2010] [Accepted: 08/18/2010] [Indexed: 11/19/2022]
|
|
32
|
Cabrera Villalba SR, Hernández Miguel MV, Sanmartí Sala R. How does one manage patients with rheumatoid arthritis and positive serology to hepatitis B, hepatitis C, human immunodeficiency virus? ACTA ACUST UNITED AC 2011. [DOI: 10.1016/s2173-5743(11)70042-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/16/2022]
|
|
33
|
Meyer-Olson D, Hoeper K, Schmidt RE. [Infectious complications of biologic therapy in patients with rheumatoid arthritis]. Z Rheumatol 2010; 69:879-88. [PMID: 21128049 DOI: 10.1007/s00393-010-0677-2] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
The introduction of biological disease-modifying drugs (DMARDs) has substantially improved the treatment options for patients with rheumatoid arthritis. However, infectious complications represent the most common side effects of these drugs, including severe infections as well as rare opportunistic infections. Treating patients on biological DMARDs is therefore one of the biggest challenges in rheumatology care. The present review describes the current state of knowledge regarding frequency and type of infectious complications associated with biological DMARDs. The article focuses mainly on risk management, in particular on diagnosis and recurrence prevention of tuberculosis and reactivation of hepatitis B virus infection. Furthermore, we discuss the importance of vaccinations in primary disease prevention in patients with rheumatoid arthritis.
Collapse
Affiliation(s)
- D Meyer-Olson
- Klinik für Immunologie und Rheumatologie, Medizinische Hochschule Hannover, Carl-Neuberg-Strasse 1, Hannover, Germany.
| | | | | |
Collapse
|
|
34
|
Schmajuk G, Yazdany J. Drug monitoring in systemic lupus erythematosus: a systematic review. Semin Arthritis Rheum 2010; 40:559-75. [PMID: 21030066 DOI: 10.1016/j.semarthrit.2010.07.010] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2010] [Revised: 07/27/2010] [Accepted: 07/29/2010] [Indexed: 12/16/2022]
Abstract
OBJECTIVES To conduct an evidence-based review of the common medication toxicities and strategies and utility of drug toxicity monitoring among patients with systemic lupus erythematosus (SLE). METHODS PubMed and other databases were searched for articles published between the years 1960 and 2010 for keywords referring to medication toxicity or monitoring strategies for 7 drugs commonly used in SLE. All relevant English-language articles were reviewed. Most of the evidence we reviewed comprised studies that addressed the incidence of toxicity-randomized trials that compare different monitoring strategies for these drugs do not exist. RESULTS Data to describe the frequency of adverse events and appropriate strategies for screening for these events are scarce. Toxicities do not appear to be substantially more common among patients with SLE compared to other conditions for which these drugs are used. CONCLUSIONS Our review demonstrates that the scientific basis for many aspects of drug toxicity monitoring is weak and that most current recommendations are based largely on expert consensus. We present a future research agenda to address these gaps.
Collapse
Affiliation(s)
- Gabriela Schmajuk
- Department of Medicine, Division of Rheumatology, Stanford University, CA, USA.
