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Ye X, Xiong W, Xu X, Zeng J, Xie H, Li B, He B, Chen L, Mo Q. Cost-benefit analysis of serological and nucleic acid testing for hepatitis B virus in blood donors in southern China. BMC Infect Dis 2024; 24:909. [PMID: 39223540 PMCID: PMC11370271 DOI: 10.1186/s12879-024-09786-z] [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: 03/16/2024] [Accepted: 08/21/2024] [Indexed: 09/04/2024] Open
Abstract
BACKGROUND Most Chinese blood centers have implemented mini pool (MP) HBV nucleic acid testing (NAT) together with HBsAg ELISA in routine blood donor screening for HBV infection since 2015, and a few centers upgraded MP to individual donation (ID) NAT screening recently, raising urgent need for cost-benefit analysis of different screening strategies. In an effort to prevent transfusion-transmitted infections (TTIs) for HBV, cost-benefit analyses of three different screening strategies: HBsAg alone, HBsAg plus MP NAT and HBsAg plus ID NAT were performed in blood donors from southern China where HBV infection was endemic. METHODS MP-6 HBV NAT and ID NAT were adopted in parallel to screen blood donors for further comparative analysis. On the basis of screening data and the documented parameters, the number of window period (WP) infection, HBV acute infection, chronic hepatitis B infection (CHB) and occult hepatitis B infection (OBI) was evaluated, and the potential prevented HBV TTIs and benefits of these three strategies were predicted based on cost-benefit analysis by an estimation model. RESULTS Of 132,323 donations, the yield rate for HBsAg-/DNA + screened by ID NAT (0.12%) was significantly higher than that by MP NAT (0.058%, P < 0.05). Furthermore, the predicted transfusion-transmitted HBV cases prevented was 1.25 times more by ID NAT compared to MP-6 NAT. The cost-benefit ratio of the universal HBsAg screening, HBsAg plus ID NAT and HBsAg plus MP NAT were 1:58, 1:27 and 1:22, respectively. CONCLUSIONS Universal HBsAg ELISA screening in combination with HBV ID NAT or MP-6 NAT strategies was highly cost effective in China. To further improve blood safety, HBsAg plus HBV DNA ID NAT screening should be considered in HBV endemic regions/countries.
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Affiliation(s)
- Xianlin Ye
- Department of Laboratory, Shenzhen Blood Center, Shenzhen, Guangdong, 518035, China
| | - Wen Xiong
- Department of Laboratory, Shenzhen Blood Center, Shenzhen, Guangdong, 518035, China
| | - Xiaoxuan Xu
- Department of Laboratory, Shenzhen Blood Center, Shenzhen, Guangdong, 518035, China
| | - Jinfeng Zeng
- Department of Laboratory, Shenzhen Blood Center, Shenzhen, Guangdong, 518035, China
| | - He Xie
- The Hospital of Xidian Group, Xi'an, Shaanxi, 710077, China
| | - Bin Li
- The Joint-laboratory of Transfusion-transmitted Diseases (TTDs) between Institute of Blood Transfusion (IBT), Chinese Academy of Medical Sciences (CAMS) and Nanning Blood Center, Nanning Blood Center, Nanning, Guangxi, 530003, China
| | - Baoren He
- The Joint-laboratory of Transfusion-transmitted Diseases (TTDs) between Institute of Blood Transfusion (IBT), Chinese Academy of Medical Sciences (CAMS) and Nanning Blood Center, Nanning Blood Center, Nanning, Guangxi, 530003, China
| | - Limin Chen
- The Hospital of Xidian Group, Xi'an, Shaanxi, 710077, China.
- The Joint-laboratory of Transfusion-transmitted Diseases (TTDs) between Institute of Blood Transfusion (IBT), Chinese Academy of Medical Sciences (CAMS) and Nanning Blood Center, Nanning Blood Center, Nanning, Guangxi, 530003, China.
- Provincial Key Laboratory for Transfusion-transmitted Infectious Diseases, Institute of Blood Transfusion (IBT), Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Chengdu, Sichuan, 610052, China.
| | - Qiuhong Mo
- The Joint-laboratory of Transfusion-transmitted Diseases (TTDs) between Institute of Blood Transfusion (IBT), Chinese Academy of Medical Sciences (CAMS) and Nanning Blood Center, Nanning Blood Center, Nanning, Guangxi, 530003, China.
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Alkhazashvili M, Bloch EM, Shadaker S, Kuchuloria T, Getia V, Turdziladze A, Armstrong PA, Gamkrelidze A. Advancing blood transfusion safety using molecular detection in the country of Georgia. Transfus Clin Biol 2023; 30:307-313. [PMID: 36907246 PMCID: PMC10958484 DOI: 10.1016/j.tracli.2023.03.002] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2022] [Revised: 03/06/2023] [Accepted: 03/08/2023] [Indexed: 03/13/2023]
Abstract
BACKGROUND In 2015, the country of Georgia initiated its hepatitis C virus (HCV) elimination program. Given a high background incidence of HCV infection, centralized nucleic acid testing (NAT) of blood donations was prioritized for implementation. STUDY DESIGN AND METHODS Multiplex NAT screening for HIV, HCV and hepatitis B virus (HBV) was launched in January 2020. An analysis was conducted of serological and NAT donor/donation data for the first year of screening (through December 2020). RESULTS A total of 54,116 donations representing 39,164 unique donors were evaluated. Overall, 671 donors (1.7%) tested positive for at least one infectious marker by serology or NAT, with the highest prevalence among donors aged 40-49 years (2.5%; n = 200), male (1.9%; n = 524), replacement (2.8%; n = 153) and first time (2.1%; n = 642) donors. Sixty donations were seronegative but NAT positive, and therefore would not have been found by traditional serology testing alone. These were more likely among female vs. male (adjusted odds ratio [aOR] 2.06; 95% confidence interval [95%CI]: 1.05-4.05), paid (aOR 10.15; 95%CI: 2.80-36.86) or voluntary (aOR 4.30; 95%CI: 1.27-14.56) vs replacement, and repeat vs. first time (aOR 13.98; 95%CI: 4.06-48.12) donors. On repeat serological testing (including HBV core antibody [HBcAb] testing), 6 HBV + donations, 5 HCV + donations and 1 HIV + donations were deemed NAT yield (detected through the implementation of NAT, and would have otherwise been missed by serology screening alone). CONCLUSION This analysis offers a regional model for NAT implementation, demonstrating the feasibility and clinical utility in a nationwide blood program.
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Affiliation(s)
- Maia Alkhazashvili
- National Center for Disease Control and Public Health of Georgia, Tbilisi, Georgia; The University of Georgia, School of Health Sciences, Tbilisi, Georgia.
| | - Evan M Bloch
- Johns Hopkins University School of Medicine, Baltimore, United States
| | - Shaun Shadaker
- Division of Viral Hepatitis, National Center for HIV, Viral Hepatitis, STD and TB Prevention, CDC, Atlanta, United States
| | | | - Vladimer Getia
- National Center for Disease Control and Public Health of Georgia, Tbilisi, Georgia
| | | | - Paige A Armstrong
- Johns Hopkins University School of Medicine, Baltimore, United States
| | - Amiran Gamkrelidze
- National Center for Disease Control and Public Health of Georgia, Tbilisi, Georgia; The University of Georgia, School of Health Sciences, Tbilisi, Georgia
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Sarowar A, Hirode G, Janssen HLA, Feld JJ. Controversies in Treating Chronic Hepatitis B Virus Infection: Discordant Serologic Results. Clin Liver Dis 2021; 25:805-816. [PMID: 34593154 DOI: 10.1016/j.cld.2021.06.007] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Despite effective vaccines and approved therapeutic agents, hepatitis B virus (HBV) remains a prevalent global health problem. Current guidelines rely on a combination of serologic, virological, and biochemical markers to identify the phase in the natural history of chronic HBV infection. Discordant serologic results can occur, which may lead to misclassification. Commonly encountered results that differ from the typical profiles seen in chronic HBV infection are described. For each scenario, the frequency of occurrence, possible explanations, and recommendations for clinical management are discussed. Recognition of discordant serologic findings is crucial for optimal clinical decision.
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Affiliation(s)
- Arif Sarowar
- Toronto Centre for Liver Disease, University Health Network, 200 Elizabeth Street, Toronto, Ontario M5G 2C4, Canada
| | - Grishma Hirode
- Toronto Centre for Liver Disease, University Health Network, 200 Elizabeth Street, Toronto, Ontario M5G 2C4, Canada
| | - Harry L A Janssen
- Toronto Centre for Liver Disease, University Health Network, 200 Elizabeth Street, Toronto, Ontario M5G 2C4, Canada
| | - Jordan J Feld
- Toronto Centre for Liver Disease, University Health Network, 200 Elizabeth Street, Toronto, Ontario M5G 2C4, Canada.
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Bloch EM, Kipiani E, Shadaker S, Alkhazashvili M, Gvinjilia L, Kuchuloria T, Chitadze N, Keating SM, Gamkrelidze A, Turdziladze A, Getia V, Nasrullah M, Averhoff F, Izoria M, Skaggs B. Blood transfusion safety in the country of Georgia: collateral benefit from a national hepatitis C elimination program. Transfusion 2020; 60:1243-1252. [PMID: 32542715 DOI: 10.1111/trf.15815] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2020] [Revised: 03/14/2020] [Accepted: 03/23/2020] [Indexed: 01/24/2023]
Abstract
BACKGROUND In April 2015, the government of Georgia (country) initiated the world's first national hepatitis C elimination program. An analysis of blood donor infectious screening data was conducted to inform a strategic plan to advance blood transfusion safety in Georgia. STUDY DESIGN AND METHODS Descriptive analysis of blood donation records (2015-2017) was performed to elucidate differences in demographics, donor type, remuneration status, and seroprevalence for infectious markers (hepatitis C virus antibody [anti-HCV], human immunodeficiency virus [HIV], hepatitis B virus surface antigen [HBsAg], and Treponema pallidum). For regression analysis, final models included all variables associated with the outcome in bivariate analysis (chi-square) with a p value of less than 0.05. RESULTS During 2015 to 2017, there were 251,428 donations in Georgia, representing 112,093 unique donors; 68.5% were from male donors, and 51.2% of donors were paid or replacement (friends or family of intended recipient). The overall seroprevalence significantly declined from 2015 to 2017 for anti-HCV (2.3%-1.4%), HBsAg (1.5%-1.1%), and T. pallidum (1.1%-0.7%) [p < 0.0001]; the decline was not significant for HIV (0.2%-0.1%). Only 41.0% of anti-HCV seropositive donors underwent additional testing to confirm viremia. Infectious marker seroprevalence varied by age, sex, and geography. In multivariable analysis, first-time and paid donor status were associated with seropositivity for all four infectious markers. CONCLUSION A decline during the study period in infectious markers suggests improvement in blood safety in Georgia. Areas that need further improvement are donor recruitment, standardization of screening and diagnostic follow-up, quality assurance, and posttransfusion surveillance.
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Affiliation(s)
- Evan M Bloch
- Johns Hopkins School of Medicine, Baltimore, Maryland, USA
| | - Eteri Kipiani
- National Center for Disease Control and Public Health, Tbilisi, Georgia
| | - Shaun Shadaker
- Division of Viral Hepatitis National Center for HIV, Hepatitis, STD&TB Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
| | | | - Lia Gvinjilia
- South Caucasus Office of the U.S. Centers for Disease Control (CDC), Tbilisi, Georgia
| | - Tinatin Kuchuloria
- South Caucasus Office of the U.S. Centers for Disease Control (CDC), Tbilisi, Georgia
| | | | - Sheila M Keating
- Vitalant Research Institute (formerly Blood Systems Research Institute), San Francisco, California, USA.,University of California San Francisco, San Francisco, California, USA
| | | | | | - Vladimer Getia
- National Center for Disease Control and Public Health, Tbilisi, Georgia
| | - Muazzam Nasrullah
- Division of Viral Hepatitis National Center for HIV, Hepatitis, STD&TB Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
| | - Francisco Averhoff
- Division of Viral Hepatitis National Center for HIV, Hepatitis, STD&TB Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
| | - Mariam Izoria
- National Center for Disease Control and Public Health, Tbilisi, Georgia
| | - Beth Skaggs
- South Caucasus Office of the U.S. Centers for Disease Control (CDC), Tbilisi, Georgia
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El-Adly AM, Meshaal AK, Mekky MA, Hetta HF, Wardany AA, El-Shanawany AA. Diagnostic strategy for occult hepatitis B virus infection and its clinical implications among patients at Upper Egypt. JOURNAL OF RADIATION RESEARCH AND APPLIED SCIENCES 2020. [DOI: 10.1080/16878507.2020.1740396] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Affiliation(s)
- A. M. El-Adly
- Department of Botany and Microbiology, Faculty of Science, Al-Azhar University, Assiut, Egypt
| | - A. K. Meshaal
- Department of Botany and Microbiology, Faculty of Science, Al-Azhar University, Assiut, Egypt
| | - M. A. Mekky
- Department of Tropical Medicine and Gastroenterology, Faculty of Medicine, Assiut University Hospital, Assiut, Egypt
| | - H. F. Hetta
- Department of Medical Microbiology and Immunology, Faculty of Medicine, Assiut University, Assiut, Egypt
- Department of Internal Medicine, University of Cincinnati Medical Center, Cincinnati, OH, USA
| | - A. A. Wardany
- Department of Botany and Microbiology, Faculty of Science, Al-Azhar University, Assiut, Egypt
| | - A. A. El-Shanawany
- Department of Botany and Microbiology, Faculty of Science, Al-Azhar University, Assiut, Egypt
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Daniel K, Palavecino EL, Nunez M. Low Yield of Hepatitis B Virus DNA Testing in the Absence of Surface Antigen. Am J Med Qual 2020; 36:68. [PMID: 32126795 DOI: 10.1177/1062860620908059] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Affiliation(s)
- Krupa Daniel
- Wake Forest School of Medicine, Winston Salem, NC
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Samardžija M, Drenjančević D, Miletić M, Slavulj B, Jukić I, Zibar L, Mihaljević S, Ferenac Kiš M, Samardžija M. THE IMPACT OF POSITIVE ANTI-HBC MARKER ON PERMANENT DEFERRAL OF VOLUNTARY BLOOD DONORS IN EASTERN CROATIA AND ESTIMATION OF OCCULT HEPATITIS B VIRUS INFECTION RATE. Acta Clin Croat 2020; 59:126-134. [PMID: 32724283 PMCID: PMC7382879 DOI: 10.20471/acc.2020.59.01.15] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022] Open
Abstract
Recently an increase has been reported in the number of HBV transmissions from anti-HBc positive blood donors that were repeatedly negative in HBsAg and nucleic acid testing using the most sensitive tests available. The aim of the study was to show the effect of anti-HBc antibody testing performed in 2006 on permanent deferral of voluntary blood donors (VBDs), and to estimate occult hepatitis B infection (OBI) rate in this population after the introduction of mandatory molecular testing in the 2013-2016 period. More than 30,000 blood donations collected during the 2005-2007 period and more than 14,000 VBDs having donated blood during the 2013-2016 period after the introduction of molecular testing from eastern Croatia were included in the study. Serologic testing was performed with HBsAg assay throughout the study period, and anti-HBc assay was only performed in 2006. As part of the confirmatory algorithm testing, all HBsAg positive and unclear results were tested with molecular tests. Anti-HBc prevalence among VBDs in 2006 was 1.5%, with a rate of 1:197, whereas HBsAg prevalence was stable from 2005 to 2007 (0.04%, 0.1% and 0.1%, respectively). The calculated OBI rate from 2013 to 2016 was 1:30,250. Ten of 161 (12.4%) VBDs had serologic anti-HBc-only pattern. Anti-HBc testing in 2006 resulted in statistically more deferrals of VBDs compared to 2005 and 2007, and to the rest of Republic of Croatia. The strategy of universal anti-HBc testing of VBDs in addition to the existing HBsAg and molecular screening could be an additional measure to prevent HBV transmission by blood and blood components.
