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Maung ST, Deepan N, Decharatanachart P, Chaiteerakij R. Screening for viral hepatitis B infection in cancer patients before receiving chemotherapy - A systematic review and meta-analysis. Asia Pac J Clin Oncol 2024; 20:335-345. [PMID: 38512893 DOI: 10.1111/ajco.14055] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2023] [Revised: 02/08/2024] [Accepted: 03/03/2024] [Indexed: 03/23/2024]
Abstract
AIM We conducted a systematic review and meta-analysis to assess the hepatitis B virus (HBV) screening rate in cancer patients before systemic chemotherapy, aiming to identify those needing antiviral prophylaxis for HBV reactivation. METHODS We searched PubMed, Embase, Scopus, and Google Scholar for relevant studies. The pooled screening rate was estimated using a random effects model. Subgroup analyses were conducted based on malignancy types, chemotherapy regimens, study period, and HBV endemic regions. RESULTS The meta-analysis included 29 studies from various endemic regions (19 low-endemic, three lower intermediate-endemic, and seven higher intermediate-endemic). These studies encompassed hematologic malignancies (n = 10), solid-organ tumors (n = 4), and combinations (n = 15). Seven studies used rituximab-containing regimens, four did not, and the remaining 11 did not specify chemotherapy regimens. The pooled screening rate was 57% (95% confidence interval [95%CI]: 46%-68%, I2 = 100%). Over time, screening rates improved from 37% (95%CI: 23%-53%) in 2006-2010 to 68% (54%-80%) in 2011-2015 and 69% (48%-84%) in 2016-2020. Screening rates were highest at 89% (74%-96%) in high endemic countries, followed by 60% (45-73%) in lower-intermediate and 49% (34-64%) in low-endemic countries. Patients with hematological malignancies had a higher screening rate than those with solid organ tumors, 65% (55%-74%) versus 37% (21%-57%), respectively. A screening rate was higher in patients receiving rituximab-containing chemotherapy than non-rituximab regimens, 68% (55%-79%) versus 45% (27%-65%). CONCLUSION Despite existing guidelines, pre-chemotherapy HBV screening rate remains unsatisfactory, with substantial heterogeneous rates globally. These findings underscore the need for effective strategies to align practices with clinical guidelines.
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Affiliation(s)
- Soe Thiha Maung
- Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand
- Ma Har Myaing Hospital, Yangon, Myanmar
| | - Natee Deepan
- Division of Academic Affairs, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | | | - Roongruedee Chaiteerakij
- Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand
- Center of Excellence for Innovation and Endoscopy in Gastrointestinal Oncology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
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2
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Yano Y, Sato I, Imanishi T, Yoshida R, Matsuura T, Ueda Y, Kodama Y. Clinical Significance and Remaining Issues of Anti-HBc Antibody and HBV Core-Related Antigen. Diagnostics (Basel) 2024; 14:728. [PMID: 38611641 PMCID: PMC11011781 DOI: 10.3390/diagnostics14070728] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2024] [Revised: 03/17/2024] [Accepted: 03/26/2024] [Indexed: 04/14/2024] Open
Abstract
Currently, hepatitis B virus (HBV) core antibody (anti-HBc antibody) and HBV core-related antigen (HBcrAg) are widely used as serum markers for diagnosis based on the HBV core region. This review focused on anti-HBc antibodies and HBcrAg and aimed to summarize the clinical significance of currently used assay systems and the issues involved. While anti-HBc is very significant for clinical diagnosis, the clinical significance of quantitative assay of anti-HBc antibody has been reevaluated with improvements in diagnostic performance, including its association with clinical stage and prediction of carcinogenesis and reactivation. In addition, concerning the new HBcrAg, a high-sensitivity assay method has recently been established, and its diagnostic significance, including the prediction of reactivation, is being reevaluated. On the other hand, the quantitative level of anti-HBc antibody expressed in different units among assay systems complicates the interpretation of the results. However, it is difficult to standardize assay systems as they vary in advantages, and caution is needed in interpreting the assay results. In conclusion, with the development of highly sensitive HBcrAg and anti-HBc antibody, a rapid and sensitive detection assay system has been developed and used in clinical practice. In the future, it is hoped that a global standard will be created based on the many clinical findings.
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Affiliation(s)
- Yoshihiko Yano
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan; (R.Y.); (T.M.); (Y.U.); (Y.K.)
- Department of Clinical Laboratory, Kobe University Hospital, Kobe 650-0017, Japan; (I.S.); (T.I.)
| | - Itsuko Sato
- Department of Clinical Laboratory, Kobe University Hospital, Kobe 650-0017, Japan; (I.S.); (T.I.)
| | - Takamitsu Imanishi
- Department of Clinical Laboratory, Kobe University Hospital, Kobe 650-0017, Japan; (I.S.); (T.I.)
| | - Ryutaro Yoshida
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan; (R.Y.); (T.M.); (Y.U.); (Y.K.)
| | - Takanori Matsuura
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan; (R.Y.); (T.M.); (Y.U.); (Y.K.)
| | - Yoshihide Ueda
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan; (R.Y.); (T.M.); (Y.U.); (Y.K.)
| | - Yuzo Kodama
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan; (R.Y.); (T.M.); (Y.U.); (Y.K.)
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Bibas M. Plasmablastic Lymphoma. A State-of-the-Art Review: Part 2-Focus on Therapy. Mediterr J Hematol Infect Dis 2024; 16:e2024015. [PMID: 38468838 PMCID: PMC10927196 DOI: 10.4084/mjhid.2024.015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2024] [Accepted: 02/14/2024] [Indexed: 03/13/2024] Open
Abstract
The objective of this two-part review is to present a current and comprehensive understanding of the diagnosis and management of plasmablastic lymphoma. The first part, which was published previously, focused on the study of epidemiology, etiology, clinicopathological characteristics, differential diagnosis, prognostic variables, and the impact of plasmablastic lymphoma on specific populations. This second part addresses the difficult topic of the treatment of plasmablastic lymphoma, specifically examining both the conventional, consolidated approach and the novel therapeutic strategy.
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Affiliation(s)
- Michele Bibas
- Department of Clinical Research, Hematology. National Institute for Infectious Diseases "Lazzaro Spallanzani" I.R.C.S.S. Via Portuense 292 00148 Rome Italy
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4
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Cetin M, Gumy-Pause F, Gualtieri R, Posfay-Barbe KM, Blanchard-Rohner G. Vaccine Immunity in Children After Hematologic Cancer Treatment: A Retrospective Single-center Study. J Pediatr Hematol Oncol 2024; 46:e51-e59. [PMID: 37922437 PMCID: PMC10756701 DOI: 10.1097/mph.0000000000002774] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/25/2023] [Accepted: 09/20/2023] [Indexed: 11/05/2023]
Abstract
BACKGROUND Children lose their vaccine-induced protection and are particularly vulnerable to vaccine-preventable diseases after chemotherapy. However, revaccination guidelines are heterogeneous, and there is often a lack of revaccination post-treatment. AIMS We conducted a retrospective study of children with hematologic cancer to evaluate vaccine immunity before and after the end of treatment and to determine whether the current institutional revaccination program based on vaccine serology results was followed and effective. MATERIALS AND METHODS Data of all children treated by chemotherapy between April 2015 and July 2021 were extracted from hospital medical records for analysis. Serum antibody levels and time of vaccination were evaluated for diphtheria, tetanus, Streptococcus pneumoniae , Haemophilus influenzae type b (Hib), measles, varicella, and hepatitis B. RESULTS We included 31 patients (median age, 9 years). At cancer diagnosis, 90% of children were protected against tetanus, diphtheria, and measles; 65% to 67% were protected against pneumococcus and varicella; and 25% against hepatitis B. At the end of chemotherapy, 67% to 71% of patients were protected against tetanus, varicella, and measles; 40% remained protected against hepatitis B; and 27% to 33% against pneumococcus and diphtheria. Patients were revaccinated at various times after the end of treatment but not systematically. During the first-year post-treatment, 20% to 25% of children remained unprotected against pneumococcus, measles, and hepatitis B, one third against diphtheria, but all were protected against tetanus and varicella. CONCLUSIONS An effective individualized vaccination program post-cancer based on serology results should be accompanied by an appropriate serology tracking method and follow-up to assess if booster doses are necessary. Our study supports vaccinating all children with a dose of the 13-valent pneumococcal conjugate at cancer diagnosis and at 3 months post-treatment with the combined diphtheria-tetanus-acellular pertussis/poliomyelitis vaccine/hepatitis B virus plus or minus Hib and 13-valent pneumococcal conjugate and meningococcal vaccine, including measles/mumps/rubella-varicella zoster virus vaccine if good immune reconstitution is present.
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Affiliation(s)
| | - Fabienne Gumy-Pause
- Pediatric Oncology and Hematology Unit, Department of Women, Child and Adolescent, University Hospitals of Geneva
- CANSEARCH Research Platform for Pediatric Oncology and Hematology, Department of Pediatrics, Gynecology and Obstetrics, Faculty of Medicine, University of Geneva
| | - Renato Gualtieri
- Pediatric Platform for Clinical Research, Department of Woman, Child and Adolescent Medicine, Geneva University Hospitals, Faculty of Medicine, University of Geneva, Geneva, Switzerland
| | - Klara M. Posfay-Barbe
- Pediatric Infectious Diseases Unit, Department of Pediatrics, Gynecology and Obstetrics, Division of General Pediatrics, Geneva University Hospitals and Faculty of Medicine
| | - Geraldine Blanchard-Rohner
- Immunology and Vaccinology Unit, Department of Pediatrics, Gynecology and Obstetrics, Division of General Pediatrics, Geneva University Hospitals, University of Geneva, Geneva, Switzerland
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Vaidya R, Unger JM, Loomba R, Hwang JP, Chugh R, Tincopa MA, Arnold KB, Hershman DL, Ramsey SD. Universal Viral Screening of Patients with Newly Diagnosed Cancer in the United States: A Cost-efficiency Evaluation. CANCER RESEARCH COMMUNICATIONS 2023; 3:1959-1965. [PMID: 37707388 PMCID: PMC10541082 DOI: 10.1158/2767-9764.crc-23-0255] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/18/2023] [Revised: 08/11/2023] [Accepted: 09/08/2023] [Indexed: 09/15/2023]
Abstract
Recommendations for universal screening of patients with cancer for hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV) are inconsistent. A recent multisite screening study (S1204) from the SWOG Cancer Research Network found that a substantial number of patients with newly diagnosed cancer had previously unknown viral infections. The objective of this study was to determine the cost-efficiency of universal screening of patients with newly diagnosed cancer. We estimated the cost-efficiency of universal screening of new cancer cases for HBV, HCV, or HIV, expressed as cost per virus detected, from the health care payer perspective. The prevalence of each virus among this cohort was derived from S1204. Direct medical expenditures included costs associated with laboratory screening tests. Costs per case detected were estimated for each screening strategy. Secondary analysis examined the cost-efficiency of screening patients whose viral status at cancer diagnosis was unknown. Among the possible options for universal screening, screening for HBV alone ($581), HCV alone ($782), HBV and HCV ($631) and HBV, HCV, and HIV ($841) were most efficient in terms of cost per case detected. When screening was restricted to patients with unknown viral status, screening for HBV alone ($684), HBV and HCV ($872), HBV and HIV ($1,157), and all three viruses ($1,291) were most efficient in terms of cost per newly detected case. Efficient viral testing strategies represent a relatively modest addition to the overall cost of managing a patient with cancer. Screening for HBV, HCV, and HIV infections may be reasonable from both a budget and clinical standpoint. SIGNIFICANCE Screening patients with cancer for HBV, HCV, and HIV is inconsistent in clinical practice despite national recommendations and known risks of complications from viral infection. Our study shows that while costs of viral screening strategies vary by choice of tests, they present a modest addition to the cost of managing a patient with cancer.