| | | |
Collapse
|
|
35
|
Stine JG, Khokhar OS, Charalambopoulos J, Shanmugam VK, Lewis JH. Rheumatologists' awareness of and screening practices for hepatitis B virus infection prior to initiating immunomodulatory therapy. Arthritis Care Res (Hoboken) 2010; 62:704-11. [PMID: 20461789 DOI: 10.1002/acr.20209] [Citation(s) in RCA: 40] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
OBJECTIVE To assess the degree of awareness of the American College of Rheumatology (ACR) guidelines and package insert information on the screening for and management of hepatitis B virus (HBV) infection by rheumatologists in patients receiving immunomodulation drug therapies. METHOD A questionnaire survey was administered to a nationwide sample of 1,000 members of the ACR. Each participating physician answered questions regarding their awareness of the risk of HBV reactivation, familiarity with published guidelines regarding HBV reactivation, their decision process in screening patients for HBV, knowledge of antiviral treatments for HBV, personal experience with HBV reactivation, and preferred approach to prophylaxis and subsequent monitoring of those patients. RESULTS Responses were highly variable with regard to awareness, screening, and treatment options. The overall response rate was 15.3%. Of those surveyed, 7.4% had seen HBV reactivation. Depending on the agent, 19-53% were aware of manufacturers' warnings for HBV reactivation within drug package inserts. Nearly three-quarters (72%) would screen for HBV reactivation regardless of the presence/absence of manufacturers' warnings. Only 69% reported performing universal screening prior to initiating therapy with biologic disease-modifying antirheumatic drugs. The majority (81%) would defer to a gastroenterologist/hepatologist to determine prophylactic therapy for HBV. Only 22% had managed patients who were given prophylaxis against HBV reactivation while receiving immunosuppressants. CONCLUSION Based on this survey, improving education among rheumatologists regarding the risks of HBV reactivation and its prevention for patients receiving immunosuppressants seems warranted. More specific consensus guidelines are recommended to achieve universal screening as the standard of care in these patients, especially with the increasing prevalence of HBV infection estimated in the US.
Collapse
|
|
36
|
Guennoc X, Narbonne V, Jousse-Joulin S, Devauchelle-Pensec V, Dougados M, Daurès JP, Saraux A. Is screening for hepatitis B and hepatitis C useful in patients with recent-onset polyarthritis? The ESPOIR cohort study. J Rheumatol 2009; 36:1407-13. [PMID: 19531755 DOI: 10.3899/jrheum.081308] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
OBJECTIVE To evaluate the seroprevalence of hepatitis B (HBV) and C (HCV) in patients living in France with recent-onset polyarthritis suggesting rheumatoid arthritis. METHODS The 813 patients in the ESPOIR cohort were screened for anti-HCV antibodies and HBs antigen. RESULTS Seroprevalence was 0.86% for HCV (n = 7) and 0.12% for HBV (n = 1). HCV-related arthritis was diagnosed in 4 (0.5%) patients; no patient had HBV-related arthritis. HCV-seropositive patients had significantly higher transaminase levels (ALAT, 41.5 IU vs 23.2 IU, p = 0.02; and ASAT, 39.2 IU vs 21.8 IU, p = 0.001) but only 2 patients had ASAT or ALAT levels > 40 IU. No significant differences were found for anti-CCP antibodies, C-reactive protein, erythrocyte sedimentation rate, or other test. HCV seroprevalence was significantly higher in the subgroup with history of blood transfusion than in other patients (3.7% vs 0.42%, p = 0.02). Two of the 7 HCV positive patients and the single patient with confirmed hepatitis B infection were born in areas with higher prevalence of viral hepatitis (Togo, Senegal, Vietnam). Positive hepatitis status was known before study inclusion in 4 of the 7 HCV-positive patients and in the HBV-positive patient. CONCLUSION The prevalence of HBV and HCV in a population of patients with recent-onset polyarthritis suggestive of RA was not greater than expected based on data from the general population in the same geographic area. Routine HBV and HCV serological testing did not contribute substantially to the diagnosis of recent-onset polyarthritis. Although advisable before initiating immunosuppressive or hepatotoxic drugs, serological testing for HCV and HBV is unnecessary in routine diagnostic evaluation of recent-onset polyarthritis.