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Affiliation(s)
| | - Domagoj Drenjančević
- 1Nord-Trøndelag Hospital Trust, Namsos Hospital, Department of Internal Medicine, Namsos, Norway; 2Osijek University Hospital Centre, Department of Transfusion Medicine, Osijek, Croatia; 3Faculty of Medicine, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia; 4Croatian Institute of Transfusion Medicine, Zagreb, Croatia; 5Merkur University Hospital, Department of Internal Medicine, Zagreb, Croatia; 6Osijek University Hospital Centre, Department of Internal Medicine, Division of Gastroenterology and Hepatology, Osijek, Croatia
| | - Manuela Miletić
- 1Nord-Trøndelag Hospital Trust, Namsos Hospital, Department of Internal Medicine, Namsos, Norway; 2Osijek University Hospital Centre, Department of Transfusion Medicine, Osijek, Croatia; 3Faculty of Medicine, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia; 4Croatian Institute of Transfusion Medicine, Zagreb, Croatia; 5Merkur University Hospital, Department of Internal Medicine, Zagreb, Croatia; 6Osijek University Hospital Centre, Department of Internal Medicine, Division of Gastroenterology and Hepatology, Osijek, Croatia
| | - Blaženka Slavulj
- 1Nord-Trøndelag Hospital Trust, Namsos Hospital, Department of Internal Medicine, Namsos, Norway; 2Osijek University Hospital Centre, Department of Transfusion Medicine, Osijek, Croatia; 3Faculty of Medicine, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia; 4Croatian Institute of Transfusion Medicine, Zagreb, Croatia; 5Merkur University Hospital, Department of Internal Medicine, Zagreb, Croatia; 6Osijek University Hospital Centre, Department of Internal Medicine, Division of Gastroenterology and Hepatology, Osijek, Croatia
| | - Irena Jukić
- 1Nord-Trøndelag Hospital Trust, Namsos Hospital, Department of Internal Medicine, Namsos, Norway; 2Osijek University Hospital Centre, Department of Transfusion Medicine, Osijek, Croatia; 3Faculty of Medicine, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia; 4Croatian Institute of Transfusion Medicine, Zagreb, Croatia; 5Merkur University Hospital, Department of Internal Medicine, Zagreb, Croatia; 6Osijek University Hospital Centre, Department of Internal Medicine, Division of Gastroenterology and Hepatology, Osijek, Croatia
| | - Lada Zibar
- 1Nord-Trøndelag Hospital Trust, Namsos Hospital, Department of Internal Medicine, Namsos, Norway; 2Osijek University Hospital Centre, Department of Transfusion Medicine, Osijek, Croatia; 3Faculty of Medicine, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia; 4Croatian Institute of Transfusion Medicine, Zagreb, Croatia; 5Merkur University Hospital, Department of Internal Medicine, Zagreb, Croatia; 6Osijek University Hospital Centre, Department of Internal Medicine, Division of Gastroenterology and Hepatology, Osijek, Croatia
| | - Silvio Mihaljević
- 1Nord-Trøndelag Hospital Trust, Namsos Hospital, Department of Internal Medicine, Namsos, Norway; 2Osijek University Hospital Centre, Department of Transfusion Medicine, Osijek, Croatia; 3Faculty of Medicine, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia; 4Croatian Institute of Transfusion Medicine, Zagreb, Croatia; 5Merkur University Hospital, Department of Internal Medicine, Zagreb, Croatia; 6Osijek University Hospital Centre, Department of Internal Medicine, Division of Gastroenterology and Hepatology, Osijek, Croatia
| | - Marina Ferenac Kiš
- 1Nord-Trøndelag Hospital Trust, Namsos Hospital, Department of Internal Medicine, Namsos, Norway; 2Osijek University Hospital Centre, Department of Transfusion Medicine, Osijek, Croatia; 3Faculty of Medicine, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia; 4Croatian Institute of Transfusion Medicine, Zagreb, Croatia; 5Merkur University Hospital, Department of Internal Medicine, Zagreb, Croatia; 6Osijek University Hospital Centre, Department of Internal Medicine, Division of Gastroenterology and Hepatology, Osijek, Croatia
| | - Marina Samardžija
- 1Nord-Trøndelag Hospital Trust, Namsos Hospital, Department of Internal Medicine, Namsos, Norway; 2Osijek University Hospital Centre, Department of Transfusion Medicine, Osijek, Croatia; 3Faculty of Medicine, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia; 4Croatian Institute of Transfusion Medicine, Zagreb, Croatia; 5Merkur University Hospital, Department of Internal Medicine, Zagreb, Croatia; 6Osijek University Hospital Centre, Department of Internal Medicine, Division of Gastroenterology and Hepatology, Osijek, Croatia
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van Santen DK, Boyd A, Bruisten S, Sonder GJ, Prins M, van Houdt R. Frequent delayed spontaneous seroclearance of hepatitis B virus after incident HBV infection among adult high-risk groups. J Viral Hepat 2020; 27:81-87. [PMID: 31520430 DOI: 10.1111/jvh.13205] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/03/2019] [Revised: 08/06/2019] [Accepted: 08/13/2019] [Indexed: 01/26/2023]
Abstract
High rates (~25%) of developing chronic hepatitis B virus (HBV) infection (hepatitis B surface antigen (HBsAg)-positive for > 6 months following infection) have been observed in people who use drugs (PWUD) and men who have sex with men (MSM). We aimed to estimate the frequency of delayed HBsAg seroclearance, along with its determinants, and time to delayed HBsAg seroclearance. Data were used from MSM and PWUD enrolled in the Amsterdam Cohort Studies (1985-2002) who had anti-hepatitis B core antibody seroconversion. Potential determinants for standard HBsAg seroclearance, delayed HBsAg seroclearance and chronic HBV were examined using multinominal logistic regression. Time to HBsAg seroclearance was estimated using Kaplan-Meier curves. A total of 147 incident HBV infections occurred during follow-up. On initial HBsAg testing after infection (6-12 months), 42 (29%) were HBsAg-positive and 105 (71%) were HBsAg-negative ('standard HBsAg seroclearance'). Of the 42 initially HBsAg-positive individuals, 22 subsequently tested HBsAg-negative (of whom 7 (31.8%) were HBV DNA positive at last visit, suggesting occult HBV). Overall, 15 became HBsAg-negative and HBV DNA-negative ('delayed HBsAg seroclearance'), while 27 remained HBsAg and/or HBV DNA-positive ('chronic HBV'). The 5-year cumulative probability of delayed HBsAg seroclearance was 41.6% for initially HBsAg-positive individuals. Delayed HBsAg seroclearance and remaining chronically infected were associated with younger age and HIV/hepatitis C virus (HCV)-co-infection. In conclusion, delayed HBsAg seroclearance is common in these key adult populations at-risk for HBV, while proportion developing HBV chronicity (18%) is still higher compared to the general population (~5%). Given the proportion of individuals with occult HBV infection and that HCV direct-acting antivirals can lead to HBV reactivation, HBV DNA testing in HCV co-infected MSM/PWUD are warranted prior to treatment initiation.
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Affiliation(s)
- Daniela K van Santen
- Department of Infectious Diseases, Public Health Service of Amsterdam, Amsterdam, The Netherlands
| | - Anders Boyd
- Department of Infectious Diseases, Public Health Service of Amsterdam, Amsterdam, The Netherlands.,INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique, Saint Antoine Hospital, AP-HP, Sorbonne Université, Paris, France
| | - Sylvia Bruisten
- Department of Infectious Diseases, Public Health Service of Amsterdam, Amsterdam, The Netherlands.,Department of Infectious Diseases, Amsterdam Infection and Immunity Institute (AI&II), Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Gerard Jb Sonder
- Department of Infectious Diseases, Public Health Service of Amsterdam, Amsterdam, The Netherlands.,Department of Infectious Diseases, Amsterdam Infection and Immunity Institute (AI&II), Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Maria Prins
- Department of Infectious Diseases, Public Health Service of Amsterdam, Amsterdam, The Netherlands.,Department of Infectious Diseases, Amsterdam Infection and Immunity Institute (AI&II), Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Robin van Houdt
- Department of Medical Microbiology and Infection Control, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
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9
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Wang J, Zhang P, Zeng J, Du P, Zheng X, Ye X, Zhu W, Fu Y, Candotti D, Allain JP, Li C, Li T. Occurrence of occult hepatitis B virus infection associated with envelope protein mutations according to anti-HBs carriage in blood donors. Int J Infect Dis 2019; 92:38-45. [PMID: 31877352 DOI: 10.1016/j.ijid.2019.12.026] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2019] [Revised: 12/16/2019] [Accepted: 12/18/2019] [Indexed: 02/07/2023] Open
Abstract
OBJECTIVES Occult hepatitis B virus infection (OBI) carries a risk of hepatitis B virus (HBV) transmission and hepatocellular carcinoma. As previous studies have had a limited sample size, the characteristics of OBI with genotype B and C (OBIB and OBIC) mutations relating to hepatitis B surface antibody (anti-HBs) elicited by vaccination or a limited host immune response to HBV have not been fully explored. METHODS In this study, the occurrence of OBIB or OBIC strains associated with envelope protein (pre-S/S) amino acid substitutions obtained from 99 blood donors stratified according to anti-HBs carriage were characterized extensively. RESULTS According to the presence of anti-HBs within each genotype, the number and frequency of substitution sites specific for anti-HBs(-) OBIB were higher than those specific for anti-HBs(+) OBIB strains (67 vs 31; 117 vs 41), but the reverse pattern was found in OBIC strains (3 vs 24; 3 vs 26). Mutations pre-s1T68I and sQ129R/L were found uniquely in 15-25% of anti-HBs(+) OBIB carriers and mutation pre-s1A54E was found preferentially in anti-HBs(+) OBIC, while 17 substitutions were found preferentially in 11-38% of anti-HBs(-) OBIB strains. In the major hydrophilic region (MHR) region, mutations sS167 in OBIB, sT118 in OBIC, and sA166 in both genotypes were possibly immune-induced escape mutation sites. CONCLUSIONS Several mutations in pre-S/S of OBI appeared to be associated with carrier anti-HBs pressure, which might be risk factors for potential reactivation of viruses under anti-HBs selection in OBI carriers.
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Affiliation(s)
- Jiawen Wang
- Department of Transfusion Medicine, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, China
| | - Panli Zhang
- Department of Transfusion Medicine, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, China
| | | | - Peng Du
- Department of Transfusion Medicine, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, China
| | - Xin Zheng
- Shenzhen Blood Center, Shenzhen, China
| | | | | | | | - Daniel Candotti
- Department of Blood Transmitted Agents, National Institute of Blood Transfusion, Paris, France
| | - Jean-Pierre Allain
- Department of Transfusion Medicine, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, China; Emeritus Professor, University of Cambridge, Cambridge, UK
| | - Chengyao Li
- Department of Transfusion Medicine, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, China; School of Public Health, Southern Medical University, Guangzhou, China.
| | - Tingting Li
- Department of Transfusion Medicine, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, China.
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Sánchez Ibáñez J, Vilarrodona Serrat A, Seoane Pillado T, Rodriguez Aierbe C, Villalba Montoro R, Calvo Benito J, Pevida Lopez M, Fernández Paneque S, Vuelta Lopez E, Martínez Lorenzo MJ, González Romero M, Cañizares Castellanos A, Sauleda Oliveras S. Evaluation of occult hepatitis B infection in tissue donors: a multicenter analysis in Spain. Cell Tissue Bank 2019; 20:513-526. [PMID: 31451994 DOI: 10.1007/s10561-019-09784-5] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2019] [Accepted: 08/21/2019] [Indexed: 12/31/2022]
Abstract
Traditionally, when antibody to the Hepatitis B core antigen (anti-HBc) and antibody to the Hepatitis B surface antigen (anti-HBs) are positive, the donor is considered suitable. However, the literature contains cases with this profile and circulating hepatitis B virus DNA. The aim of the study is to analyze the incidence of occult hepatitis B virus infection (OBI). Retrospective data were evaluated for deceased tissue donors in ten Tissue Establishments (Spain) during 2017. The data included demographic data and the serological markers for hepatitis B that each tissue establishment performed. A total number of 1933 tissue donors were evaluated. A total of 180 donors were excluded: 6 (0.3%) with Hepatitis B surface antigen (HBs positive), and 174 in which DNA testing was not performed. Anti-HBc was positive in 175 donors (10%), in which anti-HBs was negative in 30 (17.1%) and positive in 145 (82.9%). In total, 27 donors with DNA positive (1.5%) were found, of which 3 of 117 donors (1.7%) showed anti-HBc negative and anti-HBs positive (> 10 IU/ml), 4 of 30 donors (13.3%) showed anti-HBc positive and anti-HBs negative and 20 of 145 donors (13.8%) showed both anti-HBc and anti-HBs positive. The highest probability of finding DNA occurs when anti-HBc is positive, regardless of the presence of anti-HBs. In our study, the probability of OBI was 1.5%. The classic concept that when anti-HBc and anti-HBs are positive (even with a titer of over 100 IU/ml) the donor can be accepted should, therefore, be reconsidered, and DNA testing should be mandatory.