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Affiliation(s)
- Riha Vaidya
- Fred Hutchinson Cancer Center, Seattle, Washington
- SWOG Statistics and Data Management Center, Seattle, Washington
| | - Joseph M. Unger
- Fred Hutchinson Cancer Center, Seattle, Washington
- SWOG Statistics and Data Management Center, Seattle, Washington
| | - Rohit Loomba
- University of California San Diego, Moores Cancer Center, San Diego, California
| | - Jessica P. Hwang
- The University of Texas, MD Anderson Cancer Center, Houston, Texas
| | - Rashmi Chugh
- University of Michigan, Rogel Cancer Center, Ann Arbor, Michigan
| | | | - Kathryn B. Arnold
- Fred Hutchinson Cancer Center, Seattle, Washington
- SWOG Statistics and Data Management Center, Seattle, Washington
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Alemu J, Gumi B, Tsegaye A, Abubeker A, Tadesse F, Shewaye A, Rahimeto Z, Mihret A, Mulu A, Gebremedhin A, Howe R. Frequency of viral infections in adolescent and adult in-patient Ethiopians with acute leukemia at presentation to a tertiary care teaching hospital: a cross-sectional study. Infect Agent Cancer 2023; 18:44. [PMID: 37438754 DOI: 10.1186/s13027-023-00519-6] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2023] [Accepted: 06/16/2023] [Indexed: 07/14/2023] Open
Abstract
BACKGROUND Leukemic patients are prone to infectious agents such as viruses due to dysregulated immune system resulting from infiltration of the bone marrow by malignant cells, chronic stimulation, reactivation of some viruses and viral pathogenicity as well as rarely from acquisition of a new infections leading to severe complications. However, the prevalence of these infections has not been systematically documented in resource-limited settings such as Ethiopia. OBJECTIVE To determine the prevalence of HBV, HCV, and HIV among adult and adolescent in-patients with acute leukemia before the administration of chemotherapy, at the Tikur Anbessa Specialized Hospital (TASH) in Addis Ababa, Ethiopia. METHODS A cross sectional study was conducted on 176 adult and adolescent inpatient Ethiopians, who were diagnosed with acute leukemia from April 2019 to June 2021. Socio-demographic characteristics and relevant clinical data were collected. Peripheral blood samples were collected and tested for HBV, HIV, and HCV using Enzyme-Linked Immunosorbent Assay (ELISA) and real-time PCR. Chi-square tests were used to assess associations between variables. RESULTS Of the 176 patients, 109(62%) were males. The median age was 25[IQR,18-35] yr, with a range from 13 to 76 year. The prevalence of HBV (positivity for HBsAg plus HBV DNA), HCV and HIV was 21.6%, 1.7%, and 1.7%, respectively. HBsAg was positive in 19 cases (10.8%). Among 157 HBsAg negative patients, 52(33.1%) were positive for Anti-HBcAg; of these seropositive cases, 47.5% were positive for HBV DNA. Most DNA positive, HBsAg negative cases (79.0%) had DNA concentrations below 200 IU/ml indicating true occult HBV infection (OBI). Of the 176 cases, 122 had a history of blood transfusions, but no statistically significant association was found between HBV infection and blood product transfusion history (P = 0.963). CONCLUSIONS The prevalence of HBV, HIV and HCV in patients with acute leukemia was similar to the national prevalence level of these infections. Given the HBsAg positivity and the high prevalence of occult hepatitis B infection in our study, these patients may be at increased risk for chemotherapy related hepatitis flares. Hence, clinicians caring these patients are strongly advised to screen their patients for HBV and also for HIV and HCV infections routinely.
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Affiliation(s)
- Jemal Alemu
- Department of Medical Laboratory Sciences, College of Health Sciences, Addis Ababa University, Addis, Ababa, Ethiopia.
- Armauer Hansen Research Institute, Addis Ababa, Ethiopia.
- Aklilu Lemma Institute of Pathobiology, Addis Ababa University, Addis Ababa, Ethiopia.
| | - Balako Gumi
- Aklilu Lemma Institute of Pathobiology, Addis Ababa University, Addis Ababa, Ethiopia
| | - Aster Tsegaye
- Department of Medical Laboratory Sciences, College of Health Sciences, Addis Ababa University, Addis, Ababa, Ethiopia
| | - Abdulaziz Abubeker
- Department of Internal Medicine, College of Health Sciences, Addis Ababa University, Addis, Ababa, Ethiopia
| | - Fisihatsion Tadesse
- Department of Internal Medicine, College of Health Sciences, Addis Ababa University, Addis, Ababa, Ethiopia
| | - Abel Shewaye
- Department of Laboratory, ALERT Hospital, Addis Ababa, Ethiopia
| | | | - Adane Mihret
- Armauer Hansen Research Institute, Addis Ababa, Ethiopia
- Department of Microbiology, Immunology and Parasitology, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia
| | | | - Amha Gebremedhin
- Department of Internal Medicine, College of Health Sciences, Addis Ababa University, Addis, Ababa, Ethiopia
| | - Rawleigh Howe
- Armauer Hansen Research Institute, Addis Ababa, Ethiopia
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7
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Ward JW, Wanlapakorn N, Poovorawan Y, Shouval D. Hepatitis B Vaccines. PLOTKIN'S VACCINES 2023:389-432.e21. [DOI: 10.1016/b978-0-323-79058-1.00027-x] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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8
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Nuersulitan R, Li M, Mi L, Wu M, Ji X, Liu Y, Zhao H, Wang G, Song Y, Zhu J, Liu W. Effect of infection with hepatitis B virus on the survival outcome of diffuse large B-cell lymphoma in the prophylactic antiviral era. Front Oncol 2022; 12:989258. [PMID: 36072805 PMCID: PMC9441704 DOI: 10.3389/fonc.2022.989258] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2022] [Accepted: 08/08/2022] [Indexed: 11/13/2022] Open
Abstract
Patients with lymphoma who are also infected with Hepatitis B virus (HBV) have a poor prognosis. This could be partly explained by the delay or premature termination of anti-tumor treatment because of HBV reactivation. However, there is limited data on the survival outcome of patients HBV-related lymphoma in the era of prophylactic antivirals. Data for 128 patients with HBV surface antigen-positive diffuse large B-cell lymphoma was collected. The median age was 54 years and the ratio of men to women was 1.2:1. All patients received immune-chemotherapy and prophylactic antiviral therapy. The median number of cycles of immune-chemotherapy was six. The overall response rate was 82%, with a complete remission rate of 75%. With a median follow-up of 58.4 months, the 5-year progression-free survival and overall survival rates were 75.7% and 74.7%, respectively. Nine patients experienced HBV reactivation but none experienced HBV-associated hepatitis. Patients with low and high HBV DNA loads had comparable survival outcomes. In conclusion, HBV infection had no negative effect on the prognosis of DLBCL in the era of prophylactic antiviral therapy.
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Affiliation(s)
- Reyizha Nuersulitan
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Lymphoma, Peking University Cancer Hospital & Institute, Beijing, China
| | - Miaomiao Li
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Lymphoma, Peking University Cancer Hospital & Institute, Beijing, China
| | - Lan Mi
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Lymphoma, Peking University Cancer Hospital & Institute, Beijing, China
| | - Meng Wu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Lymphoma, Peking University Cancer Hospital & Institute, Beijing, China
| | - Xinqiang Ji
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Medical Record Statistics, Peking University Cancer Hospital & Institute, Beijing, China
| | - Yiqi Liu
- Department of Infectious Diseases, Peking University First Hospital, Beijing, China
| | - Hong Zhao
- Department of Infectious Diseases, Peking University First Hospital, Beijing, China
| | - Guiqiang Wang
- Department of Infectious Diseases, Peking University First Hospital, Beijing, China
| | - Yuqin Song
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Lymphoma, Peking University Cancer Hospital & Institute, Beijing, China
| | - Jun Zhu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Lymphoma, Peking University Cancer Hospital & Institute, Beijing, China
- *Correspondence: Jun Zhu, ; Weiping Liu,
| | - Weiping Liu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Lymphoma, Peking University Cancer Hospital & Institute, Beijing, China
- *Correspondence: Jun Zhu, ; Weiping Liu,
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9
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Sagnelli C, Sica A, Creta M, Borsetti A, Ciccozzi M, Sagnelli E. Prevention of HBV Reactivation in Hemato-Oncologic Setting during COVID-19. Pathogens 2022; 11:567. [PMID: 35631088 PMCID: PMC9144674 DOI: 10.3390/pathogens11050567] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2022] [Revised: 05/06/2022] [Accepted: 05/10/2022] [Indexed: 02/04/2023] Open
Abstract
Onco-hematologic patients are highly susceptible to SARS-CoV-2 infection and, once infected, frequently develop COVID-19 due to the immunosuppression caused by tumor growth, chemotherapy and immunosuppressive therapy. In addition, COVID-19 has also been recognized as a further cause of HBV reactivation, since its treatment includes the administration of corticosteroids and some immunosuppressive drugs. Consequently, onco-hematologic patients should undergo SARS-CoV-2 vaccination and comply with the rules imposed by lockdowns or other forms of social distancing. Furthermore, onco-hematologic facilities should be adapted to new needs and provided with numerically adequate health personnel vaccinated against SARS-CoV-2 infection. Onco-hematologic patients, both HBsAg-positive and HBsAg-negative/HBcAb-positive, may develop HBV reactivation, made possible by the support of the covalently closed circular DNA (cccDNA) persisting in the hepatocytic nuclei of patients with an ongoing or past HBV infection. This occurrence must be prevented by administering high genetic barrier HBV nucleo(t)side analogues before and throughout the antineoplastic treatment, and then during a long-term post-treatment follow up. The prevention of HBV reactivation during the SARS-CoV-2 pandemic is the topic of this narrative review.
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Affiliation(s)
- Caterina Sagnelli
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, University of Campania “Luigi Vanvitelli”, 80131 Naples, Italy;
| | - Antonello Sica
- Department of Precision Medicine, University of Campania “Luigi Vanvitelli”, 80131 Naples, Italy;
| | - Massimiliano Creta
- Department of Neurosciences, Reproductive Sciences and Odontostomatology, University of Naples Federico II, 80131 Naples, Italy;
| | - Alessandra Borsetti
- National HIV/AIDS Research Center, Istituto Superiore di Sanità, 00161 Rome, Italy;
| | - Massimo Ciccozzi
- Medical Statistics and Molecular Epidemiology Unit, Campus Bio-Medico University, 00128 Rome, Italy;
| | - Evangelista Sagnelli
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, University of Campania “Luigi Vanvitelli”, 80131 Naples, Italy;
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10
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Chang ML, Liaw YF. Hepatitis B Flare in Hepatitis B e Antigen-Negative Patients: A Complicated Cascade of Innate and Adaptive Immune Responses. Int J Mol Sci 2022; 23:ijms23031552. [PMID: 35163476 PMCID: PMC8836007 DOI: 10.3390/ijms23031552] [Citation(s) in RCA: 27] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2021] [Revised: 01/19/2022] [Accepted: 01/26/2022] [Indexed: 12/11/2022] Open
Abstract
Chronic hepatitis B virus (HBV) infection is a dynamic process involving interactions among HBV, hepatocytes, and the host immune system. The natural course of chronic hepatitis B (CHB) is divided into four chronological phases, including the hepatitis B e antigen (HBeAg)-positive and HBeAg-negative phases. During HBV flare, alanine aminotransferase (ALT) levels abruptly rise to >5× the upper limit of normal; this is thought to occur due to the immune response against an upsurge in serum HBV DNA and antigen levels. Hepatitis flares may occur spontaneously, during or after antiviral therapy, or upon immunosuppression or chemotherapy in both HBeAg-positive and HBeAg-negative patients. The clinical spectrum of HBV flares varies from asymptomatic to hepatic decompensation or failure. HBeAg seroconversion with ≥ 1 year of consolidation therapy is accepted as an endpoint of oral antiviral therapy in HBeAg-positive patients, but recommendations for treating HBeAg-negative patients differ. Thus, the management of HBeAg-negative patients has attracted increasing interest. In the current review, we summarize various types of HBV flares and the associated complex cascade of innate and adaptive immune responses, with a focus on HBeAg-negative CHB patients. Hopefully, this review will provide insight into immunopathogenesis to improve the management of HBV flares in HBeAg-negative CHB patients.
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Affiliation(s)
- Ming-Ling Chang
- College of Medicine, Chang Gung University, Taoyuan 333323, Taiwan;
- Division of Hepatology, Department of Hepatogastroenterology, Chang Gung Memorial Hospital, Taoyuan 333423, Taiwan
- Correspondence: ; Tel.: +886-3-3281200 (ext. 8107); Fax: +886-3-3272236
| | - Yun-Fan Liaw
- College of Medicine, Chang Gung University, Taoyuan 333323, Taiwan;
- Division of Hepatology, Department of Hepatogastroenterology, Chang Gung Memorial Hospital, Taoyuan 333423, Taiwan
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11
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Khan MM, Ali MJ, Hanif H, Maqsood MH, Ahmad I, Alvarez JEG, Catana MA, Lau DTY. OUP accepted manuscript. Gastroenterol Rep (Oxf) 2022; 10:goac018. [PMID: 35663152 PMCID: PMC9154071 DOI: 10.1093/gastro/goac018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/04/2022] [Revised: 03/04/2022] [Accepted: 04/24/2022] [Indexed: 11/25/2022] Open
Abstract
Hepatitis B virus (HBV) remains a global public health problem despite the availability of effective vaccine and antiviral therapy. Cytomegalovirus (CMV), another hepatotropic virus, is also very prevalent in the general population worldwide. Both HBV and CMV can persist in the host and have potential to reactivate especially with weakened host cellular immunity. Superimposed CMV infection can lead to severe HBV reactivation. The pathogenesis of the co-infection of HBV and CMV remains poorly understood. Studies reported conflicting results regarding the inhibitory effect of CMV on HBV replication. There is an unmet need on the management of co-infection of HBV and CMV; research initiatives dedicated to understanding their interactions are urgently needed.
