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1
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Wodajo FA, Gebru DM, Alemneh HT. Mathematical model analysis of effective intervention strategies on transmission dynamics of hepatitis B virus. Sci Rep 2023; 13:8737. [PMID: 37253760 DOI: 10.1038/s41598-023-35815-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2022] [Accepted: 05/24/2023] [Indexed: 06/01/2023] Open
Abstract
Hepatitis B is one of the world's most common and severe infectious diseases. Worldwide, over 350 million people are currently estimated to be persistent carriers of the hepatitis B virus (HBV), with the death of 1 million people from the chronic stage of HBV infection. In this work, developed a nonlinear mathematical model for the transmission dynamics of HBV. We constructed the mathematical model by considering vaccination, treatment, migration, and screening effects. We calculated both disease-free and endemic equilibrium points for our model. Using the next-generation matrix, an effective reproduction number for the model is calculated. We also proved the asymptotic stability of both local and global asymptotically stability of disease-free and endemic equilibrium points. By calculating the sensitivity indices, the most sensitive parameters that are most likely to affect the disease's endemicity are identified. From the findings of this work, we recommend vaccination of the entire population and screening all the exposed and migrants. Additionally, early treatment of both the exposed class after screening and the chronically infected class is vital to decreasing the transmission of HBV in the community.
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2
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Wang T, Shen C, Qi J, Chen L, Liu S, Li H. Haplotype-dependent HLA-DRB1-DQB1 susceptibility to occult HBV infection in Xi'an Han population. Mol Genet Genomic Med 2023; 11:e2102. [PMID: 36852518 PMCID: PMC10094095 DOI: 10.1002/mgg3.2102] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2021] [Revised: 07/04/2022] [Accepted: 11/03/2022] [Indexed: 03/01/2023] Open
Abstract
BACKGROUND Occult hepatitis B virus (HBV) infection (OBI) is primarily characterized by the persistence of HBV-DNA in the liver tissues and/or in the serum without detectable HBsAg. Human leukocyte antigen (HLA) polymorphisms have been found to be strongly associated with HBV in different ethnic backgrounds. The association of HLA-DRB1-DQB1 haplotypes with OBI has not been previously reported in China. The aim of this study was to identify the potential association of HLA-DRB1-DQB1 haplotypes that may be involved in OBI genetic susceptibility. METHODS A case-control study was conducted between 107 OBI subjects and 280 healthy controls from the blood donors in the Shaanxi Province Blood Center. The HLA-DRB1, DQB1 loci were genotyped using polymerase chain reaction-sequence based typing (PCR-SBT). Based on the genotype data of the two loci, haplotype estimation was performed. RESULTS HLA-DRB1*07:01-DQB1*02:02 (pc = 0.344 × 10-3 , OR = 3.489, 95%CI = 2.000-6.088) and HLA-DRB1*09:01-DQB1*03:03 (pc = 0.02, OR = 2.370, 95%CI = 1.450-3.873) serve as the possible risk and susceptibility haplotypes for OBI in Xi'an Han after Bonferroni correction. CONCLUSIONS This study demonstrated that HLA II haplotypes were significantly associated with OBI in the Xi'an Han population. To the best of our knowledge, this is the first study to associate HLA-DRB1-DQB1 haplotypes with OBI, which can provide valuable insights into the relationship between the various genetic factors and immune responses in the Xi'an population. The findings can also form the basis for future studies about the role of HLA in OBI.
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Affiliation(s)
- Tianju Wang
- Shaanxi Province Blood Center, Xi'an, People's Republic of China
| | - Chunmei Shen
- Shaanxi Province Blood Center, Xi'an, People's Republic of China
| | - Jun Qi
- Shaanxi Province Blood Center, Xi'an, People's Republic of China
| | - Liping Chen
- Shaanxi Province Blood Center, Xi'an, People's Republic of China
| | - Sheng Liu
- Shaanxi Province Blood Center, Xi'an, People's Republic of China
| | - Hengxin Li
- Shaanxi Province Blood Center, Xi'an, People's Republic of China
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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: 82] [Impact Index Per Article: 27.3] [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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4
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Wang H, Liao F, Xie J, Gao W, Wang M, Huang J, Xu R, Liao Q, Shan Z, Zheng Y, Rong X, Li C, Fu Y. E2 Site Mutations in S Protein Strongly Affect Hepatitis B Surface Antigen Detection in the Occult Hepatitis B Virus. Front Microbiol 2021; 12:664833. [PMID: 34867835 PMCID: PMC8635997 DOI: 10.3389/fmicb.2021.664833] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2021] [Accepted: 10/11/2021] [Indexed: 12/22/2022] Open
Abstract
The mechanism of occult hepatitis B infection (OBI) has not yet been fully clarified. Our previous research found that novel OBI-related mutation within S protein, E2G, could cause the hepatitis B surface antigen (HBsAg) secretion impairment, which resulted in intracellular accumulation in OBI of genotype B. Here, to further explore the role of E2 site mutations in the occurrence of OBI, we analyzed these site mutations among 119 OBI strains identified from blood donors. Meanwhile, 109 wild-type HBV strains (HBsAg positive/HBV DNA positive) were used as control group. Furthermore, to verify the E2 site mutations, two conservative 1.3-fold full-gene expression vectors of HBV genotype B and C (pHBV1.3B and pHBV1.3C) were constructed. Then, the E2 mutant plasmids on the basis of pHBV1.3B or pHBV1.3C were constructed and transfected into HepG2 cells, respectively. The extracellular and intracellular HBsAg were analyzed by electrochemical luminescence and cellular immunohistochemistry. The structural characteristics of S proteins with or without E2 mutations were analyzed using relevant bioinformatics software. E2 mutations (E2G/A/V/D) existed in 21.8% (26/119) of OBIs, while no E2 mutations were found in the control group. E2G/A/V/D mutations could strongly affect extracellular and intracellular level of HBsAg (p < 0.05). Notably, unlike E2G in genotype B that could cause HBsAg intracellular accumulation and secretion decrease (p < 0.05), E2G in genotype C could lead to a very significant HBsAg decrease both extracellularly (0.46% vs. pHBV1.3C) and intracellularly (11.2% vs. pHBV1.3C) (p < 0.05). Meanwhile, for E2G/A mutations, the relative intracellular HBsAg (110.7-338.3% vs. extracellular) and its fluorescence intensity (1.5-2.4-fold vs. with genotype-matched pHBV1.3B/C) were significantly higher (p < 0.05). Furthermore, N-terminal signal peptides, with a typical cleavage site for peptidase at positions 27 and 28, were exclusively detected in S proteins with secretion-defective mutants (E2G/A). Our findings suggest that: (1) E2G/A/V/D mutations were confirmed to significantly influence the detection of HBsAg, (2) the underlying mechanism of OBI caused by E2G mutation is quite different between genotype B and genotype C, and (3) E2G/A could produce a N-terminal truncated S protein, which might attribute to the HBsAg secretion impairment in the OBIs.