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Affiliation(s)
- Jacinto Sánchez Ibáñez
- Cryobiology Unit - Tissue Establishment, Complejo Hospitalario Universitario de A Coruña, A Coruña University Hospital, Avenida As Xubias 84, 15006, A Coruña, Spain.
| | | | - Teresa Seoane Pillado
- Clinical Epidemiology and Biostatistics Research Group, Instituto de Investigacion Biomedica de A Coruña, A Coruña University Hospital, A Coruña, Spain
| | | | | | - Javier Calvo Benito
- Tissue Establishment, Balearic Island Blood and Tissue Bank Foundation (FBSTIB), Cell Therapy and Tissue Engineering Group (TERCIT), Balearic Islands Institute of Health Research (IdISBa), Palma de Mallorca, Spain
| | - Marta Pevida Lopez
- Tissue Establishment, Centro Comunitario de Sangre y Tejidos del Principado de Asturias, Oviedo, Spain
| | | | - Elena Vuelta Lopez
- Tissue Establishment, Establecimiento de Tejidos Humanos, Fundación Clinica San Francisco, León, Spain
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11
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Ye X, Li T, Shao W, Zeng J, Hong W, Lu L, Zhu W, Li C, Li T. Nearly half of Ultrio plus NAT non-discriminated reactive blood donors were identified as occult HBV infection in South China. BMC Infect Dis 2019; 19:574. [PMID: 31269905 PMCID: PMC6609378 DOI: 10.1186/s12879-019-4215-9] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2019] [Accepted: 06/23/2019] [Indexed: 12/19/2022] Open
Abstract
Background Blood donor plasma samples were detected by the Ultrio Plus NAT system for HBV, HCV and HIV-1 in Shenzhen blood center, China. Reactive samples underwent further discriminatory testing of a single virus by the same methodology. A large number of cases of non-discriminated reactive (NDR) donors were found, leaving potential risk of transmitting HBV if not deferrals. This study identified those non-discriminated samples. Methods The NDR plasma samples from blood donation screening were detected and classified by additional molecular and serological tests. Molecular characterizations of DNA+ NDR were determined by sequencing analysis. Results A number of 259 (0.21%) NDR plasma samples from screening of 123,280 eligible blood donors were detected, which presented a higher rate (91.1%) of anti-HBc reactivity and nearly half (46.7%) of HBV DNA+ that classified as occult HBV infection (OBI). Most OBI strains were wild-type HBV, but some substitutions V168A, S174 N, V177A, Q129R/L/H, G145A/R in S region of genotype B (OBIB) and T47K/V/A, P49H/L, Q101R/H/K, S174 N, L175S, V177A, T118 M/R/K, G145R/A/K/E, R160K/N in S region of genotype C (OBIC) strains were identified in high frequency. Conclusion Nearly half of NDR blood samples were identified as OBI, in which a number of important mutations were detected. NDR donation might have potential risk for HBV transmission, but need to be further investigated.
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Affiliation(s)
| | - Tong Li
- Shenzhen Blood Centre, Shenzhen, China
| | - Wen Shao
- Shenzhen Blood Centre, Shenzhen, China
| | | | | | - Liang Lu
- Shenzhen Blood Centre, Shenzhen, China
| | | | - Chengyao Li
- Department of Transfusion Medicine, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, China
| | - Tingting Li
- Department of Transfusion Medicine, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, China.
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12
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Seed CR, Allain J, Lozano M, Laperche S, Gallian P, Gross S, Kwon S, Oh E, Kim J, Chua SS, Lam S, Ang AL, Tsoi W, Hewitt PE, Davison KL, Tettmar K, O'Flaherty N, Boland F, Williams P, Pomeroy L, Wendel S, Fachini R, Scuracchio P, Carminato P, Fearon M, O'Brien SF, Delage G, Kiely P, Hoad V, Matsubayashi K, Satake M, Taira R, Stramer SL, Sauleda S, Bes M, Piron M, El Ekiaby M, Vermeulen M, Levičnik Stezinar S, Nograšek P, Jarvis LM, Petrik J, Charlewood R, Flanagan P, Grabarczyk P, Kopacz A, Łętowska M, Seifried E, Schmidt M. International Forum on Occult hepatitis B infection and transfusion safety. Vox Sang 2019; 114:e1-e35. [DOI: 10.1111/vox.12743] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Affiliation(s)
| | | | | | - Syria Laperche
- Institut National de la Transfusion Sanguine Département des agents transmissibles par le sang Centre National de Référence Risques Infectieux Transfusionnels 6 rue Alexandre Cabanel Paris 75015 France
| | - Pierre Gallian
- Etablissement Français du Sang 20 Avenue du Stade de France La Plaine Saint‐Denis 93218 France
| | - Sylvie Gross
- Etablissement Français du Sang 20 Avenue du Stade de France La Plaine Saint‐Denis 93218 France
| | - So‐Yong Kwon
- Jungbu Blood Laboratory Center Korean Red Cross 22 Songchonam‐ro, Daedeok‐gu Daejeon Korea
| | - E.Y. Oh
- Jungbu Blood Laboratory Center Korean Red Cross 22 Songchonam‐ro, Daedeok‐gu Daejeon Korea
| | - J.N. Kim
- Division of Human Blood Safety Surveillance Korea Centers for Disease Control and Prevention Osong Korea
| | - Sze Sze Chua
- Health Sciences Authority Blood Services Group 11 Outram Road Singapore 169078 Singapore
| | - Sally Lam
- Health Sciences Authority Blood Services Group 11 Outram Road Singapore 169078 Singapore
| | - Ai Leen Ang
- Health Sciences Authority Blood Services Group 11 Outram Road Singapore 169078 Singapore
| | - Wai‐Chiu Tsoi
- Hong Kong Red Cross Blood Transfusion Service 15 King's Park Rise Kowloon Hong Kong China
| | | | - Katy L. Davison
- NHS Blood and Transplant Public Health England Epidemiology Unit Colindale Avenue Colindale UK
| | - Kate Tettmar
- NHS Blood and Transplant Colindale Centre Charcot Road Colindale UK
| | - Niamh O'Flaherty
- Irish Blood Transfusion Service National Blood Centre St. James's Gate Dublin 8 Ireland
| | - Fiona Boland
- Irish Blood Transfusion Service National Blood Centre St. James's Gate Dublin 8 Ireland
| | - Padraig Williams
- Irish Blood Transfusion Service National Blood Centre St. James's Gate Dublin 8 Ireland
| | - Louise Pomeroy
- Irish Blood Transfusion Service National Blood Centre St. James's Gate Dublin 8 Ireland
| | - Silvano Wendel
- Hospital Sirio Libanês Rua Adma Jafet 91 São Paulo 01308‐050 Brasil
| | - Roberta Fachini
- Hospital Sirio Libanês Rua Adma Jafet 91 São Paulo 01308‐050 Brasil
| | | | | | | | | | - Gilles Delage
- Héma Québec 4045 boul. Cote‐Vertu ville Saint Laurent QC Canada
| | - Philip Kiely
- Australian Red Cross Blood Service 100‐154 Batman Street West Melbourne VIC 3003 Australia
| | - Veronica Hoad
- Australian Red Cross Blood Service 290 Wellington Street Perth WA 6000 Australia
| | - Keiji Matsubayashi
- Central Blood Institute Blood Service Headquarters Japanese Red Cross Society 2‐1‐67 Tatsumi, Koto‐ku Tokyo Japan
| | - Masahiro Satake
- Central Blood Institute Blood Service Headquarters Japanese Red Cross Society 2‐1‐67 Tatsumi, Koto‐ku Tokyo Japan
| | - Rikizo Taira
- Technical Department Blood Service Headquarters Japanese Red Cross Society 1‐2‐1 Shibakoen, Minato‐ku Tokyo Japan
| | | | - Silvia Sauleda
- Transfusion Safety Laboratory Banc de Sang i Teixits Doctor Frederic Duran i Jorda Building, Passeig Taulat, 116 08005 Barcelona Spain
| | - Marta Bes
- Transfusion Safety Laboratory Banc de Sang i Teixits Doctor Frederic Duran i Jorda Building, Passeig Taulat, 116 08005 Barcelona Spain
| | - Maria Piron
- Transfusion Safety Laboratory Banc de Sang i Teixits Doctor Frederic Duran i Jorda Building, Passeig Taulat, 116 08005 Barcelona Spain
| | - Magdy El Ekiaby
- Shabrawishi Hospital Blood Transfusion Centre Finni Square Dokki, Giza Egypt
| | - Marion Vermeulen
- The South African National Blood Service 1 Constantia Boulevard, ConstantiaKloof Roodepoort, Gauteng South Africa
| | | | - Polona Nograšek
- Blood Transfusion Centre of Slovenia Šlajmerjeva 6 SI‐1000 Ljubljana Slovenia
| | - Lisa M. Jarvis
- Scottish National Blood Transfusion Service The Jack Copland Centre 52 Research Avenue North Edinburgh EH14 4BE UK
| | - Juraj Petrik
- Scottish National Blood Transfusion Service The Jack Copland Centre 52 Research Avenue North Edinburgh EH14 4BE UK
| | - Richard Charlewood
- New Zealand Blood Service 71 Great South Road Epsom, Auckland New Zealand
| | - Peter Flanagan
- New Zealand Blood Service 71 Great South Road Epsom, Auckland New Zealand
| | - Piotr Grabarczyk
- Department of Virology Institute of Hematology and Transfusion Medicine Gandhi Str. 14th 02 776 Warsaw Poland
| | - Aneta Kopacz
- Department of Virology Institute of Hematology and Transfusion Medicine Gandhi Str. 14th 02 776 Warsaw Poland
| | - Magdalena Łętowska
- Department of Transfusion Institute of Hematology and Transfusion Medicine Gandhi Str. 14th 02 776 Warsaw Poland
| | - Erhard Seifried
- German Red Cross Institute for Transfusion medicine and Immunohematology German Red Cross Baden‐Wuerrtemberg – Hesse Goethe University Frankfurt Sandhof Street 1 60528 Frankfurt
| | - Michael Schmidt
- German Red Cross Institute for Transfusion medicine and Immunohematology German Red Cross Baden‐Wuerrtemberg – Hesse Goethe University Frankfurt Sandhof Street 1 60528 Frankfurt
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13
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Alabdallat NG, Bin Dukhyil AAA. Significance of HBV NAT Among HBs Antigen-Negative Blood Donors in Saudi Arabia. Lab Med 2018; 49:342-346. [PMID: 29767761 DOI: 10.1093/labmed/lmy023] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
Background Bloodborne hepatitis B virus (HBV) transmission from asymptomatic donors with acute HBV infections who have undetectable surface antigen of HBV (HBsAg), or from donors with chronic infections in whom serological markers were not detected, could cause residual infections leading to relevant transfusion-transmitted infections (RTTIs). HBV nucleic acid testing (NAT) can detect HBV DNA in the HBsAg-negative and total hepatitis B core antibody (anti-HBc)-negative window period of infection and in chronic cases. Objective To assess the presence or absence of HBV DNA in blood donors with HBsAg negativity. Methods We collected 3014 blood specimens from volunteer blood donors at the blood bank of King Khalid University Hospital in Riyadh, Saudia Arabia. Specimens from each donor were tested for HBsAg, anti-HBc, and hepatitis B surface antibody (anti-HBs) by commercial immunoassays and for qualitative assessments of HBV-DNA by HBV-NAT testing. Results Of the 3014 donors, 7 (0.23%) tested positive for HBsAg and anti-HBc, 1 for HBsAg (0.03%) only, and of those 264 donors (8.8%) for anti-HBc. Of these last, 6.9% also tested positive for anti-HBs and 1.9% tested negative for anti-HBs. HBV-NAT testing was reactive in 75.0% of subjects who tested HBsAg positive, and nonreactive in 100% of subjects who tested anti-HBc positive/HBsAg negative (with or without anti-HBs). Among 2742 donors who tested seronegative, 1 specimen was determined to be reactive via HBV-NAT testing. Conclusions The frequency of HBV DNA in blood donors who tested seronegative was low. This finding may indicate the significance of the HBV NAT technique in reducing the residual risk of transfusion-transmitted HBV infection.
