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Shuaib BI, Momodu A, Ohenhen JE, Umeche IE, Muhibi MA. Prevalence of overt and occult hepatitis B viral infection among pregnant women attending antenatal clinics in Edo state university teaching hospital Auchi, Nigeria. BMC Infect Dis 2024; 24:1468. [PMID: 39731052 DOI: 10.1186/s12879-024-10376-2] [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: 09/29/2024] [Accepted: 12/19/2024] [Indexed: 12/29/2024] Open
Abstract
BACKGROUND Hepatitis B virus (HBV) infection remains a major health challenge in Nigeria, with high prevalence rates among pregnant women. The prevalence of overt and occult hepatitis B infection (HBIOV and HBIOC) among pregnant women was investigated to understand the burden and associated risk factors in this population. METHODS A cross-sectional study was conducted among 200 pregnant women. Socio-demographic and clinical data were collected, and blood samples were screened for hepatitis B surface antigen (HBsAg) and hepatitis B virus DNA (HBV-DNA) using Enzyme-Linked Immunosorbent Assay (ELISA) and real time Polymerase Chain Reaction max Eco 48 system. Data were analyzed using GraphPad Prism software (v6) and Statistical Package for the Social Sciences (IBM SPSS 23.0). A significance level of P ≤ 0.05 was considered statistically significant. RESULTS The overall prevalence of hepatitis B infection was 6.0% (12/200), comprising 2.5% HBIOC and 3.5% HBIOV. The participants, aged 19 to 43 years, were predominantly married (89.5%) and urban-dwelling (69.0%), with diverse educational levels and occupations. There were no statistically significant differences in demographic factors such as age, marital status, or education between HBIOC and HBIOV groups. However, significant associations were observed between HBV infection and risk factors including blood transfusion (p = 0.01), cigarette exposure (p = 0.03), and alcohol consumption (p = 0.01). Viral load was significantly higher in the HBIov group [4.84 log IU/mL (IQR: 4.00-9.14)] compared to the HBIoc group [2.30 log IU/mL (IQR: 2.19-3.00)] (p = 0.001). CONCLUSION The findings reveal a 6.0% prevalence of hepatitis B infection among pregnant women, with 3.5% overt and 2.5% occult infections. The results emphasize the need for HBV DNA testing in screening protocols to detect occult and overt HB infections and address key risk factors to improve antenatal care and prevention strategies.
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Affiliation(s)
- Bukhari Isah Shuaib
- Department of Medical Laboratory Science, Faculty of Applied Health Sciences, Edo State University, Uzairue, Edo State, Nigeria.
| | - Amina Momodu
- Department of Medical Laboratory Science, Faculty of Applied Health Sciences, Edo State University, Uzairue, Edo State, Nigeria
| | - Johnsolomon Eghosa Ohenhen
- Department of Medical Laboratory Science, Faculty of Applied Health Sciences, Edo State University, Uzairue, Edo State, Nigeria
| | - Ijeoma Evangeline Umeche
- Department of Medical Laboratory Science, Faculty of Applied Health Sciences, Edo State University, Uzairue, Edo State, Nigeria
| | - Musa Abidemi Muhibi
- Department of Medical Laboratory Science, Faculty of Applied Health Sciences, Edo State University, Uzairue, Edo State, Nigeria
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Eilard A, Andersson ME, Wejstål R, Norkrans G, Lindh M. Occult hepatitis B infection in children born to HBeAg-positive women confers a low long-term risk for HBsAg-positive infection. Infection 2024; 52:2351-2357. [PMID: 38727925 PMCID: PMC11621201 DOI: 10.1007/s15010-024-02290-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2024] [Accepted: 05/01/2024] [Indexed: 12/07/2024]
Abstract
PURPOSE Mother-to-child transmission (MTCT) has been the main cause of chronic hepatitis B virus (HBV) infection, particularly in East Asia. Hepatitis B immunoglobulin (HBIG) and vaccination given directly after birth effectively prevents hepatitis B surface antigen (HBsAg)-positive (overt) HBV infection, but occult hepatitis B infection (OBI) may develop despite adequate prophylaxis. The aim of this study was to investigate the long-term outcome in children born to mothers with very high HBV DNA levels with special focus on children discovered in early childhood with OBI. METHODS One-year and long-term outcome regarding overt and occult HBV infection were analysed in 66 children born to hepatitis B e antigen (HBeAg)-positive mothers, and were compared with one-year outcome in 69 children born to HBeAg-negative mothers. The children were born between 1998 and 2018. RESULTS Six children born to HBeAg-positive mothers developed overt chronic HBV infection, in two cases after normal pregnancies and despite HBIG and vaccination, but never when nucleotide analogue treatment was given during pregnancy. OBI with HBV DNA detected in serum in the absence of surface antigen (HBsAg) was observed in four children at the age of 1 year. One of them was transiently HBsAg-positive at the age of 7 years. At long-term follow-up, six children had overt chronic infection, one had OBI and six had previous OBI or positive anti-HBc suggesting resolved unidentified infections. CONCLUSION The results indicate that children born to mothers with high HBV DNA levels have approximately 10% risk to develop OBI despite antiviral treatment, vaccination and HBIG, but that such OBI confers a minimal long-term risk for overt infection, at least in immunocompetent children.
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Affiliation(s)
- Anders Eilard
- Department of Infectious Diseases, University of Gothenburg, 413 46, Gothenburg, Sweden.
- Department of Infectious Diseases, Sahlgrenska University Hospital, 416 85, Gothenburg, Sweden.
| | - Maria E Andersson
- Department of Infectious Diseases, University of Gothenburg, 413 46, Gothenburg, Sweden
| | - Rune Wejstål
- Department of Infectious Diseases, Sahlgrenska University Hospital, 416 85, Gothenburg, Sweden
| | - Gunnar Norkrans
- Department of Infectious Diseases, Sahlgrenska University Hospital, 416 85, Gothenburg, Sweden
| | - Magnus Lindh
- Department of Infectious Diseases, University of Gothenburg, 413 46, Gothenburg, Sweden
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Louhab I, Daoudi H, Elcadi M, El Amin G, Zouaki A, Zirar J, Seffar M, Salihoun M, Kabbaj H. Serological Profiles of Hepatitis B Virus in Patients With Crohn's Disease Undergoing Anti-Tumor Necrosis Factor Alpha (TNFα) Therapy at Ibn Sina University Hospital, Rabat. Cureus 2024; 16:e73550. [PMID: 39677079 PMCID: PMC11638146 DOI: 10.7759/cureus.73550] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/11/2024] [Indexed: 12/17/2024] Open
Abstract
Introduction Anti-tumor necrosis factor alpha (TNFα) therapies have revolutionized the management of Crohn's disease (CD). However, they increase the risk of viral reactivation, particularly hepatitis B virus (HBV). This study aims to define the HBV serological profiles of patients with CD who are candidates for biological therapy, identifying profiles at potential risk for reactivation or exacerbation following immunosuppressive treatment. Materials and methods This descriptive retrospective study included patients with CD, aged over 16 years, who were candidates for anti-TNFα treatment at Ibn Sina University Hospital Center (UHC) in Rabat, Morocco, from January 2015 to March 2023. The serological profiles of patients, including hepatitis B surface antigen (HBsAg), hepatitis B surface antibodies, and total hepatitis B core antibodies (HBcAb), were determined using microparticle chemiluminescence immunoassay with the ARCHITECT i2000sr or Alinity (Abbott Diagnostics, Chicago, Illinois, United States) automated systems at the Central Virology Laboratory (CVL) of Ibn Sina UHC Rabat. HBV DNA quantification was performed using the m2000 Abbott Diagnostic or GeneXpert system. Results Out of 249 patients with CD who were candidates for biological therapy, 131 (52.6%) received anti-TNFα treatment, including 39 (29.8%) with adalimumab and 92 (70.2%) with infliximab. The median age was 41 years, and the male-to-female ratio was 0.52. The overall HBV screening rate before starting biological therapy was 68.7%. HBV screening was conducted for 90 patients at the CVL, where serological marker analysis categorized five distinct profiles. A majority of patients (65, 72.2%) had negative serological profiles for HBV, while 10 (11.1%) were immunized via vaccination. Profiles at risk of viral reactivation or worsening following immunosuppressive therapy included 12 (13.3%) patients immunized by contact, two (2.3%) with isolated HBcAb, and one (1.1%) with active viral hepatitis (positive HBsAg and HBcAb), who was initiated on tenofovir 300 mg before starting combination therapy. No cases of primary infection or viral B reactivation were observed during the study. Conclusions In our study, 15 patients (16.7%) exhibited a potential risk of viral reactivation or worsening of HBV following the initiation of immunosuppressive therapy. The authors recommend precise patient selection, thorough pretreatment evaluation, and regular follow-up during therapy to minimize adverse events associated with anti-TNFα treatment. Additionally, a prophylactic or preemptive strategy should be considered. The risk of late reactivation after discontinuation of biological therapy should also be carefully monitored.
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Affiliation(s)
- Imane Louhab
- Central Laboratory of Hematology, Ibn Sina University Hospital, Faculty of Medicine and Pharmacy, Mohammed V University, Rabat, MAR
| | - Hajar Daoudi
- Department of Pharmacy, Ibn Sina University Hospital, Faculty of Medicine and Pharmacy, Mohammed V University, Rabat, MAR
| | - Mina Elcadi
- Department of Pharmacy, Ibn Sina University Hospital, Faculty of Medicine and Pharmacy, Mohammed V University, Rabat, MAR
| | - Ghizlane El Amin
- Central Laboratory of Virology, Ibn Sina University Hospital, Faculty of Medicine and Pharmacy, Mohammed V University, Rabat, MAR
| | - Amal Zouaki
- Central Laboratory of Virology, Ibn Sina University Hospital, Faculty of Medicine and Pharmacy, Mohammed V University, Rabat, MAR
| | - Jalila Zirar
- Central Laboratory of Virology, Ibn Sina University Hospital, Faculty of Medicine and Pharmacy, Mohammed V University, Rabat, MAR
| | - Myriam Seffar
- Central Laboratory of Virology, Ibn Sina University Hospital, Faculty of Medicine and Pharmacy, Mohammed V University, Rabat, MAR
| | - Mouna Salihoun
- Department of Gastroenterology, Ibn Sina University Hospital, Faculty of Medicine and Pharmacy, Mohammed V University, Rabat, MAR
| | - Hakima Kabbaj
- Central Laboratory of Virology, Ibn Sina University Hospital, Faculty of Medicine and Pharmacy, Mohammed V University, Rabat, MAR
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Yang SS, Fu F, Xuan QK, Zhang ZX, Li ZJ, Li GB, Yu XY. Hepatitis B surface antigen-negative but hepatitis B envelope antigen-positive false occult hepatitis B virus infection: A case report. World J Hepatol 2024; 16:1199-1207. [PMID: 39474578 PMCID: PMC11514620 DOI: 10.4254/wjh.v16.i10.1199] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2024] [Revised: 08/13/2024] [Accepted: 09/14/2024] [Indexed: 10/21/2024] Open
Abstract
BACKGROUND Occult hepatitis B infection (OBI) is characterized by the detection of hepatitis B virus (HBV) DNA in serum (usually HBV DNA < 200 IU/mL) or the liver but negativity for hepatitis B surface antigen (HBsAg). The diagnosis of OBI relies on the sensitivity of assays used in the detection of HBV DNA and HBsAg. HBsAg assays with inadequate sensitivity or inability to detect HBV S variants may lead to misdiagnosis of OBI in people with overt HBV infection.
CASE SUMMARY We report a HBsAg-negative but hepatitis B envelope antigen-positive patient who had a significant HBV DNA level. The patient was initially diagnosed as having OBI. However, sequence analysis revealed a unique insertion of amino acid residues at positions 120-124 in the S protein, which affects the formation of a disulfide bond that is associated with the formation of a loop. It is well known that there is an overlap between the S protein and Pol protein. We found that this new insertion site occurred in polymerase/reverse transcriptase domain, indicating that this insertion might be involved in HBV pathogenicity. The patient was finally diagnosed with a false OBI.
CONCLUSION An insertion of amino acid residues at positions 120-124 of the S protein affects the formation of immunodominant epitopes and results in negative HBsAg levels.
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Affiliation(s)
- Shu-Sheng Yang
- Department of Laboratory Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200123, China
| | - Fei Fu
- Department of Obstetrics and Gynecology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200123, China
| | - Qian-Kun Xuan
- Department of Laboratory Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200123, China
| | - Zhou-Xiang Zhang
- Department of Obstetrics and Gynecology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200123, China
| | - Zhi-Jun Li
- Department of Laboratory Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200123, China
| | - Guang-Bo Li
- Department of Laboratory Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200123, China
| | - Xiao-Yu Yu
- Department of Laboratory Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200123, China
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5
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Yang SS, Fu F, Xuan QK, Zhang ZX, Li ZJ, Li GB, Yu XY. Hepatitis B surface antigen-negative but hepatitis B envelope antigen-positive false occult hepatitis B virus infection: A case report. World J Hepatol 2024; 16:1379-1387. [DOI: 10.4254/wjh.v16.i10.1379] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2024] [Revised: 08/13/2024] [Accepted: 09/14/2024] [Indexed: 11/22/2024] Open
Abstract
BACKGROUND Occult hepatitis B infection (OBI) is characterized by the detection of hepatitis B virus (HBV) DNA in serum (usually HBV DNA < 200 IU/mL) or the liver but negativity for hepatitis B surface antigen (HBsAg). The diagnosis of OBI relies on the sensitivity of assays used in the detection of HBV DNA and HBsAg. HBsAg assays with inadequate sensitivity or inability to detect HBV S variants may lead to misdiagnosis of OBI in people with overt HBV infection.
CASE SUMMARY We report a HBsAg-negative but hepatitis B envelope antigen-positive patient who had a significant HBV DNA level. The patient was initially diagnosed as having OBI. However, sequence analysis revealed a unique insertion of amino acid residues at positions 120-124 in the S protein, which affects the formation of a disulfide bond that is associated with the formation of a loop. It is well known that there is an overlap between the S protein and Pol protein. We found that this new insertion site occurred in polymerase/reverse transcriptase domain, indicating that this insertion might be involved in HBV pathogenicity. The patient was finally diagnosed with a false OBI.
CONCLUSION An insertion of amino acid residues at positions 120-124 of the S protein affects the formation of immunodominant epitopes and results in negative HBsAg levels.
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Affiliation(s)
- Shu-Sheng Yang
- Department of Laboratory Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200123, China
| | - Fei Fu
- Department of Obstetrics and Gynecology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200123, China
| | - Qian-Kun Xuan
- Department of Laboratory Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200123, China
| | - Zhou-Xiang Zhang
- Department of Obstetrics and Gynecology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200123, China
| | - Zhi-Jun Li
- Department of Laboratory Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200123, China
| | - Guang-Bo Li
- Department of Laboratory Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200123, China
| | - Xiao-Yu Yu
- Department of Laboratory Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200123, China
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Delghandi S, Raoufinia R, Shahtahmasbi S, Meshkat Z, Gouklani H, Gholoobi A. An overview of occult hepatitis B infection (OBI) with emphasis on HBV vaccination. Heliyon 2024; 10:e37097. [PMID: 39281486 PMCID: PMC11402251 DOI: 10.1016/j.heliyon.2024.e37097] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2024] [Revised: 08/25/2024] [Accepted: 08/27/2024] [Indexed: 09/18/2024] Open
Abstract
Background The prevalence of chronic hepatitis B virus (HBV) poses a significant threat to the lives of 257 million individuals globally, potentially resulting in severe outcomes such as liver cirrhosis or hepatocellular carcinoma. Among the existing preventive measures, yeast-derived vaccines have proven to be the most efficacious approach in combatting hepatitis B. Nonetheless, as scientific inquiries focus more on occult HBV infection (OBI) in vaccinated persons and the lingering risk of vertical transmission affecting 10-30 % of babies born to HBsAg-positive mothers, there is a growing apprehension regarding the inability of HBV vaccines to ensure complete immunity. This study aims to offer a more comprehensive understanding of the implications of widespread HBV vaccination initiatives on OBI while tackling the primary limitations associated with current vaccine formulations. Methods The exploration was conducted on PubMed, Scopus, and Web of Science databases to pinpoint research on OBI within vaccinated cohorts. A sum of 76 suitable studies was recognized. Discussion Multiple studies have documented the occurrence of OBI in fully vaccinated individuals, including both the general population and high-risk groups, such as newborns born to HBsAg-positive mothers. Factors contributing to vaccine failures include low-level anti-HBs antibodies, high maternal viral loads in mother-to-child transmission cases, as well as the presence of vaccine escape mutants and heterologous HBV genotypes. However, further research is needed to precisely understand the impact of active immunization on the emergence of OBI in vaccinated populations. Nonetheless, it is apparent that the advancement of more effective HBV vaccines could potentially lead to the extinction of HBV.
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Affiliation(s)
- Sara Delghandi
- Medical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
- Division of Immunology and Genomic Medicine, Center for Cancer Immunotherapy and Immunobiology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Ramin Raoufinia
- Noncommunicable Diseases Research Center, Neyshabur University of Medical Sciences, Neyshabur, Iran
- Medical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Sahar Shahtahmasbi
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Zahra Meshkat
- Antimicrobial Resistance Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Hamed Gouklani
- Infectious and Tropical Diseases Research Center, Hormozgan Health Institute, Hormozgan University of Medical Sciences, Bandar Abbas, Iran
| | - Aida Gholoobi
- Medical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
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7
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Bucio-Ortiz L, Enriquez-Navarro K, Maldonado-Rodríguez A, Torres-Flores JM, Cevallos AM, Salcedo M, Lira R. Occult Hepatitis B Virus Infection in Hepatic Diseases and Its Significance for the WHO's Elimination Plan of Viral Hepatitis. Pathogens 2024; 13:662. [PMID: 39204261 PMCID: PMC11357063 DOI: 10.3390/pathogens13080662] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2024] [Revised: 07/30/2024] [Accepted: 08/02/2024] [Indexed: 09/03/2024] Open
Abstract
Liver damage can progress through different stages, resulting in cirrhosis or hepatocellular carcinoma (HCC), conditions that are often associated with viral infections. Globally, 42% and 21% of cirrhosis cases correlate with HBV and HCV, respectively. In the Americas, the prevalence ranges from 1% to 44%. The WHO has the goal to eliminate viral hepatitis, but it is important to consider occult HBV infection (OBI), a clinical condition characterized by the presence of HBV genomes despite negative surface antigen tests. This review aims to provide an overview of recent data on OBI, focusing on its role in the development of hepatic diseases and its significance in the WHO Viral Hepatitis Elimination Plan. Specific HBV gene mutations have been linked to HCC and other liver diseases. Factors related to the interactions between OBI and mutated viral proteins, which induce endoplasmic reticulum stress and oxidative DNA damage, and the potential role of HBV integration sites (such as the TERT promoter) have been identified in HCC/OBI patients. Health initiatives for OBI research in Latin American countries are crucial to achieving the WHO's goal of eradicating viral hepatitis by 2030, given the difficulty in diagnosing OBI and its unclear association with hepatic diseases.