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Affiliation(s)
- Hao Wang
- Guangzhou Blood Center, Guangzhou, China
| | | | - Junmo Xie
- Guangzhou Blood Center, Guangzhou, China
| | - Wenbo Gao
- Guangzhou Blood Center, Guangzhou, China
| | - Min Wang
- Guangzhou Blood Center, Guangzhou, China
| | | | - Ru Xu
- Guangzhou Blood Center, Guangzhou, China
| | - Qiao Liao
- Guangzhou Blood Center, Guangzhou, China
| | | | | | - Xia Rong
- Guangzhou Blood Center, Guangzhou, China
| | - Chengyao Li
- Department of Transfusion Medicine, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, China
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5
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Sarowar A, Hirode G, Janssen HLA, Feld JJ. Controversies in Treating Chronic Hepatitis B Virus Infection: Discordant Serologic Results. Clin Liver Dis 2021; 25:805-816. [PMID: 34593154 DOI: 10.1016/j.cld.2021.06.007] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Despite effective vaccines and approved therapeutic agents, hepatitis B virus (HBV) remains a prevalent global health problem. Current guidelines rely on a combination of serologic, virological, and biochemical markers to identify the phase in the natural history of chronic HBV infection. Discordant serologic results can occur, which may lead to misclassification. Commonly encountered results that differ from the typical profiles seen in chronic HBV infection are described. For each scenario, the frequency of occurrence, possible explanations, and recommendations for clinical management are discussed. Recognition of discordant serologic findings is crucial for optimal clinical decision.
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Affiliation(s)
- Arif Sarowar
- Toronto Centre for Liver Disease, University Health Network, 200 Elizabeth Street, Toronto, Ontario M5G 2C4, Canada
| | - Grishma Hirode
- Toronto Centre for Liver Disease, University Health Network, 200 Elizabeth Street, Toronto, Ontario M5G 2C4, Canada
| | - Harry L A Janssen
- Toronto Centre for Liver Disease, University Health Network, 200 Elizabeth Street, Toronto, Ontario M5G 2C4, Canada
| | - Jordan J Feld
- Toronto Centre for Liver Disease, University Health Network, 200 Elizabeth Street, Toronto, Ontario M5G 2C4, Canada.
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6
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Gessain A, Montange T, Betsem E, Bilounga Ndongo C, Njouom R, Buseyne F. Case-Control Study of the Immune Status of Humans Infected With Zoonotic Gorilla Simian Foamy Viruses. J Infect Dis 2021; 221:1724-1733. [PMID: 31822908 DOI: 10.1093/infdis/jiz660] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2019] [Accepted: 12/10/2019] [Indexed: 12/26/2022] Open
Abstract
BACKGROUND Zoonotic simian foamy viruses (SFVs) establish persistent infections in humans, for whom the long-term consequences for health are poorly described. In this study, we aimed to characterize blood-cell phenotypes and plasma biomarkers associated with gorilla SFV infection in humans. METHODS We used a case-control design to compare 15 Cameroonian hunters infected with gorilla SFV (cases) to 15 controls matched for age and ethnicity. A flow cytometry-based phenotypic study and quantification of plasma immune biomarkers were carried out on blood samples from all participants. Wilcoxon signed-rank tests were used to compare cases and controls. RESULTS Cases had a significantly higher percentage of CD8 T lymphocytes than controls (median, 17.6% vs 13.7%; P = .03) but similar levels of B, natural killer, and CD4 T lymphocytes. Cases also had a lower proportion of recent CD4 thymic emigrants (10.9% vs 18.6%, P = .05), a higher proportion of programmed death receptor 1 (PD-1) expressing memory CD4 T lymphocytes (31.7% vs 24.7%, P = .01), and higher plasma levels of the soluble CD163 scavenger receptor (0.84 vs .59 µg/mL, P = .003) than controls. CONCLUSIONS We show, for the first time, that chronic infection with SFV is associated with T lymphocyte differentiation and monocyte activation.