Collapse
Affiliation(s)
- Xavier Guennoc
- Rheumatology Unit and Immunology Department, Brest Teaching Hospital, F 29609 Brest Cedex, France
| | | | | | | | | | | | | |
Collapse
|
|
37
|
Zingarelli S, Frassi M, Bazzani C, Scarsi M, Puoti M, Airò P. Use of tumor necrosis factor-alpha-blocking agents in hepatitis B virus-positive patients: reports of 3 cases and review of the literature. J Rheumatol 2009; 36:1188-94. [PMID: 19447932 DOI: 10.3899/jrheum.081246] [Citation(s) in RCA: 60] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
OBJECTIVE To evaluate the development of hepatitis B virus (HBV) infection in patients receiving tumor necrosis factor-alpha-blocking agents (TNFBA), and to evaluate whether lamivudine (LAM) prophylaxis can reduce the risk of viral reactivation in inactive HBsAg carriers. METHODS Local experience and published reports were reviewed. Patients with HBV infection were classified as having chronic HBV hepatitis, or being inactive HBsAg carriers or occult carriers. RESULTS Three patients in our series and 24 patients in the literature were identified: 2 had active HBV-associated disease, 23 were inactive HBsAg carriers, and 2 occult carriers. When exposed to TNFBA, HBsAg-inactive carriers pretreated with LAM had lower risk of having detectable HBV-DNA (p=0.02) or viral reactivation (p=0.046) than those without LAM prophylaxis. In 3 patients who discontinued TNFBA, LAM prophylaxis was also discontinued 10-12 months thereafter without hepatitis flares. Two cases of reactivation in occult carriers (HBsAg-negative, anti-HBs+, anti-HBc+) were described in the literature. CONCLUSION TNFBA should be avoided in patients with active HBV replication and should be used with caution in inactive HBsAg carriers. In these patients, the risk of viral reactivation seems to be high, but it might be reduced by prophylactic LAM, which should probably be given for a long time when TNFBA are discontinued (e.g., 12 mo). Potential occult carriers might carry a low, but not negligible, risk of viral reactivation. They should therefore be monitored with particular care.
Collapse
Affiliation(s)
- Stefania Zingarelli
- Rheumatology and Clinical Immunology Service, Infectious and Tropical Diseases Department, Spedali Civili and University of Brescia, Brescia, Italy
| | | | | | | | | | | |
Collapse
|
|
38
|
Abstract
Reactivation of hepatitis B refers to the abrupt increase in hepatitis B virus (HBV) replication in a patient with inactive or resolved hepatitis B. Reactivation can occur spontaneously, but more typically is triggered by immunosuppressive therapy of cancer, autoimmune disease, or organ transplantation. Reactivation can be transient and clinically silent, but often causes a flare of disease that can be severe resulting in acute hepatic failure. Most instances of reactivation resolve spontaneously, but if immune suppression is continued, re-establishment of chronic hepatitis occurs which can lead to progressive liver injury and cirrhosis. The best-described instances of reactivation occur in hepatitis B surface antigen (HBsAg) carriers with inactive or minimally active disease who are given cancer chemotherapy for lymphoma or leukemia. Typically, serum HBV DNA rises during chemotherapy, followed by a disease flare and HBV DNA clearance with immune reconstitution after chemotherapy is stopped. Special forms of reactivation occur after solid organ and bone marrow transplantation in which chronic infection often results. Several randomized, placebo-controlled trials have shown that reactivation can be prevented by antiviral prophylaxis. Routine prophylaxis is therefore recommended for persons with HBsAg undergoing cancer chemotherapy or transplantation, but major questions remain. Which patients should be screened for HBsAg and should all be treated? Which antiviral should be used and for how long? Should persons with resolved hepatitis B without HBsAg receive prophylaxis? Future research should address the underlying molecular mechanisms of reactivation as well as its optimal means of diagnosis, treatment, and prevention in different patient populations.
Collapse
Affiliation(s)
- Jay H Hoofnagle
- Division of Digestive Diseases and Nutrition, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health (NIH), Bethesda, MD 20892, USA.