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Affiliation(s)
- Leticia Bucio-Ortiz
- Medicina y Carcinogénesis Experimental, Universidad Autónoma Metropolitana Iztapalapa, Ciudad de Mexico 09340, Mexico; (L.B.-O.); (K.E.-N.)
| | - Karina Enriquez-Navarro
- Medicina y Carcinogénesis Experimental, Universidad Autónoma Metropolitana Iztapalapa, Ciudad de Mexico 09340, Mexico; (L.B.-O.); (K.E.-N.)
- Unidad de Investigación Médica en Enfermedades Infecciosas y Parasitarias, UMAE Hospital de Pediatría, CMN Siglo XXI, Instituto Mexicano del Seguro Social (IMSS), Ciudad de Mexico 06720, Mexico;
| | - Angélica Maldonado-Rodríguez
- Unidad de Investigación Médica en Enfermedades Infecciosas y Parasitarias, UMAE Hospital de Pediatría, CMN Siglo XXI, Instituto Mexicano del Seguro Social (IMSS), Ciudad de Mexico 06720, Mexico;
| | - Jesús Miguel Torres-Flores
- Laboratorio Nacional de Vacunología y Virus Tropicales, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Ciudad de Mexico 11350, Mexico;
| | - Ana María Cevallos
- Departamento de Biología Molecular y Biotecnología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de Mexico, Ciudad de Mexico 04510, Mexico;
| | - Mauricio Salcedo
- Unidad de Investigación Biomédica Oncológica Genómica, Hospital de Gineco Pediatría 3-A, Instituto Mexicano del Seguro Social, Órgano de Operación Administrativa Desconcentrada (OOAD) Cd Mx Norte, Ciudad de Mexico 07760, Mexico;
| | - Rosalia Lira
- Unidad de Investigación Biomédica Oncológica Genómica, Hospital de Gineco Pediatría 3-A, Instituto Mexicano del Seguro Social, Órgano de Operación Administrativa Desconcentrada (OOAD) Cd Mx Norte, Ciudad de Mexico 07760, Mexico;
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Liu B, Yang H, Liao Q, Wang M, Huang J, Xu R, Shan Z, Zhong H, Li T, Li C, Fu Y, Rong X. Altered gut microbiota is associated with the formation of occult hepatitis B virus infection. Microbiol Spectr 2024; 12:e0023924. [PMID: 38785430 PMCID: PMC11218497 DOI: 10.1128/spectrum.00239-24] [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: 01/24/2024] [Accepted: 04/18/2024] [Indexed: 05/25/2024] Open
Abstract
Hepatitis B virus (HBV), a common blood transmission pathogen worldwide, can lead to viral hepatitis, cirrhosis, liver cancer, and other liver diseases. In particular, occult hepatitis B virus infection (OBI) may be caused by an immune response leading to suppressed virus replication. Gut microbiota can change the immunity status of the human body and, therefore, affect the replication of HBV. Thus, to identify whether there are differences in gut microbiota between HBV carriers and OBI carriers, we collected fecal samples from 18 HBV carriers, 24 OBI blood donors, and also 20 healthy blood donors as negative control. After 16S sequencing, we found that the abundance of Faecalibacterium was significantly reduced in samples from OBI blood donors compared with those from healthy blood donors. Compared with samples from HBV carriers, the samples from OBI blood donors had a significantly increased abundance of Subdoligranulum, which might stimulate immune activation, thus inhibiting HBV replication and contributing to the formation of occult infection. Our findings revealed the potential role of gut microbiota in the formation of OBI and further provided a novel strategy for the treatment of HBV infection.IMPORTANCEOccult hepatitis B virus infection (OBI) is a special form of hepatitis B virus infection with hepatitis B surface antigen (HBsAg) positive and hepatitis B virus (HBV) DNA negative. Gut microbiota may contribute to the immune response leading to suppressed virus replication and, thus, participates in the development of OBI. The study on gut microbiota of OBI blood donors provides novel data considerably advancing our understanding of the immune mechanism for the determination of occult hepatitis B virus infection, which is helpful for improving the strategy of the treatment of HBV infection.
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Affiliation(s)
- Bochao Liu
- Institute of Blood Transfusion and Hematology, Guangzhou Blood Center, Guangzhou Medical University, Guangzhou, Guangdong, China
- The Key Medical Laboratory of Guangzhou, Guangzhou, Guangdong, China
| | - Hualong Yang
- Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Qiao Liao
- Institute of Blood Transfusion and Hematology, Guangzhou Blood Center, Guangzhou Medical University, Guangzhou, Guangdong, China
- The Key Medical Laboratory of Guangzhou, Guangzhou, Guangdong, China
| | - Min Wang
- Institute of Blood Transfusion and Hematology, Guangzhou Blood Center, Guangzhou Medical University, Guangzhou, Guangdong, China
- The Key Medical Laboratory of Guangzhou, Guangzhou, Guangdong, China
| | - Jieting Huang
- Institute of Blood Transfusion and Hematology, Guangzhou Blood Center, Guangzhou Medical University, Guangzhou, Guangdong, China
- The Key Medical Laboratory of Guangzhou, Guangzhou, Guangdong, China
| | - Ru Xu
- Institute of Blood Transfusion and Hematology, Guangzhou Blood Center, Guangzhou Medical University, Guangzhou, Guangdong, China
- The Key Medical Laboratory of Guangzhou, Guangzhou, Guangdong, China
| | - Zhengang Shan
- Institute of Blood Transfusion and Hematology, Guangzhou Blood Center, Guangzhou Medical University, Guangzhou, Guangdong, China
- The Key Medical Laboratory of Guangzhou, Guangzhou, Guangdong, China
| | - Huishan Zhong
- Institute of Blood Transfusion and Hematology, Guangzhou Blood Center, Guangzhou Medical University, Guangzhou, Guangdong, China
- The Key Medical Laboratory of Guangzhou, Guangzhou, Guangdong, China
| | - Tingting Li
- Department of Transfusion Medicine, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, China
| | - Chengyao Li
- Department of Transfusion Medicine, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, China
| | - Yongshui Fu
- Institute of Blood Transfusion and Hematology, Guangzhou Blood Center, Guangzhou Medical University, Guangzhou, Guangdong, China
- The Key Medical Laboratory of Guangzhou, Guangzhou, Guangdong, China
- Nanfang Hospital, Southern Medical University, Guangzhou, China
- Department of Blood Transfusion, Guangzhou First People's Hospital, Guangzhou, Guangdong, China
| | - Xia Rong
- Institute of Blood Transfusion and Hematology, Guangzhou Blood Center, Guangzhou Medical University, Guangzhou, Guangdong, China
- The Key Medical Laboratory of Guangzhou, Guangzhou, Guangdong, China
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9
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Salia E, Nartey YA, Djankpa FT, Pappoe F, Nuvor SV, Obiri-Yeboah D. Prevalence of occult hepatitis B infection among treatment-naive persons living with HIV in Ghana. PLoS One 2024; 19:e0305862. [PMID: 38924017 PMCID: PMC11207135 DOI: 10.1371/journal.pone.0305862] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2023] [Accepted: 06/05/2024] [Indexed: 06/28/2024] Open
Abstract
Hepatitis B virus (HBV) constitutes a significant global health challenge, with more than 2 billion people infected globally and almost 291 million chronic cases. In Africa, coinfection of HBV with Human Immunodeficiency Virus (HIV) is high, yet the condition remains overlooked in many countries. While antiretroviral therapy (ART) has improved HIV survival, viral hepatitis continues to contribute to morbidity and mortality. Occult Hepatitis B infection (OBI), characterized by a low-level of HBV DNA in individuals with negative hepatitis B surface antigen (HBsAg), is an emerging concern among HIV seropositive individuals due to the risk of HBV reactivation and associated complications, especially hepatocellular carcinoma (HCC). Ghana has an estimated HBV/HIV coinfection prevalence of 13.6% making it important to also determine potential cases of OBI. This study aims to assess OBI prevalence in persons living with HIV (PLHIV). A cross-sectional study was conducted in five health facilities in the Cape Coast Metropolis. HBV-related serological markers were determined among 116 PLHIV using the Enzyme-Linked Immunosorbent Assay (ELISA) method. HBV DNA was extracted from 30 participants found to be HBsAg negative but positive for hepatitis B core antibody (HBcAb+). Nested PCR was employed in detecting HBV DNA and HBV viral load was performed using qPCR. The median age of the participants was 37 years (IQR 22-65). Serologically, 7.8% (n = 9, 95% CI: 3.5-22.7), 12.1% (n = 14), and 25.9% (n = 30) tested positive for solely HBsAg, HBsAb, and HBcAb respectively. OBI prevalence among HBsAg-/HBcAb+ participants was 16.7% (n = 5, 95% CI: 6.5-23.7) with a median HBV DNA level of 139.2 IU/ml (IQR, 96.7-142.0). The prevalence of OBI among HIV-positive participants in the Cape Coast Metropolis highlights the need to consider screening for HBV among HIV patients using nucleic acid amplification tests. This can inform medical management and reduce the risk of liver complications, including HCC.
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Affiliation(s)
- Emmanuel Salia
- Department of Microbiology and Immunology, School of Medical Sciences, University of Cape Coast, Cape Coast, Ghana
- Central Laboratory Sub-BMC, Korle-Bu Teaching Hospital, Accra, Ghana
| | - Yvonne Ayerki Nartey
- Departmment of Internal Medicine and Therapeutics, School of Medical Sciences, University of Cape Coast, Cape Coast, Ghana
- Department of Internal Medicine, Cape Coast Teaching Hospital, Cape Coast, Ghana
| | - Francis Tanam Djankpa
- Department of Anatomical Pathology and Physiology, School of Medical Sciences, University of Cape Coast, Cape Coast, Ghana
| | - Faustina Pappoe
- Department of Microbiology and Immunology, School of Medical Sciences, University of Cape Coast, Cape Coast, Ghana
| | - Samuel Victor Nuvor
- Department of Microbiology and Immunology, School of Medical Sciences, University of Cape Coast, Cape Coast, Ghana
| | - Dorcas Obiri-Yeboah
- Department of Microbiology and Immunology, School of Medical Sciences, University of Cape Coast, Cape Coast, Ghana
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10
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Bazie MM, Sanou M, Djigma FW, Compaore TR, Obiri-Yeboah D, Kabamba B, Nagalo BM, Simpore J, Ouédraogo R. Genetic diversity and occult hepatitis B infection in Africa: A comprehensive review. World J Hepatol 2024; 16:843-859. [PMID: 38818293 PMCID: PMC11135261 DOI: 10.4254/wjh.v16.i5.843] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/14/2023] [Revised: 02/06/2024] [Accepted: 04/15/2024] [Indexed: 05/22/2024] Open
Abstract
BACKGROUND Occult hepatitis B infection (OBI) is a globally prevalent infection, with its frequency being influenced by the prevalence of hepatitis B virus (HBV) infection in a particular geographic region, including Africa. OBI can be transmitted through blood transfusions and organ transplants and has been linked to the development of hepatocellular carcinoma (HCC). The associated HBV genotype influences the infection. AIM To highlight the genetic diversity and prevalence of OBI in Africa. METHODS This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and involved a comprehensive search on PubMed, Google Scholar, Science Direct, and African Journals Online for published studies on the prevalence and genetic diversity of OBI in Africa. RESULTS The synthesis included 83 articles, revealing that the prevalence of OBI varied between countries and population groups, with the highest prevalence being 90.9% in patients with hepatitis C virus infection and 38% in blood donors, indicating an increased risk of HBV transmission through blood transfusions. Cases of OBI reactivation have been reported following chemotherapy. Genotype D is the predominant, followed by genotypes A and E. CONCLUSION This review highlights the prevalence of OBI in Africa, which varies across countries and population groups. The study also demonstrates that genotype D is the most prevalent.
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Affiliation(s)
- Michee M Bazie
- Department of Medicine, Transmissible Diseases Laboratory, Université Joseph KI-ZERBO, Ouagadougou 0000, Burkina Faso
| | - Mahamoudou Sanou
- Department of Medicine, Transmissible Diseases Laboratory, Université Joseph KI-ZERBO, Ouagadougou 0000, Burkina Faso
| | - Florencia Wendkuuni Djigma
- Department of Biochemistry and Microbiology, Molecular Biology and Genetics Laboratory, University Joseph KI-ZERBO, Ouagadougou 0000, Burkina Faso.
| | - Tegwinde Rebeca Compaore
- Infectious and parasitic disease Laboratory, Health Sciences Research Institute, IRSS/CNRST, National Center for Scientific and Technological Research, Ouagadougou 0000, Burkina Faso
| | - Dorcas Obiri-Yeboah
- Department of Microbiology and Immunology, School of Medical Sciences, University of Cape Coast, PMB, Cape Coast 0000, Ghana
| | - Benoît Kabamba
- Department of Clinical Biology, Virology Laboratory, Cliniques Universitaires Saint Luc, Université Catholique de Louvain, Bruxelles 0000, Belgium
| | | | - Jacques Simpore
- Department of Biochemistry and Microbiology, Molecular Biology and Genetics Laboratory, University Joseph KI-ZERBO, Ouagadougou 0000, Burkina Faso
| | - Rasmata Ouédraogo
- Department of Medicine, Transmissible Diseases Laboratory, Université Joseph KI-ZERBO, Ouagadougou 0000, Burkina Faso
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11
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He C, Liu Y, Jiang X, Xu Z, Xiang Z, Lu Z. Frequency of HBsAg variants in occult hepatitis B virus infected patients and detection by ARCHITECT HBsAg quantitative. Front Cell Infect Microbiol 2024; 14:1368473. [PMID: 38766475 PMCID: PMC11099262 DOI: 10.3389/fcimb.2024.1368473] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2024] [Accepted: 04/17/2024] [Indexed: 05/22/2024] Open
Abstract
Objective To analyze the amino acid substitution caused by mutations in the major hydrophilic region (MHR) of the S-region genes in the serum samples of occult hepatitis B virus infection (OBI), and to explore the reasons for the missed detection of HBsAg. Method The full-length gene of the S-region in hepatitis B virus(HBV) in the chronic hepatitis B virus(CHB)(10 samples) and OBI groups(42 samples) was amplified using a lab-developed, two-round PCR amplification technology. The PCR amplification products were sequenced/clone sequenced, and the nucleotide sequences of the S-region gene in HBV were compared to the respective genotype consensus sequence. Results Only 20 of the 42 samples in the OBI group had the S-region genes successfully amplified, with the lowest HBV DNA load of 20.1IU/ml. As S-region genes in HBV, 68 cloned strains were sequenced. In the OBI and CHB groups MHR region, with a mutation rate of 3.21% (155/4828) and 0.70% (5/710). The genetic mutation rate was significantly higher in the OBI group than in the CHB group (P<0.05). The common mutation types in the MHR region were: I126T, L162R, K122E, C124R, and C147Y.Mutations at s122, s126, and s162 were associated with subgenotypes, most of which being C genotypes. The high-frequency mutation sites L162R and K122E found in this study have not been reported in previous literature. Conclusion The results of this study confirmed that MHR mutations can cause the missed detection of HBsAg, giving rise to OBI.
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Affiliation(s)
| | | | | | | | | | - Zhicheng Lu
- Department of Clinical Laboratory, The Seventh People’s Hospital of Shanghai University of Traditional Chinese Medicine, Shanghai, China
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12
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Liu H, Chen S, Liu X, Lou J. Effect of S-region mutations on HBsAg in HBsAg-negative HBV-infected patients. Virol J 2024; 21:92. [PMID: 38654327 PMCID: PMC11040738 DOI: 10.1186/s12985-024-02366-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2024] [Accepted: 04/15/2024] [Indexed: 04/25/2024] Open
Abstract
BACKGROUND Occult HBV infection (OBI) is a special form of hepatitis B virus (HBV) infection that may cause Liver cirrhosis and hepatocellular carcinoma, causing significant harm to patients. Given the insidious nature of OBI, it is usually not easy to be detected. Most of the samples currently studied are concentrated on blood donors, however, patients in this special state have not been fully studied. This project aimed to study the effect of HBV S region mutations on HBsAg in patients with clinical OBI. METHODS Collect 107 HBsAg-/HBV DNA + blood samples from Beijing Youan Hospital, Capital Medical University from August 2022 to April 2023. Next, the successfully extracted and amplified HBV DNA S regions were sequenced. Construct mutant plasmids to verify the cell function of the high-frequency mutation sites and explore the possible molecular mechanism. RESULTS Sixty-eight HBsAg-negative samples were sequenced, revealing high-frequency amino acid substitution sites in the HBV S protein, including immune escape mutations (i.e., sY100C、sK122R、sI126T、sT131P、and sS114T) and TMD (Transmembrane domain) region substitutions (i.e., sT5A、sG10D、sF20S、and sS3N). We constructed a portion of the mutant plasmids and found that sT5A, sF20S, sG10D, sS3N, sI68T, and sI126T single point mutations or combined mutations may decrease HBsAg expression or change the antigenicity of HBsAg leading to detection failure. CONCLUSIONS HBsAg-negative patients may show various mutations and amino acid replacement sites at high frequency in the HBV S-region, and these mutations may lead to undetectable Hepatitis B surface antigen (HBsAg), HBsAg antigenic changes or secretion inhibition.
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Affiliation(s)
- Hui Liu
- Clinical Laboratory Center, Beijing Youan Hospital, Capital Medical University, 100069, Beijing, China
| | - Shuxiang Chen
- Clinical Laboratory Center, Beijing Youan Hospital, Capital Medical University, 100069, Beijing, China
| | - Xin Liu
- Clinical Laboratory Center, Beijing Youan Hospital, Capital Medical University, 100069, Beijing, China
| | - Jinli Lou
- Clinical Laboratory Center, Beijing Youan Hospital, Capital Medical University, 100069, Beijing, China.
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13
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Haghtalab A, Hejazi M, Goharnia N, Yekanlou A, Hazhir K, Barghi A, Bazzaz Z, Allahverdizadeh I, GhalibafSabbaghi A. Investigating the correlation between prominent viruses and hematological malignancies: a literature review. Med Oncol 2024; 41:102. [PMID: 38546893 DOI: 10.1007/s12032-024-02345-1] [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: 01/11/2024] [Accepted: 02/23/2024] [Indexed: 04/02/2024]
Abstract
Extensive research has been conducted on the correlation between viral infections and hematological cancers ever since the identification of the Rous Sarcoma Virus as a cancer-causing agent. Numerous viruses, such as the Epstein-Barr virus, hepatitis B virus, hepatitis C virus, human immunodeficiency virus, human T-lymphotropic virus 1, and severe acute respiratory syndrome-related coronavirus 2, have been identified as potential contributors to the development and progression of cancer by disrupting normal cellular processes. Different viruses are associated with distinct forms of blood cancers, each exhibiting unique infection mechanisms, pathogenesis, and clinical symptoms. Understanding these connections is crucial for the development of effective prevention and treatment strategies. Healthcare professionals who possess a solid understanding of these associations can offer precise treatments and closely monitor potential complications in individuals with blood cancers and viral infections. By leveraging this information, healthcare providers can optimize patient care and improve outcomes for those affected by both viral infections and hematological cancers.