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Affiliation(s)
- Antoine Gessain
- Unité d'Épidémiologie et Physiopathologie des Virus Oncogènes, Institut Pasteur, Paris, France.,Unité Mixte de Recherche du Centre National de la Recherche Scientifique 3569, Paris, France
| | - Thomas Montange
- Unité d'Épidémiologie et Physiopathologie des Virus Oncogènes, Institut Pasteur, Paris, France.,Unité Mixte de Recherche du Centre National de la Recherche Scientifique 3569, Paris, France
| | | | | | | | - Florence Buseyne
- Unité d'Épidémiologie et Physiopathologie des Virus Oncogènes, Institut Pasteur, Paris, France.,Unité Mixte de Recherche du Centre National de la Recherche Scientifique 3569, Paris, France
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7
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Ayana DA, Mulu A, Mihret A, Seyoum B, Aseffa A, Howe R. Occult Hepatitis B virus infection among HIV negative and positive isolated anti-HBc individuals in eastern Ethiopia. Sci Rep 2020; 10:22182. [PMID: 33335238 PMCID: PMC7747707 DOI: 10.1038/s41598-020-79392-x] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2020] [Accepted: 12/02/2020] [Indexed: 01/05/2023] Open
Abstract
The absence of hepatitis B surface antigen (HBsAg) and the presence of antibody to hepatitis B core antigen (anti-HBc) in the blood of apparently healthy individuals may not indicate the absence of circulating hepatitis B virus (HBV) and might be infectious. Despite the risk of HBV transmission, there has been no report from Ethiopia examining this issue; therefore, this study determined occult HBV infection (OBI) among isolated anti-HBc (IAHBc) HIV negative and HIV positive individuals on ART in eastern Ethiopia. A total of 306 IAHBc individuals were included in this study. DNA was extracted, amplified, and detected from plasma using a commercially available RealTime PCR platform (Abbott m2000rt) following the manufacturer's instructions. Data were entered into EPI Data version 3.1, cleaned, and analyzed using Stata version 13. Descriptive analysis was used to calculate prevalence, summarize sociodemographic data and other factors. From the 306 IAHBc individuals (184 HIV positive and 122 HIV negative) included in the study, 183 (59.8%) were female of which 142 (77.6%) were within the reproductive age group. DNA extraction, amplified and detection was conducted in 224 individuals. The overall OBI prevalence was 5.8% (5.6% in HIV negative and 6% in HIV positive) among the IAHBc individuals. The HBV DNA concentration among the occult hepatitis B individuals was < 200 IU/mL, indicating a true occult. This study reported the burden of OBI, which pauses a significant public health problem due to the high burden of HBV infection in the country. OBI may cause substantial risk of HBV transmission from blood transfusion, organ transplantation as well as vertical transmission as screening is solely dependent on HBsAg testing.
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Affiliation(s)
- Desalegn Admassu Ayana
- College of Health and Medical Sciences, Haramaya University, Haramaya, Ethiopia.
- Armauer Hansen Research Institute, Addis Ababa, Ethiopia.
| | - A Mulu
- College of Health and Medical Sciences, Haramaya University, Haramaya, Ethiopia
- Armauer Hansen Research Institute, Addis Ababa, Ethiopia
| | - A Mihret
- College of Health and Medical Sciences, Haramaya University, Haramaya, Ethiopia
- Armauer Hansen Research Institute, Addis Ababa, Ethiopia
| | - B Seyoum
- College of Health and Medical Sciences, Haramaya University, Haramaya, Ethiopia
- Armauer Hansen Research Institute, Addis Ababa, Ethiopia
| | - A Aseffa
- College of Health and Medical Sciences, Haramaya University, Haramaya, Ethiopia
- Armauer Hansen Research Institute, Addis Ababa, Ethiopia
| | - R Howe
- College of Health and Medical Sciences, Haramaya University, Haramaya, Ethiopia
- Armauer Hansen Research Institute, Addis Ababa, Ethiopia
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8
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Wang H, Wang M, Huang J, Xu R, Liao Q, Shan Z, Zheng Y, Rong X, Tang X, Li T, Wang W, Li C, Fu Y. Novel hepatitis B virus surface antigen mutations associated with occult genotype B hepatitis B virus infection affect HBsAg detection. J Viral Hepat 2020; 27:915-921. [PMID: 32336003 DOI: 10.1111/jvh.13309] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/11/2019] [Revised: 02/12/2020] [Accepted: 03/30/2020] [Indexed: 02/06/2023]
Abstract
The causative factors of occult hepatitis B infection are complicated and not yet been fully elucidated. Mutations in hepatitis B virus (HBV) S gene are one of the factors may contributing to occult infection. In this study, 89 blood donors with genotype B occult HBV infection were investigated. Fifty-seven hepatitis B surface antigen (HBsAg)-positive/HBV DNA-positive blood donors served as control group for comparison. Occult HBV-related mutations with a high incidence (P < .05) in the S gene were identified. To further verify these occult infection-related mutations, a conservative full-gene expression vector of HBV B genotype (pHBV1.3B) was constructed. Then, the mutant plasmids on the basis of pHBV1.3B were constructed and transfected into HepG2 cells. Extracellular as well as intracellular HBsAg was analysed by electrochemical luminescence and cellular immunohistochemistry. Ten occult infection-related mutations (E2G, Q101R, K122R, M133T, D144E, G145R, V168A, S174N, L175S and I226S) were significantly more frequent in the occult infection group (P < .05). Five of the ten mutations (E2G, D144E, G145R, V168A and S174N) strongly decreased extracellular HBsAg level (P < .05) in the transfection system. Notably, the E2G mutation had the most significant impact on the ratio of extracellular HBsAg (3.8% vs pHBV1.3B) and intracellular HBsAg (239.3% vs pHBV1.3B) (P < .05), and the fluorescence density of E2G mutant HBsAg was significantly higher than that of pHBV1.3B (P < .0001). Hence, ten mutations were associated with genotype B occult HBV infection; E2G and V168A were novel mutations which we confirmed significantly affect HBsAg detection. E2G might cause HBsAg secretion impairment that results in intracellular accumulation and a decrease in HBsAg secretion.