| |
Collapse
|
|
39
|
Katz LH, Fraser A, Leibovici L, Tur-Kaspa R. Lamivudine for preventing reactivation of hepatitis B infection in patients planned to undergo immunosuppressive therapy. Hippokratia 2009. [DOI: 10.1002/14651858.cd005264.pub2] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022]
Affiliation(s)
- Lior H Katz
- Sheba Medical Center; Gastroenterology Department; Tel-Hashomer Ramat-Gan Israel 52621
| | - Abigail Fraser
- University of Bristol, Oakfield House; Department of Social Medicine, MRC Centre for Causal Analysis in Translational Epidemiology; Oakfield Road Bristol UK BS8 2BN
| | - Leonard Leibovici
- Beilinson Campus, Rabin Medical Center; Department of Medicine E; 39 Jabotinsky Street Petah-Tiqva Israel 49100
| | - Rani Tur-Kaspa
- Rabin Medical Center - Beilison Campus; Department of Internal Medicine D; - Beilinson Campus Petah Tigva Israel 49100
| |
Collapse
|
|
40
|
Tratamiento de situaciones clínicas difíciles en pacientes que presentan artritis reumatoide con hepatitis. ACTA ACUST UNITED AC 2009; 5 Suppl 1:53-60. [DOI: 10.1016/j.reuma.2008.11.006] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2008] [Accepted: 11/27/2008] [Indexed: 12/17/2022]
|
|
41
|
Chakravarty EF. Viral infection and reactivation in autoimmune disease. ACTA ACUST UNITED AC 2008; 58:2949-57. [DOI: 10.1002/art.23883] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
|
|
42
|
Lau GKK. Hepatitis B reactivation after chemotherapy: two decades of clinical research. Hepatol Int 2008; 2:152-62. [PMID: 19669300 PMCID: PMC2716860 DOI: 10.1007/s12072-008-9056-3] [Citation(s) in RCA: 75] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/13/2007] [Accepted: 01/23/2008] [Indexed: 02/06/2023]
Abstract
Hepatitis due to hepatitis B virus reactivation after cytotoxic or immunosuppressive therapy is a serious cause of liver-related morbidity and mortality. With the characterization of the underlying pathogenesis, much progress in the management of this important clinical problem has been made in the past 2 decades. By year 2008, it is mandatory to screen for hepatitis B surface antigen status before initiating intensive chemotherapy or immunosuppressive therapy. All those who are hepatitis B surface antigen positive should be started on preemptive nucleos(t)ide analogues. However, there remains important issues, such as the type and duration of nucleos(t)ide analogue therapy, which need to be understood. As not all hepatitis B surface antigen-positive patients will suffer from HBV reactivation, it is therefore useful to identify risk factors related to HBV reactivation so that patients will not be treated unnecessarily with nucleos(t)ide analogues. To date, a high baseline level of viral replication, as reflected by high serum HBV DNA level, positive serum hepatitis B e antigen, and a high intrahepatic covalently closed circular DNA level, is the most important predictor for HBV reactivation. Recently, there has been an increased awareness of reactivation of occult hepatitis B virus, especially in hepatitis B virus endemic area, such as the Asia-Pacific region. Careful epidemiological study will be needed to clarify the impact of occult hepatitis B infection in patients treated with cytotoxic or immunosuppressive therapy.
Collapse
Affiliation(s)
- George K K Lau
- Department of Medicine, The University of Hong Kong, Room 1838, Block K, Queen Mary Hospital, 102 Pokfulum Road, Hong Kong, Hong Kong SAR China,
| |
Collapse
|
|
43
|
Abstract
Acute liver failure (ALF) is a rare but challenging clinical syndrome with multiple causes; a specific etiology cannot be identified in 15% of adult and 50% of pediatric cases. The course of ALF is variable and the mortality rate is high. Liver transplantation is the only therapy of proven benefit, but the rapidity of progression and the variable course of ALF limit its use. Currently in the United States, spontaneous survival occurs in approximately 45%, liver transplantation in 25%, and death without transplantation in 30% of adults with ALF. Higher rates of spontaneous recovery (56%) and transplantation (31%) with lower rates of death (13%) occur in children. The outcome of ALF varies by etiology, favorable prognoses being found with acetaminophen overdose, hepatitis A, and ischemia (approximately 60% spontaneous survival), and poor prognoses with drug-induced ALF, hepatitis B, and indeterminate cases (approximately 25% spontaneous survival). Excellent intensive care is critical in management of patients with ALF. Nonspecific therapies are of unproven benefit. Future possible therapeutic approaches include N-acetylcysteine, hypothermia, liver assist devices, and hepatocyte transplantation. Advances in stem cell research may allow provision of cells for bioartificial liver support. ALF presents many challenging opportunities in both clinical and basic research.