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Affiliation(s)
- Muzammil M Khan
- Department of Medicine, Division of Gastroenterology, Liver Research Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - Mukarram J Ali
- Department of Medicine, Division of Gastroenterology, Liver Research Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - Hira Hanif
- Department of Medicine, Division of Gastroenterology, Liver Research Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - Muhammad H Maqsood
- Department of Medicine, Division of Gastroenterology, Liver Research Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - Imama Ahmad
- Department of Medicine, North Shore Medical Center, Salem, MA, USA
| | - Javier E G Alvarez
- Department of Medicine, Division of Gastroenterology, Liver Research Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - Maria-Andreea Catana
- Department of Medicine, Division of Gastroenterology, Liver Research Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - Daryl T Y Lau
- Department of Medicine, Division of Gastroenterology, Liver Research Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
- Corresponding author. Department of Medicine, Liver Research Center, 110 Francis Street, Suite 4A, Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA. Tel: +1 (617) 632-1070; Fax: (617) 632-1065;
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12
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de Faria AC, Correa BHM, Faria LC, Vidigal PVT, Xavier MAP, Ferrari TCA. Occult hepatitis B virus infection in patients with chronic liver disease of different etiology in a Brazilian referral center: comparison of two different hepatitis B virus deoxyribonucleic acid amplification protocols: a cross-sectional study. SAO PAULO MED J 2022; 141:e2022147. [PMID: 36169566 PMCID: PMC10065104 DOI: 10.1590/1516-3180.2022.0147.r1.12072022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2022] [Accepted: 07/12/2022] [Indexed: 11/22/2022] Open
Abstract
BACKGROUND Occult hepatitis B virus infection (OBI) is defined as the presence of hepatitis B virus (HBV) deoxyribonucleic acid (DNA) in the liver of individuals with undetectable hepatitis B virus surface antigen (HBsAg) in the serum. The actual prevalence of OBI and its clinical relevance are not yet fully understood. OBJECTIVE To evaluate the prevalence of HBV DNA in liver biopsies of HBsAg-negative patients with chronic liver disease of different etiologies in a referral center in Brazil and compare two different HBV DNA amplification protocols to detect HBV. DESIGN AND SETTING This cross-sectional observational study was conducted at the Liver Outpatient Clinic, Hospital das Clínicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil, between January 2016 and December 2019. METHODS HBV DNA was investigated in 104 liver biopsy samples from individuals with chronic liver disease of different etiologies, in whom HBsAg was undetectable in serum by nested-polymerase chain reaction (nested-PCR), using two different protocols. RESULTS OBI, diagnosed by detecting HBV DNA using both protocols, was detected in 6.7% of the 104 individuals investigated. Both protocols showed a good reliability. CONCLUSION In addition to the differences in the prevalence of HBV infection in different regions, variations in the polymerase chain reaction technique used for HBV DNA amplification may be responsible for the large variations in the prevalence of OBI identified in different studies. There is a need for better standardization of the diagnostic methods used to diagnose this entity.
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Affiliation(s)
- Alessandra Coutinho de Faria
- MD, MSc. Physician, Department of Internal Medicine, Faculty of
Medicine, Hospital das Clínicas, Universidade Federal de Minas Gerais (UFMG),
Belo Horizonte (MG), Brazil
| | - Bernardo Henrique Mendes Correa
- Research Associate, Undergraduate Student, Department of
Internal Medicine, Faculty of Medicine, Universidade Federal de Minas Gerais
(UFMG), Belo Horizonte (MG), Brazil
| | - Luciana Costa Faria
- MD, PhD. Professor Associate, Department of Internal Medicine,
Faculty of Medicine, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte
(MG), Brazil
| | - Paula Vieira Teixeira Vidigal
- MD, PhD. Professor Associate, Department of Pathological
Anatomy and Forensic Medicine, Faculty of Medicine, Universidade Federal de
Minas Gerais (UFMG), Belo Horizonte (MG), Brazil
| | - Marcelo Antônio Pascoal Xavier
- MD, PhD. Professor, Department of Pathological Anatomy and
Forensic Medicine, Faculty of Medicine, Universidade Federal de Minas Gerais
(UFMG), Belo Horizonte (MG), Brazil
| | - Teresa Cristina Abreu Ferrari
- MD, PhD. Professor, Department of Internal Medicine, Faculty of
Medicine, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte (MG),
Brazil
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13
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Shirmast P, Shahri MA, Pashangzadeh S, Mirshahabi H, Samadi E, Motamed N. Detection of occult hepatitis B virus in patients undergoing chemotherapy in Iran. Future Virol 2022. [DOI: 10.2217/fvl-2020-0386] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
Aim: Occult hepatitis B infection (OBI) is life threatening and has a high mortality rate despite applying antiviral treatments in cancer patients. This study aimed to investigate the prevalence of OBI in patients undergoing chemotherapy in Iran. Materials & methods: A total of 342 patients undergoing chemotherapy were enrolled. OBI detection in anti-HBc positive individuals was conducted using nested PCR. Results: Among 342 subjects, 103 (30.1%) were positive for anti-HBc. Fifteen (14.6%) cases of 103 anti-HBc positive samples were also positive for HBsAg. Overall, HBV DNA was positive in three (3.4%) of 88 anti-HBc subjects. Conclusion: Our results indicated that OBI might occur in almost one in 25 anti-HBc-positive patients undergoing chemotherapy.
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Affiliation(s)
- Paniz Shirmast
- Department of Microbiology & Virology, Faculty of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Mahdi Abedinzade Shahri
- Department of Biology, Faculty of Sciences, Mashhad Branch, Islamic Azad University, Mashhad, Iran
| | - Salar Pashangzadeh
- Iranian Research Center of HIV/AIDS, Iranian Institute for Reduction of High-Risk Behaviors, Tehran University of Medical Sciences, Tehran, Iran
- Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Hessam Mirshahabi
- Department of Microbiology & Virology, Faculty of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Elham Samadi
- Department of Microbiology & Virology, Faculty of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Nima Motamed
- Department of Community Medicine, Faculty of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
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14
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Shalabi RA, Worst MA, Hughes TE, Walsh-Chocolaad T, Cook L, Gunn K, Wells B, Ciurea R, Aue G, Tian X, Childs RW. Haematopoietic stem cell transplant patients have a high initial failure rate to hepatitis B vaccination that can be overcome with subsequent vaccination series. Br J Haematol 2021; 196:1404-1407. [PMID: 34881432 DOI: 10.1111/bjh.17991] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2021] [Accepted: 11/24/2021] [Indexed: 11/30/2022]
Affiliation(s)
- Reem A Shalabi
- Clinical Center Pharmacy Department, National Institutes of Health, Bethesda, MD, USA
| | - Michelle A Worst
- Clinical Center Pharmacy Department, National Institutes of Health, Bethesda, MD, USA
| | - Thomas E Hughes
- Clinical Center Pharmacy Department, National Institutes of Health, Bethesda, MD, USA
| | | | - Lisa Cook
- Cellular and Molecular Therapeutics Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA
| | - Kristen Gunn
- Cellular and Molecular Therapeutics Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA
| | - Brian Wells
- Cellular and Molecular Therapeutics Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA
| | - Rodica Ciurea
- Office of Biostatistics Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA
| | - Georg Aue
- Cellular and Molecular Therapeutics Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA
| | - Xin Tian
- Office of Biostatistics Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA
| | - Richard W Childs
- Cellular and Molecular Therapeutics Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA
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Abstract
Hepatitis B virus (HBV) can hide in the liver in the form of covalently closed circular DNA. When the body’s immunity changes, HBV reactivation (HBV-R) can occur. The risk of HBV-R is determined by the complex interaction among virological factors, medication factors and host factors. However, many patients do not know that they are infected with HBV, and doctors often do not invest enough time to systematically evaluate the patient’s HBV-R risk factors before immunosuppressive treatment. Therefore, HBV clinical screening should be vigorously promoted to achieve early detection and early prevention for patients with high risk of HBV-R. The mechanism, clinical features, risk factors, HBV-R under different disease etiologies, prevention and treatment of HBV-R were summarized to improve the in-depth understanding and awareness.
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Affiliation(s)
- Wei Huang
- Center of Infectious Diseases, West China Hospital of Sichuan University, Chengdu, 610041, China
- Division of Infectious Diseases, State Key Laboratory of Biotherapy & Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Lingyao Du
- Center of Infectious Diseases, West China Hospital of Sichuan University, Chengdu, 610041, China
- Division of Infectious Diseases, State Key Laboratory of Biotherapy & Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Hong Tang
- Center of Infectious Diseases, West China Hospital of Sichuan University, Chengdu, 610041, China
- Division of Infectious Diseases, State Key Laboratory of Biotherapy & Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, 610041, China
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16
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Hepatitis B Virus Infection in Patients Receiving Allogeneic Hematopoietic Stem Cell Transplantation. J Pers Med 2021; 11:jpm11111108. [PMID: 34834460 PMCID: PMC8619006 DOI: 10.3390/jpm11111108] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2021] [Revised: 10/20/2021] [Accepted: 10/25/2021] [Indexed: 01/12/2023] Open
Abstract
Considering a steady increase in the number of allogeneic hematopoietic stem cell transplantations (allo-HSCT) worldwide and the significant proportion of the world’s population that has been exposed to hepatitis B virus (HBV) infection, HBV reactivation following allo-HSCT remains an important issue for post-transplant morbidity and mortality. Antiviral prophylaxis can reduce HBV replication, severity of HBV-related hepatitis, and mortality; therefore, identification of patients at risk is crucial. It is recommended that all recipients and donors should be screened for active or prior HBV infection, including HBsAg, antiHBc, and antiHBs. Adoptive immunity transfer from the donor seems to have protective effects against HBV reactivation. Antiviral prophylaxis should be initiated in all HBsAg-positive patients. HBsAg-negative, antiHBc-positive patients remain at risk; therefore, antiviral prophylaxis should be considered if baseline serum HBV DNA is detectable. In HBsAg-negative, antiHBc-positive patients without detectable HBV DNA, close monitoring of viral load with an on-demand therapy is necessary. Entecavir or tenofovir rather than lamivudine are more appropriate for the emergence of lamivudine resistance. The treatment duration remains unclear, with 6- to 12-month therapy after cessation of immunosuppressive therapy commonly recommended. Here we review the updated evidence and recent recommendations regarding HBV reactivation in patients undergoing allo-HSCT for individualized therapy.
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Shih CA, Chen WC. Prevention of hepatitis B reactivation in patients requiring chemotherapy and immunosuppressive therapy. World J Clin Cases 2021; 9:5769-5781. [PMID: 34368296 PMCID: PMC8316946 DOI: 10.12998/wjcc.v9.i21.5769] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2021] [Revised: 04/12/2021] [Accepted: 06/02/2021] [Indexed: 02/06/2023] Open
Abstract
Hepatitis B virus (HBV) reactivation can lead to severe acute hepatic failure and death in patients with HBV infection. HBV reactivation (HBVr) most commonly develops in patients undergoing cancer chemotherapy, especially B cell-depleting agent therapy such as rituximab and ofatumumab for hematological or solid organ malignancies and that receiving hematopoietic stem cell transplantation without antiviral prophylaxis. In addition, the potential consequences of HBVr is particularly a concern when patients are exposed to either immunosuppressive or biologic therapies for the management of rheumatologic diseases, inflammatory bowel disease and dermatologic diseases. Thus, screening with HBV serological markers and prophylactic or pre-emptive antiviral treatment with nucleos(t)ide analogues should be considered in these patients to diminish the risk of HBVr. This review discusses the clinical manifestation, prognosis and management of HBVr, risk stratifications of cancer chemotherapy and immunosuppressive therapy and international guideline recommendations for the prevention of HBVr in patients with HBV infection and resolved hepatitis B.
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Affiliation(s)
- Chih-An Shih
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung 813, Taiwan
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Antai Medical Care Corporation, Antai Tian-Sheng Memorial Hospital, Pingtung County 928, Taiwan
- Department of Nursing, Meiho University, Pingtung County 928, Taiwan
| | - Wen-Chi Chen
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung 813, Taiwan
- Faculty of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei 112, Taiwan
- Institute of Biomedical Sciences, College of Science, National Sun Yat-sen University, Kaohsiung 8424, Taiwan
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18
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Udompap P, Kim WR. Hepatitis B Virus Reactivation and Management of Patients Undergoing Immunosuppression. HEPATITIS B VIRUS AND LIVER DISEASE 2021:427-454. [DOI: 10.1007/978-981-16-3615-8_18] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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Pisaturo M, Onorato L, Russo A, Coppola N. Prevalence of occult HBV infection in Western countries. J Med Virol 2020; 92:2917-2929. [PMID: 32275083 DOI: 10.1002/jmv.25867] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2019] [Accepted: 03/19/2020] [Indexed: 12/11/2022]
Abstract
Due to a lack of standardized tests, it is difficult to obtain prevalence data and define the real impact of occult HBV infection (OBI) in Western countries. The present review article addresses the prevalence of OBI, defined as presence of hepatitis B virus (HBV) DNA in liver tissue or plasma in HBsAg-negative subjects, in Western countries. This varies in different studies according to the different methodologies used (based on serology vs virology), to the sample analyzed for the diagnosis (liver tissue vs plasma), to the different populations studied, to the different geographical variations in the HBV spread, to the host characteristics (age, gender, risk factors for acquiring HBV infection) and to the presence of other parenteral infections (hepatitis C virus and/or human immunodeficiency virus [HIV] infections). Considering the different liver diseases analyzed, that is in patients with cryptogenic cirrhosis or advanced liver fibrosis, the prevalence of OBI ranges 4% to 38%. Considering the different populations studied, in the case of parenteral blood exposure it is about 45%, in patients with chronic hepatitis C it is estimated at about 52%, in HIV-infected patients it ranges from 0% to 45%, in blood donors from 0% to 22.7% and in hemodialysis patients it ranges from 0% to 54%. In conclusion, OBI is a virological entity to be considered when performing the patient's evaluation for immunosuppressive diseases, liver pathologies, or for blood transfusions. Knowing the prevalence and clinical impact of OBI will allow better patient management.