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Affiliation(s)
- Arian Haghtalab
- Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran.
| | - Milad Hejazi
- Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran
| | - Naeem Goharnia
- Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran
| | - Ali Yekanlou
- Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran
| | - Kousha Hazhir
- Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran
| | - Asma Barghi
- Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran
| | - Zahra Bazzaz
- Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran
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14
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Fu MX, Simmonds P, Andersson M, Harvala H. Biomarkers of transfusion transmitted occult hepatitis B virus infection: Where are we and what next? Rev Med Virol 2024; 34:e2525. [PMID: 38375981 DOI: 10.1002/rmv.2525] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2023] [Revised: 02/10/2024] [Accepted: 02/13/2024] [Indexed: 02/21/2024]
Abstract
Blood transfusion is a vital procedure, where transfusion-transmitted infection of hepatitis B virus (HBV) remains an important issue, especially from blood donors with occult hepatitis B virus infection (OBI). Occult hepatitis B virus infection is a complex entity to detect using surrogate blood biomarkers for intrahepatic viral transcriptional activity, requiring a continually refined battery of tests utilised for screening. This review aims to critically evaluate the latest advances in the current blood biomarkers to guide the identification of OBI donors and discuss novel HBV markers that could be introduced in future diagnostic practice. Challenges in detecting low HBV surface antigen levels, mutants, and complexes necessitate ultrasensitive multivalent dissociation assays, whilst HBV DNA testing requires improved sensitivity but worsens inaccessibility. Anti-core antibody assays defer almost all potentially infectious donations but have low specificity, and titres of anti-surface antibodies that prevent infectivity are poorly defined with suboptimal sensitivity. The challenges associated with these traditional blood HBV markers create an urgent need for alternative biomarkers that would help us better understand the OBI. Emerging viral biomarkers, such as pre-genomic RNA and HBV core-related antigen, immunological HBV biomarkers of T-cell reactivity and cytokine levels, and host biomarkers of microRNA and human leucocyte antigen molecules, present potential advances to gauge intrahepatic activity more accurately. Further studies on these markers may uncover an optimal diagnostic algorithm for OBI using quantification of various novel and traditional blood HBV markers. Addressing critical knowledge gaps identified in this review would decrease the residual risk of transfusion-transmitted HBV infection without compromising the sustainability of blood supplies.
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Affiliation(s)
- Michael X Fu
- Nuffield Department of Medicine, University of Oxford, Oxford, UK
| | - Peter Simmonds
- Nuffield Department of Medicine, University of Oxford, Oxford, UK
| | - Monique Andersson
- Department of Infection, Oxford University Hospitals NHS Foundation Trust, Oxford, UK
- Radcliffe Department of Medicine, University of Oxford, Oxford, UK
| | - Heli Harvala
- Radcliffe Department of Medicine, University of Oxford, Oxford, UK
- Microbiology Services, NHS Blood and Transplant, Colindale, UK
- Infection and Immunity, University College London, London, UK
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15
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O'Brien SF, Ehsani-Moghaddam B, Goldman M, Drews SJ. Prevalence of Hepatitis B in Canadian First-Time Blood Donors: Association with Social Determinants of Health. Viruses 2024; 16:117. [PMID: 38257817 PMCID: PMC11326446 DOI: 10.3390/v16010117] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2023] [Revised: 01/03/2024] [Accepted: 01/08/2024] [Indexed: 01/24/2024] Open
Abstract
Hepatitis B is transmitted sexually, by blood contact, and vertically from mother to child. Chronic hepatitis B is often seen in immigrants from higher-prevalence countries and their Canadian-born children. We assessed the relationship between hepatitis B and social determinants of health. Included were 1,539,869 first-time Canadian blood donors from April 2005 to December 2022. All donations were tested for hepatitis B markers. Logistic regression was fit with chronic hepatitis B as the dependent variable and age, sex, year, and ethnocultural composition and material deprivation quintiles as independent variables. Chronic hepatitis B prevalence was 47.5/100,000 (95% CI 41.5-53.5, years 2017-2022). Chronic hepatitis B prevalence was elevated in males, older age groups, and those living in more materially deprived and higher ethnocultural neighbourhoods. Of 212,518 donors from 2020 to 2022 with race/ethnicity data, chronic hepatitis B prevalence was highest in East Asians. The findings are consistent with infections in immigrants, acquired in their country of origin, in their Canadian-born children and in those with other risks. As blood donors are a low-risk population unaware of their infection and unlikely to seek testing, our results highlight the ongoing public health challenges of diagnosing chronic hepatitis B and treating it when appropriate.
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Affiliation(s)
- Sheila F O'Brien
- Epidemiology & Surveillance, Canadian Blood Services, Ottawa, ON K1G 4J5, Canada
- School of Epidemiology & Public Health, University of Ottawa, Ottawa, ON K1G 192, Canada
| | - Behrouz Ehsani-Moghaddam
- Epidemiology & Surveillance, Canadian Blood Services, Ottawa, ON K1G 4J5, Canada
- Centre for Studies in Primary Care, Department of Family Medicine, Queens University, Kingston, ON K7L 3N6, Canada
| | - Mindy Goldman
- Donation and Policy Studies, Canadian Blood Services, Ottawa, ON K1G 4J5, Canada
- Department of Pathology & Laboratory Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON K1G 192, Canada
| | - Steven J Drews
- Microbiology, Canadian Blood Services, Edmonton, AB T6G 2R8, Canada
- Department of Laboratory Medicine & Pathology, Faculty of Medicine & Dentistry, University of Alberta, Edmonton, AB T6G 2E1, Canada
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16
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Damiani AS, Holzmayer V, Galli C, De Nuzzo M, Anderson M, Cloherty G, Di Renzo N. Serological and Molecular Characterization of Occult HBV Infection in Blood Donors from South Italy. Viruses 2023; 16:71. [PMID: 38257771 PMCID: PMC10819115 DOI: 10.3390/v16010071] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2023] [Revised: 12/22/2023] [Accepted: 12/28/2023] [Indexed: 01/24/2024] Open
Abstract
Despite good vaccine coverage and careful blood donor selection policies, hepatitis B virus (HBV) is still the most frequent viral infection among blood donors (BDs) in Italy, mostly in the occult form (OBI). We studied the virological features of OBI in BDs from South Italy by serology, molecular testing for HBV-DNA, and sequencing for HBV genotypes and mutations. One hundred and two samples from 95 BDs (22.1% first time, 87.9% regular, median age 57 years) positive for HBV-DNA and negative for HBsAg were retrospectively analyzed. HBV biomarkers were detected in 96.9% (anti-HBc in 44.2%, anti-HBc plus anti-HBs in 49.5%, anti-HBs alone in 3.2%). No risk factor was declared by 45.3% of donors. HBV-DNA levels were very low (median: 7 IU/mL). All samples harbored HBV genotype D and single or multiple mutations in the S gene were found in 28/36 sequences analyzed and in 75% of donors. Mutations were unrelated to gender, donor group or serological patterns. An HBsAg assay with enhanced sensitivity was positive in samples from seven donors (7.4%), two of which negative for HBV-DNA by real-time PCR. OBI still represents a risk for HBV transmission from blood donations; screening by highly sensitive serological and molecular assays is warranted.
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Affiliation(s)
| | - Vera Holzmayer
- R&D, Abbott Diagnostics, Chicago, IL 60064, USA; (V.H.); (M.A.); (G.C.)
| | | | - Mariangela De Nuzzo
- Servizio Immunotrasfusionale, A.O. Vito Fazzi, 73100 Lecce, Italy; (M.D.N.); (N.D.R.)
| | - Mark Anderson
- R&D, Abbott Diagnostics, Chicago, IL 60064, USA; (V.H.); (M.A.); (G.C.)
| | - Gavin Cloherty
- R&D, Abbott Diagnostics, Chicago, IL 60064, USA; (V.H.); (M.A.); (G.C.)
| | - Nicola Di Renzo
- Servizio Immunotrasfusionale, A.O. Vito Fazzi, 73100 Lecce, Italy; (M.D.N.); (N.D.R.)
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17
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Tang X, Yang L, Zhang P, Wang C, Luo S, Liu B, Fu Y, Candotti D, Allain JP, Zhang L, Li C, Li T. Occult Hepatitis B Virus Infection and Liver Fibrosis in Chinese Patients. J Infect Dis 2023; 228:1375-1384. [PMID: 37170968 DOI: 10.1093/infdis/jiad140] [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: 01/11/2023] [Revised: 04/20/2023] [Accepted: 05/11/2023] [Indexed: 05/13/2023] Open
Abstract
BACKGROUND The impact of hepatitis B surface antigen (HBsAg)-negative/hepatitis B virus (HBV) DNA-positive occult HBV infection (OBI) on the severity of liver fibrosis remains unclear. METHODS A total of 1772 patients negative for HBsAg but positive for antibody to hepatitis B core antigen (HBcAg), stratified by the presence or absence of OBI, were selected for long-term carriage leading to elevation of ≥2 of 4 liver fibrosis indexes-hyaluronic acid (HA), laminin, type III procollagen peptide (PCIII), and type IV collagen (CIV)-at testing in a Chinese hospital. Patients were tested for serum viral load, HBV markers, and histopathological changes in liver biopsy specimens. RESULTS OBI was identified in 148 patients with liver fibrosis (8.4%), who had significantly higher levels of HA, laminin, PCIII, and CIV than 1624 fibrotic patients without OBI (P < .05). In 36 patients with OBI who underwent liver biopsy, significant correlations were observed between OBI viral load and serum HA levels (P = .01), PCIII levels (P = .01), and pathological histological activity index (HAI) scores (P < .001), respectively; HAI scores and PCIII levels (P = .04); HBcAg immunohistochemical scores and HA levels (P < .001); and HBcAg immunohistochemical scores and PCIII levels (P = .03). Positive fluorescent in situ hybridization results were significantly more frequent in patients with OBIs (80.6% vs 37.5% in those without OBIs). Among patients with OBIs, HBcAg was detected in the liver tissue in 52.8% and HBsAg in 5.6%. CONCLUSIONS OBI status appears to be associated with liver fibrosis severity.
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Affiliation(s)
- Xi Tang
- Department of Transfusion Medicine, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, China
- Department of Infectious Diseases, The First Foshan People's Hospital, Foshan, China
| | - Liu Yang
- Department of Transfusion Medicine, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, China
- Department of Cardiology, Jiangxi Provincial People's Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang, China
| | - Panli Zhang
- Department of Transfusion Medicine, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, China
| | - Cong Wang
- Department of Transfusion Medicine, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, China
| | - Shengxue Luo
- Department of Transfusion Medicine, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, China
| | - Bochao Liu
- Department of Transfusion Medicine, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, China
| | - Yongshui Fu
- Department of Transfusion Medicine, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, China
- Institute of Blood Transfusion, Guangzhou Blood Center, Guangzhou, China
| | - Daniel Candotti
- Department of Virology, Henri Mondor Hospital, AP-HP and University of Paris-Est, INSERM U955, IMRB, Créteil, France
| | - Jean-Pierre Allain
- Department of Transfusion Medicine, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, China
- Depratment of Haematology, University of Cambridge, Cambridge, United Kingdom
| | - Ling Zhang
- Department of Transfusion Medicine, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, 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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18
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Liu H, He Z, Gui R, Guo J, Chen L, Zhong M, Li J, Cao L, Fan L. Stratified management based on surface antibody for the prevention of hepatitis B virus reactivation in lymphoma patients. Br J Haematol 2023; 203:571-580. [PMID: 37803485 DOI: 10.1111/bjh.19140] [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: 07/14/2023] [Revised: 09/25/2023] [Accepted: 09/25/2023] [Indexed: 10/08/2023]
Abstract
This study aimed to investigate a stratified approach based on hepatitis B virus (HBV) surface antibody (anti-HBs) for managing HBV reactivation (HBVr) in lymphoma patients with serological protection against HBV. A retrospective analysis was conducted on 209 lymphoma patients with a baseline anti-HBs titre of ≥10 iu/L, who were either positive or negative for HBV core antibody (anti-HBc). The results revealed that 15.7% of patients lost serological protection following 6-month anti-lymphoma therapy. With a median follow-up of 28.1 months, the cumulative rates of HBVr at 6 months, 2 years and 4 years were 2.9%, 4.7% and 6.3% respectively. Without intervention, the overall rate of reactivation was 2.0% for patients with isolated anti-HBs and 10.5% for those with positive anti-HBs and anti-HBc. To identify patients at high risk of losing seroprotection and susceptible to HBVr, a predictive model was developed. The high-risk group had significantly higher rates of serological protection loss (27.8% vs. 2.2%) and cumulative incidence of HBVr (22.0% vs. 0%) compared to the low-risk group. Overall, this study highlights the risk of HBVr in lymphoma patients with positive anti-HBs, with or without positive anti-HBc, and recommends periodic monitoring for low-risk patients and early intervention for high-risk patients.
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Affiliation(s)
- Hailing Liu
- Department of Hematology, Jiangsu Province Hospital and Nanjing Medical University First Affiliated Hospital, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Personalized Cancer Medicine, Nanjing Medical University, Nanjing, Jiangsu, China
| | - Zhen He
- Department of Hematology, Jiangsu Province Hospital and Nanjing Medical University First Affiliated Hospital, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Personalized Cancer Medicine, Nanjing Medical University, Nanjing, Jiangsu, China
| | - Renfu Gui
- Department of Hematology, Jiangsu Province Hospital and Nanjing Medical University First Affiliated Hospital, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Personalized Cancer Medicine, Nanjing Medical University, Nanjing, Jiangsu, China
| | - Jingjing Guo
- Department of Geriatric, Nanjing Second Hospital, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Lvwen Chen
- Department of Hematology, Jiangsu Province Hospital and Nanjing Medical University First Affiliated Hospital, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Personalized Cancer Medicine, Nanjing Medical University, Nanjing, Jiangsu, China
| | - Miao Zhong
- Department of Hematology, Jiangsu Province Hospital and Nanjing Medical University First Affiliated Hospital, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Personalized Cancer Medicine, Nanjing Medical University, Nanjing, Jiangsu, China
| | - Jianyong Li
- Department of Hematology, Jiangsu Province Hospital and Nanjing Medical University First Affiliated Hospital, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Personalized Cancer Medicine, Nanjing Medical University, Nanjing, Jiangsu, China
| | - Lei Cao
- Department of Hematology, Jiangsu Province Hospital and Nanjing Medical University First Affiliated Hospital, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Personalized Cancer Medicine, Nanjing Medical University, Nanjing, Jiangsu, China
| | - Lei Fan
- Department of Hematology, Jiangsu Province Hospital and Nanjing Medical University First Affiliated Hospital, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Personalized Cancer Medicine, Nanjing Medical University, Nanjing, Jiangsu, China
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Koc ER, Turan OF, Saridas F, Menguc B, Minaz SN, Ozkaya G. Efficacy of Accelerated Vaccination against Hbv to Achieve Antibody formation in Multiple Sclerosis Patients Receiving Anti-Cd20 Therapy. Ann Indian Acad Neurol 2023; 26:697-701. [PMID: 38022448 PMCID: PMC10666883 DOI: 10.4103/aian.aian_205_23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2023] [Revised: 05/25/2023] [Accepted: 08/14/2023] [Indexed: 12/01/2023] Open
Abstract
Aim Ocrelizumab is a monoclonal antibody that has been approved for use in both relapsing-remitting multiple sclerosis (RRMS) and primary progressive multiple sclerosis (PPMS). Since ocrelizumab acts on B cells, it also affects humoral immunity, thus reducing the vaccine response. In this study, we aimed to elucidate the relationship between the antibody response following rapid vaccination against hepatitis B virus (HBV) in multiple sclerosis (MS) patients receiving ocrelizumab treatment, and the time of vaccination. Materials and Methods A total of 220 MS patients were included in this retrospective analysis. The patients' baseline HBV serostatuses (HbsAg, Anti-HbsAb, Anti-HbcAb), previous drug history for MS, whether they were vaccinated against HBV in the past, vaccination status before or after ocrelizumab treatment, and protective antibody titers according to vaccination times, occult HBV incidence and initiation of antiviral treatment were evaluated. Results Forty-nine percent of MS patients using ocrelizumab were not vaccinated against HBV. The patients were divided into three groups according to their vaccination status as: individuals vaccinated in the past (7.3%, n = 16), vaccinated before treatment (4.5%, n = 10), and vaccinated after treatment (22.3%, n = 49). The antibody titers of the patients in the 6th month after ocrelizumab treatment were measured as 78 mIU/ml, 193 mIU/ml, and 0, respectively. The number of patients with occult HBV infection was 38. Conclusion In patients with a suspected diagnosis of MS, HBV serostatus should be evaluated at the beginning and if necessary, patients should be vaccinated in the early period. Vaccinating patients at least 1 month before initiating multiple sclerosis treatment is more effective in terms of protective antibody formation.
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Affiliation(s)
- Emine Rabia Koc
- Department of Neurology, Bursa Uludag University Faculty of Medicine, Turkey
| | - Omer Faruk Turan
- Department of Neurology, Bursa Uludag University Faculty of Medicine, Turkey
| | - Furkan Saridas
- Department of Neurology, Bursa Uludag University Faculty of Medicine, Turkey
| | - Bedirhan Menguc
- Department of Neurology, Bursa Uludag University Faculty of Medicine, Turkey
| | - Sema Nur Minaz
- Department of Neurology, Bursa Uludag University Faculty of Medicine, Turkey
| | - Guven Ozkaya
- Department of Biostatistics, Bursa Uludag University Faculty of Medicine, Turkey
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20
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Azzam A, Khaled H, El-Kayal ES, Gad FA, Omar S. Prevalence of occult hepatitis B virus infection in Egypt: a systematic review with meta-analysis. J Egypt Public Health Assoc 2023; 98:13. [PMID: 37491501 PMCID: PMC10368600 DOI: 10.1186/s42506-023-00138-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2022] [Accepted: 06/17/2023] [Indexed: 07/27/2023]
Abstract
BACKGROUND Occult hepatitis B virus (HBV) infection (OBI) is a major public health problem. The clinical importance of OBI stems from the fact that it can be transmitted to healthy individuals at extremely low viral load levels. Additionally, immunosuppression has the potential to trigger viral replication, which can result in life-threatening liver decompensation. Despite several studies examining the prevalence of OBI, the pooled prevalence of OBI in Egypt remains unknown, particularly among blood donors and high-risk individuals, to whom intervention should be targeted. METHODS A comprehensive literature search of the following databases was conducted from inception to October 2022 using the following keywords: occult hepatitis B virus infection or occult HBV infection or OBI and Egypt in MEDLINE [PubMed], Scopus, Google Scholar, and Web of Science. The review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement. I-squared and Cochran's Q were used to measure the heterogeneity between the studies, and based on the random effects model, results were reported as proportions (%) with a 95% confidence interval (CI). Analyses of subgroup analyses were conducted based on the target population. Sensitivity analyses were conducted using the leave-one-out approach to test the robustness of the results. RESULTS A total of 50 studies with 62 estimations of OBI were included, 19 in patients who were HBsAg-negative and anti-HBc-positive and 43 in patients who were HBsAg-negative. The highest prevalence (41%) was among multi-transfused patients according to studies that report occult hepatitis B virus prevalence in an HBsAg-negative population, while the pooled prevalence of OBI among patients on hemodialysis, patients with chronic hepatitis C infection, patients with hepatocellular carcinoma (HCC), and patients with liver cirrhosis was 17%, 10%, 24%, and 13%, respectively. On the other hand, among studies that report OBI prevalence in HBsAg-negative and anti-HBc-positive individuals, the pooled prevalence of OBI among blood donors, patients with chronic hepatitis C infection, and patients with HCC was 12%, 15%, and 31%, respectively. Also, the majority of studies examining the genetic background of OBI have found that genotype D is the most prevalent. CONCLUSION This study highlights the high prevalence in OBI among blood donors and high-risk populations in Egypt. The implementation of HBV nucleic acid amplification testing (NAT) may increase the safety of blood transfusions by excluding all HBV DNA-positive donations. However, the cost-effectiveness of these tests should be investigated.