Collapse
Affiliation(s)
- William M Lee
- Division of Digestive and Liver Diseases, University of Texas Southwestern Medical School, Dallas, TX 75390-8887, USA.
| | | | | | | | | |
Collapse
|
|
44
|
Pullukcu H, Ertem E, Karaca Y, Yamazhan T, Sertoz RY, Altuglu I. Efficacy of accelerated hepatitis B vaccination program in patients being actively treated for hematologic malignancies. Int J Infect Dis 2008; 12:166-70. [PMID: 17720599 DOI: 10.1016/j.ijid.2007.06.004] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2006] [Revised: 04/27/2007] [Accepted: 06/18/2007] [Indexed: 11/26/2022] Open
Abstract
BACKGROUND The goal of this study was to conduct an accelerated vaccination program and to determine its efficacy in patients susceptible to hepatitis B virus (HBV) receiving chemotherapy because of their hematologic malignancies. METHODS Over a one-year period, a total of 327 patients who were diagnosed as having a hematologic malignancy were serologically analyzed in terms of HBV infection. Of those found to be susceptible to HBV infection, a total of 42 patients consisting of 16 females and 26 males were enrolled in the accelerated vaccination program. All the patients were administered a 20-microg yeast-derived recombinant hepatitis B vaccine on days 0, 14, and 28. Anti-HBs titers above 10IU/l at 1 and 3 months after the final dose were accepted as protective. RESULTS A total of 146 (44.6%) patients were susceptible to HBV, while 13 (4.0%) were carriers, 28 (8.6%) were vaccinated, and 113 (34.5%) had had a previous HBV infection. A total of 42 patients (16 females and 26 males, mean age 34.5+/-10.9 years) were enrolled in the vaccination program. Overall, 23.8% (10/42) of the patients in the program had developed anti-HBs at one month after the last vaccination. CONCLUSIONS Poor results obtained by different vaccination programs suggest the need for alternative strategies to prevent the disease.
Collapse
Affiliation(s)
- Husnu Pullukcu
- Department of Infectious Diseases and Clinical Microbiology, Ege University Faculty of Medicine, Izmir, Turkey.
| | | | | | | | | | | |
Collapse
|
|
45
|
Katz LH, Fraser A, Gafter-Gvili A, Leibovici L, Tur-Kaspa R. Lamivudine prevents reactivation of hepatitis B and reduces mortality in immunosuppressed patients: systematic review and meta-analysis. J Viral Hepat 2008; 15:89-102. [PMID: 18184191 DOI: 10.1111/j.1365-2893.2007.00902.x] [Citation(s) in RCA: 38] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
To assess the effects of prophylactic lamivudine on reactivation and mortality following immunosuppressive therapy in hepatitis B surface antigen (HBsAg)-positive patients, we performed a meta-analysis. Systematic review and meta-analysis of randomized and nonrandomized prospective controlled trials and retrospective comparative case series were identified through The Cochrane Hepato-Biliary Group Controlled Trials Register, The Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE and LILACS. The primary outcomes were virological reactivation, clinical reactivation and mortality. Secondary outcomes included hepatitis B virus (HBV)-related mortality, liver histology, discontinuation or disruption of immunosuppressive therapy, lamivudine-resistant HBV strains and adverse events. A total of 21 studies were included, two of which were randomized controlled trials. Clinical and virological reactivation were significantly reduced in the lamivudine group [odds ratio (OR) 0.09; 95% confidence interval (CI) 0.05-0.15 and OR 0.04; 95% CI 0.01-0.14 respectively]. All-cause mortality was significantly reduced in the lamivudine group (OR 0.36; 95% CI 0.23-0.56) which translates to only 11 patients who need to be treated to prevent one death. Lamivudine significantly reduced HBV-related mortality, and discontinuations or disruptions of the immunosuppressive treatment. No adverse effects of lamivudine were recorded, and resistance to lamivudine occurred in low rates. We demonstrated a clear benefit of lamivudine in terms of clinical and virological HBV reactivation, overall mortality, HBV-related mortality and interruptions or discontinuations in the immunosuppressive treatment. Lamivudine should be administered prophylactically to HBsAg-positive patients who are about to receive immunosuppressive therapy.