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Affiliation(s)
- Mariantonietta Pisaturo
- Department of Mental Health and Public Medicine-Infectious Diseases Unit, University of Campania Luigi Vanvitelli, Naples, Italy
| | - Lorenzo Onorato
- Department of Mental Health and Public Medicine-Infectious Diseases Unit, University of Campania Luigi Vanvitelli, Naples, Italy
| | - Antonio Russo
- Department of Mental Health and Public Medicine-Infectious Diseases Unit, University of Campania Luigi Vanvitelli, Naples, Italy
| | - Nicola Coppola
- Department of Mental Health and Public Medicine-Infectious Diseases Unit, University of Campania Luigi Vanvitelli, Naples, Italy
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20
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Zhang X, Liang Y, Li X, Wang W, Tong J, Xu Y. Clearance of HBsAg in a patient with familial multiple myeloma after a bortezomib-based regimen combined with anti-HBV drug: A case report. Medicine (Baltimore) 2020; 99:e22642. [PMID: 33019490 PMCID: PMC7535632 DOI: 10.1097/md.0000000000022642] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2020] [Revised: 07/18/2020] [Accepted: 09/09/2020] [Indexed: 11/26/2022] Open
Abstract
RATIONALE Reactivation of hepatitis B virus (HBV) after treatment with bortezomib-based regimens in HBV-positive patients with multiple myeloma (MM) has been reported in the past few years. Nevertheless, there is evidence of inhibition of HBV replication by bortezomib in transgenic mice. However, there is still no clinical evidence that bortezomib inhibits HBV. PATIENT CONCERNS A 55-year-old MM patient with a family history of MM, who was also a chronic HBV carrier, achieved HBV clearance after treatment with a bortezomib-based regimen in combination with anti-HBV drugs. DIAGNOSES The diagnosis was MM with chronic carrier of HBV. INTERVENTIONS He received bortezomib-based regimen for MM as well as entecavir as a prophylaxis to prevent HBV reactivation. OUTCOMES This patient achieved HBsAg and HBV-DNA clearance after 2 months and the remission was maintained during the next 2 years. He also achieved complete remission of MM and underwent consolidation therapy with autologous hematopoietic stem cell transplantation. LESSONS This is the first case of MM with HBV clearance after receiving a bortezomib-based regimen combined with anti-HBV drug. Research on related mechanisms might provide new suggestions and hope for better management of HBV positive patients with MM and for the treatment of HBV patients.
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Affiliation(s)
- Xuzhao Zhang
- Department of Hematology
- Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education), The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
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21
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Toka B, Koksal AS, İskender G, Çakmak E, Üsküdar O, Sezikli M, Şirin G, Yildirim AE, Fidan S, Acar Ş, Eminler AT, Uslan MI, Hülagü S. HBV flare associated with immunosuppressive treatments: it is still dangerous in the third-generation antivirals era. Antivir Ther 2020; 25:121-129. [PMID: 32364531 DOI: 10.3851/imp3356] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/22/2020] [Indexed: 10/24/2022]
Abstract
BACKGROUND There are limited data about the mortality and morbidity of patients with HBV flare related to immunosuppressive treatments (IST) in the third-generation antivirals era. Herein, we performed a multi-centric study in patients treated with entecavir (ETV) or tenofovir disoproxil fumarate (TDF) and evaluated their clinical course. METHODS The study group included patients who were referred to gastroenterology or infectious disease specialists at eight different hospitals in Turkey. HBV flare was defined as at least a threefold elevation in alanine aminotransferase (ALT) levels above the upper limit of normal range. The demographic data, IST protocol, virological markers, liver tests, international normalized ratio (INR), HBV DNA, reactivation risk profile according to AGA guideline, MELD and MELD-Na scores were retrospectively evaluated. The primary aim of the study was to determine the liver-related mortality, including transplantation, at 12 weeks and factors predicting it. Secondary aims were to compare ETV and TDF with respect to mortality and time to ALT, bilirubin normalization and HBV DNA undetectability. RESULTS The study group included 40 patients (29 males, mean age: 57 ±12 years). Twenty-five patients (62.5%) had a high risk of reactivation. Twenty-six patients received TDF and 14 patients received ETV treatment. Eight (20%) patients developed acute liver failure and one patient (2.5%) underwent living donor liver transplantation. Seven patients died due to liver-related complications, revealing a mortality rate of 17.5%. In multivariate analysis, total bilirubin levels at the onset, ALT levels and delta-MELD score at the first week were the independent risk factors for liver related mortality (HR: 1.222, 1.003, 1.253 and 95% CI: 1.096, 1.362; 1.001, 1.004 and 1.065, 1.470, respectively). There was no significant difference between the TDF and ETV groups with respect to time to normalize ALT and bilirubin levels, HBV DNA undetectability and mortality rates (16% and 21.4%, respectively). CONCLUSIONS HBV flare associated with IST has a high mortality in the third-generation antivirals era. High total bilirubin at the onset and high ALT and delta-MELD score at the first week predict poor prognosis.
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Affiliation(s)
- Bilal Toka
- Department of Gastroenterology, University of Medical Sciences, Konya Education and Research Hospital, Konya, Turkey
| | - Aydin Seref Koksal
- Department of Gastroenterology, University Faculty of Medicine, Sakarya, Turkey
| | - Gülşen İskender
- Department of Infectious Diseases and Clinical Microbiology, Dr. Abdurrahman Yurtaslan Ankara Oncology Training and Research Hospital, Ankara, Turkey
| | - Erol Çakmak
- Department of Gastroenterology, Cumhuriyet University Faculty of Medicine, Sivas, Turkey
| | - Oğuz Üsküdar
- Department of Gastroenterology, Çukurova University Faculty of Medicine, Adana, Turkey
| | - Mesut Sezikli
- Department of Gastroenterology, Hitit University Faculty of Medicine, Çorum, Turkey
| | - Göktuğ Şirin
- Department of Gastroenterology, Kocaeli University Faculty of Medicine, Kocaeli, Turkey
| | - Abdullah Emre Yildirim
- Department of Gastroenterology, Gaziantep University Faculty of Medicine, Gaziantep, Turkey
| | - Sami Fidan
- Department of Gastroenterology, Karadeniz Technical University Faculty of Medicine, Trabzon, Turkey
| | - Şencan Acar
- Department of Gastroenterology, University Faculty of Medicine, Sakarya, Turkey
| | - Ahmet Tarik Eminler
- Department of Gastroenterology, University Faculty of Medicine, Sakarya, Turkey
| | - Mustafa Ihsan Uslan
- Department of Gastroenterology, University Faculty of Medicine, Sakarya, Turkey
| | - Sadettin Hülagü
- Department of Gastroenterology, Kocaeli University Faculty of Medicine, Kocaeli, Turkey
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22
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Entecavir is Safe and Effective in Long Term for the Treatment of Hepatitis B in Immunocompromised Children. J Clin Exp Hepatol 2020; 10:150-154. [PMID: 32189930 PMCID: PMC7067991 DOI: 10.1016/j.jceh.2019.04.002] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/21/2019] [Accepted: 04/03/2019] [Indexed: 12/12/2022] Open
Abstract
OBJECTIVE Hepatitis B infection is common in patients with cancer, and prompt treatment is necessary; otherwise, it can result in life-threatening complications. The objective of this study was to assess the long-term safety and efficacy of entecavir in immunocompromised children with hepatitis B. METHODS This single-center prospective study was conducted on children with different malignancies referred to our department with evidence of hepatitis B infection. Only those children were included in the study who had HBsAg positive and alanine aminotransferase (ALT) more than 2 times the upper limit of normal and whose hepatitis B virus (HBV) DNA was more than 20,000IU/ml. These children were put on entecavir and prospectively observed upto 192 weeks. Primary efficacy end point was the proportion of patients who achieved undetectable HBV DNA at 48 weeks of treatment. Other efficacy end points were the proportion of patients with HBeAg seroconversion, undetectable HBV DNA, and ALT normalization at weeks 48 and 96 weeks. RESULTS A total of 41 children met the inclusion criteria, of which 5 children died because of malignancy and 5 were lost to follow-up. Mean log DNA was 7.67 at the start which after starting entecavir reduced to 4.1, 2.8, 1.19, 1.09, and 0.84 at 12, 24, 48, 72, and 96 weeks, respectively (P value < 0.0001). Mean ALT decreased from 332.5 which reduced to 190, 115, 63, and 46 at 4, 12, 24, and 48 weeks, respectively (P < 0.0001). 67.7% achieved the primary outcome and had undetectable DNA at 48 weeks which increased to 26 (83.9%) at 96 weeks. At 48 weeks, 80.6% patients achieved ALT normalization. Thirty percent developed HBeAg seroconversion. Two patients developed virological breakthrough, one at 96 weeks and another at 192 weeks. No significant adverse effects were observed. CONCLUSION Entecavir is safe and effective in long term for the treatment of hepatitis B in immunocompromised children.
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Key Words
- AASLD, American Association of Study of Liver Diseases
- ADR, adverse drug reaction
- ALT, alanine aminotransferase
- CHB, chronic hepatitis B
- CT, chemotherapy
- EASL, European Association of Study of Liver
- HBV, hepatitis B virus
- HBVR, hepatitis B virus reactivation
- HCC, hepatocellular carcinoma
- INASL, Indian National Association of Study of Liver
- PCR, polymerase chain reaction
- TAF, tenofovir alafenamide
- USG, ultrasonography
- chemotherapy
- reactivation
- transfusion
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2018 Korean Liver Cancer Association-National Cancer Center Korea Practice Guidelines for the Management of Hepatocellular Carcinoma. Korean J Radiol 2019; 20:1042-1113. [PMID: 31270974 PMCID: PMC6609431 DOI: 10.3348/kjr.2019.0140] [Citation(s) in RCA: 191] [Impact Index Per Article: 31.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2019] [Accepted: 02/24/2019] [Indexed: 01/10/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the fifth most common cancer globally and the fourth most common cancer in men in Korea, where the prevalence of chronic hepatitis B infection is high in middle-aged and elderly patients. These practice guidelines will provide useful and constructive advice for the clinical management of patients with HCC. A total of 44 experts in hepatology, oncology, surgery, radiology, and radiation oncology in the Korean Liver Cancer Association-National Cancer Center Korea Practice Guideline Revision Committee revised the 2014 Korean guidelines and developed new recommendations that integrate the most up-to-date research findings and expert opinions.
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2018 Korean Liver Cancer Association-National Cancer Center Korea Practice Guidelines for the Management of Hepatocellular Carcinoma. Gut Liver 2019; 13:227-299. [PMID: 31060120 PMCID: PMC6529163 DOI: 10.5009/gnl19024] [Citation(s) in RCA: 241] [Impact Index Per Article: 40.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2019] [Accepted: 01/24/2019] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the fifth most common cancer globally and the fourth most common cancer in men in Korea, where the prevalence of chronic hepatitis B infection is high in middle-aged and elderly patients. These practice guidelines will provide useful and constructive advice for the clinical management of patients with HCC. A total of 44 experts in hepatology, oncology, surgery, radiology and radiation oncology in the Korean Liver Cancer Association-National Cancer Center Korea Practice Guideline Revision Committee revised the 2014 Korean guidelines and developed new recommendations that integrate the most up-to-date research findings and expert opinions.
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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.
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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
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Ciccullo A, Ponziani FR, Maiolo E, Pallavicini F, Pompili M. Late reactivation of hepatitis B virus after rituximab-containing chemotherapy for mantle cell lymphoma: a case report. Infection 2018; 47:313-316. [PMID: 30368733 DOI: 10.1007/s15010-018-1242-1] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2018] [Accepted: 10/21/2018] [Indexed: 02/07/2023]
Abstract
BACKGROUND Hepatitis B virus (HBV) reactivation is commonly observed in HBsAg-positive hematologic patients undergoing immunosuppressive chemotherapy. Recent guidelines recommend antiviral prophylaxis to be continued for up to 12 months after the discontinuation of the anticancer regimen. CASE PRESENTATION We report a case of a patient who underwent antiviral prophylaxis for 26 months after the discontinuation of a rituximab-containing chemotherapy regimen for a lymphoma and was admitted in the infectious diseases department with a 3-day history of jaundice, itching, and dark urine. After excluding other possible causes of acute liver damage, HBV reactivation was suspected. HBV-DNA was 4497000 IU/mL. Following reintroduction of entecavir, we observed a steady decline of ALT, AST, bilirubin and HBV-DNA serum levels, with a rapid resolution of acute hepatitis and an improvement in clinical conditions; one year after the event of HBV reactivation and beginning of antiviral therapy, the patient was virologically suppressed. DISCUSSION Our study demonstrates that the risk of HBV reactivation in HBsAg-positive patients with undetectable HBV-DNA can occur even after three years from the last administration of rituximab and several months after the withdrawal of prophylactic antiviral therapy in patients with hematological malignancies. This implies that a close monitoring of HBV-related markers including HBV-DNA must continue after the withdrawal of prophylactic NA therapy.