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Affiliation(s)
- Hao Wang
- Department of Transfusion Medicine, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, China.,Guangzhou Blood Center, Guangzhou, China
| | - Min Wang
- Guangzhou Blood Center, Guangzhou, China
| | | | - Ru Xu
- Guangzhou Blood Center, Guangzhou, China
| | - Qiao Liao
- Guangzhou Blood Center, Guangzhou, China
| | | | | | - Xia Rong
- Guangzhou Blood Center, Guangzhou, China
| | - Xi Tang
- 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
| | - Wenjing Wang
- 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
- Department of Transfusion Medicine, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, China.,Guangzhou Blood Center, Guangzhou, China
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Joshi SS, Coffin CS. Hepatitis B and Pregnancy: Virologic and Immunologic Characteristics. Hepatol Commun 2020; 4:157-171. [PMID: 32025602 PMCID: PMC6996345 DOI: 10.1002/hep4.1460] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/31/2019] [Accepted: 11/23/2019] [Indexed: 12/18/2022] Open
Abstract
The hepatitis B virus (HBV) is an important human pathogen. Unvaccinated infants infected through mother-to-child transmission (MTCT) are at >95% risk of developing serum hepatitis B surface antigen-positive chronic hepatitis B (CHB). Despite complete passive-active HBV immunoprophylaxis, approximately 10% of infants born to mothers who are highly viremic develop CHB, and thus maternal treatment with nucleos(t)ide analogs (tenofovir disoproxil fumarate, lamivudine, or telbivudine) is recommended in the third trimester of pregnancy to reduce MTCT risk. Viral rebound usually occurs after stopping treatment and, in the context of maternal immunologic reconstitution postpartum, can also precipitate host immune-mediated hepatic (biochemical) flares. In this article, we review the epidemiology of HBV MTCT, discuss management and potential mechanisms of HBV vertical transmission, and highlight recent studies on virologic and immunologic aspects of hepatitis B in pregnancy and postpartum.
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Affiliation(s)
- Shivali S. Joshi
- Liver UnitDivision of Gastroenterology and HepatologyDepartment of MedicineUniversity of CalgaryCalgaryCanada
- Department of Microbiology, Immunology and Infectious DiseasesCumming School of MedicineUniversity of CalgaryCalgaryCanada
| | - Carla S. Coffin
- Liver UnitDivision of Gastroenterology and HepatologyDepartment of MedicineUniversity of CalgaryCalgaryCanada
- Department of Microbiology, Immunology and Infectious DiseasesCumming School of MedicineUniversity of CalgaryCalgaryCanada
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10
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Muche M, Berg T, Rimpler S, Staedtler A, Böhm S, Nickel P, Baid-Agrawal S. Low prevalence of occult hepatitis B virus infection in chronic haemodialysis and kidney transplant patients. Liver Int 2019; 39:263-270. [PMID: 30171739 DOI: 10.1111/liv.13951] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/04/2018] [Revised: 08/09/2018] [Accepted: 08/12/2018] [Indexed: 12/15/2022]
Abstract
BACKGROUND Occult hepatitis B virus infection (OBI) is defined as the presence of hepatitis B virus (HBV) DNA in serum and/or liver in HBsAg-negative patients. We investigated the prevalence of OBI in large chronic haemodialysis (CHD) and kidney transplant recipients (KTxR) cohorts, including determination of HBV DNA in peripheral blood mononuclear cells (PBMCs). METHODS HBV DNA was determined in both serum and PBMCs in 417 CHD patients, 417 KTxR, 20 HBsAg-positive non-CHD non-KTx patients (positive controls) and 40 HBsAg-negative healthy subjects (negative controls). RESULTS Chronic haemodialysis group: two of 376 patients were HBsAg-positive. The 374 HBsAg-negative patients tested negative for HBV DNA in both serum and PBMCs. KTxR group: 14 of 417 patients were HBsAg-positive. One of 403 HBsAg-negative patients tested positive for HBV DNA in serum but not in PBMCs. Positive controls: six of 20 patients were under antiviral therapy and had negative HBV DNA in both serum and PBMCs. In 11 of 14 remaining patients, HBV DNA was detected in serum and in both serum and PBMCs in 3 patients. Negative controls: All 34 patients were anti-HBc-negative and HBV DNA-negative in both serum and PBMCs. In the long term, the only case of anti-HBc-negative OBI lost anti-HBs 5 years after inclusion in the study and showed HBV reactivation with HBsAg re-seroconversion. CONCLUSIONS We found nil prevalence of OBI in CHD patients and a very low prevalence (<1%) in KTxR suggesting that routine screening for HBV DNA is not required in CHD population in our region. However, in KTxR, pretransplant screening with HBV DNA should be considered. Testing for HBV DNA in PBMCs does not seem to be of additional value.