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Affiliation(s)
- Nessrin Ghazi Alabdallat
- Department of Medical Laboratory Sciences, College of Applied Medical Sciences, Majmaah University, Al Majma'ah, Saudi Arabia
| | - Abdul Aziz A Bin Dukhyil
- Department of Medical Laboratory Sciences, College of Applied Medical Sciences, Majmaah University, Al Majma'ah, Saudi Arabia
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14
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Samiee S, Kanavi MR, Javadi MA, Bagheri A, Balagholi S, Hashemi MS. Real Time Polymerase Chain Reaction for Hepatitis B Screening in Donor Corneas in the Central Eye Bank of Iran. J Ophthalmic Vis Res 2018; 13:392-396. [PMID: 30479707 PMCID: PMC6210878 DOI: 10.4103/jovr.jovr_157_17] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2017] [Accepted: 01/31/2018] [Indexed: 01/13/2023] Open
Abstract
PURPOSE The aim of this study was to report the results of the use of real-time polymerase chain reaction (PCR) for the diagnosis of hepatitis B virus (HBV) infection in cornea donors at the Central Eye Bank of Iran. METHODS Between 2014 and 2016, all cornea donors that had negative screening serologic results for hepatitis B (HB) surface antigen, HB surface antibody (Ab), hepatitis C virus Ab, human immune deficiency virus Ab, human T-cell leukemia virus Ab, and syphilis, and positive serology for HB core Ab were subjected to real-time PCR with a detection limit of 400 IU/mL to identify HBV DNA. Positive results for HBV DNA were considered occult HBV infections in these donors. RESULTS Over the 3-year period, 122 out of 10448 cornea donors had negative screening serologic tests outside of HB core Ab. Of which, 90 cases were subjected to real-time PCR. Occult HBV was detected in 11 cases (12.2%), resulting in the rejection of the corresponding corneas. The remaining 79 cases (87.8%) had negative results for HBV DNA and the corresponding corneas were used for transplantation. CONCLUSION Implementation of PCR for the detection of occult HBV in cornea donors is necessary to not only increase the security level of cornea donation but also minimize the rejection rate of donors that have isolated HB core Ab reactivity.
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Affiliation(s)
- Shahram Samiee
- Iranian Blood Transfusion Organization Research Center, Tehran, Iran
| | - Mozhgan Rezaei Kanavi
- Ocular Tissue Engineering Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
- Central Eye Bank of Iran, Tehran, Iran
| | - Mohammad Ali Javadi
- Ophthalmic Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Abouzar Bagheri
- Department of Clinical Biochemistry and Genetics, Molecular and Cell Biology Research Center, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
| | - Sahar Balagholi
- Ocular Tissue Engineering Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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15
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Tang X, Allain JP, Wang H, Rong X, Chen J, Huang K, Xu R, Wang M, Huang J, Liao Q, Shan Z, Luo S, Li T, Li C, Fu Y. Incidence of hepatitis B virus infection in young Chinese blood donors born after mandatory implementation of neonatal hepatitis B vaccination nationwide. J Viral Hepat 2018; 25:1008-1016. [PMID: 29624818 DOI: 10.1111/jvh.12901] [Citation(s) in RCA: 30] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2017] [Accepted: 02/16/2018] [Indexed: 01/17/2023]
Abstract
This study was carried out to determine the incidence of hepatitis B virus (HBV) infection in the young generation born after mandatory implementation of hepatitis B vaccination since 1992. Repeat blood donors born between 1992 and 1997 were enrolled, who gave blood at least twice during the past 3 years. Donors were tested for HBV infection markers of HBsAg, anti-HBc, anti-HBs and viral DNA by immunoassays (EIAs) and nucleic acid tests (NAT). A total of 14 937 pre-donation screening qualified young repeat donors aged 18-23 years were tested with 9 (0.06%) being HBsAg by EIA and 10 (1:1494) HBV DNA positive by Ultrio NAT (10.4 IU/mL), respectively. HBV DNA was further detected in 1:192 (9/1732) anti-HBc+ repeat donors with Ultrio Plus NAT (3.4 IU/mL). Most cases were identified as occult HBV infection (OBI). Of 14 937 repeat donors, 20.9% were anti-HBc+ positive, while approximately 50% of 12 024 repeat donors were anti-HBs negative or had levels <100 IU/L. HBsAg+ or OBI strains were classified as wild type of genotype B or genotype C. Incident HBV infection in repeat donors was approximately 1:18.5 person-years (1.1%/year) but significantly less frequent in donors with confirmed HBV vaccination (2.4%-3.3%) than those unsure of vaccination status (10.5%; P = .0023). Hepatitis B virus vaccination appears largely protective of HBV infection, but incidence of infections increases in young adults with mostly undetectable or low anti-HBs or occasionally high anti-HBs. A boost of hepatitis B vaccine for adolescents prior to age 18 years may reduce HBV infection, and implementation of more sensitive NAT in blood donation screening may improve HBV safety in blood transfusion.
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Affiliation(s)
- X Tang
- Department of Transfusion Medicine, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, China.,Guangzhou Blood Center, Guangzhou, China
| | - J-P Allain
- Department of Transfusion Medicine, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, China.,University of Cambridge, Cambridge, UK
| | - H Wang
- Guangzhou Blood Center, Guangzhou, China
| | - X Rong
- Guangzhou Blood Center, Guangzhou, China
| | - J Chen
- Guangzhou Blood Center, Guangzhou, China
| | - K Huang
- Guangzhou Blood Center, Guangzhou, China
| | - R Xu
- Guangzhou Blood Center, Guangzhou, China
| | - M Wang
- Guangzhou Blood Center, Guangzhou, China
| | - J Huang
- Guangzhou Blood Center, Guangzhou, China
| | - Q Liao
- Guangzhou Blood Center, Guangzhou, China
| | - Z Shan
- Guangzhou Blood Center, Guangzhou, China
| | - S Luo
- Department of Transfusion Medicine, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, China
| | - T Li
- Department of Transfusion Medicine, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, China
| | - C Li
- Department of Transfusion Medicine, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, China.,School of Public Health, Southern Medical University, Guangzhou, China
| | - Y Fu
- Department of Transfusion Medicine, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, China.,Guangzhou Blood Center, Guangzhou, China
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16
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Zhou S, Li T, Allain JP, Zhou B, Zhang Y, Zhong M, Fu Y, Li C. Low occurrence of HBsAg but high frequency of transient occult HBV infection in vaccinated and HBIG-administered infants born to HBsAg positive mothers. J Med Virol 2017; 89:2130-2137. [PMID: 28543299 DOI: 10.1002/jmv.24861] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2017] [Accepted: 05/01/2017] [Indexed: 01/05/2023]
Affiliation(s)
- Shan Zhou
- Department of Transfusion Medicine; Southern Medical University; Guangzhou China
| | - Tingting Li
- Department of Transfusion Medicine; Southern Medical University; Guangzhou China
| | - Jean-Pierre Allain
- Department of Transfusion Medicine; Southern Medical University; Guangzhou China
- Department of Hematology; University of Cambridge; Cambridge United Kingdom
| | - Bin Zhou
- Department of Infectious Diseases; Nanfang Hospital; Southern Medical University; Guangzhou China
| | - Yuming Zhang
- Department of Paediatrics; Nanfang Hospital; Southern Medical University; Guangzhou China
| | - Mei Zhong
- Department of Obstetrics and Gynecology; Nanfang Hospital; Southern Medical University; Guangzhou China
| | | | - Chengyao Li
- Department of Transfusion Medicine; Southern Medical University; Guangzhou China
- School of Public Health and Tropical Medicine; Southern Medical University; Guangzhou China
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17
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Low Prevalence of Occult Hepatitis B Infection Among Blood Donors in Beirut, Lebanon: Reconsider the Deferral Strategy of Anti-HBc Positive Blood Donors. HEPATITIS MONTHLY 2017. [DOI: 10.5812/hepatmon.14250] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/13/2023]
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18
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Safic Stanic H, Babic I, Maslovic M, Dogic V, Bingulac-Popovic J, Miletic M, Jurakovic-Loncar N, Vuk T, Strauss-Patko M, Jukic I. Three-Year Experience in NAT Screening of Blood Donors for Transfusion Transmitted Viruses in Croatia. Transfus Med Hemother 2017; 44:415-420. [PMID: 29344018 DOI: 10.1159/000457965] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2016] [Accepted: 01/22/2017] [Indexed: 12/12/2022] Open
Abstract
Background Croatia implemented individual donation (ID)-NAT testing of blood donors in 2013 for three viruses HBV, HCV, and HIV-1 as a mandatory test for all blood donors. This study assessed the impact of NAT screening 3 years after its implementation. Methods A total of 545,463 donations were collected and screened for HBV, HCV, and HIV-1 using the Procleix Ultrio Plus Assay. All initially reactive (IR) NAT samples were retested in triplicate and, if repeatedly reactive (RR), NAT discriminatory assay (dNAT) was performed. ID-NAT positive donations were confirmed by RT-PCR on the COBAS AmpliPrep/TaqMan platform. Results Out of 545,463 samples tested, 108 (0.02%) were RR in NAT. There were 82 (75,9%) HBV reactive, 16 (14.8%) HCV reactive, and 10 (9.3%) HIV-1 reactive samples. 51 (47.2%) samples were ID-NAT positive only. Out of these 51 NAT yield cases, 1 window period HIV-1 and 50 occult HBV infections (OBI) were determined. There were only two potential HBV DNA transmissions from OBI donors. Conclusion The implementation of NAT screening for three viruses has improved blood safety in Croatia. During the 3-year period, 1 window period HIV-1 and a number of occult HBV donations were identified.
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Affiliation(s)
| | - Ivana Babic
- Croatian Institute of Transfusion Medicine (CITM), Zagreb, Croatia
| | | | - Vesna Dogic
- Croatian Institute of Transfusion Medicine (CITM), Zagreb, Croatia
| | | | - Manuela Miletic
- Croatian Institute of Transfusion Medicine (CITM), Zagreb, Croatia
| | | | - Tomislav Vuk
- Croatian Institute of Transfusion Medicine (CITM), Zagreb, Croatia
| | | | - Irena Jukic
- Croatian Institute of Transfusion Medicine (CITM), Zagreb, Croatia.,Josip Juraj Strossmayer University of Osijek, Osijek, Croatia
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19
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Wang Z, Zeng J, Li T, Zheng X, Xu X, Ye X, Lu L, Zhu W, Yang B, Allain JP, Li C. Prevalence of hepatitis B surface antigen (HBsAg) in a blood donor population born prior to and after implementation of universal HBV vaccination in Shenzhen, China. BMC Infect Dis 2016; 16:498. [PMID: 27647214 PMCID: PMC5028969 DOI: 10.1186/s12879-016-1834-2] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2016] [Accepted: 09/14/2016] [Indexed: 02/06/2023] Open
Abstract
Background Neonatal hepatitis B vaccination program at birth has been implemented nationwide since 1992 in China. However, current HBV prevalence status in blood donors has not been entirely examined, which may impact HBV safety in blood donations as the vaccinees over 18 years old progressively become the majority population of blood donors. Methods In this study, 569,145 blood donors were screened for HBsAg by rapid tests and enzyme immunoassays, among them 475,538 blood samples with negative HBsAg were further screened for HBV DNA by nucleic acid testing between 2005 and 2014 at Shenzhen blood center. Results An overall 2.3 % HBsAg prevalence was found in the blood donor population during the past 10 years (2.86 % in 2005, 1.76 % in 2010, and 2.79 % in 2014, respectively). HBsAg seroconversion occurred in 0.37 % of repeat-donors. When stratified by age, the prevalence of HBsAg was found significantly higher in younger donors age 18–25 years (2.73 %) than in those 26–35 years (2.13 %), 36–45 years (2.03 %) and 46–58 years (1.71 %) (P < 0.001), unexpectedly suggesting that younger donors remained at risk of chronic HBV infection. Assuming that donors aged 18–22 born before or after 1992 were non-vaccinated and vaccinated, respectively, HBsAg prevalence was higher in first-time donors born ≥1992 (3.9 %) than prior to 1992 (3.5 %, P = 0.005). The incidence of HBV infection in the 5-year period examined was significantly lower in repeat-donors born ≥1992 (0.27 %) than prior to 1992 (0.6 %, P = 0.008). The yield of HBV DNA+/HBsAg- donors was 1:3,302, including 1:4,486 occult infections and 1:43,231 window period infections. Conclusion Young blood donors born after implementation of universal HBV vaccination in China presented higher prevalence of HBsAg but lower incidence of HBsAg seroconversion than older, presumed unvaccinated, donors. HBV vaccine boosting for adolescents at 15–17 years old prior to reaching blood donor age might help improve blood safety.
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Affiliation(s)
- Zhen Wang
- Department of Transfusion Medicine, Southern Medical University, Guangzhou, 510515, China
| | | | - Tingting Li
- Department of Transfusion Medicine, Southern Medical University, Guangzhou, 510515, China
| | - Xin Zheng
- Baoan Central Blood Station, Shenzhen, China
| | | | | | - Liang Lu
- Shenzhen Blood Center, Shenzhen, China
| | | | | | - Jean-Pierre Allain
- Department of Transfusion Medicine, Southern Medical University, Guangzhou, 510515, China.,Department of Haematology, University of Cambridge, Cambridge, UK
| | - Chengyao Li
- Department of Transfusion Medicine, Southern Medical University, Guangzhou, 510515, China. .,School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou, China.
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20
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Seed CR, Kiely P, Hoad VC, Keller AJ. Refining the risk estimate for transfusion-transmission of occult hepatitis B virus. Vox Sang 2016; 112:3-8. [PMID: 27564651 DOI: 10.1111/vox.12446] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2016] [Revised: 08/01/2016] [Accepted: 08/01/2016] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND OBJECTIVES We previously published a model to estimate the residual risk (RR) for occult hepatitis B infection (OBI) in the absence of universal anti-HBc testing. To incorporate new information on the epidemiology of OBI, we describe model refinements and estimate a more accurate HBV RR due to OBI in Australia. MATERIALS AND METHODS In our original model, the OBI risk, p(OBI), was defined by the rate of 'non-detection' by the HBV DNA screening test in use, p(NAT non-detection), and the average infectivity of blood components from OBI donors, p(transmission). We revised the model by integrating three refinements: that donations with anti-HBs levels of >10 IU/l, or donations solely for manufactured plasma products, be excluded from the risk calculation, and an updated estimate of p(transmission). RESULTS Refining our OBI RR model resulted in a more than 10-fold reduction in the reported RR risk to recipients from OBI in our donor population. Based on the use of a common data set, the mean OBI RR risk decreased from 1 in 374 354 donations (95% CI: 1 in 191 940-1 072 681) to 1 in 3 984 033 (95% CI: 1 in 1 146 188-65 268 257) for the refined model. CONCLUSION Our model refinements provide a more realistic measure of the HBV RR in the donor population. Unlike the previous model, the new model demonstrates that the risk of HBV due to OBI in the Australian blood donor population is negligible, and further potentially cost-ineffective risk management strategies are not currently warranted.