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Affiliation(s)
- Arturo Ciccullo
- Institute of Clinical Infectious Diseases, Catholic University of the Sacred Heart, L.go F. Vito 1, 00168, Rome, Italy.
| | - F R Ponziani
- Internal Medicine, Gastroenterology and Hepatology Unit, Fondazione Agostino Gemelli Hospital, Catholic University, Rome, Italy
| | - E Maiolo
- Institute of Hematology, Università Cattolica del Sacro Cuore, Rome, Italy
| | - F Pallavicini
- Institute of Clinical Infectious Diseases, Catholic University of the Sacred Heart, L.go F. Vito 1, 00168, Rome, Italy
| | - M Pompili
- Internal Medicine, Gastroenterology and Hepatology Unit, Fondazione Agostino Gemelli Hospital, Catholic University, Rome, Italy
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Lee J, Park JY, Kim DG, Lee JY, Kim BS, Kim MS, Il Kim S, Kim YS, Huh KH. Effects of rituximab dose on hepatitis B reactivation in patients with resolved infection undergoing immunologic incompatible kidney transplantation. Sci Rep 2018; 8:15629. [PMID: 30353021 PMCID: PMC6199240 DOI: 10.1038/s41598-018-34111-5] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2018] [Accepted: 10/11/2018] [Indexed: 12/11/2022] Open
Abstract
Sensitized patients received desensitization therapy with rituximab for kidney transplantation. However, the impact of rituximab dose on hepatitis B virus (HBV) reactivation is unknown. Patients who underwent living donor kidney transplantation between 2008 and 2016 were grouped according to rituximab dose (control vs. standard-dose rituximab [375 mg/m2] vs. reduced-dose rituximab [200 mg/body]) for comparison of HBV reactivation. A total of 336 hepatitis B surface antigen (HBsAg)-negative/antibody to hepatitis B core antigen (anti-HBc)-positive patients underwent kidney transplantation, of whom 91 (27.1%) received rituximab for desensitization (57 standard-dose and 34 reduced-dose rituximab). During the study period, eight patients experienced HBV reactivation (three in the control group, five in the standard-dose group). In the standard-dose group, four patients experienced hepatitis flare, and one patient died due to hepatic failure. No HBV reactivation occurred in the reduced-dose group. Standard-dose rituximab significantly decreased hepatitis B surface antigen antibody titer (anti-HBs; −99.8 IU/L) at 12 months, compared with reduced-dose rituximab (−20.1 IU/L) and control (−39.1 IU/L, P = 0.017). Standard-dose rituximab (HR, 10.60; 95% CI, 2.52–44.60; P = 0.001) and anti-HBs < 100 IU/L at transplantation (HR, 9.06; 95% CI, 1.11–74.30; P = 0.04) were independent risk factors for HBV reactivation. Standard-dose rituximab significantly increased HBV reactivation risk for HBsAg-negative/anti-HBc-positive kidney transplant patients.
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Affiliation(s)
- Juhan Lee
- Department of Transplantation Surgery, Severance Hospital, Yonsei University Health System, Seoul, Republic of Korea.,Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Jun Yong Park
- Department of Gastroenterology, Severance Hospital, Yonsei University Health System, Seoul, Republic of Korea
| | - Deok Gie Kim
- Department of Transplantation Surgery, Severance Hospital, Yonsei University Health System, Seoul, Republic of Korea.,Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Jee Youn Lee
- Department of Transplantation Surgery, Severance Hospital, Yonsei University Health System, Seoul, Republic of Korea.,Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Beom Seok Kim
- Department of Nephrology, Severance Hospital, Yonsei University Health System, Seoul, Republic of Korea
| | - Myoung Soo Kim
- Department of Transplantation Surgery, Severance Hospital, Yonsei University Health System, Seoul, Republic of Korea.,Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Soon Il Kim
- Department of Transplantation Surgery, Severance Hospital, Yonsei University Health System, Seoul, Republic of Korea.,Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Yu Seun Kim
- Department of Transplantation Surgery, Severance Hospital, Yonsei University Health System, Seoul, Republic of Korea.,Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Kyu Ha Huh
- Department of Transplantation Surgery, Severance Hospital, Yonsei University Health System, Seoul, Republic of Korea. .,Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea.
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Wu CC, Chen YS, Cao L, Chen XW, Lu MJ. Hepatitis B virus infection: Defective surface antigen expression and pathogenesis. World J Gastroenterol 2018; 24:3488-3499. [PMID: 30131655 PMCID: PMC6102499 DOI: 10.3748/wjg.v24.i31.3488] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/03/2018] [Revised: 06/01/2018] [Accepted: 06/25/2018] [Indexed: 02/06/2023] Open
Abstract
Hepatitis B virus (HBV) infection is a global public health concern. HBV causes chronic infection in patients and can lead to liver cirrhosis, hepatocellular carcinoma, and other severe liver diseases. Thus, understanding HBV-related pathogenesis is of particular importance for prevention and clinical intervention. HBV surface antigens are indispensable for HBV virion formation and are useful viral markers for diagnosis and clinical assessment. During chronic HBV infection, HBV genomes may acquire and accumulate mutations and deletions, leading to the expression of defective HBV surface antigens. These defective HBV surface antigens have been found to play important roles in the progression of HBV-associated liver diseases. In this review, we focus our discussion on the nature of defective HBV surface antigen mutations and their contribution to the pathogenesis of fulminant hepatitis B. The relationship between defective surface antigens and occult HBV infection are also discussed.
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MESH Headings
- DNA, Viral/genetics
- DNA, Viral/isolation & purification
- Disease Progression
- Genome, Viral/genetics
- Hepatitis B Surface Antigens/genetics
- Hepatitis B Surface Antigens/immunology
- Hepatitis B Surface Antigens/metabolism
- Hepatitis B virus/genetics
- Hepatitis B virus/immunology
- Hepatitis B, Chronic/immunology
- Hepatitis B, Chronic/pathology
- Hepatitis B, Chronic/prevention & control
- Hepatitis B, Chronic/virology
- Humans
- Liver/immunology
- Liver/pathology
- Liver/virology
- Liver Failure, Acute/immunology
- Liver Failure, Acute/pathology
- Liver Failure, Acute/prevention & control
- Liver Failure, Acute/virology
- Mutation
- Virus Replication/genetics
- Virus Replication/immunology
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Affiliation(s)
- Chun-Chen Wu
- State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, Hubei Province, China
| | - Ying-Shan Chen
- State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, Hubei Province, China
| | - Liang Cao
- State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, Hubei Province, China
- Department of Microbiology and Immunology, Feinberg School of Medicine Northwestern University, Chicago, IL 60611, United States
| | - Xin-Wen Chen
- State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, Hubei Province, China
| | - Meng-Ji Lu
- Institute of Virology, University Hospital of Essen, Essen 45122, Germany
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Lopetuso LR, Mocci G, Marzo M, D'Aversa F, Rapaccini GL, Guidi L, Armuzzi A, Gasbarrini A, Papa A. Harmful Effects and Potential Benefits of Anti-Tumor Necrosis Factor (TNF)-α on the Liver. Int J Mol Sci 2018; 19:E2199. [PMID: 30060508 PMCID: PMC6121684 DOI: 10.3390/ijms19082199] [Citation(s) in RCA: 60] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2018] [Revised: 07/19/2018] [Accepted: 07/24/2018] [Indexed: 02/08/2023] Open
Abstract
Anti-tumor necrosis factor (TNF)-α agents represent an effective treatment for chronic inflammatory diseases. However, some concerns about their potentially undesirable effects on liver function have been reported. On the other hand, evidence of their therapeutic effects on certain liver diseases is accumulating. Many data showed the safety of anti-TNF-α in patients with chronic hepatitis B and C and in liver transplanted patients even if a strict follow-up and prophylaxis are recommended in well-defined subgroups. On the other side, anti-TNF-α-induced liver injury is not a rare event. However, it is often reversible after anti-TNF-α withdrawal. Anti-TNF-α agents have been tested in advanced stages of severe alcoholic hepatitis and non-alcoholic fatty liver disease. Limited data on the efficacy of anti-TNF-α in patients with autoimmune hepatitis and primary biliary cholangitis are also available. In this review, we explored the hepatic safety concerns in patients receiving anti-TNF-α agents with and without pre-existent hepatic diseases. In addition, the available evidence on their potential benefits in the treatment of specific hepatic diseases is discussed.
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Affiliation(s)
- Loris Riccardo Lopetuso
- Internal Medicine and Gastroenterology Department, Fondazione Policlinico Universitario A. Gemelli IRCCS-Università Cattolica del Sacro Cuore, 00168 Roma, Italy.
| | - Giammarco Mocci
- Gastroenterology Unit, Brotzu Hospital, 09121 Cagliari, Italy.
| | - Manuela Marzo
- Internal Medicine and Gastroenterology Department, Fondazione Policlinico Universitario A. Gemelli IRCCS-Università Cattolica del Sacro Cuore, 00168 Roma, Italy.
| | - Francesca D'Aversa
- Internal Medicine and Gastroenterology Department, Fondazione Policlinico Universitario A. Gemelli IRCCS-Università Cattolica del Sacro Cuore, 00168 Roma, Italy.
| | - Gian Lodovico Rapaccini
- Internal Medicine and Gastroenterology Department, Fondazione Policlinico Universitario A. Gemelli IRCCS-Università Cattolica del Sacro Cuore, 00168 Roma, Italy.
| | - Luisa Guidi
- Internal Medicine and Gastroenterology Department, Fondazione Policlinico Universitario A. Gemelli IRCCS-Università Cattolica del Sacro Cuore, 00168 Roma, Italy.
| | - Alessandro Armuzzi
- Internal Medicine and Gastroenterology Department, Fondazione Policlinico Universitario A. Gemelli IRCCS-Università Cattolica del Sacro Cuore, 00168 Roma, Italy.
| | - Antonio Gasbarrini
- Internal Medicine and Gastroenterology Department, Fondazione Policlinico Universitario A. Gemelli IRCCS-Università Cattolica del Sacro Cuore, 00168 Roma, Italy.
| | - Alfredo Papa
- Internal Medicine and Gastroenterology Department, Fondazione Policlinico Universitario A. Gemelli IRCCS-Università Cattolica del Sacro Cuore, 00168 Roma, Italy.
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Koffas A, Dolman GE, Kennedy PT. Hepatitis B virus reactivation in patients treated with immunosuppressive drugs: a practical guide for clinicians. Clin Med (Lond) 2018; 18:212-218. [PMID: 29858430 PMCID: PMC6334086 DOI: 10.7861/clinmedicine.18-3-212] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Hepatitis B virus reactivation (HBVr) is emerging as an important clinical entity, with the advent of highly potent immunosuppression licensed for use as the treatment of a widening range of clinical indications. HBVr can lead to severe acute liver failure and death. Risk can be minimised through appropriate screening, monitoring and antiviral prophylaxis. Screening for serological markers at the -earliest opportunity is recommended. Risk stratification should then be performed on the basis of characteristics of the -underlying disease, markers of viral activity and the potency of proposed immunosuppression. In this review, we summarise the most recent recommendations from the relevant international societies. We also provide suggestions on how a robust multidisciplinary service can be delivered to prevent HBVr in UK clinical practice through optimisation of resources and introduction of checkpoints to prevent the inappropriate administration of immunosuppression to those at significant risk of HBVr.
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Affiliation(s)
- Apostolos Koffas
- Gastroenterology Unit, University Hospital of Larisa, Thessaly, Greece
| | - Grace E Dolman
- Barts Liver Centre, Blizard Institute, Barts and the London School of Medicine and Dentistry, London, UK
| | - Patrick Tf Kennedy
- Barts Liver Centre, Blizard Institute, Barts and the London School of Medicine and Dentistry, London, UK
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Fang J, Li W, Tan M, Chen W, Zhang C, Wang W, Xu Q, Guo X. Discontinuation of antiviral prophylaxis increased the risk of hepatitis B virus reactivation in glomerulonephritis patients under immunotherapy: a real-life observation. Int Urol Nephrol 2018; 50:1653-1660. [PMID: 29644524 DOI: 10.1007/s11255-018-1867-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2017] [Accepted: 04/01/2018] [Indexed: 11/30/2022]
Abstract
PURPOSE Antiviral prophylaxis is proved to be effective in reducing the risk of hepatitis B virus (HBV) reactivation in hepatitis B surface antigen (HBsAg)-positive patients under immunotherapy. But outcomes referring to discontinuation of antiviral prophylaxis in these patients are lacking. METHODS We performed a retrospective study of 105 HBsAg-positive patients under immunotherapy for glomerulonephritis and evaluated the incidence and risk factors for HBV reactivation. RESULTS Among 105 patients, 55.24% completed antiviral prophylaxis, while 20.00% discontinued and 24.76% rejected antiviral prophylaxis. HBV reactivation was significantly different among completion, discontinuation, and rejection of antiviral prophylaxis: 5.17% versus 38.10% versus 15.38% in the incidence of HBV reactivation (P = 0.001), 3.45% versus 23.81% versus 11.54% in HBV DNA ≥ 5 Log copies/ml (P = 0.023), and 0 versus 14.29% versus 3.85% in hepatitis B e antigen seroconversion from negative to positive (P = 0.014). Survival curve showed the median occurrence time of HBV reactivation in discontinuation group was 32 months (95% CI 24-39 months), earlier than 69 months (95% CI 65-72 months) of completion group and 43 months (95% CI 37-49 months) of rejection group (χ2 = 13.780, P = 0.001). Univariate and multivariate analysis identified two independent risk factors for HBV reactivation: baseline HBV DNA detectable (OR 5.009, 95% CI 1.717-16.335, P = 0.012) and discontinuation of antiviral prophylaxis (OR 5.213, 95% CI 1.688-18.105, P = 0.011). CONCLUSIONS Discontinuation of antiviral prophylaxis increased the risk of HBV reactivation in HBsAg-positive patients under immunotherapy for glomerulonephritis.