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Affiliation(s)
- Marion Muche
- Department of Gastroenterology and Hepatology, Charité Universitaetsmedizin Berlin, Berlin, Germany
| | - Thomas Berg
- Section Hepatology, Clinic for Gastroenterology and Rheumatology, University Hospital Leipzig, Leipzig, Germany
| | - Sunda Rimpler
- Department of Nephrology and Medical Intensive Care, Charite Universitaetsmedizin Berlin, Berlin, Germany
| | - Adrienne Staedtler
- Department of Nephrology and Medical Intensive Care, Charite Universitaetsmedizin Berlin, Berlin, Germany
| | - Stefan Böhm
- Max von Pettenkofer-Institute for Hygiene and Clinical Microbiology, Ludwig-Maximilians-Universität, Munich, Germany
| | - Peter Nickel
- Department of Nephrology and Medical Intensive Care, Charite Universitaetsmedizin Berlin, Berlin, Germany
| | - Seema Baid-Agrawal
- Department of Nephrology and Medical Intensive Care, Charite Universitaetsmedizin Berlin, Berlin, Germany.,Department of Nephrology and Transplant Center, Sahlgrenska University Hospital, University of Gothenburg, Gothenburg, Sweden
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11
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Effectiveness of PCR primers for the detection of occult hepatitis B virus infection in Mexican patients. PLoS One 2018; 13:e0205356. [PMID: 30304056 PMCID: PMC6179258 DOI: 10.1371/journal.pone.0205356] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2018] [Accepted: 09/24/2018] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Occult hepatitis B infection (OBI) is defined as the presence of hepatitis B virus (HVB) DNA in the liver of HBsAg negative individuals with or without detectable viral DNA in serum. OBI is a diagnostic challenge as it is characterized by a very low viral load, intermittently detectable through time. Individuals with OBI can develop chronic hepatic disease, including liver cirrhosis and hepatocellular carcinoma. The aim of this work was to produce tools to improve OBI detection of the HVB genotypes prevalent in Mexico. METHODS We designed and tested primers to detect OBI in serum samples by nested and real-time PCR. Conserved sites in the viral genome were determined by alignment of the most frequent HBV genotypes in Mexico (H, G/H, F and D) and primers spanning the entire viral genome were designed for first round and nested PCR. Primers were tested in serum samples of 45 patients not co-infected with hepatitis C virus or with HIV, out of a group of 116 HBsAg (-)/anti-HBc (+) individuals. Primers were also tested in a control group with chronic HBV. Nested PCR products obtained from HBsAg (-)/anti-HBc (+) were sequenced and used to design primers for real-time PCR (SYBR Green). RESULTS The most effective primer pairs to detect HBV products by nested PCR targeted ORF regions: PreS2/P, S/P, X/PreC, and C; while by real-time PCR they targeted ORF regions PreS2/P, S/P, X, and C. Out of the 45 HBsAg (-)/anti-HBc (+) patients tested, the viral genome was detected in 28 (62.2%) and 34 (75.5%), with nPCR and real-time PCR respectively. CONCLUSION Primers designed for real-time PCR detected up to 75.5% of suspected OBI Mexican patients, with or without liver disease, which represents an improvement from previous PCR strategies.
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12
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Anikhindi SA, Kumar A, Sharma P, Singla V, Bansal N, Arora A. Ideal Cure for Hepatitis B Infection: The Target is in Sight. J Clin Exp Hepatol 2018; 8:188-194. [PMID: 29892183 PMCID: PMC5992304 DOI: 10.1016/j.jceh.2017.10.002] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2017] [Accepted: 10/30/2017] [Indexed: 12/12/2022] Open
Abstract
Hepatitis B virus (HBV) is one of the most common causes of liver cirrhosis and hepatocellular carcinoma. Despite recent strides in pharmacotherapy, complete cure of HBV infection still remains an enigma. The biggest obstacle in HBV therapy is clearance of covalently closed circular deoxyribonucleic acid (cccDNA). We discuss about the role of cccDNA in HBV life cycle, efficacy and shortcomings of currently available antivirals as well as promising novel targets to achieve ideal HBV cure.
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Affiliation(s)
- Shrihari A. Anikhindi
- Department of Gastroenterology, Sir Ganga Ram Hospital, New Delhi, India
- Department of Pathology, Sir Ganga Ram Hospital, New Delhi, India
| | - Ashish Kumar
- Department of Gastroenterology, Sir Ganga Ram Hospital, New Delhi, India
- Department of Pathology, Sir Ganga Ram Hospital, New Delhi, India
| | - Praveen Sharma
- Department of Gastroenterology, Sir Ganga Ram Hospital, New Delhi, India
- Department of Pathology, Sir Ganga Ram Hospital, New Delhi, India
| | - Vikas Singla
- Department of Gastroenterology, Sir Ganga Ram Hospital, New Delhi, India
- Department of Pathology, Sir Ganga Ram Hospital, New Delhi, India
| | - Naresh Bansal
- Department of Gastroenterology, Sir Ganga Ram Hospital, New Delhi, India
- Department of Pathology, Sir Ganga Ram Hospital, New Delhi, India
| | - Anil Arora
- Department of Gastroenterology, Sir Ganga Ram Hospital, New Delhi, India
- Department of Pathology, Sir Ganga Ram Hospital, New Delhi, India
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Joshi SS, Coffin CS. Hepatitis B virus lymphotropism: emerging details and challenges. Biotechnol Genet Eng Rev 2018; 34:139-151. [DOI: 10.1080/02648725.2018.1474324] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Affiliation(s)
- Shivali S. Joshi
- Calgary Liver Unit, Division of Gastroenterology and Hepatology, Department of Medicine, Cumming School of Medicine, University of Calgary, Calgary, Canada
- Department of Microbiology, Immunology and Infectious Diseases, Cumming School of Medicine, University of Calgary, Calgary, Canada
| | - Carla S. Coffin
- Calgary Liver Unit, Division of Gastroenterology and Hepatology, Department of Medicine, Cumming School of Medicine, University of Calgary, Calgary, Canada
- Department of Microbiology, Immunology and Infectious Diseases, Cumming School of Medicine, University of Calgary, Calgary, Canada