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Affiliation(s)
- Ahmed Azzam
- Department of Microbiology and Immunology, Faculty of Pharmacy, Helwan University, Ain Helwan, Cairo, Egypt.
| | - Heba Khaled
- Department of Biochemistry, Faculty of Pharmacy, Cairo University, Cairo, Egypt
| | - Esraa S El-Kayal
- Biotechnology Program, Faculty of Science, Tanta University, Tanta, Egypt
| | - Fathy A Gad
- Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Sarah Omar
- Faculty of Medicine and Health Sciences, Aden University, Aden, Yemen
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21
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Alemu J, Gumi B, Tsegaye A, Abubeker A, Tadesse F, Shewaye A, Rahimeto Z, Mihret A, Mulu A, Gebremedhin A, Howe R. Frequency of viral infections in adolescent and adult in-patient Ethiopians with acute leukemia at presentation to a tertiary care teaching hospital: a cross-sectional study. Infect Agent Cancer 2023; 18:44. [PMID: 37438754 DOI: 10.1186/s13027-023-00519-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2023] [Accepted: 06/16/2023] [Indexed: 07/14/2023] Open
Abstract
BACKGROUND Leukemic patients are prone to infectious agents such as viruses due to dysregulated immune system resulting from infiltration of the bone marrow by malignant cells, chronic stimulation, reactivation of some viruses and viral pathogenicity as well as rarely from acquisition of a new infections leading to severe complications. However, the prevalence of these infections has not been systematically documented in resource-limited settings such as Ethiopia. OBJECTIVE To determine the prevalence of HBV, HCV, and HIV among adult and adolescent in-patients with acute leukemia before the administration of chemotherapy, at the Tikur Anbessa Specialized Hospital (TASH) in Addis Ababa, Ethiopia. METHODS A cross sectional study was conducted on 176 adult and adolescent inpatient Ethiopians, who were diagnosed with acute leukemia from April 2019 to June 2021. Socio-demographic characteristics and relevant clinical data were collected. Peripheral blood samples were collected and tested for HBV, HIV, and HCV using Enzyme-Linked Immunosorbent Assay (ELISA) and real-time PCR. Chi-square tests were used to assess associations between variables. RESULTS Of the 176 patients, 109(62%) were males. The median age was 25[IQR,18-35] yr, with a range from 13 to 76 year. The prevalence of HBV (positivity for HBsAg plus HBV DNA), HCV and HIV was 21.6%, 1.7%, and 1.7%, respectively. HBsAg was positive in 19 cases (10.8%). Among 157 HBsAg negative patients, 52(33.1%) were positive for Anti-HBcAg; of these seropositive cases, 47.5% were positive for HBV DNA. Most DNA positive, HBsAg negative cases (79.0%) had DNA concentrations below 200 IU/ml indicating true occult HBV infection (OBI). Of the 176 cases, 122 had a history of blood transfusions, but no statistically significant association was found between HBV infection and blood product transfusion history (P = 0.963). CONCLUSIONS The prevalence of HBV, HIV and HCV in patients with acute leukemia was similar to the national prevalence level of these infections. Given the HBsAg positivity and the high prevalence of occult hepatitis B infection in our study, these patients may be at increased risk for chemotherapy related hepatitis flares. Hence, clinicians caring these patients are strongly advised to screen their patients for HBV and also for HIV and HCV infections routinely.
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Affiliation(s)
- Jemal Alemu
- Department of Medical Laboratory Sciences, College of Health Sciences, Addis Ababa University, Addis, Ababa, Ethiopia.
- Armauer Hansen Research Institute, Addis Ababa, Ethiopia.
- Aklilu Lemma Institute of Pathobiology, Addis Ababa University, Addis Ababa, Ethiopia.
| | - Balako Gumi
- Aklilu Lemma Institute of Pathobiology, Addis Ababa University, Addis Ababa, Ethiopia
| | - Aster Tsegaye
- Department of Medical Laboratory Sciences, College of Health Sciences, Addis Ababa University, Addis, Ababa, Ethiopia
| | - Abdulaziz Abubeker
- Department of Internal Medicine, College of Health Sciences, Addis Ababa University, Addis, Ababa, Ethiopia
| | - Fisihatsion Tadesse
- Department of Internal Medicine, College of Health Sciences, Addis Ababa University, Addis, Ababa, Ethiopia
| | - Abel Shewaye
- Department of Laboratory, ALERT Hospital, Addis Ababa, Ethiopia
| | | | - Adane Mihret
- Armauer Hansen Research Institute, Addis Ababa, Ethiopia
- Department of Microbiology, Immunology and Parasitology, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia
| | | | - Amha Gebremedhin
- Department of Internal Medicine, College of Health Sciences, Addis Ababa University, Addis, Ababa, Ethiopia
| | - Rawleigh Howe
- Armauer Hansen Research Institute, Addis Ababa, Ethiopia
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22
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Chu HS, Killeen OJ, Hsieh YT, Su TH, Soong HK, Shih CL, Hu FR. Maximize Donor Cornea Use in a Hepatitis B Endemic Area via Serology Matching. Transplantation 2023; 107:1341-1347. [PMID: 36706071 DOI: 10.1097/tp.0000000000004460] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/28/2023]
Abstract
BACKGROUND This study aims to investigate the rationality of the allocation guidelines in a hepatitis B endemic area that uses corneas from hepatitis B donors. METHODS Under Taiwan's current guidelines, corneas donated from hepatitis B surface antigen (HBsAg)(+) donors can be allocated to HBsAg(+) or hepatitis B surface antibody recipients. From January 1, 2015, to December 31, 2019, corneas donated to National Taiwan University Hospital were divided into HBsAg(+), HBsAg(-)/hepatitis B core antibody (anti-HBc)(+), and HBsAg(-)/anti-HBc(-) groups. Hepatitis B virus (HBV) DNA extracted from corneoscleral rims was quantified by polymerase chain reaction and correlated with donor serum HBsAg, anti-HBc, and HBV DNA. Recipients of HBV DNA(+) grafts were called back for serology and serum HBV DNA tests. RESULTS The corneoscleral HBV DNA of 170 corneas (113 donors) was quantified, of which 45 corneas were from 28 HBsAg(+) donors, 87 were from 57 HBsAg(-)/anti-HBc(+) donors, and 38 were from 28 HBsAg(-)/anti-HBc(-) donors, and HBV DNA was detected in 80.0%, 9.2%, and 0% of the corneoscleral rims in each group. Donor anti-HBc(+) provided the highest sensitivity (1.00) and negative predictive value (1.00) for corneoscleral HBV DNA. Twenty-eight of 40 recipients (70%) using HBV DNA(+) grafts were called back, and none developed hepatitis in follow-up periods ranging from 6 to 55.5 mo. CONCLUSIONS Donor anti-HBc should be tested routinely with HBsAg. Allocating corneas from HBsAg(+) or anti-HBc(+) donors to HBsAg(+) or hepatitis B surface antibody recipients maximizes cornea usage from hepatitis B donors without compromising transplant safety in a hepatitis B endemic setting.
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Affiliation(s)
- Hsiao-Sang Chu
- Department of Ophthalmology, National Taiwan University Hospital, Taipei City, Taiwan
- National Eye Bank of Taiwan, Ministry of Health and Welfare, Taipei City, Taiwan
- Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei City, Taiwan
| | - Olivia J Killeen
- Department of Ophthalmology and Visual Sciences, W.K. Kellogg Eye Center, University of Michigan, Ann Arbor, MI
| | - Yi-Ting Hsieh
- Department of Ophthalmology, National Taiwan University Hospital, Taipei City, Taiwan
| | - Tung-Hung Su
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei City, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei City, Taiwan
| | - H Kaz Soong
- Department of Ophthalmology and Visual Sciences, W.K. Kellogg Eye Center, University of Michigan, Ann Arbor, MI
| | | | - Fung-Rong Hu
- Department of Ophthalmology, National Taiwan University Hospital, Taipei City, Taiwan
- National Eye Bank of Taiwan, Ministry of Health and Welfare, Taipei City, Taiwan
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23
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Stroffolini T, Stroffolini G. A Historical Overview on the Role of Hepatitis B and C Viruses as Aetiological Factors for Hepatocellular Carcinoma. Cancers (Basel) 2023; 15:cancers15082388. [PMID: 37190317 DOI: 10.3390/cancers15082388] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2023] [Revised: 04/14/2023] [Accepted: 04/19/2023] [Indexed: 05/17/2023] Open
Abstract
Hepatitis B virus (HBV) and hepatitis C virus (HCV) are the leading cause of hepatocellular carcinoma (HCC) worldwide. Currently, HBV-related HCC predominates in Sub-Saharan Africa and South-East-Asia, while HCV-related HCC predominates in northern Africa and in the western world. Liver cirrhosis is the underlying condition in most HBV cases and in nearly all HCV cases. Several cofactors, viral and non-viral, play a role in the progression toward HCC: dual HBV/HCV infection, HDV, HIV, alcohol intake, smoking, diabetes mellitus, obesity, and NAFLD/NASH. HBV vaccine is effective in preventing both infection and HCC; antiviral drugs may suppress HBV replication and eradicate HCV infection, halting progression to HCC. Inequalities exist between high- and low-income countries with respect to vaccine availability and access to antivirals. These factors represent barriers to the control of HCC incidence. Lack of an effective vaccine against HCV is also a serious barrier to HCV elimination and HCC prevention. The most crucial steps and knowledge that have arisen over time on the association between the two major hepatotropic viruses and HCC are discussed in this historical review.
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Affiliation(s)
- Tommaso Stroffolini
- Department of Tropical and Infectious Diseases, Policlinico Umberto I, 00161 Rome, Italy
| | - Giacomo Stroffolini
- Department of Infectious-Tropical Diseases and Microbiology, IRCCS Sacro Cuore Don Calabria Hospital, Via Don A. Sempreboni, 5, Negrar, 37024 Verona, Italy
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24
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Ho JCL, Mak JWY, Yip TCF, Lam HM, Cheng TY, Lam TO, Tam LS, Law MF, Cheung CKM, Ng SC, Wong VWS, Wong GLH. Risk of alanine aminotransferase flare in patients with previous hepatitis B virus exposure on biological modifier therapies-A population-based study. Liver Int 2023; 43:588-598. [PMID: 36516362 DOI: 10.1111/liv.15499] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/11/2022] [Revised: 09/22/2022] [Accepted: 11/28/2022] [Indexed: 01/01/2023]
Abstract
BACKGROUND It is uncertain whether biological therapies would increase the risk of hepatitis among patients with past hepatitis B virus (HBV) infection. This study aimed to evaluate the risk of alanine aminotransferase (ALT) flare in patients with past HBV infection while using biological therapies. METHODOLOGY Patients who received biological therapies for ≥3 months from 2000 to 2019 were identified from a population-based database in Hong Kong. Patients with past HBV infection were compared with a control group without prior HBV exposure. The primary endpoint was development of ALT flare within 5 years of starting biological therapies, defined as ALT >80 IU/L. RESULTS There were 2471 and 2394 patients with and without past HBV infection respectively. There was a non-significant increase in risk of ALT flare among the HBV-exposed group (27.6% vs. 23.7%, p = .055). In multivariable analysis, using prednisolone-equivalent dose of >20 mg daily, male sex and concomitant immunosuppressants were risk factors for ALT flare. The risk of ALT flare was significantly higher with anti-CD20 when compared to other biological agents (36.1% vs. 14.5%, p < .01), but was not significantly different among anti-tumour necrosis factor, anti-cytokine, Janus kinase inhibitors and T cell/B cell inhibitors or anti-integrin (15.2% vs. 14.6% vs. 11.7% vs. 11.1%, p = .82). Among patients with documented hepatitis B surface antigen seroreversion, 96% were on anti-CD20. CONCLUSIONS Our study further supports the current suggestion of prophylactic anti-viral before starting anti-CD20 in HBV-exposed patients. While other biological therapies appear to have a lower risk for ALT flare, this result needs further confirmation.
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Affiliation(s)
- Jacky C L Ho
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, Hong Kong
| | - Joyce W Y Mak
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, Hong Kong.,Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, Hong Kong.,Medical Data Analytics Centre, The Chinese University of Hong Kong, Hong Kong, Hong Kong
| | - Terry C F Yip
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, Hong Kong.,Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, Hong Kong.,Medical Data Analytics Centre, The Chinese University of Hong Kong, Hong Kong, Hong Kong
| | - Hong Man Lam
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, Hong Kong
| | - Tsz Yan Cheng
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, Hong Kong
| | - Tsz On Lam
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, Hong Kong
| | - Lai Shan Tam
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, Hong Kong
| | - Man Fai Law
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, Hong Kong
| | - Carmen K M Cheung
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, Hong Kong
| | - Siew C Ng
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, Hong Kong.,Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, Hong Kong
| | - Vincent W S Wong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, Hong Kong.,Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, Hong Kong.,Medical Data Analytics Centre, The Chinese University of Hong Kong, Hong Kong, Hong Kong
| | - Grace L H Wong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, Hong Kong.,Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, Hong Kong.,Medical Data Analytics Centre, The Chinese University of Hong Kong, Hong Kong, Hong Kong
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25
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Kazim NA, Lilo KM, Ibraheem SR, Saleh YA, Shabeeb SB. EVALUATION OF SEROLOGICAL SCREENING AND PCR-AMPLIFICATION OF HEPATITIS B VIRUS DNA AMONG IRAQI BLOOD DONORS. WIADOMOSCI LEKARSKIE (WARSAW, POLAND : 1960) 2023; 75:2915-2919. [PMID: 36723303 DOI: 10.36740/wlek202212104] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Abstract
OBJECTIVE The aim: Infection with the hepatitis B virus (HBV) caused by blood transfusion is a big problem throughout the world. The aim of study is to determine the faster and more accurate methods for detection of hepatitis B infections by serological screening and PCR- amplification. PATIENTS AND METHODS Materials and methods: A total of 140528 donors were tested for HBsAg and total anti-HBc from January to October 2021 in Iraq's National Blood Transfusion Center; however, only 100 samples with HBsAg (-) and anti-HBc (+) were collected and tested for HBV DNA using quantitative real-time PCR. RESULTS Results: From 2015 to 2021, the percentage of HBsAg positive donors was 0.33 percent in 2015, 0.32 percent in 2016, 0.30 percent in 2017, 0.28 percent in 2018, 0.23 percent in 2019, 0.22 percent in 2020, and 0.27 percent in 2021. Between January and October of 2021, the overall anti-HBc rate among the (140528) donors was 4.42 percent. According to our findings, only 7% of blood samples from NBTC donors with HBsAg (-) anti-HBc (+) were positive for HBV DNA. The results showed no significant change in HBs Ag (+) and total anti-HBc rates among blood donors between 2015 and 2021. CONCLUSION Conclusions: HBV infection could be transmitted from a blood donor with OBI. PCR (RT PCR) is substantially more sensitive and effective. Despite this the use of an anti-HBc test for blood donors could be seen as a second choice to control HBV from spreading during blood transfusions.
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Affiliation(s)
- Noor A Kazim
- BIOTECHNOLOGY DEPARTMENT, COLLEGE OF SCIENCE, UNIVERSITY OF BAGHDAD, BAGHDAD, IRAQ
| | - Kareem M Lilo
- MINISTRY OF HEALTH, NATIONAL CENTER FOR DRUG RESEARCH AND CONTROL, BAGHDAD, IRAQ
| | - Shaima R Ibraheem
- BIOTECHNOLOGY DEPARTMENT, COLLEGE OF SCIENCE, UNIVERSITY OF BAGHDAD, BAGHDAD, IRAQ
| | - Yaqoob A Saleh
- MINISTRY OF HEALTHE, NATIONAL BLOOD TRANSFUSION CENTER, BAGHDAD, IRAQ
| | - Sally B Shabeeb
- MINISTRY OF HEALTHE, NATIONAL BLOOD TRANSFUSION CENTER, BAGHDAD, IRAQ
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26
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Ward JW, Wanlapakorn N, Poovorawan Y, Shouval D. Hepatitis B Vaccines. PLOTKIN'S VACCINES 2023:389-432.e21. [DOI: 10.1016/b978-0-323-79058-1.00027-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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27
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Kramvis A, Chang KM, Dandri M, Farci P, Glebe D, Hu J, Janssen HLA, Lau DTY, Penicaud C, Pollicino T, Testoni B, Van Bömmel F, Andrisani O, Beumont-Mauviel M, Block TM, Chan HLY, Cloherty GA, Delaney WE, Geretti AM, Gehring A, Jackson K, Lenz O, Maini MK, Miller V, Protzer U, Yang JC, Yuen MF, Zoulim F, Revill PA. A roadmap for serum biomarkers for hepatitis B virus: current status and future outlook. Nat Rev Gastroenterol Hepatol 2022; 19:727-745. [PMID: 35859026 PMCID: PMC9298709 DOI: 10.1038/s41575-022-00649-z] [Citation(s) in RCA: 56] [Impact Index Per Article: 18.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 06/16/2022] [Indexed: 12/13/2022]
Abstract
Globally, 296 million people are infected with hepatitis B virus (HBV), and approximately one million people die annually from HBV-related causes, including liver cancer. Although there is a preventative vaccine and antiviral therapies suppressing HBV replication, there is no cure. Intensive efforts are under way to develop curative HBV therapies. Currently, only a few biomarkers are available for monitoring or predicting HBV disease progression and treatment response. As new therapies become available, new biomarkers to monitor viral and host responses are urgently needed. In October 2020, the International Coalition to Eliminate Hepatitis B Virus (ICE-HBV) held a virtual and interactive workshop on HBV biomarkers endorsed by the International HBV Meeting. Various stakeholders from academia, clinical practice and the pharmaceutical industry, with complementary expertise, presented and participated in panel discussions. The clinical utility of both classic and emerging viral and immunological serum biomarkers with respect to the course of infection, disease progression, and response to current and emerging treatments was appraised. The latest advances were discussed, and knowledge gaps in understanding and interpretation of HBV biomarkers were identified. This Roadmap summarizes the strengths, weaknesses, opportunities and challenges of HBV biomarkers.