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Affiliation(s)
- Jing Fang
- Department of Nephrology, China-Japan Friendship Hospital, No.2 East Yinghua Street, Chaoyang District, Beijing, 100029, China.
| | - Wenge Li
- Department of Nephrology, China-Japan Friendship Hospital, No.2 East Yinghua Street, Chaoyang District, Beijing, 100029, China
| | - Min Tan
- Department of Nephrology, China-Japan Friendship Hospital, No.2 East Yinghua Street, Chaoyang District, Beijing, 100029, China
| | - Wen Chen
- Department of Nephrology, China-Japan Friendship Hospital, No.2 East Yinghua Street, Chaoyang District, Beijing, 100029, China
| | - Cong Zhang
- Department of Nephrology, China-Japan Friendship Hospital, No.2 East Yinghua Street, Chaoyang District, Beijing, 100029, China
| | - Wenbo Wang
- Department of Nephrology, China-Japan Friendship Hospital, No.2 East Yinghua Street, Chaoyang District, Beijing, 100029, China
| | - Qianqian Xu
- Department of Nephrology, China-Japan Friendship Hospital, No.2 East Yinghua Street, Chaoyang District, Beijing, 100029, China
| | - Xinzhen Guo
- Department of Hepatology, China-Japan Friendship Hospital, Beijing, China
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Siyahian A, Malik SU, Mushtaq A, Howe CL, Majeed A, Zangeneh T, Iftikhar S, Habib S, Zahid U, Riaz IB, Warraich Z, Faridi W, Anwer F. Prophylaxis for Hepatitis B Virus Reactivation after Allogeneic Stem Cell Transplantation in the Era of Drug Resistance and Newer Antivirals: A Systematic Review and Meta-Analysis. Biol Blood Marrow Transplant 2018; 24:1483-1489. [PMID: 29545185 DOI: 10.1016/j.bbmt.2018.02.027] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2017] [Accepted: 02/27/2018] [Indexed: 02/07/2023]
Abstract
Patients undergoing allogenic hematopoietic stem cell transplantation (allo-HSCT) are at a very high risk of hepatitis B virus reactivation (HBVr). Lamivudine is commonly used as prophylaxis against HBVr in high-risk patients undergoing allo-HSCT. Unfortunately, its efficacy is diminishing due to the development of HBV mutant drug-resistant strains. With the availability of newer antiviral agents such as entecavir, telbivudine, adefovir, and tenofovir, it is important to assess their role in HBVr prophylaxis. A comprehensive search of 7 databases was performed to evaluate efficacy of antiviral prophylaxis against HBVr in allo-HSCT patients (PubMed/Medline, Embase, Scopus, Cochrane Library, Web of Science, CINAHL, and ClinicalTrials.gov (June 21, 2017)). We identified 10 studies, with 2067 patients undergoing allo-HSCT; these primarily evaluated the use of lamivudine and entecavir as prophylaxis against HBVr in patients undergoing allo-HSCT because there were little or no data about adefovir, telbivudine, or tenofovir as prophylaxis in this specific patient population. Thus, included studies were categorized into 2 main prophylaxis groups: lamivudine and entecavir. Results of our meta-analysis suggest that entecavir is very effective against HBVr, although further clinical trials are required to test efficacy of new antivirals and explore the emerging threat of drug resistance.
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Affiliation(s)
- Aida Siyahian
- College of Medicine, University of Arizona, Tucson, Arizona
| | - Saad Ullah Malik
- Department of Medicine, Hematology/Oncology, Blood and Marrow Transplantation, University of Arizona, Tucson, Arizona
| | - Adeela Mushtaq
- Department of Medicine, Hematology/Oncology, Blood and Marrow Transplantation, University of Arizona, Tucson, Arizona
| | - Carol L Howe
- University of Arizona Health Sciences Library, Tucson, Arizona
| | - Aneela Majeed
- Transplant Infectious Diseases, Division of Infectious Diseases, Department of Medicine, University of Arizona, Tucson, Arizona
| | - Tirdad Zangeneh
- Transplant Infectious Diseases, Division of Infectious Diseases, Department of Medicine, University of Arizona, Tucson, Arizona
| | - Samar Iftikhar
- Department of Physiology, University of Arizona, Tucson, Arizona
| | - Shahid Habib
- Liver Institute, Southern Arizona VA Health Care System, Tucson, Arizona
| | - Umar Zahid
- Department of Medicine, Hematology/Oncology, Blood and Marrow Transplantation, University of Arizona, Tucson, Arizona; Department of Biostatistics, Mel and Enid Zuckerman College of Public Health, University of Arizona, Tucson, Arizona
| | - Irbaz Bin Riaz
- Hematology Oncology Fellowship Program, Department of Medicine, Mayo Clinic, Rochester, Minnesota
| | - Zabih Warraich
- Department of Medicine, Hematology/Oncology, Blood and Marrow Transplantation, University of Arizona, Tucson, Arizona
| | - Warda Faridi
- Department of Medicine, Hematology/Oncology, Blood and Marrow Transplantation, University of Arizona, Tucson, Arizona
| | - Faiz Anwer
- Department of Medicine, Hematology/Oncology, Blood and Marrow Transplantation, University of Arizona, Tucson, Arizona.
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Abstract
PURPOSE OF REVIEW Acquired thrombotic thrombocytopenic purpura is an immune-mediated thrombotic microangiopathy caused by antibodies to ADAMTS13 (A Disintegrin And Metalloproteinase with a ThromboSpondin type 1 motif, member 13). Standard treatment with therapeutic plasma exchange and immunosuppression with steroids results in high remission and low mortality rates. However, a number of patients remain refractory to frontline therapy and/or experience multiple relapses. This study reviews emerging therapies for thrombotic thrombocytopenic purpura. RECENT FINDINGS Studies indicate that reducing anti-ADAMTS13 antibody levels through B-cell depletion or proteasome inhibition is effective for the management of refractory disease. Preliminary reports examining anti-CD20 therapy for the treatment of initial disease or as maintenance therapy for seropositive patients suggest the addition of immunosuppression in other disease phases may delay relapse. Exciting developments in targeted therapies to von Willebrand Factor and recombinant ADAMTS13 hold promise for transforming disease management. SUMMARY Approximately half of patients diagnosed with acquired thrombotic thrombocytopenic purpura experience refractory and/or relapsing disease. For these patients, a hematologic remission may be an insufficient therapeutic goal. With recent developments, it is now possible to envision a multifaceted approach targeting disease mechanisms that may dramatically improve outcomes for this otherwise debilitating disease.
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Miralles P, Navarro JT, Berenguer J, Gómez Codina J, Kwon M, Serrano D, Díez-Martín JL, Villà S, Rubio R, Menárguez J, Ribera Santasusana JM. GESIDA/PETHEMA recommendations on the diagnosis and treatment of lymphomas in patients infected by the human immunodeficiency virus. Med Clin (Barc) 2018; 151:39.e1-39.e17. [PMID: 29357988 DOI: 10.1016/j.medcli.2017.11.037] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2017] [Revised: 10/21/2017] [Accepted: 11/02/2017] [Indexed: 01/20/2023]
Abstract
The incidence of non-Hodgkin's lymphoma and Hodgkin's lymphoma is higher in patients with HIV infection than in the general population. Following the introduction of combination antiretroviral therapy (cART), the prognostic significance of HIV-related variables has decreased, and lymphoma-related factors have become more pronounced. Currently, treatments for lymphomas in HIV-infected patients do not differ from those used in the general population. However, differentiating characteristics of seropositive patients, such as the need for cART and specific prophylaxis and treatment of certain opportunistic infections, should be considered. This document updates recommendations on the diagnosis and treatment of lymphomas in HIV infected patients published by GESIDA/PETHEMA in 2008.
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Affiliation(s)
- Pilar Miralles
- Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, España.
| | - José Tomás Navarro
- Institut Català d'Oncologia, Hospital Universitari Germans Trias i Pujol, Institut de Recerca Josep Carreras, Universitat Autónoma de Barcelona, Badalona, Barcelona, España
| | - Juan Berenguer
- Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, España
| | | | - Mi Kwon
- Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, España
| | - David Serrano
- Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, España
| | - José Luis Díez-Martín
- Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, España
| | - Salvador Villà
- Institut Català d'Oncologia, Hospital Universitari Germans Trias i Pujol, Institut de Recerca Josep Carreras, Universitat Autónoma de Barcelona, Badalona, Barcelona, España
| | | | - Javier Menárguez
- Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, España
| | - José-María Ribera Santasusana
- Institut Català d'Oncologia, Hospital Universitari Germans Trias i Pujol, Institut de Recerca Josep Carreras, Universitat Autónoma de Barcelona, Badalona, Barcelona, España
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Hsu JW, Hiemenz JW, Wingard JR, Leather H. Viral Infections in Patients with Hematological Malignancies. NEOPLASTIC DISEASES OF THE BLOOD 2018:1079-1127. [DOI: 10.1007/978-3-319-64263-5_51] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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The Clinical Spectrum of Hepatic Manifestations in Chronic Lymphocytic Leukemia. CLINICAL LYMPHOMA MYELOMA & LEUKEMIA 2017; 17:863-869. [DOI: 10.1016/j.clml.2017.07.008] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/08/2017] [Accepted: 07/19/2017] [Indexed: 12/18/2022]
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Choi J, Lim YS. Characteristics, Prevention, and Management of Hepatitis B Virus (HBV) Reactivation in HBV-Infected Patients Who Require Immunosuppressive Therapy. J Infect Dis 2017; 216:S778-S784. [PMID: 29156044 DOI: 10.1093/infdis/jix178] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Hepatitis B virus (HBV) reactivation becomes a challenging issue with increasing use of immunosuppressive agents and cytotoxic chemotherapy for varied medical conditions, including cancer. The spectrum of HBV reactivation in the setting of immunosuppression may vary from asymptomatic reactivation to liver failure leading to death. HBV reactivation can hamper the course of planned therapies and diminish the effects of therapies; thus, it adversely affects the prognosis of the original disease and the survival of the patients. There is mounting evidence that HBV reactivation can be prevented and managed if patients are screened to determine their risk for HBV reactivation and are treated prophylactically before therapy with immunosuppressive agents or cytotoxic chemotherapy is initiated. In this article, we review the diagnostic criteria and clinical outcomes of HBV reactivation, discuss how immunosuppressive therapy may influence the risk of HBV reactivation, and outline strategies to prevent HBV reactivation.
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Affiliation(s)
- Jonggi Choi
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Young-Suk Lim
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
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Consensus Report by the Pediatric Acute Lung Injury and Sepsis Investigators and Pediatric Blood and Marrow Transplantation Consortium Joint Working Committees on Supportive Care Guidelines for Management of Veno-Occlusive Disease in Children and Adolescents, Part 3: Focus on Cardiorespiratory Dysfunction, Infections, Liver Dysfunction, and Delirium. Biol Blood Marrow Transplant 2017; 24:207-218. [PMID: 28870776 DOI: 10.1016/j.bbmt.2017.08.035] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2017] [Accepted: 08/29/2017] [Indexed: 12/19/2022]
Abstract
Some patients with veno-occlusive disease (VOD) have multiorgan dysfunction, and multiple teams are involved in their daily care in the pediatric intensive care unit. Cardiorespiratory dysfunction is critical in these patients, requiring immediate action. The decision of whether to use a noninvasive or an invasive ventilation strategy may be difficult in the setting of mucositis or other comorbidities in patients with VOD. Similarly, monitoring of organ functions may be very challenging in these patients, who may have fulminant hepatic failure with or without hepatic encephalopathy complicated by delirium and/or infections. In this final guideline of our series on supportive care in patients with VOD, we address some of these questions and provide evidence-based recommendations on behalf of the Pediatric Acute Lung Injury and Sepsis Investigators and Pediatric Blood and Marrow Transplantation Consortium Joint Working Committees.