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Affiliation(s)
- C R Seed
- Australian Red Cross Blood Service, Perth, WA, Australia
| | - P Kiely
- Australian Red Cross Blood Service, Melbourne, Vic., Australia
| | - V C Hoad
- Australian Red Cross Blood Service, Perth, WA, Australia
| | - A J Keller
- Australian Red Cross Blood Service, Perth, WA, Australia
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Characterisation and follow-up study of occult hepatitis B virus infection in anti-HBc-positive qualified blood donors in southern China. BLOOD TRANSFUSION = TRASFUSIONE DEL SANGUE 2016; 15:6-12. [PMID: 27416568 DOI: 10.2450/2016.0268-15] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Subscribe] [Scholar Register] [Received: 10/10/2015] [Accepted: 01/28/2016] [Indexed: 01/01/2023]
Abstract
BACKGROUND Most major Chinese blood centres look for hepatitis B surface antigen (HBsAg) and perform nucleic acid testing to screen blood for hepatitis B virus infection. The search for antibodies to the core of hepatitis B virus (anti-HBc) has not been implemented because it would lead to a high rate of discarded blood units. The aim of this study was to evaluate the prevalence of occult HBV infection among anti-HBc-positive qualified blood donors in southern China. MATERIALS AND METHODS We tested anti-HBc-positive blood donations negative for HBsAg and HBV DNA by standard NAT from Shenzhen for the presence of HBV DNA by sensitive nested and quantitative polymerase chain reactions. Anti-HBs titres were quantified. HBV DNA-positive donors were traced and followed-up. RESULTS Of the 1,033 qualified donors, 47.4% (95% CI: 44.4 to 50.5%) carried anti-HBc as evidence of exposure to HBV. The rate of anti-HBc positivity increased steadily with age, ranging from 32.6% in the age group <30 years to 69.8% in the age group <50 years (p<0.001). Of the 1,033 donors, 777 (75.2%; 95% CI: 72.4 to 77.8%) carried anti-HBs (>10 IU/L). HBV DNA was detected in 14 donors who were anti-HBc-positive, HBsAg-negative and negative by routine NAT. Seven of those 14 specimens had an anti-HBs titre above 100 mIU/mL. The prevalence of OBI in anti-HBc-positive qualified blood donors was 2.86% (95% CI: 1.57 to 4.75%). Eight of the 14 OBI cases were genotype B and one was genotype C; 7/14 cases were followed-up, one case converted to anti-HBe. HBV DNA became undetectable in all follow-up samples. DISCUSSION A small proportion of anti-HBc-positive qualified donors carry HBV DNA after HBsAg and NAT screening. This finding suggests the possibility of HBV transmission from asymptomatic donors, especially in areas of high HBV prevalence. More sensitive NAT rather than anti-HBc testing should be considered to improve blood safety.
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An apparent low level of hepatitis B surface antigen (HBsAg) in the presence of significant viral replication. J Clin Virol 2015; 77:111-4. [PMID: 26705961 DOI: 10.1016/j.jcv.2015.11.030] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2015] [Revised: 11/24/2015] [Accepted: 11/25/2015] [Indexed: 01/13/2023]
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Kishk R, Nemr N, Elkady A, Mandour M, Aboelmagd M, Ramsis N, Hassan M, Soliman N, Iijima S, Murakami S, Tanaka Y, Ragheb M. Hepatitis B surface gene variants isolated from blood donors with overt and occult HBV infection in north eastern Egypt. Virol J 2015; 12:153. [PMID: 26420301 PMCID: PMC4588243 DOI: 10.1186/s12985-015-0389-y] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2015] [Accepted: 09/21/2015] [Indexed: 01/15/2023] Open
Abstract
BACKGROUND Major hydrophilic region in genomic HBV extending from aa99 to aa169, clustered with a highly conformational epitope, is critical to the antigenicity of hepatitis B surface antigen (HBsAg) and may affect the diagnosis of HBV in HBV screening test. So, this study aimed to characterize variants of S gene product of hepatitis B virus (HBV) isolated from patients with overt or occult HBV infection in north-eastern Egypt. METHODS The study included sera of two different groups of volunteer blood donors (VBDs), 82 with overt HBV that were positive for HBsAg and anti-HBc and 343 donors negative for HBsAg eligible for donation. Of the latter group, only 44 were positive for anti-HBc. All anti-HBc positive sera were subjected to HBV DNA detection and partial sequence analysis targeting the HBV S gene. RESULTS HBV DNA was detected in 22.7 % of HBsAg-/anti-HBc + (10/44 patients) and in 90 % of HBsAg + donors (74/82 patients) with significant statistical difference (P = 0.0001). Phylogenetic analysis showed that HBV strains retrieved from both groups were of genotype D. Amino acid escape mutation T125M was detected in only 2 samples of the occult infection group and in none of the overt group (P = 0.01). Different amino acid substitutions were identified in overt infection group: S143L/T (16.2 %, 12/74) and P120T/S (2.7 %, 2/74). Q129R was significantly more frequent in cases with occult HBV infection (40 %, 4/10) than overt group (6.8 %, 5/74) (P = 0.01). CONCLUSIONS HBV genotype D predominated both in patients with overt and occult HBV infection. Different profiles of amino acid substitutions in the major hydrophilic region were seen in these two groups in Egypt.
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Affiliation(s)
- Rania Kishk
- Department of Microbiology and Immunology, Faculty of Medicine, Suez Canal University, El Salam District, Ismaïlia, Egypt.
| | - Nader Nemr
- Department of Endemic and Infectious diseases, Faculty of Medicine, Suez Canal University, El Salam District, Ismaïlia, Egypt.
| | - Abeer Elkady
- Department of Clinical and Chemical Pathology, Faculty of Medicine, South Valley University, Qena, Egypt.
- Department of Virology and Liver Unit, Nagoya City University Graduate School of Medical Science, Nagoya, 467-8601, Japan.
| | - Mohamed Mandour
- Department of Clinical Pathology, Faculty of Medicine, Suez Canal University, El Salam District, Ismaïlia, Egypt.
| | - Mohamed Aboelmagd
- Department of Endemic and Infectious diseases, Faculty of Medicine, Suez Canal University, El Salam District, Ismaïlia, Egypt.
| | - Nevene Ramsis
- Department of Clinical Pathology, Faculty of Medicine, Suez Canal University, El Salam District, Ismaïlia, Egypt.
| | - Mohamed Hassan
- Department of Endemic and Infectious diseases, Faculty of Medicine, Suez Canal University, El Salam District, Ismaïlia, Egypt.
| | - Nashaat Soliman
- Department of Endemic and Infectious diseases, Faculty of Medicine, Suez Canal University, El Salam District, Ismaïlia, Egypt.
| | - Sayuki Iijima
- Department of Virology and Liver Unit, Nagoya City University Graduate School of Medical Science, Nagoya, 467-8601, Japan.
| | - Shuko Murakami
- Department of Virology and Liver Unit, Nagoya City University Graduate School of Medical Science, Nagoya, 467-8601, Japan.
| | - Yasuhito Tanaka
- Department of Virology and Liver Unit, Nagoya City University Graduate School of Medical Science, Nagoya, 467-8601, Japan.
| | - Mostafa Ragheb
- Department of Internal Medicine, Faculty of Medicine, Aljouf University, Sakaka, KSA, Saudi Arabia.
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Correlation of the content of hepatitis B core antigen in peripheral blood mononuclear cells with HBV virus load. Diagn Microbiol Infect Dis 2015; 85:154-8. [PMID: 26680298 DOI: 10.1016/j.diagmicrobio.2015.09.017] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2015] [Revised: 09/22/2015] [Accepted: 09/24/2015] [Indexed: 12/18/2022]
Abstract
The dysfunction of peripheral blood mononuclear cell (PBMC) plays an important role in hepatitis B virus (HBV) chronic infection and tolerance. This study is aimed to explore the changes of expression and distribution of Hepatitis B virus core antigen (HBcAg) in the PBMCs of patients infected with chronic hepatitis B virus by using confocal laser scanning microscopy (CLSM). The levels of HBcAg in PBMCs were correlated with the HBV load in serum, and the change of HBcAg distribution in different PBMC organelles may represent various HBV infection states. HBcAg was mainly distributed in the nuclei of PBMC in the cases of immune tolerance and no inflammatory activity. Taken together, our data suggest that the measurement of HBcAg and its distribution in PBMCs using CLSM may serve as an alternative approach to monitor HBV load and the immune states of HBV infection with ease of using and improved sensitivity.
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Confirmation and follow up of initial "NAT yields": Prospective study from a tertiary healthcare center in India. Transfus Apher Sci 2015; 54:242-7. [PMID: 26321477 DOI: 10.1016/j.transci.2015.08.003] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2015] [Revised: 08/11/2015] [Accepted: 08/14/2015] [Indexed: 11/22/2022]
Abstract
BACKGROUND In India variable rate of "NAT yield" has been demonstrated in several published reports. This study was performed with the objective to know the rate of "true NAT yield" in blood donors by confirmation with supplementary tests and follow up of initial "NAT yield" donors. MATERIALS AND METHODS A total of 48,441 blood donors were tested for HIV, HBV and HCV with enhanced chemiluminescence and ID-NAT. To know the true NAT yield status confirmation of NAT yield donors was done as with an array of serological tests, repeat ID-NAT and alternate NAT. RESULTS The cumulative initial "NAT yield" rate was 1:4404 (11/48,441). Seven of 11 initial "NAT yields" were for hepatitis B whereas two each were in HIV and HCV. Among the 11 "NAT-yield" donors, eight donors were followed-up for confirmation. Out of these eight donors only 4 were found to be true HBV NAT yields. Out of four true NAT yields two were window period donations while the other two were occult hepatitis B infection with anti-HBcore total positive. CONCLUSION Our findings suggest that all "initial NAT yields" may not be "true NAT yields". We would also like to suggest that to demonstrate the true "NAT yield" status supplementary tests and donor follow up are important to differentiate true NAT yields.
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26
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Oluyinka OO, Tong HV, Bui Tien S, Fagbami AH, Adekanle O, Ojurongbe O, Bock CT, Kremsner PG, Velavan TP. Occult Hepatitis B Virus Infection in Nigerian Blood Donors and Hepatitis B Virus Transmission Risks. PLoS One 2015; 10:e0131912. [PMID: 26148052 PMCID: PMC4492924 DOI: 10.1371/journal.pone.0131912] [Citation(s) in RCA: 46] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2015] [Accepted: 06/08/2015] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Occult hepatitis B virus infection (OBI) characterized by the absence of detectable HBsAg remains a potential threat in blood safety. We investigated the actual prevalence, viral factors and genotype of OBI infections in Nigerian blood donors. METHODS Serum collected from two blood banks were reconfirmed as HBsAg seronegative by ELISA. Forty HBsAg positive samples were employed as controls. HBV-DNA was amplified from all donors and viral loads were determined using quantitative real-time PCR. Antibodies to the HBV core, surface and HBe antigen (anti-HBc,anti-HBs,HBeAg) were measured. The PreS/S and PreC/C regions of the HBV genome were sequenced. RESULTS Of the 429 blood donors, 72(17%) were confirmed as OBI by DNA detection in different reference labs and excluded the concern of possible contamination. Of the 72 OBI samples, 48(67%) were positive for anti-HBc, 25(35%) positive for anti-HBs, and 2(3%) positive for HBeAg. Of the 72 OBI samples, 31(43%) were seropositive for either anti-HBc, anti-HBs or HBeAg, 21 (30%) positive for both anti-HBc and anti-HBs,one positive for both anti-HBc and HBeAg. None of the OBI samples were positive for all three serological markers. The viral load was <50copies/ml in the OBI samples and genotype E was predominant. The L217R polymorphism in the reverse transcriptase domain of the HBV polymerase gene was observed significantly higher in OBI compared with HBsAg positive individuals (P<0.0001). CONCLUSION High incidence of OBI is relevant in high endemic areas worldwide and is a general burden in blood safety. This study signifies the high prevalence of OBI and proposes blood donor samples in Nigeria should be pre-tested for OBI by nucleic acid testing (NAT) and/or anti-HBc prior to transfusion to minimize the HBV infection risk.
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Affiliation(s)
- Opaleye O. Oluyinka
- Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany
- Deparment of Medical Microbiology and Parasitology, Ladoke Akintola University of Technology, Ogbomosho, Nigeria
| | - Hoang Van Tong
- Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany
| | - Sy Bui Tien
- Department of Infectious Diseases, Robert Koch Institute, Berlin, Germany
- Department of Molecular Biology, 108 Military Central Hospital, Hanoi, Vietnam
| | - Ademola H. Fagbami
- Deparment of Medical Microbiology and Parasitology, Ladoke Akintola University of Technology, Ogbomosho, Nigeria
| | | | - Olusola Ojurongbe
- Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany
- Deparment of Medical Microbiology and Parasitology, Ladoke Akintola University of Technology, Ogbomosho, Nigeria
| | - C.-Thomas Bock
- Department of Infectious Diseases, Robert Koch Institute, Berlin, Germany
- Department of Molecular Pathology, University of Tübingen, Tübingen, Germany
| | - Peter G. Kremsner
- Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany
| | - Thirumalaisamy P. Velavan
- Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany
- Fondation Congolaise pour la Recherche Medicale, Brazzaville, Republic of Congo
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Zhou L, Gong R, Lu X, Zhang Y, Tang J. Development of a Multiplex Real-Time PCR Assay for the Detection of Treponema pallidum, HCV, HIV-1, and HBV. Jpn J Infect Dis 2015; 68:481-7. [PMID: 25866106 DOI: 10.7883/yoken.jjid.2014.416] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Abstract
Treponema pallidum, hepatitis C virus (HCV), human immunodeficiency virus (HIV)-1, and hepatitis B virus (HBV) are major causes of sexually transmitted diseases passed through blood contact. The development of a sensitive and efficient method for detection is critical for early diagnosis and for large-scale screening of blood specimens in China. This study aims to establish an assay to detect these pathogens in clinical serum specimens. We established a TaqMan-locked nucleic acid (LNA) real-time polymerase chain reaction (PCR) assay for rapid, sensitive, specific, quantitative, and simultaneous detection and identification. The copy numbers of standards of these 4 pathogens were quantified. Standard curves were generated by determining the mean cycle threshold values versus 10-fold serial dilutions of standards over a range of 10(6) to 10(1) copies/μL, with the lowest detection limit of the assay being 10(1) copies/μL. The assay was applied to 328 clinical specimens and compared with enzyme-linked immunosorbent assay (ELISA) and commercial nucleic acid testing (NAT) methods. The assay identified 39 T. pallidum-, 96 HCV-, 13 HIV-1-, 123 HBV-, 5 HBV/HCV-, 1 T. pallidum/HBV-, 1 HIV-1/HCV-, and 1 HIV-1/T. pallidum-positive specimens. The high sensitivity of the assay confers strong potential for its use as a highly reliable, cost-effective, and useful molecular diagnostic tool for large-scale screening of clinical specimens. This assay will assist in the study of the pathogenesis and epidemiology of sexually transmitted blood diseases.