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Wen X, Su H, Wang Y, Pu Z, Gao J, Ji Z, Yuan X, Li X, Zhang W, Zhang L, Long Y, Yan Y, Shao Z. Prevalence and natural course of occult hepatitis B virus infection in residents of 2 communities of Wuwei City, Gansu Province, China. J Viral Hepat 2018; 25:281-288. [PMID: 29032635 DOI: 10.1111/jvh.12805] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/20/2017] [Accepted: 08/02/2017] [Indexed: 12/14/2022]
Abstract
Occult hepatitis B infection (OBI) is characterized by serum hepatitis B surface antigen (HBsAg) negative and hepatitis B virus (HBV) DNA positive (HBsAg-/HBV DNA+). Occult hepatitis B infection in community-based populations has been scarcely investigated, and OBI outcomes remain unclear, especially in Wuwei, a region located in Northwest China. This region is one of the areas in China that has the highest prevalence of chronic HBV infection. A prospective study was performed in the general population of 2 towns of Wuwei from June 2011 to May 2014. A questionnaire was used to collect demographic and medical data, and serum samples were collected from the participants and stored until analysis. DNA was detected using quantitative PCR (qPCR) or nested PCR, the HBV DNA from HBV DNA-positive or possible positive (below the detection limit) subjects was extracted and amplified by nested PCR, and the PCR products were sequenced. Sequence analysis was performed using the Mega 6.0 program and CLC sequence viewer software. Hepatitis B virus DNA was detected in 90 of 3,080 HBsAg-negative subjects, and the prevalence of OBI in the study population was 2.92% (90/3,080, 95% CI: 2.33%-3.51%). Hepatitis B virus genomes in 51 of 80 objects (63.75%) contained mutations in the "a" determinant of HBsAg. After 2 years follow-up, 42 of 90 HBV DNA of OBI subjects remained positive, and the natural clearance rate of OBI subjects was 53.3%. Occult hepatitis B infection prevalence in this cohort was much lower than chronic HBV infection in the same region. HBV DNA was cleared in most OBI subjects during the 2 year period. Our data suggest that some OBI may represent a late stage of resolving the HBV infection process.
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Affiliation(s)
- X Wen
- Department of Epidemiology, School of Public Health, Fourth Military Medical University, Xi'an, China
| | - H Su
- Department of Epidemiology, School of Public Health, Fourth Military Medical University, Xi'an, China
| | - Y Wang
- Department of Epidemiology, School of Public Health, Fourth Military Medical University, Xi'an, China
| | - Z Pu
- Department of Epidemiology, School of Public Health, Fourth Military Medical University, Xi'an, China
| | - J Gao
- Department of Epidemiology, School of Public Health, Fourth Military Medical University, Xi'an, China
| | - Z Ji
- Department of Epidemiology, School of Public Health, Fourth Military Medical University, Xi'an, China
| | - X Yuan
- Department of Epidemiology, School of Public Health, Fourth Military Medical University, Xi'an, China
| | - X Li
- Center of disease control Of Wuwei, Gansu province, China
| | - W Zhang
- Department of Epidemiology, School of Public Health, Fourth Military Medical University, Xi'an, China
| | - L Zhang
- Department of Epidemiology, School of Public Health, Fourth Military Medical University, Xi'an, China
| | - Y Long
- Department of Epidemiology, School of Public Health, Fourth Military Medical University, Xi'an, China
| | - Y Yan
- Department of Epidemiology, School of Public Health, Fourth Military Medical University, Xi'an, China
| | - Z Shao
- Department of Epidemiology, School of Public Health, Fourth Military Medical University, Xi'an, China
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Peeridogaheh H, Meshkat Z, Habibzadeh S, Arzanlou M, Shahi JM, Rostami S, Gerayli S, Teimourpour R. Current concepts on immunopathogenesis of hepatitis B virus infection. Virus Res 2017; 245:29-43. [PMID: 29273341 DOI: 10.1016/j.virusres.2017.12.007] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2017] [Revised: 10/04/2017] [Accepted: 12/18/2017] [Indexed: 02/07/2023]
Abstract
Hepatitis B virus (HBV) infection is a leading cause of liver damage and hepatic inflammation. Upon infection, effective antiviral responses by CD8+ T cells, CD4+ T cells, Natural killer (NK) cells, and monocytes can lead to partial or complete eradication of the viral infection. To date, many studies have shown that the production of inhibitory cytokines such as Interleukin 10 (IL-10), Transforming growth factor beta (TGF-β), along with dysfunction of the dendritic cells (DCs), and the absence of efficient innate immune responses could lead to T cell exhaustion, development of persistent infection, and inability to eradicate the viral infection from liver. Understanding the immunopathogenesis of the virus could be useful in providing further insights toward novel strategies in the eradication of HBV infection.
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Affiliation(s)
- Hadi Peeridogaheh
- Department of Microbiology, School of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran
| | - Zahra Meshkat
- Antimicrobial Resistance Research Center, Bu Ali Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, IR Iran
| | - Shahram Habibzadeh
- Department of Infectious Diseases, School of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran
| | - Mohsen Arzanlou
- Department of Microbiology, School of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran
| | - Jafar Mohammad Shahi
- Department of Infectious Diseases, School of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran
| | - Sina Rostami
- Department of Clinical and Molecular Medicine Faculty of Medicine and Health Science, Norwegian University of Science and Technology, Trondheim, Norway
| | - Sina Gerayli
- Departments of Biology, Western University, London, Ontario, N6A 5B7, Canada
| | - Roghayeh Teimourpour
- Department of Microbiology, School of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran.