Collapse
Affiliation(s)
- L H Katz
- Department of Medicine D and Liver Institute, Beilinson Campus, Rabin Medical Center, Petah-Tiqva, Israel.
| | | | | | | | | |
Collapse
|
|
46
|
Abstract
Although chemotherapy generally is accompanied by regular testing for liver enzyme abnormalities, atypical reactions may occur that escape ordinary detection, because hepatocyte injury is not the primary event. The presence of fatty liver, mitochondrial changes, and even biliary abnormalities can be associated with normal or nearly normal liver enzyme levels. This article discusses unique aspects of liver damage associated with cancer chemotherapy. These unique reactions merit special attention and a special vigilance from clinicians.
Collapse
Affiliation(s)
- Edmundo A Rodriguez-Frias
- Department of Internal Medicine, The University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Boulevard, Dallas, Texas 75390, USA
| | | |
Collapse
|
|
47
|
Abstract
Although hepatotoxicity is a frequent concern with all medications, chemotherapeutic agents are more often implicated in causing liver damage than most other drug classes. In many instances, these reactions are considered dose related because cytotoxic therapy directed at rapidly growing cancer cells may readily impact hepatocytes even though they are dividing more slowly. Because the stakes (remission of cancer) are high, so are the risks that the oncologist and the patient are willing to assume. The dose of many chemotherapeutic agents is limited by the toxic effects on the lungs, bone marrow, kidneys, and gastrointestinal system, including the liver. An awareness of the toxic potential of each chemotherapeutic agent is necessary before initiation of new oncologic treatments.
Collapse
Affiliation(s)
- Edmundo A Rodriguez-Frias
- Department of Internal Medicine, The University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA
| | | |
Collapse
|
|
48
|
Calabrese LH, Zein NN, Vassilopoulos D. Hepatitis B virus (HBV) reactivation with immunosuppressive therapy in rheumatic diseases: assessment and preventive strategies. Ann Rheum Dis 2006; 65:983-9. [PMID: 16627542 PMCID: PMC1798254 DOI: 10.1136/ard.2005.043257] [Citation(s) in RCA: 171] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/05/2006] [Indexed: 12/23/2022]
Abstract
Understanding of the natural history and basic biology of hepatitis B virus (HBV) has increased greatly in recent years. In view of this, the following are reviewed here: (a) recent advances in HBV biology pertinent to the rheumatic disease population; (b) the risks of HBV reactivation in patients with rheumatic disease undergoing immunosuppression; and (c) potential strategies to manage these risks.
Collapse
Affiliation(s)
- L H Calabrese
- Department of Rheumatic and Immunological Disease, Cleveland Clinic Foundation, 9500 Euclid Ave., Cleveland, OH 44195, USA.