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Mittal M, Hu KQ. Clinical Implications and Management of Chronic Occult Hepatitis B Virus Infection. CURRENT HEPATOLOGY REPORTS 2017; 16:90-96. [DOI: 10.1007/s11901-017-0339-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/16/2025]
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Yağcı M, Suyanı E, Kızıl Çakar M. The Impact of Chemotherapy on Hepatitis B Antibody Titer in Patients with Hematological Malignancies. Turk J Haematol 2017; 32:251-6. [PMID: 26376591 PMCID: PMC4563201 DOI: 10.4274/tjh.2013.0342] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/28/2023] Open
Abstract
Objective: To investigate the influence of chemotherapy (CT) on HBsAb titer in patients receiving CT due to hematological malignancy. Materials and Methods: The data of 75 patients who received CT with the diagnosis of various hematological malignancies and who had serum HBsAb levels measured prior to and after the cessation of CT were evaluated retrospectively. Results: The median age of the patients was 52 years (range: 16-78) with 49 (65%) males and 26 (35%) females. Median HBsAb titer decreased significantly after CT compared to the pre-CT median HBsAb titer [68 (range: 0-1000) vs. 100 (range: 6.2-1000)] (p=0.001). In subgroup analysis, median HBsAb titer decreased significantly after CT in acute leukemia patients [110 (range: 6.2-1000) vs. 67.8 (range: 0-1000)] (p=0.003) and in patients receiving intensive CT [97.2 (range: 6.2-1000) vs. 71 (range: 0-1000)] (p=0.036). The decrease in median HBsAb titer was significant in male patients (p<0.001). HBsAb became negative after CT in 9 patients who were HBcAb-negative and had lower pre-CT HBsAb levels. Conclusion: HBsAb decreased after CT, especially in acute leukemia and male patients, and in patients receiving intensive CT.
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Affiliation(s)
- Münci Yağcı
- Gazi University Faculty of Medicine, Department of Hematology, Ankara, Turkey Phone: +90 312 202 63 17 E-mail:
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Baghbanian M, Halvani M, Roghani HS, Lotfi MH, Yazdi MF, Vahedian-Ardakani HA. PREVALENCE OF OCCULT HEPATITIS B INFECTION IN IRANIAN CANCER PATIENTS BEFORE CHEMOTHERAPY TREATMENT. ARQUIVOS DE GASTROENTEROLOGIA 2016; 53:175-9. [PMID: 27438423 DOI: 10.1590/s0004-28032016000300010] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/01/2015] [Accepted: 03/30/2016] [Indexed: 01/06/2023]
Abstract
BACKGROUND Occult hepatitis B infection is characterized by negative hepatitis B surface antigen (HBsAg) and also detectable hepatitis B virus (HBV) -DNA, with or without hepatitis B core antibody (anti-HBc). HBV reactivation in individuals under immunosuppressive therapy is critical, occurring in occult HBV. OBJECTIVE In this study, we aimed to determine the prevalence of occult HBV infection among hepatitis B surface antigen negative in cancer patients before receiving chemotherapy. METHODS Sera from 204 cancer patients who were negative for HBsAg, were tested for anti-HBc antibodies. The samples that were negative for HBsAg but positive for anti-HBc also examined for HBV-DNA by polymerase chain reaction (PCR). RESULTS Of the 204 HBsAg negative blood samples, 11 (5.4%) samples were positive for anti-HBc antibodies. HBV-DNA was detected in 9/11 (81%) of anti-HBc positive samples. Occult HBV infection in hematological cancers was more than solid cancers, 4.8% and 4.3% respectively. There was no significant difference in HBc antibody positivity based on vaccination, previous blood transfusions, history of familial hepatitis or biochemical parameters (ALT, AST, total and direct bilirubin levels) (P>0.05). CONCLUSION Screening of occult HBV infection by HBsAg, HBV DNA and anti HB core antibody should be suggested as a routine investigation in cancer patients before receiving chemotherapy.
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Affiliation(s)
- Mahmud Baghbanian
- Department of Gastroenterology, Shahid Sadoughi University of Medical Sciences and Health Services, Yazd, Iran
| | - Mehdi Halvani
- Department of Internal Medicine, Shahid Sadoughi University of Medical Sciences and Health Services, Yazd, Iran
| | - Hassan Salman Roghani
- Department of Gastroenterology, Shahid Sadoughi University of Medical Sciences and Health Services, Yazd, Iran
| | - Mohammad Hassan Lotfi
- Biostatistics & Epidemiology, Health Faculty, Shaheed Sadoughi University of Medical Sciences, Daneshju Blv. Yazd, Iran
| | - Mohammad Frahat Yazdi
- Department of haematology, Shahid Sadoughi University of Medical Sciences and Health Services, Yazd, Iran
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Degasperi E, Caprioli F, El Sherif O, Back D, Colombo M, Aghemo A. Challenges in treating patients with inflammatory bowel disease and concurrent viral hepatitis infection. Expert Rev Gastroenterol Hepatol 2016; 10:1373-1383. [PMID: 27718758 DOI: 10.1080/17474124.2016.1246181] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Inflammatory bowel diseases (IBD) require long-term administration of immunomodulatory treatments to maintain disease remission. Due to the high worldwide prevalence of hepatitis B (HBV) or C (HCV) virus infections, presence of concurrent hepatitis can be a relevant clinical issue to manage when treating IBD. Areas covered: The paper summarizes epidemiological data about IBD and HBV/HCV infection and reviews current knowledge about the natural history of HBV and HCV in the IBD setting, concentrating on risk of hepatitis reactivation during immunosuppressive treatment. Most updated recommendations for management of HBV and HCV infections in IBD patients are discussed. Expert commentary: The development of new drugs for IBD with different molecular targets and the availability of potent and efficacious antiviral drugs for HBV and HCV will simplify management of hepatitis infection in IBD patients in the near future.
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Affiliation(s)
- Elisabetta Degasperi
- a A.M. and A. Migliavacca Center for Liver Disease, Division of Gastroenterology and Hepatology , Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano , Milan , Italy
| | - Flavio Caprioli
- b Department of Pathophysiology and Transplantation , Università degli Studi di Milano , Milan , Italy.,c Gastroenterology and Endoscopy Unit , Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico , Milan , Italy
| | - Omar El Sherif
- d Gastroenterology Specialist Registrar , St. James's Hospital , Dublin , Ireland.,e Research Fellow, School of Medicine , Trinity College Dublin , Dublin , Ireland
| | - David Back
- f Department of Molecular and Clinical Pharmacology , University of Liverpool , Liverpool , UK
| | - Massimo Colombo
- a A.M. and A. Migliavacca Center for Liver Disease, Division of Gastroenterology and Hepatology , Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano , Milan , Italy
| | - Alessio Aghemo
- a A.M. and A. Migliavacca Center for Liver Disease, Division of Gastroenterology and Hepatology , Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano , Milan , Italy
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Sagnelli C, Macera M, Pisaturo M, Zampino R, Coppola M, Sagnelli E. Occult HBV infection in the oncohematological setting. Infection 2016; 44:575-582. [PMID: 27076347 DOI: 10.1007/s15010-016-0891-1] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2015] [Accepted: 03/07/2016] [Indexed: 12/15/2022]
Abstract
INTRODUCTION Occult hepatitis B infection (OBI), a virological condition characterized by a low release of Hepatitis B Virus (HBV) from liver cells and low HBV-DNA levels in serum and/or liver tissue of HBsAg-negative subjects, may reactivate in oncohematological patients undergoing immunosuppression by aggressive chemotherapy or hematopoietic stem cell transplantation. The entity of OBI reactivation varies from an increase in HBV replication without liver damage to an active HBV replication followed by liver cell necrosis, frequently severe and in some cases life threatening. Because of a possible severe outcome associated with OBI reactivation (hepatic failure or death due to the discontinuation of chemotherapy), prophylaxis with anti-HBV nucleot(s)ide analogues is recommended in relation to the foreseeable degree of immunosuppression. MATERIALS AND METHODS This review article focuses on the clinical impact of OBI in the oncohematological setting and is addressed to all health care workers having in care oncohematological patients or involved in the treatment of HBV infection and OBI prophylaxis. CONCLUSION International guidelines have indicated lamivudine prophylaxis in hematopoietic stem cell transplantation and when high-dose corticosteroids or anti-CD20 or anti-CD52 monoclonal antibodies are used. Entecavir or tenofovir should replace lamivudine for patients with advanced liver diseases for whom reactivation of OBI may be life threatening. When anti-CD20 or anti-CD52 sparing schedules or other non-aggressive chemotherapies are used, monitoring may be indicated, but very early treatment with highly effective antiviral drugs (entecavir or tenofovir) should be administered once a reactivation of OBI has occurred.
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Affiliation(s)
- C Sagnelli
- Department of Clinical and Experimental Medicine and Surgery "F. Magrassi e A. Lanzara", Second University of Naples, 80131, Naples, Italy
| | - M Macera
- Azienda Ospedaliera Universitaria-Second University of Naples, 80131, Naples, Italy
| | - M Pisaturo
- Division of Infectious Diseases, AORN Sant'Anna e San Sebastiano di Caserta, 81100, Caserta, Italy
| | - R Zampino
- Department of Medical, Surgical, Neurological, Metabolic and Geriatric Sciences, Second University of Naples, 80131, Naples, Italy
| | - M Coppola
- Section of Infectious Diseases, Department of Mental Health and Public Medicine, Second University of Naples, Via: L. Armanni 5, 80131, Naples, Italy
| | - E Sagnelli
- Section of Infectious Diseases, Department of Mental Health and Public Medicine, Second University of Naples, Via: L. Armanni 5, 80131, Naples, Italy.
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Lin XJ, Lao XM, Shi M, Li SP. Changes of HBV DNA After Chemoembolization for Hepatocellular Carcinoma and the Efficacy of Antiviral Treatment. Dig Dis Sci 2016; 61:2465-76. [PMID: 27105647 DOI: 10.1007/s10620-016-4167-5] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2015] [Accepted: 04/13/2016] [Indexed: 02/07/2023]
Abstract
Unlike systemic chemotherapy for hematological malignancies with hepatitis B virus (HBV) infection, transarterial chemoembolization (TACE) for HBV-related hepatocellular carcinoma (HCC) has only recently been reported to cause HBV reactivation and subsequent hepatitis. Most patients with HBV-related HCC have an underlying disease with liver fibrosis or cirrhosis, and TACE may potentially induce HBV reactivation and liver decompensation. Currently, there are no clinical guidelines for managing TACE-caused HBV reactivation. In this review, we summarize the changes of HBV status and liver function after TACE and the effect of antiviral treatment before, during, or after TACE.
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Affiliation(s)
- Xiao-Jun Lin
- Department of Hepatobiliary Oncology, Sun Yat-sen University Cancer Center, 651, Dongfeng Road East, Guangzhou, 510060, Guangdong, People's Republic of China
- State Key Laboratory of Southern China, Guangzhou, 510060, Guangdong, People's Republic of China
- Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong, People's Republic of China
| | - Xiang-Ming Lao
- Department of Hepatobiliary Oncology, Sun Yat-sen University Cancer Center, 651, Dongfeng Road East, Guangzhou, 510060, Guangdong, People's Republic of China.
- State Key Laboratory of Southern China, Guangzhou, 510060, Guangdong, People's Republic of China.
- Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong, People's Republic of China.
| | - Ming Shi
- Department of Hepatobiliary Oncology, Sun Yat-sen University Cancer Center, 651, Dongfeng Road East, Guangzhou, 510060, Guangdong, People's Republic of China
- State Key Laboratory of Southern China, Guangzhou, 510060, Guangdong, People's Republic of China
- Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong, People's Republic of China
| | - Sheng-Ping Li
- Department of Hepatobiliary Oncology, Sun Yat-sen University Cancer Center, 651, Dongfeng Road East, Guangzhou, 510060, Guangdong, People's Republic of China
- State Key Laboratory of Southern China, Guangzhou, 510060, Guangdong, People's Republic of China
- Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong, People's Republic of China
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Sorà F, Ponziani FR, Laurenti L, Chiusolo P, Autore F, Gasbarrini A, Sica S, Pompili M. Low risk of hepatitis B virus reactivation in patients with resolved infection and chronic myeloid leukemia treated with tyrosine kinase inhibitors. Leuk Lymphoma 2016; 58:993-995. [DOI: 10.1080/10428194.2016.1219906] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
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Law MF, Ho R, Cheung CKM, Tam LHP, Ma K, So KCY, Ip B, So J, Lai J, Ng J, Tam THC. Prevention and management of hepatitis B virus reactivation in patients with hematological malignancies treated with anticancer therapy. World J Gastroenterol 2016; 22:6484-6500. [PMID: 27605883 PMCID: PMC4968128 DOI: 10.3748/wjg.v22.i28.6484] [Citation(s) in RCA: 66] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/01/2016] [Revised: 05/24/2016] [Accepted: 06/15/2016] [Indexed: 02/06/2023] Open
Abstract
Hepatitis due to hepatitis B virus (HBV) reactivation can be severe and potentially fatal, but is preventable. HBV reactivation is most commonly reported in patients receiving cancer chemotherapy, especially rituximab-containing therapy for hematological malignancies and those receiving stem cell transplantation. All patients with hematological malignancies receiving anticancer therapy should be screened for active or resolved HBV infection by blood tests for hepatitis B surface antigen (HBsAg) and antibody to hepatitis B core antigen (anti-HBc). Patients found to be positive for HBsAg should be given prophylactic antiviral therapy to prevent HBV reactivation. For patients with resolved HBV infection, no standard strategy has yet been established to prevent HBV reactivation. There are usually two options. One is pre-emptive therapy guided by serial HBV DNA monitoring, whereby antiviral therapy is given as soon as HBV DNA becomes detectable. However, there is little evidence regarding the optimal interval and period of monitoring. An alternative approach is prophylactic antiviral therapy, especially for patients receiving high-risk therapy such as rituximab, newer generation of anti-CD20 monoclonal antibody, obinutuzumab or hematopoietic stem cell transplantation. This strategy may effectively prevent HBV reactivation and avoid the inconvenience of repeated HBV DNA monitoring. Entecavir or tenofovir are preferred over lamivudine as prophylactic therapy. Although there is no well-defined guideline on the optimal duration of prophylactic therapy, there is growing evidence to recommend continuing prophylactic antiviral therapy for at least 12 mo after cessation of chemotherapy, and even longer for those who receive rituximab or who had high serum HBV DNA levels before the start of immunosuppressive therapy. Many novel agents have recently become available for the treatment of hematological malignancies, and these agents may be associated with HBV reactivation. Although there is currently limited evidence to guide the optimal preventive measures, we recommend antiviral prophylaxis in HBsAg-positive patients receiving novel treatments, especially the Bruton tyrosine kinase inhibitors and the phosphatidylinositol 3-kinase inhibitors, which are B-cell receptor signaling modulators and reduce proliferation of malignant B-cells. Further studies are needed to clarify the risk of HBV reactivation with these agents and the best prophylactic strategy in the era of targeted therapy for hematological malignancies.