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Affiliation(s)
- Anna Kramvis
- Hepatitis Virus Diversity Research Unit, Department of Internal Medicine, School of Clinical Medicine, University of the Witwatersrand, Johannesburg, South Africa.
| | - Kyong-Mi Chang
- The Corporal Michael J. Crescenz Veterans Affairs Medical Center and University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA
| | - Maura Dandri
- Department of Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
- German Centre for Infection Research (DZIF), Hamburg-Lübeck-Borstel-Riems partner site, Hamburg, Germany
| | - Patrizia Farci
- Hepatic Pathogenesis Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA
| | - Dieter Glebe
- National Reference Center for Hepatitis B Viruses and Hepatitis D Viruses, Institute of Medical Virology, Justus Liebig University Giessen, Giessen, Germany
- German Center for Infection Research (DZIF), Partner Site Giessen-Marburg-Langen, Giessen, Germany
| | - Jianming Hu
- Department of Microbiology and Immunology, The Pennsylvania State University College of Medicine, Philadelphia, PA, USA
| | - Harry L A Janssen
- Toronto Centre for Liver Disease, University of Toronto, Toronto, Canada
| | - Daryl T Y Lau
- Division of Gastroenterology and Hepatology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
| | - Capucine Penicaud
- Peter Doherty Institute for Infection and Immunity, Melbourne, Australia
| | - Teresa Pollicino
- Laboratory of Molecular Hepatology, Department of Human Pathology, University Hospital "G. Martino" of Messina, Messina, Italy
| | - Barbara Testoni
- INSERM U1052, CNRS UMR-5286, Cancer Research Center of Lyon (CRCL), Lyon, France
- University of Lyon, Université Claude-Bernard (UCBL), Lyon, France
| | - Florian Van Bömmel
- Department of Hepatology, Leipzig University Medical Center, Leipzig, Germany
| | - Ourania Andrisani
- Basic Medical Sciences, Purdue University, West Lafayette, Indiana, USA
| | | | | | - Henry L Y Chan
- Chinese University of Hong Kong, Shatin, Hong Kong
- Union Hospital, Shatin, Hong Kong
| | | | | | - Anna Maria Geretti
- Roche Pharma Research & Early Development, Basel, Switzerland
- Department of Infectious Diseases, Fondazione PTV, Faculty of Medicine, University of Rome Tor Vergata, Rome, Italy
- Department of Infectious Diseases, School of Immunology & Microbial Sciences, King's College London, London, UK
| | - Adam Gehring
- Toronto Centre for Liver Disease, University Health Network, Toronto, Canada
| | - Kathy Jackson
- Victorian Infectious Diseases Reference Laboratory, Royal Melbourne Hospital at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia
| | | | - Mala K Maini
- Division of Infection & Immunity, Institute of Immunity & Transplantation, University College London, London, UK
| | - Veronica Miller
- Forum for Collaborative Research, University of California Berkeley School of Public Health, Washington DC Campus, Washington, DC, USA
| | - Ulrike Protzer
- Institute of Virology, School of Medicine, Technical University of Munich, Helmholtz Zentrum München, Munich, Germany
| | | | - Man-Fung Yuen
- Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong, China
- State Key Laboratory of Liver Research, The University of Hong Kong, Hong Kong, China
| | - Fabien Zoulim
- INSERM Unit 1052 - Cancer Research Center of Lyon, Hospices Civils de Lyon, Lyon University, Lyon, France
| | - Peter A Revill
- Victorian Infectious Diseases Reference Laboratory, Royal Melbourne Hospital at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.
- Department of Microbiology and Immunology, University of Melbourne, Parkville, Victoria, Australia.
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Ndow G, Cessay A, Cohen D, Shimakawa Y, Gore ML, Tamba S, Ghosh S, Sanneh B, Baldeh I, Njie R, D’Alessandro U, Mendy M, Thursz M, Chemin I, Lemoine M. Prevalence and Clinical Significance of Occult Hepatitis B Infection in The Gambia, West Africa. J Infect Dis 2022; 226:862-870. [PMID: 34160616 PMCID: PMC9470103 DOI: 10.1093/infdis/jiab327] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2021] [Accepted: 06/21/2021] [Indexed: 01/05/2023] Open
Abstract
BACKGROUND Prevalence and clinical outcomes of occult hepatitis B infection (OBI) have been poorly studied in Africa. METHODS Using the PROLIFICA cohort, we compared the prevalence of OBI between hepatitis B surface antigen (HBsAg)-negative healthy adults screened from the general population (controls) and HBsAg-negative patients with advanced liver disease (cases), and estimated the population attributable fraction for the effect of OBI on advanced liver disease. RESULTS OBI prevalence was significantly higher among cases (15/82, 18.3%) than controls (31/330, 9.4%, P = .03). After adjusting for age, sex, and anti-hepatitis C virus (HCV) serology, OBI was significantly associated with advanced liver disease (odds ratio, 2.8; 95% confidence interval [CI], 1.3-6.0; P = .006). In HBsAg-negative people, the proportions of advanced liver disease cases attributable to OBI and HCV were estimated at 12.9% (95% CI, 7.5%-18.1%) and 16.9% (95% CI, 15.2%-18.6%), respectively. CONCLUSIONS OBI is endemic and an independent risk factor for advanced liver disease in The Gambia, West Africa. This implies that HBsAg-negative people with liver disease should be systematically screened for OBI. Moreover, the impact of infant hepatitis B immunization to prevent end-stage liver disease might be higher than previous estimates based solely on HBsAg positivity.
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Affiliation(s)
- Gibril Ndow
- Division of Digestive Diseases, Department of Metabolism, Digestion, and Reproduction, Imperial College London, London, United Kingdom
- Disease Control and Elimination, Medical Research Council Unit The Gambia, London School of Hygiene and Tropical Medicine, Fajara, The Gambia
| | - Amie Cessay
- Disease Control and Elimination, Medical Research Council Unit The Gambia, London School of Hygiene and Tropical Medicine, Fajara, The Gambia
| | - Damien Cohen
- INSERM U1052, CNRS UMR5286, Center de Recherche en Cancérologie, Université Claude Bernard, Lyon, France
| | - Yusuke Shimakawa
- Unité D’Épidémiologie des Maladies Émergentes, Institut Pasteur, Paris, France
| | - Mindy L Gore
- National Heart and Lung Institute, Faculty of Medicine, Imperial College London, London, United Kingdom
| | - Saydiba Tamba
- Edward Francis Small Teaching Hospital, Banjul, The Gambia
| | - Sumantra Ghosh
- INSERM U1052, CNRS UMR5286, Center de Recherche en Cancérologie, Université Claude Bernard, Lyon, France
| | - Bakary Sanneh
- National Public Health Laboratories, Ministry of Health, Kotu, The Gambia
| | - Ignatius Baldeh
- National Public Health Laboratories, Ministry of Health, Kotu, The Gambia
| | - Ramou Njie
- Edward Francis Small Teaching Hospital, Banjul, The Gambia
- School of Medicine and Allied Health Sciences, University of The Gambia, Banjul, The Gambia
| | - Umberto D’Alessandro
- Disease Control and Elimination, Medical Research Council Unit The Gambia, London School of Hygiene and Tropical Medicine, Fajara, The Gambia
| | - Maimuna Mendy
- International Agency for Research on Cancer, World Health Organization, Lyon, France
| | - Mark Thursz
- Division of Digestive Diseases, Department of Metabolism, Digestion, and Reproduction, Imperial College London, London, United Kingdom
| | - Isabelle Chemin
- INSERM U1052, CNRS UMR5286, Center de Recherche en Cancérologie, Université Claude Bernard, Lyon, France
| | - Maud Lemoine
- Division of Digestive Diseases, Department of Metabolism, Digestion, and Reproduction, Imperial College London, London, United Kingdom
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Ostankova YV, Serikova EN, Semenov AV, Totolian AA. Method for hepatitis B virus DNA detecting in biological material at low viral load based on nested PCR with detection on three viral targets in real-time mode. Klin Lab Diagn 2022; 67:530-537. [PMID: 36099463 DOI: 10.51620/0869-2084-2022-67-9-530-537] [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] [Indexed: 06/15/2023]
Abstract
A method has been developed for HBV DNA finding in biological material at low viral load based on nested PCR with real-time detection of three viral targets. When developing the method, blood plasma samples were used from 128 CHB patients living in the regions of the Russian Federation and countries of Central Asia and 173 hemodialysis center patients living in the North-West Federal District. Analytical sensitivity was tested using the stepwise dilution method. HBV was detected by nested PCR. According to the method developed by us, at the first stage, the HBV DNA is amplified using at the first stage oligonucleotides complementary to the greatest similarity regions of the various HBV isolates genomes flanking the entire virus genome. At the second stage, when using the amplification product of the first stage as a template, PCR was performed using three pairs of oligonucleotides and the corresponding oligonucleotide fluorescently labeled probes to three virus genome regions (Core gene, S gene and X gene), as well as one pair of primers and the corresponding probe complementary to a human HPRT gene region. The method sensitivity for DNA extraction from plasma with a 100 μl volume was 10 IU/ml. Obtaining a threshold Ct cycle for only one fluorophore may indicate the presence of HBV DNA in the sample at a load of less than 10 IU/ml, HBV detection in this case is possible with a repeated PCR study of the corresponding sample with HBV DNA extraction from an increased plasma volume (200-1000 μl). The developed method makes it possible to identify the disease in various HBV subgenotypes and can be used to diagnose CHB in the population and risk groups, including those with the HBsAg-negative form of the disease.
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30
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Khamseh A, Poortahmasebi V, Soltani S, Nasiritoosi M, Jafarian A, Ghaziasadi A, Norouzi M, Ghorbani S, Eslami N, Jazayeri SM. Characterization of occult hepatitis B infection among Iranian liver transplant recipients. J Clin Lab Anal 2022; 36:e24614. [PMID: 36086860 PMCID: PMC9551123 DOI: 10.1002/jcla.24614] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2021] [Revised: 07/05/2022] [Accepted: 07/05/2022] [Indexed: 11/17/2022] Open
Abstract
Background The prevalence of occult hepatitis B infection (OBI) among Iranian liver transplant recipient patients has not been explored yet. The present study aimed to determine the OBI prevalence among Iranian liver transplant recipients. Methods This study encompassed 97 patients having undergone liver transplantation due to several clinical backgrounds in the Liver Transplantation Center, Tehran, Iran. After serological evaluation, two different types of PCR methods were applied for amplification of HBV DNA, followed by the direct sequencing of whole hepatitis B virus (HBV) surface genes. Results At the time of admission, none of the patients were positive for HBsAg. However, 24 (25%), 12 (12.3%), and 5 (5.1%) cases were positive for anti‐HBc, hepatitis C virus (HCV), and hepatitis delta virus (HDV) antibodies, respectively. Moreover, two males were positive for OBI (2.1%). Both were positive for anti‐HBc and negative for anti‐HBs, anti‐HCV, and anti‐HDV. HBV‐related cirrhosis was the underlying reason for their liver transplantation. HBsAg sequences revealed no amino acid substitution. Conclusions The prevalence of OBI in the Iranian liver transplantation patients was relatively low. Future longitudinal studies with a larger sample size are suggested to explore the significance of this clinical finding, including the reactivation of cryptic HBV DNA, in liver transplant subjects.
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Affiliation(s)
- Azam Khamseh
- Research Center for Clinical Virology, Tehran University of Medical Sciences, Tehran, Iran.,Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | - Vahdat Poortahmasebi
- Research Center for Clinical Virology, Tehran University of Medical Sciences, Tehran, Iran.,Infectious and Tropical Disease Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.,Department of Bacteriology and Virology, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Saber Soltani
- Research Center for Clinical Virology, Tehran University of Medical Sciences, Tehran, Iran.,Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohsen Nasiritoosi
- Liver Transplantation Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Ali Jafarian
- Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | - Azam Ghaziasadi
- Research Center for Clinical Virology, Tehran University of Medical Sciences, Tehran, Iran.,Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | - Mehdi Norouzi
- Research Center for Clinical Virology, Tehran University of Medical Sciences, Tehran, Iran.,Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | - Saied Ghorbani
- Research Center for Clinical Virology, Tehran University of Medical Sciences, Tehran, Iran.,Department of Virology, Iran University of Medical Sciences, Tehran, Iran
| | - Narges Eslami
- Infectious and Tropical Disease Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.,Department of Bacteriology and Virology, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Seyed Mohammad Jazayeri
- Research Center for Clinical Virology, Tehran University of Medical Sciences, Tehran, Iran.,Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.,Department of Virology, Iran University of Medical Sciences, Tehran, Iran
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31
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Saitta C, Caruso A, Maimone S, Filomia R, Cacciola I, Caccamo G, Franzè MS, Pitrone C, Alibrandi A, Gaeta M, Mandraffino G, Squadrito G, Raimondo G. Antibody to hepatitis B virus core antigen positivity is a predictor of non-alcoholic fatty liver disease severity. Intern Emerg Med 2022; 17:1609-1616. [PMID: 35332431 DOI: 10.1007/s11739-022-02971-5] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/10/2021] [Accepted: 03/08/2022] [Indexed: 12/16/2022]
Abstract
Insufficient information is available about co-factors favoring the progression of non-alcoholic fatty liver disease (NAFLD) toward cirrhosis. We aimed to evaluate the impact of a limited alcohol intake and of occult hepatitis B virus (HBV) infection (OBI) on the severity of NAFLD. Three-hundred-seventy-four alcohol non-abusers and HBV surface antigen negative NAFLD patients (223 males; mean age 55.4 years), consecutively admitted to the outpatients clinic of a referral liver unit from January 1st, 2018 to December 31st, 2019, were studied. Anti-HBV core antigen antibody [(anti-HBc), a surrogate marker of OBI] was assessed in all patients. Patients were distinguished between teetotal and moderate alcohol consumers (intake of less than 30 g and 20 g if males or females, respectively). Liver fibrosis was non-invasively assessed by FIB-4 and transient elastography. Uni- and multivariate analyses were performed to identify predictors of advanced fibrosis. Patients had a mean BMI of 28.5 kg/m2, and the majority presented metabolic and cardio-vascular comorbidities [258 patients (69%) had insulin resistance/diabetes, 249 (66.6%) dyslipidemia, 200 (53.5%) arterial hypertension]. Multivariate analysis showed that anti-HBc positivity (p = 0.046, OR 2.153) was a factor associated with advanced fibrosis at FIB-4 score testing, whereas moderate alcohol intake was not associated with severe NAFLD both at FIB-4 and transient elastography evaluations. The study showed that a moderate alcohol intake has no impact on NAFLD severity and suggested that OBI might negatively affect the NAFLD outcome.
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Affiliation(s)
- Carlo Saitta
- Division of Medicine and Hepatology, University Hospital of Messina, Messina, Italy.
- Division of Medicine and Hepatology, Department of Clinical and Experimental Medicine, University of Messina, Via Consolare Valeria, 1, 98124, Messina, Italy.
| | - Alessia Caruso
- Division of Medicine and Hepatology, University Hospital of Messina, Messina, Italy
- Division of Medicine and Hepatology, Department of Clinical and Experimental Medicine, University of Messina, Via Consolare Valeria, 1, 98124, Messina, Italy
| | - Sergio Maimone
- Division of Medicine and Hepatology, University Hospital of Messina, Messina, Italy
| | - Roberto Filomia
- Division of Medicine and Hepatology, University Hospital of Messina, Messina, Italy
| | - Irene Cacciola
- Division of Medicine and Hepatology, University Hospital of Messina, Messina, Italy
- Division of Medicine and Hepatology, Department of Clinical and Experimental Medicine, University of Messina, Via Consolare Valeria, 1, 98124, Messina, Italy
| | - Gaia Caccamo
- Division of Medicine and Hepatology, University Hospital of Messina, Messina, Italy
| | - Maria Stella Franzè
- Division of Medicine and Hepatology, University Hospital of Messina, Messina, Italy
- Division of Medicine and Hepatology, Department of Clinical and Experimental Medicine, University of Messina, Via Consolare Valeria, 1, 98124, Messina, Italy
| | - Concetta Pitrone
- Division of Medicine and Hepatology, University Hospital of Messina, Messina, Italy
- Division of Medicine and Hepatology, Department of Clinical and Experimental Medicine, University of Messina, Via Consolare Valeria, 1, 98124, Messina, Italy
| | - Angela Alibrandi
- Division of Statistical and Mathematical Sciences, Department of Economics, University of Messina, Messina, Italy
| | - Michele Gaeta
- Division of Diagnostic Imaging, Department of Biomedical and Dental Sciences and of Morphologic and Functional Imaging, University of Messina, Messina, Italy
| | - Giuseppe Mandraffino
- Division of Medicine and Hepatology, Department of Clinical and Experimental Medicine, University of Messina, Via Consolare Valeria, 1, 98124, Messina, Italy
- Division of Internal Medicine, University Hospital of Messina, Messina, Italy
| | - Giovanni Squadrito
- Division of Medicine and Hepatology, Department of Clinical and Experimental Medicine, University of Messina, Via Consolare Valeria, 1, 98124, Messina, Italy
- Division of Internal Medicine, University Hospital of Messina, Messina, Italy
| | - Giovanni Raimondo
- Division of Medicine and Hepatology, University Hospital of Messina, Messina, Italy
- Division of Medicine and Hepatology, Department of Clinical and Experimental Medicine, University of Messina, Via Consolare Valeria, 1, 98124, Messina, Italy
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32
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Takuissu GR, Kenmoe S, Amougou Atsama M, Atenguena Okobalemba E, Mbaga DS, Ebogo-Belobo JT, Bowo-Ngandji A, Oyono MG, Magoudjou-Pekam JN, Kame-Ngasse GI, Menkem EZ, Selly Ngaloumo AA, Banlock ATR, Feudjio AF, Zemnou-Tepap C, Meta-Djomsi D, Nyimbe Mviena GL, Nyebe Eloundou I, Yéngué JF, Kenfack-Zanguim J, Ndzie Ondigui JL, Zekeng Mekontchou RM, Touangnou-Chamda SA, Kamtchueng Takeu Y, Taya-Fokou JB, Mbongue Mikangue CA, Kenfack-Momo R, Kengne-Nde C, Nkie Esemu S, Njouom R, Ndip L. Global epidemiology of occult hepatitis B virus infections in blood donors, a systematic review and meta-analysis. PLoS One 2022; 17:e0272920. [PMID: 35994469 PMCID: PMC9394819 DOI: 10.1371/journal.pone.0272920] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2022] [Accepted: 07/28/2022] [Indexed: 11/19/2022] Open
Abstract
This study aimed to assess the global prevalence of occult hepatitis B in blood donors. We searched PubMed, Web of Science, Global Index Medicus, and Excerpta Medica Database. Study selection and data extraction were performed by at least two independent investigators. Heterogeneity (I2) was assessed using the χ2 test on the Cochran Q statistic and H parameters. Sources of heterogeneity were explored by subgroup analyses. This study is registered with PROSPERO, number CRD42021252787. We included 82 studies in this meta-analysis. The overall prevalence of OBI was 6.2% (95% CI: 5.4-7.1) in HBsAg negative and anti-HBc positive blood donors. Only sporadic cases of OBI were reported in HBsAg negative and anti-HBc negative blood donors. The overall prevalence of OBI was 0.2% (95% CI: 0.1-0.4) in HBsAg negative blood donors. The prevalence of OBI was generally higher in countries with low-income economic status. The results of this study show that despite routine screening of blood donors for hepatitis B, the transmission of HBV by blood remains possible via OBI and/or a seronegative window period; hence there is a need for active surveillance and foremost easier access to molecular tests for the screening of blood donors before transfusion.