| | | | | |
Collapse
|
|
49
|
Pavy S, Constantin A, Pham T, Gossec L, Maillefert JF, Cantagrel A, Combe B, Flipo RM, Goupille P, Le Loët X, Mariette X, Puéchal X, Schaeverbeke T, Sibilia J, Tebib J, Wendling D, Dougados M. Methotrexate therapy for rheumatoid arthritis: clinical practice guidelines based on published evidence and expert opinion. Joint Bone Spine 2006; 73:388-95. [PMID: 16626993 DOI: 10.1016/j.jbspin.2006.01.007] [Citation(s) in RCA: 82] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2006] [Accepted: 01/25/2006] [Indexed: 01/11/2023]
Abstract
OBJECTIVES To develop clinical practice guidelines for the use of methotrexate in rheumatoid arthritis (RA), using the evidence-based approach and expert opinion. METHODS A scientific committee used a Delphi procedure to select five questions, which formed the basis for developing recommendations. Evidence providing answers to the five questions was sought in the Cochrane databases, PubMed, and proceedings of meetings of the French Society for Rheumatology, European League Against Rheumatism, and American College of Rheumatology. Using this evidence, a group of rheumatologists developed and validated the recommendations. For each recommendation, the level of evidence and the extent of agreement among experts were specified. RESULTS The recommendations were as follows: 1: The starting dosage for methotrexate in patients with RA should not be less than 10 mg/week and should be determined based on disease severity and patient-related factors; 2: When a patient with RA shows an inadequate response to methotrexate, the dosage should be increased at intervals of 6 weeks, up to 20 mg/week, according to tolerance and patient-related factors; 3: When starting methotrexate treatment in a patient with RA, preference should be given to the oral route. A switch to the intramuscular or subcutaneous route should be considered in patients with poor compliance, inadequate effectiveness, or gastrointestinal side effects; 4: At present, there is no evidence indicating that a change in methotrexate dosage is in order when a TNF antagonist is given concomitantly; 5: The investigations that are mandatory before starting methotrexate therapy in a patient with RA consist of a full blood cell count, serum transaminase levels, serum creatinine with computation of creatinine clearance, and a chest radiograph. In addition, serological tests for the hepatitis viruses B and C and a serum albumin assay are recommended. In patients with a history of respiratory disease or current respiratory symptoms, lung function tests with determination of the diffusing capacity for carbon monoxide are recommended; 6: Investigations that are mandatory for monitoring methotrexate therapy in patients with RA consist of full blood cell counts and serum transaminase and creatinine assays. These tests should be obtained at least once a month for the first 3 months then every 4-12 weeks; 7: Folate supplementation can be given routinely to patients treated with methotrexate for RA. In practice, a minimal dosage of 5 mg of folic acid once a week, at a distance from the methotrexate dose, is appropriate; 8: In the event of respiratory symptoms possibly related to methotrexate toxicity, the drug must be stopped and symptom severity evaluated. Should evidence of serious disease be found, the patient should be admitted immediately or advice from a pulmonologist should be obtained immediately. CONCLUSION Recommendations about methotrexate therapy for RA were developed. These recommendations should help to improve practice uniformity and, ultimately, to improve the management of RA.
Collapse
Affiliation(s)
- Stephan Pavy
- Service de rhumatologie A, CHU Cochin, 27, rue du Faubourg-Saint-Jacques, 75014 Paris, France
| | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
50
|
Millonig G, Kern M, Ludwiczek O, Nachbaur K, Vogel W. Subfulminant hepatitis B after infliximab in Crohn’s disease: Need for HBV-screening? World J Gastroenterol 2006; 12:974-6. [PMID: 16521231 PMCID: PMC4066168 DOI: 10.3748/wjg.v12.i6.974] [Citation(s) in RCA: 113] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Infections are a major adverse effect during the treatment with anti-TNF-α. While exclusion of any bacterial infection and screening for tuberculosis are mandatory before initiating a therapy with anti-TNF- α-antibodies, there are no guidelines whether to screen for or how to deal with chronic viral infections such as hepatitis B. In this case report, we have described a patient with Crohn's disease who developed subfulminant hepatitis B after the fourth infusion of infliximab due to an unrecognized HBs-antigen carrier state. He recovered completely after lamivudine therapy was started, but this severe adverse event could have been prevented if screening for HBV and pre-emptive therapy with lamivudine would have been started prior to infliximab. We therefore strongly argue in favor of extended screening recommendations for infectious diseases including viral infections before considering a therapy with infliximab.
Collapse
Affiliation(s)
- Gunda Millonig
- Department of Gastroenterology and Hepatology, Medical University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria.
| | | | | | | | | |
Collapse
|