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Persistent risk of HBV reactivation despite extensive lamivudine prophylaxis in haematopoietic stem cell transplant recipients who are anti-HBc-positive or HBV-negative recipients with an anti-HBc-positive donor. Clin Microbiol Infect 2016; 22:946.e1-946.e8. [PMID: 27475741 DOI: 10.1016/j.cmi.2016.07.021] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2016] [Revised: 07/08/2016] [Accepted: 07/16/2016] [Indexed: 02/08/2023]
Abstract
The overall rate of hepatitis B virus (HBV) reactivation was evaluated in a population of 373 haematological stem cell transplant (HSCT) patients treated with lamivudine (LMV) if they were anti-HBc-positive/HBV-DNA-negative recipients or if they were HBV-negative recipients with an anti-HBc-positive donor. The incidence of HBV reactivation was calculated in two groups of autologous (auto) or allogeneic (allo) HSCT patients who were stratified according to their HBV serostatus. The former group included 57 cases: 10 auto-HSCT and 27 allo-HSCT anti-HBc-positive recipients, two auto-HSCT and three allo-HSCT inactive carriers, and 15 allo-HSCT recipients with an anti-HBc-positive donor. Forty-seven (82.4%) patients in this group received LMV prophylaxis (the median (interquartile range, IQR) of LMV treatment was 30 (20-38) months). The second group consisted of 320 anti-HBc-negative auto-HSCT and allo-HSCT recipients with anti-HBc-negative donors. None of these patients received any prophylaxis. Two patients in the first group and two in the second group experienced reactivation of HBV infection, with an incidence of 3.5% (95% CI 0.4-12.1%) and 0.6% (95% CI 0.1-2.2%), respectively. Only one out of four reactivated patients was LMV-treated. The cumulative probability of HBV reactivation at 6 years from HSCT was 15.8% (95% CI 15.2-16.4%). Three of four viral isolates obtained from the HBV-reactivated patients harboured mutations in the immune-active HBsAg-region. In a HSCT population carefully evaluated for HBV prophylaxis, a risk of HBV reactivation persisted in the group of patients who were not LMV-treated. Only one LMV-treated patient experienced reactivation of HBV with a resistant HBV isolate.
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Jun CH, Kim BS, Oak CY, Lee DH, Cho E, Cho SB, Choi SK, Park CH, Joo YE, Lee JJ, Kim HJ. HBV reactivation risk factors in patients with chronic HBV infection with low replicative state and resolved HBV infection undergoing hematopoietic stem cell transplantation in Korea. Hepatol Int 2016; 11:87-95. [PMID: 27351765 DOI: 10.1007/s12072-016-9747-0] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2016] [Accepted: 05/27/2016] [Indexed: 02/08/2023]
Abstract
PURPOSE To elucidate the rate and risk factors of HBV reactivation in patients with chronic HBV infection with low replicative state and resolved HBV infection undergoing allogenic/autologous hematopoietic stem-cell transplantation (HSCT) in Korea. METHODS The medical charts of 506 patients who underwent allogenic/autologous HSCT from January 2008 to December 2013 were analyzed retrospectively. We examined the reactivation rate and variables related to the risk of HBV reactivation, with a median follow-up period of 41.8 (1-245) months. Univariate analysis was used to identify any factors associated with HBV reactivation. Factors that were significant in the univariate analysis were entered into a stepwise multivariate analysis to find the most significant risk factors associated with HBV reactivation. RESULTS The reactivation rate of HBV in patients who underwent HSCT was 4.2 % (21/506). In subgroup analysis, the HBV reactivation rate (14.3 %) was the highest among HBsAg(+) patients (5/35). The reactivation rate of HBV in patients with resolved HBV infection [HBsAg(-)/HBcAb(+) with or without anti-HBs antibody] was 5.9 % (10/171). In univariate analysis for risk factors of HBV reactivation in patients who underwent HSCT, initial detectable HBV DNA (p = 0.004), age (≥60 years) (p = 0.012), recipient hepatitis B surface antigen-positive (HbsAg)(+) before HSCT (p = 0.004), recipient hepatitis B surface antibody-negative (HBsAb)(-) before HSCT (p = 0.005), recipient hepatitis B core antibody-positive (HbcAb)(+) before HSCT (p = 0.013), and donor HBsAg(+) (p < 0.001) were associated with reactivation of HBV. In multivariate analysis, significant risk factors of HBV reactivation in patients who underwent HSCT were old age (≥60 years) (p = 0.032) and donor HBsAg(+) (p = 0.026). CONCLUSION Old age (≥60 years) and donor HBsAg(+) were risk factors for HBV reactivation in HSCT patients. Preemptive antiviral treatment should be considered in these patients.
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Affiliation(s)
- Chung Hwan Jun
- Division of Gastroenterology, Department of Internal Medicine, Chonnam National University Medical School, 42, Jebong-ro, Dong-Ku, Gwangju, 501-757, Korea
| | - Ban Suk Kim
- Division of Gastroenterology, Department of Internal Medicine, Chonnam National University Medical School, 42, Jebong-ro, Dong-Ku, Gwangju, 501-757, Korea
| | - Chan Young Oak
- Division of Gastroenterology, Department of Internal Medicine, Chonnam National University Medical School, 42, Jebong-ro, Dong-Ku, Gwangju, 501-757, Korea
| | - Du Hyeon Lee
- Division of Gastroenterology, Department of Internal Medicine, Chonnam National University Medical School, 42, Jebong-ro, Dong-Ku, Gwangju, 501-757, Korea
| | - Eunae Cho
- Division of Gastroenterology, Department of Internal Medicine, Chonnam National University Medical School, 42, Jebong-ro, Dong-Ku, Gwangju, 501-757, Korea
| | - Sung Bum Cho
- Division of Gastroenterology, Department of Internal Medicine, Chonnam National University Medical School, 42, Jebong-ro, Dong-Ku, Gwangju, 501-757, Korea
| | - Sung Kyu Choi
- Division of Gastroenterology, Department of Internal Medicine, Chonnam National University Medical School, 42, Jebong-ro, Dong-Ku, Gwangju, 501-757, Korea.
| | - Chang Hwan Park
- Division of Gastroenterology, Department of Internal Medicine, Chonnam National University Medical School, 42, Jebong-ro, Dong-Ku, Gwangju, 501-757, Korea
| | - Young Eun Joo
- Division of Gastroenterology, Department of Internal Medicine, Chonnam National University Medical School, 42, Jebong-ro, Dong-Ku, Gwangju, 501-757, Korea
| | - Je-Jung Lee
- Division of Hematology, Department of Internal Medicine, Chonnam National University Medical School, 42, Jaebong-ro, Dong-Ku, Gwangju, 501-757, Korea
| | - Hyeoung-Joon Kim
- Division of Hematology, Department of Internal Medicine, Chonnam National University Medical School, 42, Jaebong-ro, Dong-Ku, Gwangju, 501-757, Korea
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Meidani M, Rostami M, Hemmati S, Ashrafi F, Gholamnezhad M, Emadi M, Ghasemian R, Ahmadian M. Screening and evaluation of chronic and occult Hepatitis B in chemo - radiotherapy patients with cancer. Adv Biomed Res 2016; 5:85. [PMID: 27274500 PMCID: PMC4879852 DOI: 10.4103/2277-9175.182216] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2014] [Accepted: 08/04/2014] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND Hepatitis B virus infection (HBV) and its complications is one of the most serious problems of the health system in many parts of the world. In the present study, we will assess chronic and occult HBV and isolated anti-Hepatitis B core antigen whose screening and evaluation is not routine in different populations. MATERIALS AND METHODS This descriptive analytical study was conducted on 213 patients undergoing chemotherapy - radiotherapy referred to the hematology - oncology clinics of Isfahan, Iran in 2012. In order to determine the serum levels of hepatitis B surface antigen (HbSAg), Hepatitis B Antigen and Antibody (HBCAb), aspartate aminotransferase (AST), alanine transaminase (ALT) and Alkaline phosphatase (ALK.P), venous blood samples were obtained. If the HBCAb sample was positive, another sample of the serum was sent to the laboratory to perform polymerase chain reaction and to determine viral load. RESULTS The mean age of the patients was 47.7 ± 9 years, with an age range of 27 -73 years; 98 (46%) and 115 (54%) cases were male and female, respectively, with mean age of 51.9 ± 8.3 and 44.1 ± 8.1 years, and there was no significant difference (P < 0.001). The mean level of liver enzymes including AST, ALT and ALK.P were 34.2 ± 36.02, 38.9 ± 47.1 and 252.1 ± 234.7, respectively. Two cases were HbSAg positive (0.9%) and six cases were HBCAb positive (2.8%) and HbSAg negative. Three cases had a high viral load at the rate of starting treatment among positive anti-HBC patients. CONCLUSION Because occult hepatitis is investigated less commonly in routine studies, it seems that screening and evaluating its prevalence is useful in the management of patients.
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Affiliation(s)
- Mohsen Meidani
- Department of Infectious Diseases, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Mojtaba Rostami
- Department of Infectious Diseases, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Simin Hemmati
- Department of Radiotherapy, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Farzaneh Ashrafi
- Department of Hematology, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Mohammad Gholamnezhad
- Department of Infectious Diseases, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Maryam Emadi
- Department of Biology, Shahrekord Azad University, Shahrekord, Iran
| | - Rasoul Ghasemian
- Department of Internal Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Mehdi Ahmadian
- Department of Internal Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
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Law ST, Lee MK, Lee AS, Tung Y, Li KK. Comparison of clinical efficacy and renal safety of telbivudine and entecavir in chronic hepatitis B patients receiving cytotoxic chemotherapy. J Dig Dis 2016; 17:325-33. [PMID: 27085094 DOI: 10.1111/1751-2980.12349] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/08/2015] [Revised: 02/23/2016] [Accepted: 04/12/2016] [Indexed: 01/10/2023]
Abstract
OBJECTIVE Limited data is available on the clinical outcomes of telbivudine (LdT) and entecavir (ETV) in pre-emptive antiviral chemoprophylaxis. This study aimed to evaluate the clinical efficacy and renal safety of LdT and ETV in patients with chronic hepatitis B (CHB) who received cytotoxic chemotherapy. METHODS Altogether 290 treatment-naïve CHB patients undergoing intense chemotherapy were enrolled to receive daily 600 mg of LdT or 0.5 mg of ETV as pre-emptive antiviral chemoprophylaxis. RESULTS The ETV group had significantly higher proportion of patients with undetectable hepatitis B viral (HBV) DNA load compared with LdT at week 24 (73.0% vs 50.3%, P = 0.000). The cumulative rates of virological breakthrough in the LdT and ETV groups were 9.15% and 3.65% at the second year of therapy, respectively (P = 0.059), which was associated with detectable HBV DNA at week 24 (P = 0.000). The MELD score of the LdT group was significantly lower than that of the ETV group after the first year (4.53 vs 7.53, P = 0.002) and the second year (1.96 vs 7.09, P = 0.000) of antiviral therapy. Moreover, the estimated glomerular filtration rate (eGFR) was significantly improved in the LdT group than in the ETV group after two years of antiviral therapy. CONCLUSION LdT has a lower clinical efficacy in viral suppression than ETV, but LdT is associated with greater extent of improvement in liver and renal functions of patients in pre-emptive prophylaxis for cytotoxic chemotherapy.
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Affiliation(s)
- Siu-Tong Law
- Departments of Medicine and Geriatrics, Tuen Mun Hospital, Tuen Mun, Hong Kong SAR, China
| | - Ming Kai Lee
- Departments of Medicine and Geriatrics, Tuen Mun Hospital, Tuen Mun, Hong Kong SAR, China
| | - Ann Shing Lee
- Department of Oncology, Tuen Mun Hospital, Tuen Mun, Hong Kong, SAR, China
| | - Yuk Tung
- Department of Oncology, Tuen Mun Hospital, Tuen Mun, Hong Kong, SAR, China
| | - Kin Kong Li
- Departments of Medicine and Geriatrics, Tuen Mun Hospital, Tuen Mun, Hong Kong SAR, China
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