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Affiliation(s)
- Li Zhou
- ABSL-III Laboratory at Center for Animal Experiment, State Key Laboratory of Virology, Wuhan University School of Medicine
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Seo DH, Whang DH, Song EY, Han KS. Occult hepatitis B virus infection and blood transfusion. World J Hepatol 2015; 7:600-606. [PMID: 25848484 PMCID: PMC4381183 DOI: 10.4254/wjh.v7.i3.600] [Citation(s) in RCA: 45] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/23/2014] [Revised: 11/29/2014] [Accepted: 12/17/2014] [Indexed: 02/06/2023] Open
Abstract
Transfusion-transmitted infections including hepatitis B virus (HBV) have been a major concern in transfusion medicine. Implementation of HBV nucleic acid testing (NAT) has revealed occult HBV infection (OBI) in blood donors. In the mid-1980s, hepatitis B core antibody (HBc) testing was introduced to screen blood donors in HBV non-endemic countries to prevent transmission of non-A and non-B hepatitis. That test remains in use for preventing of potential transmission of HBV from hepatitis B surface antigen (HBsAg)-negative blood donors, even though anti-hepatitis C virus tests have been introduced. Studies of anti-HBc-positive donors have revealed an HBV DNA positivity rate of 0%-15%. As of 2012, 30 countries have implemented HBV NAT. The prevalence of OBI in blood donors was estimated to be 8.55 per 1 million donations, according to a 2008 international survey. OBI is transmissible by blood transfusion. The clinical outcome of occult HBV transmission primarily depends on recipient immune status and the number of HBV DNA copies present in the blood products. The presence of donor anti-HBs reduces the risk of HBV infection by approximately five-fold. The risk of HBV transmission may be lower in endemic areas than in non-endemic areas, because most recipients have already been exposed to HBV. Blood safety for HBV, including OBI, has substantially improved, but the possibility for OBI transmission remains.
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Raouf HE, Yassin AS, Megahed SA, Ashour MS, Mansour TM. Seroprevalence of occult hepatitis B among Egyptian paediatric hepatitis C cancer patients. J Viral Hepat 2015; 22:103-11. [PMID: 24754376 DOI: 10.1111/jvh.12260] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2013] [Accepted: 03/26/2014] [Indexed: 12/12/2022]
Abstract
Occult hepatitis B infection is characterized by the presence of hepatitis B virus (HBV) DNA in the serum in the absence of hepatitis B surface antigen (HBsAg). Prevalence of hepatitis C virus (HCV) infections in Egypt is among the highest in the world. In this study, we aim at analysing the rates of occult HBV infections among HCV paediatric cancer patients in Egypt. The prevalence of occult HBV was assessed in two groups of paediatric cancer patients (HCV positive and HCV negative), in addition to a third group of paediatric noncancer patients, which was used as a general control. All groups were negative for HBsAg and positive for HCV antibody. HBV DNA was detected by nested PCR and real-time PCR. HCV was detected by real-time PCR. Sequencing was carried out in order to determine HBV genotypes to all HBV patients as well as to detect any mutation that might be responsible for the occult phenotype. Occult hepatitis B infection was observed in neither the non-HCV paediatric cancer patients nor the paediatric noncancer patients but was found in 31% of the HCV-positive paediatric cancer patients. All the detected HBV patients belonged to HBV genotype D, and mutations were found in the surface genome of HBV leading to occult HBV. Occult HBV infection seems to be relatively frequent in HCV-positive paediatric cancer patients, indicating that HBsAg negativity is not sufficient to completely exclude HBV infection. These findings emphasize the importance of considering occult HBV infection in HCV-positive paediatric cancer patients especially in endemic areas as Egypt.
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Affiliation(s)
- H E Raouf
- Department of Microbiology and Immunology, Faculty of Pharmacy, Modern Sciences and Arts University, Giza, Egypt
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Kwak MS, Kim YJ. Occult hepatitis B virus infection. World J Hepatol 2014; 6:860-869. [PMID: 25544873 PMCID: PMC4269905 DOI: 10.4254/wjh.v6.i12.860] [Citation(s) in RCA: 71] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/13/2014] [Revised: 09/23/2014] [Accepted: 10/29/2014] [Indexed: 02/06/2023] Open
Abstract
Occult hepatitis B virus (HBV) infection (OBI) refers to the presence of HBV DNA in the absence of detectable hepatitis B surface antigen. Since OBI was first described in the late 1970s, there has been increasing interest in this topic. The prevalence of OBI varies according to the different endemicity of HBV infection, cohort characteristics, and sensitivity and specificity of the methods used for detection. Although the exact mechanism of OBI has not been proved, intra-hepatic persistence of viral covalently closed circular DNA under the host’s strong immune suppression of HBV replication and gene expression seems to be a cause. OBI has important clinical significance in several conditions. First, OBI can be transmitted through transfusion, organ transplantation including orthotopic liver transplantation, or hemodialysis. Donor screening before blood transfusion, prophylaxis for high-risk organ transplantation recipients, and dialysis-specific infection-control programs should be considered to reduce the risk of transmission. Second, OBI may reactivate and cause acute hepatitis in immunocompromised patients or those receiving chemotherapy. Close HBV DNA monitoring and timely antiviral treatment can prevent HBV reactivation and consequent clinical deterioration. Third, OBI may contribute to the progression of hepatic fibrosis in patients with chronic liver disease including hepatitis C. Finally, OBI seems to be a risk factor for hepatocellular carcinoma by its direct proto-oncogenic effect and by indirectly causing persistent hepatic inflammation and fibrosis. However, this needs further investigation. We review published reports in the literature to gain an overview of the status of OBI and emphasize the clinical importance of OBI.
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Zheng X, Ye X, Du P, Zeng J, Zhu W, Yang B, Li C, Allain JP. High prevalence of anti-hepatitis B core antigen in hepatitis B virus-vaccinated Chinese blood donors suggests insufficient protection but little threat to the blood supply. Transfusion 2014; 55:890-7. [PMID: 25363504 DOI: 10.1111/trf.12902] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2014] [Revised: 09/04/2014] [Accepted: 09/04/2014] [Indexed: 12/12/2022]
Abstract
BACKGROUND In East Asia, individuals systematically vaccinated at birth to hepatitis B virus (HBV) are an increasing part of the blood donor population. Their environment presents a high risk of contact with HBV. HBV vaccine efficacy and potential safety risk carried by vaccinated donors were examined. STUDY DESIGN AND METHODS A total of 2028 vaccinated blood donors were recruited in 2012 and 2013 and tested for serologic (hepatitis B surface antigen [HBsAg], antibody to hepatitis B surface antigen [anti-HBs], and antibody to hepatitis B core antigen [anti-HBc]) and molecular (HBV DNA) markers of HBV. HBsAg, anti-HBs, and viral load were quantified. RESULTS Donors 18 to 21 years systematically vaccinated at birth and 22 to 25 years and older donors had both 30.0% negative serology and 1.8% anti-HBc only but the latter group carried significantly higher prevalence of anti-HBc (p < 0.0001). Anti-HBc, mostly associated with anti-HBs, increased from 10.7% at age 18 to 31.5% at age 25. The level of anti-HBs was significantly higher in anti-HBc-positive donors than in anti-HBs-only donors (p < 0.0001). Samples from 24 donors contained low viral load (25 ± 22 IU/mL), half of them undetected by standard nucleic acid testing (NAT), and were classified as four recent infections, 17 occult HBV infections (OBI), and three primary OBIs. Eighteen of 24 carried anti-HBs; 14 of 15 strains were wild-type Genotype B and one was Genotype C. CONCLUSIONS In an environment of frequent high Genotype B or C viremia, blood donors vaccinated at birth are frequently but mildly infected: asymptomatic and normal alanine aminotransferase level, identified by anti-HBc seroconversion and boosting of anti-HBs. Low viral load and frequent anti-HBs limit transfusion risk.
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Affiliation(s)
- Xin Zheng
- Shenzhen Blood Center, Shenzhen, China.,Department of Transfusion Medicine, Southern Medical University, Guangzhou, China
| | | | - Peng Du
- Department of Transfusion Medicine, Southern Medical University, Guangzhou, China
| | | | | | | | - Chengyao Li
- Department of Transfusion Medicine, Southern Medical University, Guangzhou, China
| | - Jean-Pierre Allain
- Department of Transfusion Medicine, Southern Medical University, Guangzhou, China.,Department of Haematology, University of Cambridge, Cambridge, United Kingdom
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Albertoni G, Castelo Girão MJB, Schor N. Mini review: current molecular methods for the detection and quantification of hepatitis B virus, hepatitis C virus, and human immunodeficiency virus type 1. Int J Infect Dis 2014; 25:145-9. [PMID: 24927665 DOI: 10.1016/j.ijid.2014.04.007] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2014] [Revised: 04/01/2014] [Accepted: 04/09/2014] [Indexed: 12/11/2022] Open
Abstract
The detection of acute human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV) infection is vital for controlling the spread of HIV, HBV, and HCV to uninfected individuals. Considering that these viruses have high replication rates and are undetectable by serological markers, early detection upon transmission is crucial. Various nucleic acid assays have been developed for diagnostics and therapeutic monitoring of infections. In the past decade, rapid and sensitive molecular techniques such as PCR have revolutionized the detection of a variety of infectious viruses, including HIV, HCV, and HBV. Here, we describe two of the most commonly used licensed methods for the detection and quantification of HIV, HCV, and HBV: the cobas TaqScreen MPX (PCR) test and the Tigris System. We used transcription-mediated amplification to review and compare the development and efficiency of these technologies.
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Affiliation(s)
- Guilherme Albertoni
- Federal University of São Paulo (UNIFESP), Department of Medicine, Nephrology Division, Rua Botucatu 740, São Paulo, 04023-900, SP, Brazil; Colsan (Associação Beneficente de Coleta de Sangue), São Paulo, SP, Brazil.
| | | | - Nestor Schor
- Federal University of São Paulo (UNIFESP), Department of Medicine, Nephrology Division, Rua Botucatu 740, São Paulo, 04023-900, SP, Brazil
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Chamni N, Louisirirotchanakul S, Oota S, Sakuldamrongpanish T, Saldanha J, Chongkolwatana V, Phikulsod S. Genetic characterization and genotyping of hepatitis B virus (HBV) isolates from donors with an occult HBV infection. Vox Sang 2014; 107:324-32. [PMID: 25040474 DOI: 10.1111/vox.12178] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2014] [Revised: 05/29/2014] [Accepted: 06/12/2014] [Indexed: 12/20/2022]
Abstract
BACKGROUND AND OBJECTIVES Screening of Thai blood donors has resulted in the detection of donors with an occult HBV infection (OBI), where HBsAg is undetectable, but hepatitis B virus (HBV) DNA is present in serum in low concentrations. This study was designed to determine whether the occurrence of OBI in donors was linked to the HBV genotype and possibly to mutations in the surface (S) and core (C) gene regions. MATERIALS AND METHODS Mutations in the S and C gene regions in 48 Thai donors with OBI were mapped by sequencing. Genotyping was determined with the INNO-LiPA test and by phylogenetic analysis of sequences from the S and C genes. RESULTS The majority of OBI samples were genotype C (81·3%) with 6·3% of samples being genotype B. In addition, two genotype I isolates were identified. Mutations in the S region (100%) were found especially in loop 1 of the major hydrophilic loop (MHL) at positions I110L, T114S, T126I and S113T, whereas mutations in the C region (65%) were within the basal core promoter region (position A1762T/G1764A) and precore region (position G1896A). CONCLUSION The majority of OBI samples were HBV genotype C, although genotype I, which is newly emerging in Thailand, was also detected. The study demonstrated that OBI was probably not associated with a particular HBV genotype or with certain mutations in the S and C gene regions. However, mutations in the C gene region which could potentially impair viral replication and HBsAg production and potentially lead to OBI were identified.
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Affiliation(s)
- N Chamni
- Department of Microbiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
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Lazarevic I. Clinical implications of hepatitis B virus mutations: Recent advances. World J Gastroenterol 2014; 20:7653-7664. [PMID: 24976703 PMCID: PMC4069294 DOI: 10.3748/wjg.v20.i24.7653] [Citation(s) in RCA: 102] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2013] [Revised: 01/05/2014] [Accepted: 03/05/2014] [Indexed: 02/06/2023] Open
Abstract
Hepatitis B virus (HBV) infection is a major cause of acute and chronic hepatitis, and of its long-term complications. It is the most variable among DNA viruses, mostly because of its unique life cycle which includes the activity of error-prone enzyme, reverse transcriptase, and the very high virion production per day. In last two decades, numerous research studies have shown that the speed of disease progression, reliability of diagnostic methods and the success of antiviral therapy and immunization are all influenced by genetic variability of this virus. It was shown that mutations in specific regions of HBV genome could be responsible for unwanted clinical outcomes or evasion of detection by diagnostic tools, thus making the monitoring for these mutations a necessity in proper evaluation of patients. The success of the vaccination programs has now been challenged by the discovery of mutant viruses showing amino acid substitutions in hepatitis B surface antigen (HBsAg), which may lead to evasion of vaccine-induced immunity. However, the emergence of these mutations has not yet raised concern since it was shown that they develop slowly. Investigations of HBV genetic variability and clinical implications of specific mutations have resulted in significant advances over the past decade, particularly in regard to management of resistance to antiviral drugs. In the era of drugs with high genetic barrier for resistance, on-going monitoring for possible resistance is still essential since prolonged therapy is often necessary. Understanding the frequencies and clinical implications of viral mutations may contribute to improvement of diagnostic procedures, more proper planning of immunization programs and creating the most efficient therapeutic protocols.