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Affiliation(s)
- Guy Roussel Takuissu
- Centre for Food, Food Security and Nutrition Research, Institute of Medical Research and Medicinal Plants Studies, Yaounde, Cameroon
| | - Sebastien Kenmoe
- Department of Microbiology and Parasitology, University of Buea, Buea, Cameroon
| | - Marie Amougou Atsama
- Centre de Recherche sur les Maladies Émergentes et Re-Emergentes, Institut de Recherches Médicales et d’Etudes des Plantes Médicinales, Yaounde, Cameroon
| | | | | | - Jean Thierry Ebogo-Belobo
- Medical Research Centre, Institute of Medical Research and Medicinal Plants Studies, Yaounde, Cameroon
| | - Arnol Bowo-Ngandji
- Department of Microbiology, The University of Yaounde I, Yaounde, Cameroon
| | - Martin Gael Oyono
- Centre for Research on Health and Priority Pathologies, Institute of Medical Research and Medicinal Plants Studies, Yaounde, Cameroon
| | | | - Ginette Irma Kame-Ngasse
- Medical Research Centre, Institute of Medical Research and Medicinal Plants Studies, Yaounde, Cameroon
| | | | | | | | | | | | - Dowbiss Meta-Djomsi
- Centre de Recherche sur les Maladies Émergentes et Re-Emergentes, Institut de Recherches Médicales et d’Etudes des Plantes Médicinales, Yaounde, Cameroon
| | | | | | | | | | | | | | | | - Yrene Kamtchueng Takeu
- Medical Research Centre, Institute of Medical Research and Medicinal Plants Studies, Yaounde, Cameroon
| | | | | | - Raoul Kenfack-Momo
- Department of Biochemistry, The University of Yaounde I, Yaounde, Cameroon
| | - Cyprien Kengne-Nde
- Epidemiological Surveillance, Evaluation and Research Unit, National AIDS Control Committee, Douala, Cameroon
| | | | - Richard Njouom
- Virology Department, Centre Pasteur of Cameroon, Yaounde, Cameroon
| | - Lucy Ndip
- Department of Microbiology and Parasitology, University of Buea, Buea, Cameroon
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Lalana Garcés M, Ortiz Pastor O, Solé Enrech G, Guerra-Ruiz AR, Casals Mercadal G, Almería Lafuente A, Ballesteros Vizoso MA, Medina PG, Salgüero Fernández S, Zamora Trillo A, Aured de la Serna I, Hurtado JC, Pérez-Del-Pulgar S, Forns X, Morales Ruiz M. Control of occult hepatitis B virus infection. ADVANCES IN LABORATORY MEDICINE / AVANCES EN MEDICINA DE LABORATORIO 2022. [DOI: 10.1515/almed-2022-0065] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
Abstract
Background
The diagnosis of hepatitis B virus (HBV) infection requires HBV DNA testing and serologic testing for detection of the surface antigen (HBsAg) and the hepatitis B core antibody (anti-HBc). There is a population of patients with occult HBV infection (OBI), which is not detected by HBsAg or HBV DNA quantification in blood, despite the presence of active replication in the liver.
Scope
This document provides a definition of OBI and describes the diagnostic techniques currently used. It also addresses the detection of patients with risk factors and the need for screening for OBI in these patients.
Summary
Correct diagnosis of OBI prevents HBV reactivation and transmission. Diagnosis of OBI is based on the detection of HBV DNA in patients with undetectable HBsAg in blood.
Perspectives
A high number of patients with OBI may remain undiagnosed; therefore, screening for OBI in patients with factor risks is essential. For a correct diagnosis of OBI, it is necessary that new markers such as ultrasensitive HBsAg are incorporated, and a more comprehensive marker study is performed by including markers such as cccDNA.
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Affiliation(s)
- Marta Lalana Garcés
- Comisión de Valoración Bioquímica de la Enfermedad Hepática, Sociedad Española de Medicina de Laboratorio (SEQC-ML) , Barcelona , Spain
- Servicio de Análisis Clínicos, Hospital de Barbastro , Huesca , Spain
| | - Oihana Ortiz Pastor
- Comisión de Valoración Bioquímica de la Enfermedad Hepática, Sociedad Española de Medicina de Laboratorio (SEQC-ML) , Barcelona , Spain
- Servicio de Bioquímica Clínica, Hospital Universitario Miguel Servet , Zaragoza , Spain
| | - Gemma Solé Enrech
- Comisión de Valoración Bioquímica de la Enfermedad Hepática, Sociedad Española de Medicina de Laboratorio (SEQC-ML) , Barcelona , Spain
- Servei de laboratori, UDIAT-CD, Corporació Sanitaria Parc Taulí , Sabadell , Spain
| | - Armando R. Guerra-Ruiz
- Comisión de Valoración Bioquímica de la Enfermedad Hepática, Sociedad Española de Medicina de Laboratorio (SEQC-ML) , Barcelona , Spain
- Servicio de Análisis Clínicos, Hospital Universitario Marqués de Valdecilla , Santander , Spain
| | - Gregori Casals Mercadal
- Comisión de Valoración Bioquímica de la Enfermedad Hepática, Sociedad Española de Medicina de Laboratorio (SEQC-ML) , Barcelona , Spain
- Servicio de Bioquímica y Genética Molecular, CDB, Hospital Clínic de Barcelona, IDIBAPS, CIBEREHD , Barcelona , Spain
| | - Alejandro Almería Lafuente
- Comisión de Valoración Bioquímica de la Enfermedad Hepática, Sociedad Española de Medicina de Laboratorio (SEQC-ML) , Barcelona , Spain
- Servicio de Bioquímica Clínica, Hospital Royo Villanova , Zaragoza , Spain
| | - María Antonieta Ballesteros Vizoso
- Comisión de Valoración Bioquímica de la Enfermedad Hepática, Sociedad Española de Medicina de Laboratorio (SEQC-ML) , Barcelona , Spain
- Servicio de Análisis Clínicos, Hospital Universitario Son Espases , Palma de Mallorca , Spain
| | - Pablo Gabriel Medina
- Comisión de Valoración Bioquímica de la Enfermedad Hepática, Sociedad Española de Medicina de Laboratorio (SEQC-ML) , Barcelona , Spain
- Servicio de Bioquímica Clínica, Hospital Universitari Vall d’Hebron , Barcelona , Spain
| | - Sergio Salgüero Fernández
- Comisión de Valoración Bioquímica de la Enfermedad Hepática, Sociedad Española de Medicina de Laboratorio (SEQC-ML) , Barcelona , Spain
- Servicio de Análisis Clínicos, Hospital Universitario Fundación Alcorcón , Madrid , Spain
| | - Angielys Zamora Trillo
- Comisión de Valoración Bioquímica de la Enfermedad Hepática, Sociedad Española de Medicina de Laboratorio (SEQC-ML) , Barcelona , Spain
- Servicio de Bioquímica Clínica, Hospital General Universitario Gregorio Marañón , Madrid , Spain
| | | | - Juan Carlos Hurtado
- Servicio de Microbiología, CDB, Hospital Clínic de Barcelona, Universitat de Barcelona , Barcelona , Spain
- Instituto de Salud Global de Barcelona (ISGlobal) , Barcelona , Spain
| | - Sofía Pérez-Del-Pulgar
- Servicio de Hepatología, Hospital Clínic de Barcelona, IDIBAPS, CIBEREHD , Barcelona , Spain
| | - Xavier Forns
- Servicio de Hepatología, Hospital Clínic de Barcelona, IDIBAPS, CIBEREHD , Barcelona , Spain
| | - Manuel Morales Ruiz
- Comisión de Valoración Bioquímica de la Enfermedad Hepática, Sociedad Española de Medicina de Laboratorio (SEQC-ML) , Barcelona , Spain
- Servicio de Bioquímica y Genética Molecular, CDB, Hospital Clínic de Barcelona, IDIBAPS, CIBEREHD , Barcelona , Spain
- Departamento de Biomedicina de la Facultad de Medicina y Ciencias de la Salud-Universidad de Barcelona , Barcelona , Spain
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34
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Lalana Garcés M, Pastor OO, Solé Enrech G, Guerra-Ruiz AR, Mercadal GC, Almería Lafuente A, Ballesteros Vizoso MA, Medina PG, Salgüero Fernández S, Zamora Trillo A, Aured de la Serna I, Hurtado JC, Pérez-Del-Pulgar S, Forns X, Morales Ruiz M. Revisión de la infección oculta por el virus de la hepatitis B. ADVANCES IN LABORATORY MEDICINE / AVANCES EN MEDICINA DE LABORATORIO 2022. [DOI: 10.1515/almed-2021-0084] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
Resumen
Introducción
El diagnóstico actual del virus de la hepatitis B (VHB) está basado en la detección mediante técnicas moleculares de ADN de VHB y ensayos serológicos, como el antígeno de superficie (HBsAg) y anticuerpos frente al core VHB (anti-HBc). Existe un grupo de pacientes con infección oculta de VHB (OBI) en los que estos ensayos no son capaces de detectar el HBsAg ni la cuantificación de ADN de VHB en sangre, aunque exista replicación activa en hígado.
Contenido
El documento define la OBI, y los métodos actuales para su diagnóstico. También aborda la detección de pacientes con factores de riesgo y la necesidad de realizar el cribado de OBI en ellos.
Resumen
Un correcto diagnóstico de OBI, previene la reactivación del VHB y su transmisión. El diagnóstico de OBI actualmente está basado en la detección de ADN de VHB en pacientes con HBsAg indetectable en sangre.
Perspectivas
Un número elevado de pacientes con OBI puede permanecer sin diagnosticar. Es importante realizar el cribado de OBI en determinados pacientes con factores de riesgo. La introducción de nuevos marcadores, como el HBsAg ultrasensible, y estudios más profundos de marcadores, como el ADNccc hepático, serán necesarios para un correcto diagnóstico de OBI.
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Affiliation(s)
- Marta Lalana Garcés
- Comisión de Valoración Bioquímica de la Enfermedad Hepática , Sociedad Española de Medicina de Laboratorio (SEQC-ML) , Barcelona , España
- Servicio de Análisis Clínicos , Hospital de Barbastro , Huesca , España
| | - Oihana Ortiz Pastor
- Comisión de Valoración Bioquímica de la Enfermedad Hepática , Sociedad Española de Medicina de Laboratorio (SEQC-ML) , Barcelona , España
- Servicio de Bioquímica Clínica , Hospital Universitario Miguel Servet , Zaragoza , España
| | - Gemma Solé Enrech
- Comisión de Valoración Bioquímica de la Enfermedad Hepática , Sociedad Española de Medicina de Laboratorio (SEQC-ML) , Barcelona , España
- Servei de laboratori , UDIAT-CD. Corporació Sanitaria Parc Taulí , Sabadell , España
| | - Armando Raul Guerra-Ruiz
- Comisión de Valoración Bioquímica de la Enfermedad Hepática , Sociedad Española de Medicina de Laboratorio (SEQC-ML) , Barcelona , España
- Servicio de Análisis Clínicos , Hospital Universitario Marqués de Valdecilla , Santander , España
| | - Gregori Casals Mercadal
- Comisión de Valoración Bioquímica de la Enfermedad Hepática , Sociedad Española de Medicina de Laboratorio (SEQC-ML) , Barcelona , España
- Servicio de Bioquímica y Genética Molecular, CDB , Hospital Clínic de Barcelona, IDIBAPS, CIBEREHD , Barcelona , España
| | - Alejandro Almería Lafuente
- Comisión de Valoración Bioquímica de la Enfermedad Hepática , Sociedad Española de Medicina de Laboratorio (SEQC-ML) , Barcelona , España
- Servicio de Bioquímica Clínica , Hospital Royo Villanova , Zaragoza , España
| | - María Antonieta Ballesteros Vizoso
- Comisión de Valoración Bioquímica de la Enfermedad Hepática , Sociedad Española de Medicina de Laboratorio (SEQC-ML) , Barcelona , España
- Servicio de Análisis Clínicos , Hospital Universitario Son Espases , Palma de Mallorca , España
| | - Pablo Gabriel Medina
- Comisión de Valoración Bioquímica de la Enfermedad Hepática , Sociedad Española de Medicina de Laboratorio (SEQC-ML) , Barcelona , España
- Servicio de Bioquímica Clínica , Hospital Universitari Vall d’Hebron , Barcelona , España
| | - Sergio Salgüero Fernández
- Comisión de Valoración Bioquímica de la Enfermedad Hepática , Sociedad Española de Medicina de Laboratorio (SEQC-ML) , Barcelona , España
- Servicio de Análisis Clínicos , Hospital Universitario Fundación Alcorcón , Madrid , España
| | - Angielys Zamora Trillo
- Comisión de Valoración Bioquímica de la Enfermedad Hepática , Sociedad Española de Medicina de Laboratorio (SEQC-ML) , Barcelona , España
- Servicio de Bioquímica Clínica , Hospital General Universitario Gregorio Marañón , Madrid , España
| | | | - Juan Carlos Hurtado
- Servicio de Microbiología, CDB, Hospital Clínic de Barcelona , Universitat de Barcelona , Barcelona , España
- Instituto de Salud Global de Barcelona (ISGlobal) , Barcelona , España
| | - Sofía Pérez-Del-Pulgar
- Servicio de Hepatología , Hospital Clínic de Barcelona, IDIBAPS, CIBEREHD , Barcelona , España
| | - Xavier Forns
- Servicio de Hepatología , Hospital Clínic de Barcelona, IDIBAPS, CIBEREHD , Barcelona , España
| | - Manuel Morales Ruiz
- Comisión de Valoración Bioquímica de la Enfermedad Hepática , Sociedad Española de Medicina de Laboratorio (SEQC-ML) , Barcelona , España
- Servicio de Bioquímica y Genética Molecular, CDB , Hospital Clínic de Barcelona, IDIBAPS, CIBEREHD , Barcelona , España
- Departamento de Biomedicina de la Facultad de Medicina y Ciencias de la Salud -Universidad de Barcelona , Barcelona , España
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Im YR, Jagdish R, Leith D, Kim JU, Yoshida K, Majid A, Ge Y, Ndow G, Shimakawa Y, Lemoine M. Prevalence of occult hepatitis B virus infection in adults: a systematic review and meta-analysis. Lancet Gastroenterol Hepatol 2022; 7:932-942. [PMID: 35961359 PMCID: PMC9630161 DOI: 10.1016/s2468-1253(22)00201-1] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/05/2022] [Revised: 06/14/2022] [Accepted: 06/15/2022] [Indexed: 12/03/2022]
Abstract
Background Despite growing concerns about transmissibility and clinical impact, occult hepatitis B virus (HBV) infection has received little attention in the hepatitis elimination agenda. We aimed to estimate the prevalence of occult HBV infection at a global and regional scale and in specific populations. Methods For this systematic review and meta-analysis, we searched the MEDLINE, Embase, Global Health, and Web of Science databases for articles published in any language between Jan 1, 2010, and Aug 14, 2019. We included original articles and conference abstracts of any study design that reported the proportion of HBsAg-negative adults (aged ≥18 years) who are positive for HBV DNA (ie, people with occult HBV infection). The prevalence of occult HBV infection was pooled, using the DerSimonian-Laird random-effects model, in the general population and specific groups defined by the type of study participants (blood donors; other low-risk populations; high-risk populations; and people with advanced chronic liver disease), and stratified by HBV endemicity in each country. We also assessed the performance of anti-HBc as an alternative biomarker to detect occult HBV infection. The study was registered with PROSPERO, CRD42019115490. Findings 305 of 3962 articles were eligible, allowing a meta-analysis of 140 521 993 individuals tested for HBV DNA. Overall, only two studies evaluated occult HBV infection in the general population, precluding unbiased global and regional estimates of occult HBV infection prevalence. In blood donors, occult HBV infection prevalence mirrored HBV endemicity: 0·06% (95% CI 0·00–0·26) in low-endemicity countries, 0·12% (0·04–0·23) in intermediate-endemicity countries, and 0·98% (0·44–1·72), in high-endemicity countries (p=0·0012). In high-risk groups, occult HBV infection prevalence was substantial, irrespective of endemicity: 5·5% (95% CI 2·9–8·7) in low-endemicity countries, 5·2% (2·5–8·6) in intermediate-endemicity countries, and 12·0% (3·4–24·7) in high-endemicity countries. The pooled sensitivity of anti-HBc to identify occult HBV infection was 77% (95% CI 62–88) and its specificity was 76% (68–83). Interpretation A substantial proportion of people carry occult HBV infection, especially among high-risk groups across the globe and people living in highly endemic countries. Occult HBV infection should be part of the global viral hepatitis elimination strategy. Funding None.
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Cakal B, Atasoy A, Cavus B, Poda M, Bulakci M, Gulluoglu M, Demirci M, Akyuz F. Prevalence of occult hepatitis B infection in liver biopsy sample of patients with nonviral liver disease. Future Virol 2022. [DOI: 10.2217/fvl-2021-0316] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
Aim: To determine the prevalence of occult hepatitis B (HBV) infection (OBI) in patients with nonviral liver disease. Materials & methods: This study included 83 HBsAg-negative patients followed up at a gastroenterohepatology clinic. The presence of HBV DNA was investigated by using an in-house nested-PCR method applied to liver parenchymal biopsy samples obtained from patients who underwent due nonviral chronic liver disease. Results: OBI was detected in 19 (22.9%) of the 83 cases, in 11 (44%) of 25 anti-HBc-positive patients, and 15 (31.9%) of 47 anti-HBc and/or anti-HBs antibodies-positive patients. Conclusion: There is a considerable prevalence of OBI among patients with nonviral chronic liver disease. Therefore, it is suggested that closely monitoring HBV can be useful to prevent or more effectively manage possible OBI-related complications among patients with nonviral chronic liver disease, especially those who are HBsAg seronegative or anti-HBV antibody seropositive.