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16
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Wang T, Shen C, Chen L, Liu S, Ji Y. Association of human leukocyte antigen polymorphisms with occult hepatitis B virus infection in a Shaanxi Han population. J Gene Med 2017; 19. [PMID: 28940887 DOI: 10.1002/jgm.2987] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2017] [Revised: 08/21/2017] [Accepted: 09/13/2017] [Indexed: 01/01/2023] Open
Abstract
BACKGROUND Occult hepatitis B virus (HBV) infection (OBI) is defined as HBV DNA detection in serum or in the liver by sensitive diagnostic tests in HBV surface antigen (HBsAg) negative patients with or without serologic markers of previous HBV exposure. Because the human leukocyte antigen (HLA) system is an integral component of the immune response, we hypothesized that the highly polymorphic HLA genes were the key determinants of HBV persistence and clearance. The present study aimed to calculate the allelic frequency of HLA loci and investigate the association between HLA alleles and the outcome of OBI in Shaanxi Han population in the northwest of China. METHODS We conducted a case-control study between 107 OBI subjects and 280 healthy control individuals from blood donors of Shaanxi Blood Center. Five HLA loci, including HLA-A,-B,-C,-DRB1 and -DQB1, were selected and further genotyped using a polymerase chain reaction sequence-based typing (SBT) method. RESULTS Using the chi-squared test, we found that the allele frequencies of HLA-B*44:03 [odds ratios (OR) = 2.146, 95% confidence interval (CI) = 1.070-4.306, p = 0.028]; C*07:01 (OR = 4.693, CI = 1.822-12.086, p = 0.000); DQB1*02:02 (OR = 1.919, CI = 1.188-3.101, p = 0.007); and DRB1*07:01 (OR = 2.012, CI = 1.303-3.107, p = 0.001) were markedly higher in the OBI group compared to the healthy control group. The allele frequencies of HLA-DRB1*08:03 (OR = 0.395, CI = 0.152-1.027, p = 0.049); DRB1*15:01 (OR = 0.495, CI = 0.261-0.940, p = 0.029); and DQB1*06:02 (OR = 0.500, CI = 0.249-1.005, p = 0.048) were obviously lower in the OBI group compared to the healthy control group. These data indicated that HLA-B*44:03, C*07:01, DQB1*02:02 and DRB1*07:01 were related to OBI infection, whereas HLA-DRB1*08:03, DRB1*15:01 and DQB1*06:02 alleles were associated with HBV DNA clearance in a Shaanxi Han population. CONCLUSIONS The results of the present study suggest that host HLA gene is an important influencing factor for OBI pathogenesis.
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Affiliation(s)
- Tianju Wang
- Department of Immunology and Pathogenic Biology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, People's Republic of China.,Blood Center of the Shaanxi Province, Xi'an, Shaanxi, People's Republic of China
| | - Chunmei Shen
- Blood Center of the Shaanxi Province, Xi'an, Shaanxi, People's Republic of China
| | - Liping Chen
- Blood Center of the Shaanxi Province, Xi'an, Shaanxi, People's Republic of China
| | - Sheng Liu
- Blood Center of the Shaanxi Province, Xi'an, Shaanxi, People's Republic of China
| | - Yanhong Ji
- Department of Immunology and Pathogenic Biology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, People's Republic of China
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17
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Wang Y, Zhu P, Qiu J, Wang J, Zhu H, Zhu Y, Zhang L, Zhu J, Liu X, Dong C. Identification and characterization of interferon signaling-related microRNAs in occult hepatitis B virus infection. Clin Epigenetics 2017; 9:101. [PMID: 28932321 PMCID: PMC5603019 DOI: 10.1186/s13148-017-0404-9] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2017] [Accepted: 09/07/2017] [Indexed: 12/13/2022] Open
Abstract
Background Occult hepatitis B virus infection (OBI) is an important risk factor of liver cirrhosis and hepatocellular carcinoma. Type 1 interferon (IFN) signaling-related miRNAs were significantly associated with hepatitis B virus (HBV) infection. However, the characteristics of serum IFN signaling-related miRNAs in OBI remain unclear. Therefore, this study aimed to analyze the expression levels of serum IFN signaling-related miRNAs in OBI and to evaluate their potential values for OBI diagnosis. Methods Twenty serum samples for training test (10 healthy controls and 10 OBI patients) and 438 validation serum samples from healthy controls, asymptomatic HBsAg carriers (ASC), and chronic hepatitis B (CHB) and OBI patients were collected. Expression levels of 32 IFN signaling-related miRNAs were analyzed in training and validation sets of samples using RT-qPCR. Results Among 32 IFN signaling-related miRNAs, decreased miR-122 levels and increased miR-130a levels were detected in training OBI samples. Furthermore, the results from validation test showed that the mean serum miR-122 and miR-130a level was 2.28 ± 0.96 and 3.11 ± 0.93 in OBI subjects, respectively. Compared to the healthy controls, ASC and CHB patients, miR-122 levels were significantly downregulated, while miR-130a levels were significantly upregulated in OBI patients. ROC analysis indicated that miR-122 + miR-130a could differentiate OBI from healthy controls, ASC, and CHB (≥ 0.87 of AUC). Conclusions Our study suggested that decreased serum miR-122 level and increased miR-130a level were significantly associated with OBI. Moreover, a combination of miR-122 and miR-130a could be served as a potential marker for OBI diagnosis. Electronic supplementary material The online version of this article (10.1186/s13148-017-0404-9) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Yiying Wang
- Department of Epidemiology and Statistics, School of Public Health, Jiangsu Key Laboratory and Translational Medicine for Geriatric Disease, Medical College of Soochow University, 199 Renai Road, Suzhou, Jiangsu 215123 China.,Guizhou Center for Disease Control and Prevention, Guizhou, China