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Stolz M, Tinguely C, Fontana S, Niederhauser C. Hepatitis B virus DNA viral load determination in hepatitis B surface antigen-negative Swiss blood donors. Transfusion 2014; 54:2961-7. [DOI: 10.1111/trf.12694] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2013] [Revised: 02/24/2014] [Accepted: 03/07/2014] [Indexed: 12/24/2022]
Affiliation(s)
- Martin Stolz
- Blood Transfusion Service SRC Berne; Berne Switzerland
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Kiely P, Margaritis AR, Seed CR, Yang H. Hepatitis B virus nucleic acid amplification testing of Australian blood donors highlights the complexity of confirming occult hepatitis B virus infection. Transfusion 2014; 54:2084-91. [PMID: 24650170 DOI: 10.1111/trf.12556] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2013] [Revised: 11/26/2013] [Accepted: 12/06/2013] [Indexed: 02/06/2023]
Abstract
BACKGROUND We present an analysis of the first 2 years of hepatitis B virus (HBV) nucleic acid testing (NAT) of the Australian donor population. STUDY DESIGN AND METHODS Between July 5, 2010, and July 4, 2012, all blood donations were screened for HBV DNA and hepatitis B surface antigen (HBsAg). Donors who tested HBsAg negative but HBV NAT positive were assessed as occult hepatitis B infections (OBI) if reactive for antibodies to HBV core antigen (anti-HBc). Donors who were anti-HBc reactive but with nonrepeatable or nondiscriminated NAT results were assessed as HBV inconclusive pending follow-up testing. RESULTS During the study period a total of 2,673,521 donations were screened for HBV. Forty-two chronic OBI infections (5.55/100,000 donors) were identified compared to eight acute serologic window period infections (1.06/100,000 donors). Of the 42 OBI cases, 23 (54.8%) were detected the first time they were screened for HBV DNA while 19 (45.2%) gave one or more HBV NAT-nonreactive results before detection. Of 68 donors initially assessed as HBV inconclusive and available for follow-up, 10 later confirmed as OBI cases while 51 were NAT nonreactive but remained anti-HBc reactive and OBI could not be excluded. CONCLUSION This study demonstrated a substantially higher prevalence of OBI compared to acute serologic window period HBV infections in Australian blood donors. Follow-up testing of OBI cases indicates that HBV DNA is often only intermittently detectable in OBI, highlighting the importance of including anti-HBc to optimize the HBV testing algorithm.
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Affiliation(s)
- Philip Kiely
- Australian Red Cross Blood Service, Melbourne, Australia
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Anvari FA, Alavian SM, Norouzi M, Mahabadi M, Jazayeri SM. Prevalence and molecular analysis of occult hepatitis B virus infection isolated in a sample of cryptogenic cirrhosis patients in iran. Oman Med J 2014; 29:92-96. [PMID: 24715933 PMCID: PMC3976723 DOI: 10.5001/omj.2014.23] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2013] [Accepted: 12/19/2013] [Indexed: 12/25/2022] Open
Abstract
OBJECTIVES The aims of this study are to investigate the prevalence of occult hepatitis B virus infection among patients with cryptogenic cirrhosis and to analyze the relationship between surface protein variability and occult hepatitis B virus infection, which may be related to the pathogenesis of occult hepatitis B virus infection in cryptogenic cirrhosis. Occult hepatitis B virus infection is a well-recognized clinical entity characterized by the detection of hepatitis B virus DNA in serum and/or liver in the absence of detectable hepatitis B virus surface antigen, with or without any serological markers of a past infection. METHODS Sera from patients with cryptogenic chronic liver disease were tested for hepatitis B virus DNA using both real-time and nested PCR. In the detected hepatitis B virus DNA samples, the surface gene was analyzed for mutations. RESULTS Hepatitis B virus DNA was detected in 38% of patients, all of whom had a viral load below 10,000 copies/mL. All hepatitis B virus belonged to genotype D. There were no significant associations between occult hepatitis B virus infection status and age, gender, ALT/AST levels, viral load or serologic markers of previous hepatitis B virus infection. There were 14 mutations found in 5 patients; 6 were in the major hydrophilic region, of which 4 were Y134F assigning for the "a" determinant region. All patients who acquired Y134F contained S207R (within HLA-A2-restricted CTL epitope) as a combination. CONCLUSION Hepatitis B virus surface antigen variants may arise as a result of natural selection to evade the immune surveillance of the infected host, and subsequently may go undetected by conventional hepatitis B virus surface antigen screening tests. Etiological diagnosis of cryptogenic cirrhosis is significantly underestimated with current serology testing methods alone.
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Affiliation(s)
- Fatemeh Akhavan Anvari
- Hepatitis B Molecular Laboratory, Department of Virology, School of Public Health, Tehran University of Medical Sciences, PO Box: 15155-6446, Tehran, Iran. Tel/Fax: +98-21-8899-2660
| | - Seyed Moayyed Alavian
- Baqiyatallah University of Medical Sciences, Baqiyatallah Research Center for Gastroenterology and Liver Disease, P.O. Box: 15155-6446, Tehran, Iran
| | - Mehdi Norouzi
- Hepatitis B Molecular Laboratory, Department of Virology, School of Public Health, Tehran University of Medical Sciences, PO Box: 15155-6446, Tehran, Iran. Tel/Fax: +98-21-8899-2660
| | - Mostafa Mahabadi
- Baqiyatallah University of Medical Sciences, Baqiyatallah Research Center for Gastroenterology and Liver Disease, P.O. Box: 15155-6446, Tehran, Iran
| | - Seyed Mohammad Jazayeri
- Hepatitis B Molecular Laboratory, Department of Virology, School of Public Health, Tehran University of Medical Sciences, PO Box: 15155-6446, Tehran, Iran. Tel/Fax: +98-21-8899-2660
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A pilot study on screening blood donors with individual-donation nucleic acid testing in China. BLOOD TRANSFUSION = TRASFUSIONE DEL SANGUE 2013; 12:172-9. [PMID: 24333061 DOI: 10.2450/2013.0095-13] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Subscribe] [Scholar Register] [Received: 03/18/2013] [Accepted: 05/07/2013] [Indexed: 12/29/2022]
Abstract
BACKGROUND Nucleic acid amplification testing (NAT) is not yet obligatory in China for blood donor screening and the risk of enzyme immunoassay (EIA)-negative, NAT-reactive donations in Chinese blood donors has rarely been reported. The aim of this study was to screen a population of Chinese blood donors using a triplex individual-donation (ID)-NAT assay and assess the safety benefits of implementing NAT. MATERIALS AND METHODS Between 1st August, 2010 and 31st December, 2011 all donations at a Chinese blood centre were screened individually using the Procleix® Ultrio® assay, a multiplex NAT assay for the detection of hepatitis B virus (HBV) DNA, hepatitis C virus (HCV) RNA and human immunodeficiency virus-1 (HIV-1) RNA. All donations were also screened for HBsAg, anti-HIV and anti-HCV using two different EIA for each marker. Samples with discordant results between NAT and EIA were further tested with an alternative NAT assay (Cobas® TaqMan®). Potential yield cases (serologically negative/NAT-reactive donors) were further evaluated when possible. RESULTS During the study period a total of 178,447 donations were screened by NAT and EIA, among which 169 HBV NAT yield cases (0.095%) were detected. No N AT yield cases were found for HIV-1 or HCV. For the HBV NAT yield cases, follow-up results showed that 11 (6.51%) were probable or confirmed HBV window period infections, 5 (2.96%) were chronic HBV carriers and 153 (90.53%) were probable or confirmed occult HBV infections. There was a statistically significant difference between the NAT-positive rates for first-time vs repeat donations (0.472% vs 0.146%, respectively; P<0.001). DISCUSSION Our data demonstrate that the potential HBV yield rate was 1:1,056 for blood donations in the Zhejiang province of China. Implementation of NAT will provide a significant increment in safety relative to serological screening alone.
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Yang Z, Xu L, Liu L, Feng Q, Zhang L, Ma W, Saldanha J, Wang M, Zhao L. Routine screening of blood donations at Qingdao central blood bank, China, for hepatitis B virus (HBV) DNA with a real-time, multiplex nucleic acid test for HBV, hepatitis C virus, and human immunodeficiency virus Types 1 and 2. Transfusion 2013; 53:2538-44. [DOI: 10.1111/trf.12159] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2012] [Revised: 01/04/2013] [Accepted: 01/12/2013] [Indexed: 01/26/2023]
Affiliation(s)
- Zhongsi Yang
- Qingdao Blood Centre; Qingdao ShanDong Province China
- Roche Molecular Systems; Pleasanton California
| | - Lei Xu
- Qingdao Blood Centre; Qingdao ShanDong Province China
- Roche Molecular Systems; Pleasanton California
| | - Li Liu
- Qingdao Blood Centre; Qingdao ShanDong Province China
- Roche Molecular Systems; Pleasanton California
| | - Qiuxia Feng
- Qingdao Blood Centre; Qingdao ShanDong Province China
- Roche Molecular Systems; Pleasanton California
| | - Longmu Zhang
- Qingdao Blood Centre; Qingdao ShanDong Province China
- Roche Molecular Systems; Pleasanton California
| | - Weijuan Ma
- Qingdao Blood Centre; Qingdao ShanDong Province China
- Roche Molecular Systems; Pleasanton California
| | - John Saldanha
- Qingdao Blood Centre; Qingdao ShanDong Province China
- Roche Molecular Systems; Pleasanton California
| | - Mingmin Wang
- Qingdao Blood Centre; Qingdao ShanDong Province China
- Roche Molecular Systems; Pleasanton California
| | - Lin Zhao
- Qingdao Blood Centre; Qingdao ShanDong Province China
- Roche Molecular Systems; Pleasanton California
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Grabarczyk P, van Drimmelen H, Kopacz A, Gdowska J, Liszewski G, Piotrowski D, Górska J, Kuśmierczyk J, Candotti D, Łętowska M, Lelie N, Brojer E. Head-to-head comparison of two transcription-mediated amplification assay versions for detection of hepatitis B virus, hepatitis C virus, and human immunodeficiency virus Type 1 in blood donors. Transfusion 2013; 53:2512-24. [DOI: 10.1111/trf.12190] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2012] [Revised: 02/02/2013] [Accepted: 02/15/2013] [Indexed: 01/29/2023]
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Lin KT, Chang CL, Tsai MH, Lin KS, Saldanha J, Hung CM. Detection and identification of occult HBV in blood donors in Taiwan using a commercial, multiplex, multi-dye nucleic acid amplification technology screening test. Vox Sang 2013; 106:103-10. [PMID: 23909571 DOI: 10.1111/vox.12075] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2013] [Revised: 07/09/2013] [Accepted: 07/10/2013] [Indexed: 12/13/2022]
Abstract
BACKGROUND The ability of a new generation commercial, multiplex, multi-dye test from Roche, the cobas TaqScreen MPX test, version 2.0, to detect and identify occult HBV infections was evaluated using routine donor samples from Kaohsiung Blood Bank, Taiwan. STUDY DESIGN AND METHODS A total of 5973 samples were tested by nucleic acid amplification technology (NAT); 5898 in pools of six, 66 in pools of less than six and nine samples individually. NAT-reactive samples were retested with alternative NAT tests, and follow-up samples from the donors were tested individually by NAT and for all the HBV serological markers. RESULTS Eight NAT-only-reactive donors were identified, and follow-up samples were obtained from six of the donors. The results indicated that all eight donors had an occult HBV infection with viral loads <12 IU/ml. CONCLUSION The cobas(®) TaqScreen MPX test, version 2.0, has an advantage over the current Roche blood screening test, the cobas TaqScreen MPX test, for screening donations in countries with a high prevalence of occult HBV infections since the uncertainty associated with identifying samples with very low viremia is removed by the ability of the test to identify the viral target in samples that are reactive with the cobas TaqScreen MPX test, version 2.0.