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Affiliation(s)
- Bulent Cakal
- Department of Medical Microbiology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - Alp Atasoy
- Division of Gastroenterohepatology, Department of Internal Medicine, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - Bilger Cavus
- Division of Gastroenterohepatology, Department of Internal Medicine, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - Mehves Poda
- Department of Genetics, Aziz Sancar Institute for Experimental Medical Research, Istanbul University, Istanbul, Turkey
| | - Mesut Bulakci
- Department of Radiology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - Mine Gulluoglu
- Department of Pathology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - Mehmet Demirci
- Department of Medical Microbiology, Faculty of Medicine, Kirklareli University, Kirklareli, Turkey
| | - Filiz Akyuz
- Division of Gastroenterohepatology, Department of Internal Medicine, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
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Sagnelli C, Sica A, Creta M, Calogero A, Ciccozzi M, Sagnelli E. Epidemiological and clinical aspects of hepatitis B virus infection in Italy over the last 50 years. World J Gastroenterol 2022; 28:3081-3091. [PMID: 36051347 PMCID: PMC9331523 DOI: 10.3748/wjg.v28.i26.3081] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2022] [Revised: 03/16/2022] [Accepted: 06/17/2022] [Indexed: 02/06/2023] Open
Abstract
A relevant gradual reduction of both the incidence rate of acute hepatitis B (AHB) and prevalence of chronic hepatitis B has occurred in Italy in the last 50 years, due to substantial epidemiological changes: Improvement in socioeconomic and hygienic conditions, reduction of the family unit, accurate screening of blood donations, abolition of re-usable glass syringes, hepatitis B virus (HBV)-universal vaccination started in 1991, use of effective well tolerated nucleo(t)side analogues able to suppress HBV replication available from 1998, and educational mediatic campaigns against human immunodeficiency virus infection focusing on the prevention of sexual and parenteral transmission of infections. As an example, AHB incidence has gradually decreased from 10/100000 inhabitants in 1985 to 0.21 in 2020. Unfortunately, the coronavirus disease 2019 (COVID-19) pandemic has interrupted the trend towards HBV eradication. In fact, several HBV chronic carriers living in the countryside have become unable to access healthcare facilities for screening, diagnosis, clinical management, and nucleo(t)side analogue therapy in the COVID-19 pandemic, mainly for anxiety of becoming infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), movement restrictions, and reduced gains from job loss. In addition, one-third of healthcare facilities and personnel for HBV patients have been devolved to the COVID-19 assistance.
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Affiliation(s)
- Caterina Sagnelli
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, University of Campania “Luigi Vanvitelli”, Naples 80138, Italy
| | - Antonello Sica
- Department of Precision Medicine, University of Campania “Luigi Vanvitelli”, Naples 80131, Italy
| | - Massimiliano Creta
- Department of Neurosciences, Reproductive Sciences and Odontostomatology, University of Naples Federico II, Naples 80138, Italy
| | - Armando Calogero
- Department of Advanced Biomedical Sciences-UO General Surgery, University Federico II of Naples, Naples 80127, Italy
| | - Massimo Ciccozzi
- Medical Statistics and Molecular Epidemiology Unit, Campus Bio-Medico University, Rome 80138, Italy
| | - Evangelista Sagnelli
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, University of Campania “Luigi Vanvitelli”, Naples 80138, Italy
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Saitta C, Pollicino T, Raimondo G. Occult Hepatitis B Virus Infection: An Update. Viruses 2022; 14:v14071504. [PMID: 35891484 PMCID: PMC9318873 DOI: 10.3390/v14071504] [Citation(s) in RCA: 47] [Impact Index Per Article: 15.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2022] [Revised: 06/28/2022] [Accepted: 06/29/2022] [Indexed: 11/16/2022] Open
Abstract
Occult hepatitis B virus (HBV) infection (OBI) refers to a condition in which replication-competent viral DNA is present in the liver (with detectable or undetectable HBV DNA in the serum) of individuals testing negative for the HBV surface antigen (HBsAg). In this peculiar phase of HBV infection, the covalently closed circular DNA (cccDNA) is in a low state of replication. Many advances have been made in clarifying the mechanisms involved in such a suppression of viral activity, which seems to be mainly related to the host's immune control and epigenetic factors. OBI is diffused worldwide, but its prevalence is highly variable among patient populations. This depends on different geographic areas, risk factors for parenteral infections, and assays used for HBsAg and HBV DNA detection. OBI has an impact in several clinical contexts: (a) it can be transmitted, causing a classic form of hepatitis B, through blood transfusion or liver transplantation; (b) it may reactivate in the case of immunosuppression, leading to the possible development of even fulminant hepatitis; (c) it may accelerate the progression of chronic liver disease due to different causes toward cirrhosis; (d) it maintains the pro-oncogenic properties of the "overt" infection, favoring the development of hepatocellular carcinoma.
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Affiliation(s)
- Carlo Saitta
- Division of Medicine and Hepatology, University Hospital of Messina, 98124 Messina, Italy;
- Department of Clinical and Experimental Medicine, University of Messina, 98124 Messina, Italy
| | - Teresa Pollicino
- Department of Human Pathology, University Hospital of Messina, 98124 Messina, Italy;
| | - Giovanni Raimondo
- Division of Medicine and Hepatology, University Hospital of Messina, 98124 Messina, Italy;
- Department of Clinical and Experimental Medicine, University of Messina, 98124 Messina, Italy
- Correspondence: ; Tel.: +39-(0)-902212392
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Zbinden A, Ries J, Redli PM, Shah C, Glauser A, Goslings D, Huzly D, Böni J, Gottschalk J, Frey BM. Prevalence of Occult Hepatitis B Virus Infection in Blood Donors with Negative ID-NAT in Switzerland. Transfus Med Hemother 2022; 49:338-345. [PMID: 36654973 PMCID: PMC9768291 DOI: 10.1159/000525480] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2022] [Accepted: 06/05/2022] [Indexed: 01/21/2023] Open
Abstract
Introduction Screening of hepatitis B surface antigen (HBsAg) and individual-donation nucleic acid amplification testing (ID-NAT) of blood donors have become standard to detect hepatitis B virus (HBV) infection. However, there is still a residual risk of HBV transmission by blood components of donors suffering from occult HBV infection (OBI). Therefore, many countries implemented universal testing of anti-HBV core antigen (anti-HBc) antibodies in order to increase blood safety. In Switzerland, anti-HBc testing is not part of the routine blood donor-screening repertoire. Therefore, we sought to assess prevalence of donors with OBI in a Swiss blood donor collective. Methods Blood donations were prospectively investigated for the presence of anti-HBc antibodies during two time periods (I: all donors, March 2017; II: first-time donors only, April 2017 until February 2018). Anti-HBc-positive findings were confirmed by an anti-HBc neutralization test. Discarded plasma samples of anti-HBc-confirmed positive donors were ultracentrifuged and subsequently retested by regular HBV-ID-NAT to search for traces of HBV. Results During time period I, 78 (1.6%) individuals out of 4,923 donors were confirmed anti-HBc-positive. Sixty-nine (88%) anti-HBc-positive samples were available and processed by ultracentrifugation followed by repeat HBV-ID-NAT. Four samples (5.8%) were found positive for HBV DNA. Sixty-five (94.2%) samples remained HBV NAT-negative upon ultracentrifugation. During time period II, 56 (0.9%) donor samples out of 6,509 exhibited anti-HBc-confirmed positive. Fifty-five (98%) samples could be reassessed by HBV-ID-NAT upon ultracentrifugation. Three (5.5%) samples contained HBV DNA and 52 (94.5%) samples remained HBV NAT-negative. Conclusion Overall, we detected 7 viremic OBI carriers among 11,432 blood donors, which tested negative for HBV by standard HBV-ID-NAT and HBsAg screening. In contrast, OBI carriers showed positive anti-HBc findings which could be confirmed in 83.8% of the cases. Thus, OBI might be missed by the current HBV screening process of Swiss blood donors. We suggest to review current HBV screening algorithm. Extended donor screening by anti-HBc testing may unmask OBI carriers and contribute to blood safety for the recipient of blood products.
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Affiliation(s)
- Andrea Zbinden
- Institute of Medical Virology, University of Zurich, Zurich, Switzerland
| | - Judith Ries
- Blood Transfusion Service SRC Zurich, Swiss Red Cross, Zürich, Switzerland
| | - Patrick M. Redli
- Institute of Medical Virology, University of Zurich, Zurich, Switzerland
| | - Cyril Shah
- Institute of Medical Virology, University of Zurich, Zurich, Switzerland
| | - Andreas Glauser
- Blood Transfusion Service SRC Zurich, Swiss Red Cross, Zürich, Switzerland,*Andrea Zbinden,
| | - David Goslings
- Blood Transfusion Service SRC Zurich, Swiss Red Cross, Zürich, Switzerland
| | - Daniela Huzly
- Institute of Virology, Department for Medical Microbiology and Hygiene, University of Freiburg, Freiburg im Breisgau, Germany
| | - Jürg Böni
- Institute of Medical Virology, University of Zurich, Zurich, Switzerland
| | - Jochen Gottschalk
- Blood Transfusion Service SRC Zurich, Swiss Red Cross, Zürich, Switzerland
| | - Beat M. Frey
- Blood Transfusion Service SRC Zurich, Swiss Red Cross, Zürich, Switzerland,**Beat M. Frey,
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40
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Uche EI, Chukwukaodinaka NE, Akinbami AA, Adeyemi OI, Hassan AO, Bamiro RA, Ibrahim IN, Suleiman AM, Augustine B, Anaduaka DC. Common hepatitis B virus genotypes among blood donors in Lagos, Nigeria. Niger Postgrad Med J 2022; 29:228-235. [PMID: 35900459 DOI: 10.4103/npmj.npmj_19_22] [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] [Indexed: 06/15/2023]
Abstract
BACKGROUND Hepatitis B virus (HBV) infection is one of the public health diseases causing global health problems. It is a leading cause of cirrhosis and hepatocellular carcinoma. Blood transfusion is a major route of its transmission and screening of blood is suboptimal in our environment. Occult HBV infection describes the presence of HBV DNA in blood or liver tissue in patients who are hepatitis B surface antigen (HBsAg) seronegative. This study documented the common genotypes of HBV a blood-borne infection in the population of blood donors in Lagos. METHODS This was a cross-sectional study carried out at the blood donor clinics of ten Lagos State Government-owned hospitals in Lagos State. A total of 1400 participants were recruited consecutively from November 2020 to June 2021. All participants' samples were screened using Diaspot Rapid Test Kit (RTK) and Dialabenzyme enzyme-linked immunosorbent assay (ELISA) kit. Furthermore, some of the plasma samples were used for HBV DNA extraction and genotyping using the real time-polymerase chain reaction. Statistical analysis was carried out using the Statistical Package for the Social Sciences (SPSS) software version 26 and P value was considered significant at ≤0.05. RESULTS The sero-prevalence of HBsAg using RTK and ELISA was 19.9% and 22.4%, respectively. The prevalence of occult HBV infection was 5.2%. A total of 278 and 313 HBsAg RTK and ELISA positive samples were obtained, respectively. HBV genotype result had A (46.6%) as the most prevalent followed closely by B (44.7%), E (23.8%), D (20.9%) and C (11.2%). CONCLUSION HBV infection has a high prevalence among blood donors. ELISA is a more sensitive screening tool and its use should be advocated nationally. HBV genotype A is the most prevalent genotype from our study.
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Affiliation(s)
- Ebele I Uche
- Department of Haematology and Blood Transfusion, Lagos State University College of Medicine, Lagos, Nigeria
| | - Nwakaego E Chukwukaodinaka
- Department of Haematology and Blood Transfusion, Lagos State University Teaching Hospital, Lagos, Nigeria
| | - Akinsegun A Akinbami
- Department of Haematology and Blood Transfusion, Lagos State University College of Medicine, Lagos, Nigeria
| | - Oluwatosin I Adeyemi
- Department of Haematology and Blood Transfusion, Lagos State University Teaching Hospital, Lagos, Nigeria
| | - Aderonke O Hassan
- Department of Haematology and Blood Transfusion, Lagos State University Teaching Hospital, Lagos, Nigeria
| | - Rafah A Bamiro
- Department of Haematology and Blood Transfusion, Lagos State University Teaching Hospital, Lagos, Nigeria
| | - Ismaila Nda Ibrahim
- Department of Haematology and Blood Transfusion, Ahmadu Bello University, Zaria, Kaduna, Nigeria
| | - Aisha M Suleiman
- Department of Haematology and Blood Transfusion, Ahmadu Bello University, Zaria, Kaduna, Nigeria
| | - Benjamin Augustine
- Department of Haematology and Blood Transfusion, Ahmadu Bello University, Zaria, Kaduna, Nigeria
| | - Doris Chinyelu Anaduaka
- Department of Haematology and Blood Transfusion, Lagos State University Teaching Hospital, Lagos, Nigeria
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Occult Hepatitis B Infection among Hemodialysis in Tabriz, Northwest of Iran: Prevalence and Mutations within the S Region. CANADIAN JOURNAL OF INFECTIOUS DISEASES AND MEDICAL MICROBIOLOGY 2022; 2022:3838857. [PMID: 35800327 PMCID: PMC9256460 DOI: 10.1155/2022/3838857] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/24/2022] [Revised: 05/28/2022] [Accepted: 06/02/2022] [Indexed: 11/17/2022]
Abstract
Regardless of the extensive screening for the detection of hepatitis B surface antigen (HBsAg), hemodialysis (HD) patients are still severely at the risk of occult hepatitis B virus infection (OBI), especially in developing countries. OBI is defined as the presence of HBV DNA with undetectable HBsAg in the liver and/or Serum. This study aims to determine the prevalence of OBI in HD patients in Tabriz Province, northwest of Iran, and inquire about the mutations in the detected HBsAg. In this cross-sectional descriptive study, ELISA method assessed serum and plasma samples of 118 HBsAg-negative patients undergoing HD treatment for HBV serological markers (HBsAg and Anti-HBc). Specific primers by nested polymerase chain reaction have been utilized to examine HBV DNA; also, direct sequencing of surface genes was carried out to characterize the viral genotypes and S gene mutations. Finally, followed by real-time PCR, the quantity of viral load in OBI-positive patients was determined. A total of 118 HD patients were included (63.6% were male and 36.4% female), with an overall mean age of 60.8 ± 12.8 years old. The prevalence of antihepatitis B core antibody (Anti-HBc) in the study population was 26.3% (31/118). Five patients (4.2%) were positive for HBV DNA and labeled OBI-positive; their plasma HBV-DNA load was less than 100 IU/ml. Following the phylogenetic analysis, the samples with OBI roughly belonged to genotype D, subtype ayw2 and only two had mutations within the S ’gene’s major hydrophilic region (MHR), including T123I, C124F, and P127T. This study reports the prevalence of OBI in the HBsAg-negative HD patients being at a rate of 4.2%, which can be a clinically vital consideration in this region. HBV serologic screening approaches need to be renewed to cover nucleic acid testing in the setting of hemodialysis and all the other high-risk groups associated with it (i.e., blood and organ donors).
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Gherlan GS. Occult hepatitis B — the result of the host immune response interaction with different genomic expressions of the virus. World J Clin Cases 2022; 10:5518-5530. [PMID: 35979101 PMCID: PMC9258381 DOI: 10.12998/wjcc.v10.i17.5518] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/05/2022] [Revised: 01/30/2022] [Accepted: 04/03/2022] [Indexed: 02/06/2023] Open
Abstract
With over 40 years of history, occult hepatitis B infection (OBI) continues to remain an important and challenging public health problem. Defined as the presence of replication-competent hepatitis B virus (HBV) DNA (i.e., episomal HBV covalently closed circular DNA) in the liver and/or HBV DNA in the blood of people who test negative for hepatitis B surface antigen (HBsAg) in currently available assays, OBI is currently diagnosed using polymerase chain reaction (PCR) and real-time PCR assays. However, all efforts should be made to exclude a false negative HBsAg in order to completely follow the definition of OBI. In recent years, significant advances have been made in understanding the HBV lifecycle and the molecular mechanisms that lead to the persistence of the virus in the occult form. These factors are mainly related to the host immune system and, to a smaller proportion, to the virus. Both innate and adaptive immune responses are important in HBV infection management, and epigenetic changes driven by host mechanisms (acetylation, methylation, and microRNA implication) are added to such actions. Although greater genetic variability in the S gene of HBV isolated from OBIs was found compared with overt infection, the mechanisms of OBI are not mainly viral mutations.
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Affiliation(s)
- George Sebastian Gherlan
- Department of Infectious Diseases, “Carol Davila” University of Medicine and Pharmacy, Bucharest 030303, Romania
- Department of Infectious Diseases, “Dr. Victor Babes” Hospital of Infectious and Tropical Diseases, Bucharest 030303, Romania
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Çakal B, Çavuş B, Atasoy A, Poda M, Bulakçi M, Güllüoğlu M, Demirci M, Şener LT, Altunok D, Arslan AB, Akyüz F. What is the clinical impact of occult HBV infections and anti-HBc positivity in patients with chronic hepatitis C? Microbiol Immunol 2022; 66:386-393. [PMID: 35661243 DOI: 10.1111/1348-0421.13012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2022] [Revised: 05/20/2022] [Accepted: 06/01/2022] [Indexed: 11/29/2022]
Abstract
Occult hepatitis B infection (OBI) is defined by the persistence of the hepatitis B virus (HBV) genome in the liver of individuals testing negative for hepatitis B surface antigen (HBsAg). Hepatitis B core antibody (anti-HBc) is the serological marker that indicates HBV exposure. The impact of anti-HBc and OBI on patients with chronic hepatitis C remains unclear. The aim of the present study was to determine the prevalence of anti-HBc and OBI and to evaluate their impact on the clinical and pathological outcomes of patients with chronic hepatitis C. The study included 59 HBsAg-negative chronic hepatitis C patients who underwent a liver parenchymal biopsy. The presence of HBV DNA was investigated using an in-house nested PCR method. OBI was detected in 16 (27.1%) of the 59 cases and also in 10 (62.5%) of 22 (37.3%) anti-HBc-positive patients. None of the patients had positive serum HBV DNA. OBI was associated with the presence of anti-HBV antibodies (p<0.05). There was also an association between anti-HBc positivity and the activity grades and fibrosis stages of the liver and also a prevalence of liver steatosis (p<0.05). Positive anti-HBc results may predict OBI and also be associated with the progression of liver injury in HBsAg-negative patients with chronic hepatitis C. Therefore, it is suggested that patients with chronic hepatitis C should be screened for anti-HBc positivity, and anti-HBc-positive patients should be carefully evaluated for disease progression. This article is protected by copyright. All rights reserved.
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Affiliation(s)
- Bülent Çakal
- Department of Medical Microbiology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - Bilger Çavuş
- Division of Gastroenterohepatology, Department of Internal Medicine, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - Alp Atasoy
- Division of Gastroenterohepatology, Department of Internal Medicine, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - Mehveş Poda
- Department of Genetics, Aziz Sancar Institute for Experimental Medical Research, Istanbul University, Istanbul, Turkey
| | - Mesut Bulakçi
- Department of Radiology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - Mine Güllüoğlu
- Department of Pathology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - Mehmet Demirci
- Department of Medical Microbiology, Faculty of Medicine, Kirklareli University, Kirklareli, Turkey
| | - Leyla Türker Şener
- Department of Biophysics Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - Damla Altunok
- Division of Gastroenterohepatology, Department of Internal Medicine, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | | | - Filiz Akyüz
- Division of Gastroenterohepatology, Department of Internal Medicine, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
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Buonomo AR, Viceconte G, Calabrese M, De Luca G, Tomassini V, Cavalla P, Maniscalco GT, Ferraro D, Nociti V, Radaelli M, Buscarinu MC, Paolicelli D, Gajofatto A, Annovazzi P, Pinardi F, Di Filippo M, Cordioli C, Zappulo E, Scotto R, Gentile I, Spiezia AL, Petruzzo M, De Angelis M, Brescia Morra V, Solaro C, Gasperini C, Cocco E, Moccia M, Lanzillo R. Management of hepatitis B virus prophylaxis in patients treated with disease-modifying therapies for multiple sclerosis: a multicentric Italian retrospective study. J Neurol 2022; 269:3301-3307. [PMID: 35165767 PMCID: PMC9119877 DOI: 10.1007/s00415-022-11009-x] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2021] [Revised: 02/01/2022] [Accepted: 02/02/2022] [Indexed: 10/27/2022]
Abstract
BACKGROUND Patients with multiple sclerosis (MS) often receive disease-modifying therapies (DMTs) that can expose them to reactivation of potential occult hepatitis B virus (HBV) infection (pOBI). We aimed to evaluate the MS Centers behavior regarding HBV screening and prophylaxis in a large cohort of MS patients receiving anti-CD20 or cladribine. METHODS Retrospective, multicentric study recruiting Italian MS patients treated with rituximab, ocrelizumab and cladribine. RESULTS We included 931 MS patients from 15 centers. All but 38 patients performed a complete HBV screening. Patients' age > 50 years was significantly associated with no history of vaccination and HBsAb titres < 100 mIU at baseline (p < 0.001). No significant correlation was found between post-vaccination HBsAb titres and type of treatment (p = 0.5), pre-or post-therapy vaccination (p = 0.2) and number of previous DMTs (p = 0.2). Among pOBI patients (n = 53), 21 received antiviral prophylaxis, while only 13 had HBV DNA monitoring and 19 patients neither monitored HBV DNA nor received prophylaxis. CONCLUSIONS Baseline HBV screening in patients receiving anti-CD20 and cladribine is a consolidated practice. Nonetheless, HBV vaccination coverage is still lacking in such population and age is a significant factor associated with low HBV protection. Rituximab, ocrelizumab and cladribine did not impair HBV vaccine response. Almost 35% of pOBI patients fail to receive HBVr prevention. Management of HBV prophylaxis could be improved in MS patients and further prospective studies are needed to assess the effectiveness of prophylactic strategies in such patients.
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Affiliation(s)
- Antonio Riccardo Buonomo
- Department of Clinical Medicine and Surgery-Section of Infectious Diseases, University of Naples "Federico II", Via Sergio Pansini 5, 80130, Naples, Italy
| | - Giulio Viceconte
- Department of Clinical Medicine and Surgery-Section of Infectious Diseases, University of Naples "Federico II", Via Sergio Pansini 5, 80130, Naples, Italy.
| | - Massimiliano Calabrese
- Department of Neuroscience, Biomedicine and Movement, The Multiple Sclerosis Center of the University Hospital of Verona, Verona, Italy
| | - Giovanna De Luca
- Institute for Advanced Biomedical Technologies (ITAB), Department of Neurosciences, Imaging and Clinical Sciences, University "G. d'Annunzio" of Chieti-Pescara, Chieti, Italy
| | - Valentina Tomassini
- Institute for Advanced Biomedical Technologies (ITAB), Department of Neurosciences, Imaging and Clinical Sciences, University "G. d'Annunzio" of Chieti-Pescara, Chieti, Italy
| | - Paola Cavalla
- Department of Neuroscience and Mental Health-City of Health and Science University, Hospital of Torino, Multiple Sclerosis Center, Turin, Italy
| | | | - Diana Ferraro
- Department of Biomedical, Metabolic and Neurosciences, University of Modena and Reggio Emilia, Modena, Italy
| | - Viviana Nociti
- Institute of Neurology, Fondazione Policlinico Universitario 'A. Gemelli' IRCCS, Catholic University of Sacred Heart, Rome, Italy
| | - Marta Radaelli
- Department of Neurology and Multiple Sclerosis Center, ASST Papa Giovanni XXIII, Bergamo, Italy
| | - Maria Chiara Buscarinu
- Department of Neuroscience, Mental Health and Sensory Organs, Sapienza University, S. Andrea Hospital Site, Rome, Italy
| | - Damiano Paolicelli
- Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari "Aldo Moro", Bari, Italy
| | - Alberto Gajofatto
- Department of Neuroscience, Biomedicine and Movement, The Multiple Sclerosis Center of the University Hospital of Verona, Verona, Italy
| | - Pietro Annovazzi
- Multiple Sclerosis Center, ASST Valle Olona-Gallarate Hospital, Gallarate, VA, Italy
| | | | - Massimiliano Di Filippo
- Section of Neurology, Department of Medicine and Surgery, University of Perugia, Perugia, Italy
| | - Cinzia Cordioli
- Multiple Sclerosis Center, Montichiari Hospital, ASST Spedali Civili Di Brescia, Brescia, Italy
| | - Emanuela Zappulo
- Department of Clinical Medicine and Surgery-Section of Infectious Diseases, University of Naples "Federico II", Via Sergio Pansini 5, 80130, Naples, Italy
| | - Riccardo Scotto
- Department of Clinical Medicine and Surgery-Section of Infectious Diseases, University of Naples "Federico II", Via Sergio Pansini 5, 80130, Naples, Italy
| | - Ivan Gentile
- Department of Clinical Medicine and Surgery-Section of Infectious Diseases, University of Naples "Federico II", Via Sergio Pansini 5, 80130, Naples, Italy
| | - Antonio Luca Spiezia
- Department of Neurosciences, Reproductive and Odontostomatological Sciences, University of Naples "Federico II", Naples, Italy
| | - Martina Petruzzo
- Department of Neurosciences, Reproductive and Odontostomatological Sciences, University of Naples "Federico II", Naples, Italy
| | - Marcello De Angelis
- Department of Neurosciences, Reproductive and Odontostomatological Sciences, University of Naples "Federico II", Naples, Italy
| | - Vincenzo Brescia Morra
- Department of Neurosciences, Reproductive and Odontostomatological Sciences, University of Naples "Federico II", Naples, Italy
| | | | - Claudio Gasperini
- Department of Neuroscience, San-Camillo Forlanini Hospital, Rome, Italy
| | - Eleonora Cocco
- Multiple Sclerosis Center, Binaghi Hospital, Azienda Tutela Della Salute (ATS) Sardegna, Cagliari, Italy
| | - Marcello Moccia
- Department of Neurosciences, Reproductive and Odontostomatological Sciences, University of Naples "Federico II", Naples, Italy
| | - Roberta Lanzillo
- Department of Neurosciences, Reproductive and Odontostomatological Sciences, University of Naples "Federico II", Naples, Italy
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Detection of occult hepatitis B virus infection among subjects with isolated hepatitis B core antibodies: Results from a 3-year survey in an Italian tertiary-care hospital. Clin Res Hepatol Gastroenterol 2022; 46:101892. [PMID: 35202845 DOI: 10.1016/j.clinre.2022.101892] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/16/2021] [Revised: 02/09/2022] [Accepted: 02/13/2022] [Indexed: 02/04/2023]
Abstract
BACKGROUND Hepatitis B virus (HBV) infection causes hepatitis, liver cirrhosis, hepatocellular carcinoma, and death. This study examines the subjects with isolated anti-HBV core antigen antibody (anti-HBcAg), a pattern characterized by the persistent HBV carriage in the absence of HBV surface antigen (HBsAg) and anti-HBsAg antibody. METHODS Based on medical orders, from 2017 to 2019, serological and molecular assays were performed on serum/plasma samples of 33,048 subjects (71.4% Italians, 28.6% foreigners), who referred to the Virology Unit of the University-Hospital of Parma (Northern Italy) for the laboratory diagnosis of HBV infection. RESULTS The seroprevalence was 4.6% for HBsAg and 11% for anti-HBcAg. The occurrence of the isolated anti-HBcAg status was 3.1%, with higher frequency in males than in females (66.3% vs. 33.7%, P < 0.0001), in Italians than in foreigners (54.8% vs. 45.2%, P < 0.001), and in outpatients than in inpatients (57.4% vs. 42.6%, P < 0.0001). Foreigners with isolated anti-HBcAg came mostly from Africa (67.9%) and Eastern Europe (26.2%). Among subjects with isolated anti-HBcAg, 14.8% had occult HBV infection, 26.3% hepatitis C virus co-infection, 2% human immunodeficiency virus co-infection, and 3.3% both of these latter co-infections. CONCLUSIONS The anti-HBcAg assay accurately evaluates the HBV exposure; subjects with isolated anti-HBcAg antibody should be further analysed for HBV DNA. The HBV infection prevalence in Italy is increasing, due to growing migratory flows from endemic areas.
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Araújo SDR, Malheiros AP, Sarmento VP, Nunes HM, Freitas PEB. Molecular investigation of occult hepatitis B virus infection in a reference center in Northern Brazil. Braz J Infect Dis 2022; 26:102367. [PMID: 35598631 PMCID: PMC9387453 DOI: 10.1016/j.bjid.2022.102367] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2022] [Accepted: 04/30/2022] [Indexed: 11/18/2022] Open
Abstract
The goal of this study was to investigate the prevalence of occult HBV infection in a reference center for the Northern Brazil from 2005 to 2015 and to identify mutations associated with occult hepatitis B. Molecular analysis was performed on 110 serum samples in which anti-HBc was the only positive serological marker. Regions of the HBV genome were amplified by polymerase chain reaction to detect HBV DNA. A prevalence of 4.1% (793/18,889) for anti-HBc alone was identified. Molecular analysis revealed a prevalence of occult HBV infection of 0.04%. HBV DNA detected were identified in individuals who underwent hemodialysis, infected with the hepatitis C virus and from area of high endemicity for HBV. Direct DNA nucleotide sequencing and phylogenetic analysis identified that genotypes A and D and mutations E164D, I195M, P217L and P120S were associated with occult HBV infection in the S gene. This study contributed with epidemiological and molecular information on Northern Brazil samples with a suggestive profile of occult HBV infection in addition to reinforcing the importance of molecular diagnosis in this type of infection.
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Zhang W, Luo S, Li T, Wang M, Huang J, Liao Q, Liu B, Rong X, Li L, Allain JP, Fu Y, Li C. Hepatitis B Virus-Specific Cellular Immunity Contributes to the Outcome of Occult Hepatitis B Virus Infection. Front Microbiol 2022; 13:850665. [PMID: 35464946 PMCID: PMC9022031 DOI: 10.3389/fmicb.2022.850665] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2022] [Accepted: 02/14/2022] [Indexed: 11/16/2022] Open
Abstract
There is little known of immunologic factors leading to the occurrence of occult HBV infection (OBI). Specific cellular immune response to hepatitis B virus (HBV) core/pol peptides was compared between blood donor populations, including 37 OBIs, 53 chronic HBV infections (CHB), 47 resolved infections, and 56 non-infected controls, respectively. The rate of CD4+/CD8+ T cell proliferation in OBI or CHB carriers was higher than in HBV resolved and non-infected individuals (P < 0.05). The intensity of IFN-γ-secretion T-cell response of OBI carriers was highest, followed by CHB and resolved infections, and non-infected individuals (P < 0.05). The frequency of intracellular IFN-γ and IL-17A CD4+/CD8+ and IL-21 CD4+ T-cell responses was significantly higher in resolved infections than in OBI or CHB carriers (P < 0.05), while the level of extracellular IL-17A of peripheral blood mononuclear cells (PBMCs) was higher in OBI and CHB carriers than in resolved infections (P < 0.01). The frequency of intracellular IL-10 CD4+ T-cell response in CHB, OBI, and resolved infections was higher than in HBV non-infected individuals (P < 0.01). Intracellular IL-10 CD8+ T cell and extracellular IL-10 T-cell responses were higher in CHB than in OBI (P = 0.012) or HBV resolved infections (P < 0.01). In conclusion, the higher level of effective T-cell response with IFN-γ, IL-17A, and IL-21 contributes to resolved infection outcome, while higher levels of suppressive T-cell response with IL-10 result in HBV chronicity. OBI is an intermediary status between HBV resolved and chronic infections, in which IL-21 effector and IL-10 suppressor T-cell responses play an important role in directing the outcome of HBV infection.
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Affiliation(s)
- Weiyun Zhang
- Department of Transfusion Medicine, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, China
- Department of Laboratory Medicine, General Hospital of Southern Theater Command of PLA, Guangzhou, China
| | - Shengxue Luo
- Department of Transfusion Medicine, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, China
- Department of Pediatrics, Shenzhen Hospital of Southern Medical University, Shenzhen, China
| | - Tingting Li
- Department of Transfusion Medicine, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, China
| | - Min Wang
- Guangzhou Blood Center, Guangzhou, China
| | | | - Qiao Liao
- Guangzhou Blood Center, Guangzhou, China
| | - Bochao Liu
- Department of Transfusion Medicine, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, China
| | - Xia Rong
- Guangzhou Blood Center, Guangzhou, China
| | - Linhai Li
- Department of Laboratory Medicine, General Hospital of Southern Theater Command of PLA, Guangzhou, China
| | - Jean-Pierre Allain
- Department of Transfusion Medicine, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, China
- Emeritus Professor, Department of Blood, University of Cambridge, Cambridge, United Kingdom
| | - Yongshui Fu
- Department of Transfusion Medicine, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, China
- Guangzhou Blood Center, Guangzhou, China
- Yongshui Fu,
| | - Chengyao Li
- Department of Transfusion Medicine, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, China
- *Correspondence: Chengyao Li,
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48
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KASL clinical practice guidelines for management of chronic hepatitis B. Clin Mol Hepatol 2022; 28:276-331. [PMID: 35430783 PMCID: PMC9013624 DOI: 10.3350/cmh.2022.0084] [Citation(s) in RCA: 54] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2022] [Accepted: 04/01/2022] [Indexed: 01/10/2023] Open
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Proulx J, Ghaly M, Park IW, Borgmann K. HIV-1-Mediated Acceleration of Oncovirus-Related Non-AIDS-Defining Cancers. Biomedicines 2022; 10:biomedicines10040768. [PMID: 35453518 PMCID: PMC9024568 DOI: 10.3390/biomedicines10040768] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2022] [Revised: 03/22/2022] [Accepted: 03/22/2022] [Indexed: 11/25/2022] Open
Abstract
With the advent of combination antiretroviral therapy (cART), overall survival has been improved, and the incidence of acquired immunodeficiency syndrome (AIDS)-defining cancers has also been remarkably reduced. However, non-AIDS-defining cancers among human immunodeficiency virus-1 (HIV-1)-associated malignancies have increased significantly so that cancer is the leading cause of death in people living with HIV in certain highly developed countries, such as France. However, it is currently unknown how HIV-1 infection raises oncogenic virus-mediated cancer risks in the HIV-1 and oncogenic virus co-infected patients, and thus elucidation of the molecular mechanisms for how HIV-1 expedites the oncogenic viruses-triggered tumorigenesis in the co-infected hosts is imperative for developing therapeutics to cure or impede the carcinogenesis. Hence, this review is focused on HIV-1 and oncogenic virus co-infection-mediated molecular processes in the acceleration of non-AIDS-defining cancers.
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50
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Letafati A, Najafi S, Mottahedi M, Karimzadeh M, Shahini A, Garousi S, Abbasi-Kolli M, Sadri Nahand J, Tamehri Zadeh SS, Hamblin MR, Rahimian N, Taghizadieh M, Mirzaei H. MicroRNA let-7 and viral infections: focus on mechanisms of action. Cell Mol Biol Lett 2022; 27:14. [PMID: 35164678 PMCID: PMC8853298 DOI: 10.1186/s11658-022-00317-9] [Citation(s) in RCA: 72] [Impact Index Per Article: 24.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2021] [Accepted: 01/26/2022] [Indexed: 02/06/2023] Open
Abstract
MicroRNAs (miRNAs) are fundamental post-transcriptional modulators of several critical cellular processes, a number of which are involved in host defense mechanisms. In particular, miRNA let-7 functions as an essential regulator of the function and differentiation of both innate and adaptive immune cells. Let-7 is involved in several human diseases, including cancer and viral infections. Several viral infections have found ways to dysregulate the expression of miRNAs. Extracellular vesicles (EV) are membrane-bound lipid structures released from many types of human cells that can transport proteins, lipids, mRNAs, and miRNAs, including let-7. After their release, EVs are taken up by the recipient cells and their contents released into the cytoplasm. Let-7-loaded EVs have been suggested to affect cellular pathways and biological targets in the recipient cells, and can modulate viral replication, the host antiviral response, and the action of cancer-related viruses. In the present review, we summarize the available knowledge concerning the expression of let-7 family members, functions, target genes, and mechanistic involvement in viral pathogenesis and host defense. This may provide insight into the development of new therapeutic strategies to manage viral infections.
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Affiliation(s)
- Arash Letafati
- Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | - Sajad Najafi
- Department of Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mehran Mottahedi
- Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mohammad Karimzadeh
- Department of Virology, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Ali Shahini
- Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Setareh Garousi
- Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mohammad Abbasi-Kolli
- Department of Medical Genetics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
| | - Javid Sadri Nahand
- Infectious and Tropical Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | | | - Michael R. Hamblin
- Laser Research Centre, Faculty of Health Science, University of Johannesburg, Doornfontein, 2028 South Africa
| | - Neda Rahimian
- Endocrine Research Center, Institute of Endocrinology and Metabolism, Iran University of Medical Sciences (IUMS), Tehran, Iran
- Department of Internal Medicine, School of Medicine, Firoozgar Hospital, Iran University of Medical Sciences, Tehran, Iran
| | - Mohammad Taghizadieh
- Department of Pathology, School of Medicine, Center for Women’s Health Research Zahra, Tabriz University of Medical Sciences, Tabriz, Islamic Republic of Iran
| | - Hamed Mirzaei
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan, Iran
- Student Research Committee, Kashan University of Medical Sciences, Kashan, Iran
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