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Affiliation(s)
- K T Lin
- Kaohsiung Blood Center, Taiwan Blood Services Foundation, Kaohsiung, Taiwan
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Said ZN, Sayed MHE, Salama II, Aboel-Magd EK, Mahmoud MH, Setouhy ME, Mouftah F, Azzab MB, Goubran H, Bassili A, Esmat GE. Occult hepatitis B virus infection among Egyptian blood donors. World J Hepatol 2013; 5:64-73. [PMID: 23646231 PMCID: PMC3642725 DOI: 10.4254/wjh.v5.i2.64] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2012] [Revised: 11/28/2012] [Accepted: 12/23/2012] [Indexed: 02/06/2023] Open
Abstract
AIM To identify blood donors with occult hepatitis B virus (HBV) infection (OBI) to promote safe blood donation. METHODS Descriptive cross sectional study was conducted on 3167 blood donors negative for hepatitis B surface antigen (HBsAg), hepatitis C antibody (HCV Ab) and human immunodeficiency virus Ab. They were subjected to the detection of alanine aminotransferase (ALT) and aspartate transaminase (AST) and screening for anti-HBV core antibodies (total) by two different techniques; [Monoliza antibodies to hepatitis B core (Anti-HBc) Plus-Bio-Rad] and (ARC-HBc total-ABBOT). Positive samples were subjected to quantitative detection of antibodies to hepatitis B surface (anti-HBs) (ETI-AB-AUK-3, Dia Sorin-Italy). Serum anti-HBs titers > 10 IU/L was considered positive. Quantitative HBV DNA by real time polymerase chain reaction (PCR) (QIAGEN-Germany) with 3.8 IU/mL detection limit was estimated for blood units with negative serum anti-HBs and also for 32 whose anti-HBs serum titers were > 1000 IU/L. Also, 265 recipients were included, 34 of whom were followed up for 3-6 mo. Recipients were investigated for ALT and AST, HBV serological markers: HBsAg (ETI-MAK-4, Dia Sorin-Italy), anti-HBc, quantitative detection of anti-HBs and HBV-DNA. RESULTS 525/3167 (16.6%) of blood units were positive for total anti-HBc, 64% of those were anti-HBs positive. Confirmation by ARCHITECT anti-HBc assay were carried out for 498/525 anti-HBc positive samples, where 451 (90.6%) confirmed positive. Reactivity for anti-HBc was considered confirmed only if two positive results were obtained for each sample, giving an overall prevalence of 451/3167 (14.2%) for total anti-HBc. HBV DNA was quantified by real time PCR in 52/303 (17.2%) of anti-HBc positive blood donors (viral load range: 5 to 3.5 x 10(5) IU/mL) with a median of 200 IU/mL (mean: 1.8 x 10(4) ± 5.1 x 10(4) IU/mL). Anti-HBc was the only marker in 68.6% of donors. Univariate and multivariate logistic analysis for identifying risk factors associated with anti-HBc and HBV-DNA positivity among blood donors showed that age above thirty and marriage were the most significant risk factors for prediction of anti-HBc positivity with AOR 1.8 (1.4-2.4) and 1.4 (1.0-1.9) respectively. Other risk factors as gender, history of blood transfusion, diabetes mellitus, frequent injections, tattooing, previous surgery, hospitalization, Bilharziasis or positive family history of HBV or HCV infections were not found to be associated with positive anti-HBc antibodies. Among anti-HBc positive blood donors, age below thirty was the most significant risk factor for prediction of HBV-DNA positivity with AOR 3.8 (1.8-7.9). According to HBV-DNA concentration, positive samples were divided in two groups; group one with HBV-DNA ≥ 200 IU/mL (n = 27) and group two with HBV-DNA < 200 IU/mL (n = 26). No significant difference was detected between both groups as regards mean age, gender, liver enzymes or HBV markers. Serological profiles of all followed up blood recipients showed that, all were negative for the studied HBV markers. Also, HBV DNA was not detected among studied recipients, none developed post-transfusion hepatitis (PTH) and the clinical outcome was good. CONCLUSION OBI is prevalent among blood donors. Nucleic acid amplification/HBV anti core screening should be considered for high risk recipients to eliminate risk of unsafe blood donation.
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Affiliation(s)
- Zeinab N Said
- Zeinab N Said, Enas K Aboel-Magd, Microbiology and Immunology Department, Faculty of Medicine (for Girls), Al-Azhar University, 11511 Cairo, Egypt
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Allain JP, Mihaljevic I, Gonzalez-Fraile MI, Gubbe K, Holm-Harritshøj L, Garcia JM, Brojer E, Erikstrup C, Saniewski M, Wernish L, Bianco L, Ullum H, Candotti D, Lelie N, Gerlich WH, Chudy M. Infectivity of blood products from donors with occult hepatitis B virus infection. Transfusion 2013; 53:1405-15. [PMID: 23362802 DOI: 10.1111/trf.12096] [Citation(s) in RCA: 113] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2012] [Revised: 09/21/2012] [Accepted: 10/11/2012] [Indexed: 12/18/2022]
Abstract
BACKGROUND Occult hepatitis B virus (HBV) infection (OBI) is identified in 1:1000 to 1:50,000 European blood donations. This study intended to determine the infectivity of blood products from OBI donors. STUDY DESIGN AND METHODS Recipients of previous donations from OBI donors were investigated through lookback (systematic retrieval of recipients) or traceback (triggered by clinical cases). Serologic and genomic studies were undertaken on consenting donors and recipients. Multiple variables potentially affecting infectivity were examined. RESULTS A total of 45 of 105 (42.9%) donor-recipients pairs carried antibodies to HBV core (anti-HBc) as evidence of previous HBV infection. Subtracting 15% of anti-HBc population background, the adjusted transmission rate was 28%. Anti-HBc prevalence increased to 28 of 44 (63.8%) in unvaccinated recipients receiving anti-HBs-negative OBI blood products. In contrast, four of 26 (15.4%) recipients of anti-HBs-positive products were anti-HBc positive. Transmission with anti-HBs-negative products depended on volume of plasma transfused (85%-100% with 200 mL of fresh frozen plasma [FFP], 51% with 50 mL in platelet concentrates [PCs], and 24% with 20 mL in red blood cells [RBCs], p < 0.0001 FFP vs. RBCs). The 50% minimum infectious dose of OBI HBV DNA was estimated at 1049 (117-3441) copies. Donor and recipient strains sequence homology of at least 99% confirmed transfusion-transmitted infection in 10 cases and excluded it in one case. CONCLUSION Blood products from donors with OBI carry a high risk of HBV transmission by transfusion. This risk is dependent on presence of anti-HBs and viral dose. This may justify safety measures such as anti-HBc and HBV nucleic acid test screening depending on epidemiology.
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Hepatitis B escape mutants in Scottish blood donors. Med Microbiol Immunol 2012; 202:207-14. [PMID: 23274404 DOI: 10.1007/s00430-012-0283-9] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2012] [Accepted: 12/01/2012] [Indexed: 02/06/2023]
Abstract
Hepatitis B virus (HBV) remains as the viral infection with the highest risk of transmission by transfusion. This risk is associated with window period donations, occult HBV infection (OBI) and the emergence of escape mutants, which render blood donations false negative for hepatitis B surface antigen (HBsAg) serological testing. A retrospective study was conducted to gain insights into the molecular epidemiology of HBV escape mutants in Scottish blood donors. The criterion for selection was HBV positivity either by serology or nucleic acid testing (NAT). HBsAg detection was compared across several commercial immunoassays. The full length S gene from plasma samples was PCR amplified, cloned and expressed in HepG2 cells. Eight samples showed HBsAg discordant results, while 5 OBI samples were found. Four escape mutants, containing missense mutations in the S gene, are described here. These mutations impaired HBsAg detection both from HBV infected plasma samples and from recombinant proteins derived from its infected donors. Phylogenetic analysis showed that most of the mutants were clustered in the genotype D and were closely related to strains from Asia and the Middle East. We report here a proline substitution, outside the major hydrophilic region, that impaired HBsAg detection in vivo and in vitro, warning about the risk for the emergence of vaccine escape mutants with mutations outside the major neutralisation site.
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Shahmoradi S, Yahyapour Y, Mahmoodi M, Alavian SM, Fazeli Z, Jazayeri SM. High prevalence of occult hepatitis B virus infection in children born to HBsAg-positive mothers despite prophylaxis with hepatitis B vaccination and HBIG. J Hepatol 2012; 57:515-521. [PMID: 22617152 DOI: 10.1016/j.jhep.2012.04.021] [Citation(s) in RCA: 82] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2011] [Revised: 04/05/2012] [Accepted: 04/11/2012] [Indexed: 12/12/2022]
Abstract
BACKGROUND & AIMS Occult hepatitis B virus (HBV) infection is a well-recognized clinical entity characterized by the detection of HBV DNA in serum and/or liver in the absence of detectable hepatitis B surface antigen (HBsAg). The frequency of the diagnosis depends on the relative sensitivity of both HBsAg and HBV DNA assays. We aimed at determining the prevalence of occult HBV infection in a high risk group of children who developed HBV infection despite immunoprophylaxis. METHODS The sera of 75 children born to HBsAg-positive mothers previously immunized by HBIG and prophylaxic vaccine regimen were assayed for HBV DNA by real-time PCR. Subsequently, the samples were tested using a sensitive standard PCR, with an independent set of primers for all HBV genes, and analyzed by direct sequencing. RESULTS HBV DNA was detected in 21/75 (28%) children, and ranged between 77 and 9240 copies/ml. All were positive for anti-HBs. Five (24%) children were found to be positive for anti-HBc, while anti-HBc-only positive individuals were not observed. Eight isolates (38%) did not carry any mutation. Thirteen infected children (62%) had at least one mutation in regions known to be involved in functional and/or immune epitope activity. Ten had G145R mutations. CONCLUSIONS HBV occult infection seems to be relatively frequent in immunized children born to HBsAg-positive mothers. HBsAg negativity is not sufficient to completely exclude HBV DNA presence. These findings emphasize the importance of considering occult HBV infection in hypo-endemic areas.
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Affiliation(s)
- Sajad Shahmoradi
- Hepatitis B Molecular Laboratory, Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
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Müller MM, Fraile MIG, Hourfar MK, Peris LB, Sireis W, Rubin MG, López EM, Rodriguez GT, Seifried E, Saldanha J, Schmidt M. Evaluation of two, commercial, multi-dye, nucleic acid amplification technology tests, for HBV/HCV/HIV-1/HIV-2 and B19V/HAV, for screening blood and plasma for further manufacture. Vox Sang 2012; 104:19-29. [DOI: 10.1111/j.1423-0410.2012.01635.x] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
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Alavian SM, Carman WF, Jazayeri SM. HBsAg variants: diagnostic-escape and diagnostic dilemma. J Clin Virol 2012; 57:201-8. [PMID: 22789139 DOI: 10.1016/j.jcv.2012.04.027] [Citation(s) in RCA: 59] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2011] [Revised: 01/23/2012] [Accepted: 04/18/2012] [Indexed: 12/11/2022]
Abstract
A wide variety of commercial assays is available for the detection of hepatitis B surface antigen (HBsAg). Clearly, the sensitivity of an assay to detect a variant is dependent on the anti-HBs usage. Thus, it is not surprising that there are examples of variants that cannot be detected by all assays. Data from Europe, Asia and Africa about HBsAg variants which are not recognized by either monoclonal or polyclonal antibodies specific for wild-type group 'a' determinant, but positive by DNA polymerase chain reaction (PCR) in chronic patients and from vaccinated children are increasing. This would impose a challenge for public health issues of hepatitis B virus. In this review we tried to summarize the discrepancies between results of HBsAg assays and to explain some rationales for these inconsistencies.
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Affiliation(s)
- Seyed Moayed Alavian
- Baqiyatallah University of Medical Sciences, Baqiyatallah Research Centre for Gastroenterology and Liver Disease, Tehran, Iran
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Tani Y, Aso H, Matsukura H, Tadokoro K, Tamori A, Nishiguchi S, Yoshizawa H, Shibata H. Significant background rates of HBV and HCV infections in patients and risks of blood transfusion from donors with low anti-HBc titres or high anti-HBc titres with high anti-HBs titres in Japan: a prospective, individual NAT study of transfusion-transmitted HBV, HCV and HIV infections. Vox Sang 2012; 102:285-293. [PMID: 22082342 DOI: 10.1111/j.1423-0410.2011.01561.x] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
BACKGROUND The Japanese Red Cross (JRC) conducted a prospective study to evaluate the frequency of transfusion-transmitted HBV, HCV and HIV infections to assess the risk of transfusion of blood components routinely supplied to hospitals. STUDY DESIGN AND METHODS Post-transfusion specimens from patients at eight medical institutes were examined for evidence of infection with HBV (2139 cases), HCV (2091) and HIV (2040) using individual nucleic acid amplification testing (NAT). If these specimens were reactive, pre-transfusion specimens were also examined for the virus concerned by individual NAT. In the event that the pre-transfusion specimen was non-reactive, then all repository specimens from implicated donors were tested for the viruses by individual donation NAT. In addition, a further study was carried out to evaluate the risk of transfusion of components from donors with low anti-HBc titres or high anti-HBc with high anti-HBs titres. RESULTS Transfusion-transmitted HCV and HIV infections were not observed. One case of post-transfusion HBV infection was identified (rate, 0·0004675; 95% CI for the risk of transmission, 1 in 451-41,841). The background rates of HBV, HCV and HIV infections in patients prior to transfusion were 3·4% (72/2139), 7·2% (150/2091) and 0% (0/2040), respectively. Sixty-four anti-HBc- and/or anti-HBs-reactive blood components were transfused to 52 patients non-reactive for anti-HBc or anti-HBs before and after transfusion (rate, 0; 95% CI for the risk of transmission, <1 in 22). CONCLUSION This study demonstrated that the current criteria employed by JRC have a low risk, but the background rates of HBV and HCV infections in Japanese patients are significant.
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Affiliation(s)
- Y Tani
- Japanese Red Cross Osaka Blood Center, Osaka, Japan.
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Abstract
PURPOSE OF REVIEW The availability of hepatitis B virus (HBV) nucleic acid testing (NAT) for donor blood screening led to its implementation in low prevalence and high prevalence countries. Genomic detection was a substantial addition to HBV surface protein (HBsAg) screening by detecting window period infections and 'occult' HBV infections (OBIs), characterized by undetectable HBsAg, low viral load and presence of serological markers (anti-HBc and/or anti-HBs). OBIs are the result of multiple, poorly understood mechanisms including incomplete immune control mutations of the HBsAg antigenic determinants; abnormal expression of S gene; and inhibition of genome transcription. Infectivity for the recipient is high for window period blood and relatively low for OBIs. RECENT FINDINGS The number of cases identified by NAT ranges between 1 : 1000 and 1 : 50 000, depending on epidemiology and assay sensitivity whether NAT is implemented in individual donations or pools of samples. OBI donors are generally older than 45 years except in Africa, carry very low viral load (median 11-25 IU/ml) and have normal alanine transaminase levels. Cases carrying anti-HBc alone are more infectious than those with low level of anti-HBs. Evidence of HBsAg escape mutants that are undetected by commercial assays has been published. Inhibition of HBsAg mRNA production and export are potential mechanisms of OBI occurrence. SUMMARY HBV blood safety is improved by NAT for HBV DNA when applied to individual donations. Until the sensitivity of NAT is improved, both this method and HBsAg screening are needed to eliminate potentially infectious blood donations. Occult HBV characterization clarifies new facets of HBV natural history.
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