| | - Peifu Zhu
- Zhangjiagang First People Hospital, Suzhou, China
| | - Jing Qiu
- Department of Epidemiology and Statistics, School of Public Health, Jiangsu Key Laboratory and Translational Medicine for Geriatric Disease, Medical College of Soochow University, 199 Renai Road, Suzhou, Jiangsu 215123 China
| | - Jie Wang
- Department of Epidemiology and Statistics, School of Public Health, Jiangsu Key Laboratory and Translational Medicine for Geriatric Disease, Medical College of Soochow University, 199 Renai Road, Suzhou, Jiangsu 215123 China
| | - Huijuan Zhu
- Department of Epidemiology and Statistics, School of Public Health, Jiangsu Key Laboratory and Translational Medicine for Geriatric Disease, Medical College of Soochow University, 199 Renai Road, Suzhou, Jiangsu 215123 China
| | - Yinwei Zhu
- Department of Epidemiology and Statistics, School of Public Health, Jiangsu Key Laboratory and Translational Medicine for Geriatric Disease, Medical College of Soochow University, 199 Renai Road, Suzhou, Jiangsu 215123 China
| | - Lige Zhang
- Department of Epidemiology and Statistics, School of Public Health, Jiangsu Key Laboratory and Translational Medicine for Geriatric Disease, Medical College of Soochow University, 199 Renai Road, Suzhou, Jiangsu 215123 China
| | - Jie Zhu
- Department of Epidemiology and Statistics, School of Public Health, Jiangsu Key Laboratory and Translational Medicine for Geriatric Disease, Medical College of Soochow University, 199 Renai Road, Suzhou, Jiangsu 215123 China
| | | | - Chen Dong
- Department of Epidemiology and Statistics, School of Public Health, Jiangsu Key Laboratory and Translational Medicine for Geriatric Disease, Medical College of Soochow University, 199 Renai Road, Suzhou, Jiangsu 215123 China
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18
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Salpini R, Piermatteo L, Gill U, Battisti A, Stazi F, Guenci T, Giannella S, Serafini V, Kennedy PTF, Perno CF, Svicher V, Ciotti M. Quantification of intrahepatic total HBV DNA in liver biopsies of HBV-infected patients by a modified version of COBAS ® Ampliprep/COBAS ®TaqMan HBV test v2.0. Med Microbiol Immunol 2017; 206:295-299. [PMID: 28401351 DOI: 10.1007/s00430-017-0504-3] [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: 03/01/2017] [Accepted: 04/05/2017] [Indexed: 10/19/2022]
Abstract
Intrahepatic total HBV DNA (it-HBV DNA) level might reflect the size of virus reservoir and correlate with the histological status of the liver. To quantitate it-HBV DNA in a series of 70 liver biopsies obtained from hepatitis B chronic patients, a modified version of the COBAS®Ampliprep/COBAS®TaqMan HBV test v2.0 was used for this purpose. The linearity and reproducibility of the modified protocol was tested by quantifying serial dilutions of a full-length HBV containing plasmid and it-HBV DNA from a reference patient. A good linear trend between the expected values and those generated by the assay was observed at different concentrations of both plasmid and reference patient (R 2 = 0.994 and 0.962, respectively). Differences between the values obtained in two independent runs were ≤0.3 log IU for the plasmid and ≤0.6 log IU/mg for the reference patient, showing a high inter-run reproducibility. In the 70 liver biopsies, it-HBV DNA level ranged from 1.4 to 5.4 log IU/mg, with a good linearity and reproducibility between the values obtained in two runs [R 2 = 0.981; median (IQR) difference of it-HBV DNA 0.05 (0.02-0.09) IU/mg]. The modified COBAS®Ampliprep/COBAS®TaqMan HBV test v2.0 allows an accurate quantitation of it-HBV DNA. Its determination may have prognostic value and may be a useful tool for the new therapeutic strategies aimed at eradicating the HBV infection.
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Affiliation(s)
- Romina Salpini
- Department of Experimental Medicine and Surgery, University of Rome Tor Vergata, Via Montpellier 1, 00133, Rome, Italy
| | - Lorenzo Piermatteo
- Department of Experimental Medicine and Surgery, University of Rome Tor Vergata, Via Montpellier 1, 00133, Rome, Italy
| | - Upkar Gill
- Hepatology, Centre for Immunobiology, Blizard Institute, Barts and The London SMD, QMUL, London, UK
| | - Arianna Battisti
- Department of Experimental Medicine and Surgery, University of Rome Tor Vergata, Via Montpellier 1, 00133, Rome, Italy
| | - Francesca Stazi
- Laboratory of Molecular Virology, Polyclinic Tor Vergata Foundation, Viale Oxford 81, 00133, Rome, Italy
| | - Tania Guenci
- Laboratory of Molecular Virology, Polyclinic Tor Vergata Foundation, Viale Oxford 81, 00133, Rome, Italy
| | - Sara Giannella
- Laboratory of Molecular Virology, Polyclinic Tor Vergata Foundation, Viale Oxford 81, 00133, Rome, Italy
| | - Valentina Serafini
- Laboratory of Molecular Virology, Polyclinic Tor Vergata Foundation, Viale Oxford 81, 00133, Rome, Italy
| | - Patrick T F Kennedy
- Hepatology, Centre for Immunobiology, Blizard Institute, Barts and The London SMD, QMUL, London, UK
| | - Carlo Federico Perno
- Department of Experimental Medicine and Surgery, University of Rome Tor Vergata, Via Montpellier 1, 00133, Rome, Italy
- Laboratory of Molecular Virology, Polyclinic Tor Vergata Foundation, Viale Oxford 81, 00133, Rome, Italy
| | - Valentina Svicher
- Department of Experimental Medicine and Surgery, University of Rome Tor Vergata, Via Montpellier 1, 00133, Rome, Italy
| | - Marco Ciotti
- Laboratory of Molecular Virology, Polyclinic Tor Vergata Foundation, Viale Oxford 81, 00133, Rome, Italy.
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Temporal trend of hepatitis B surface mutations in the post-immunization period: 9 years of surveillance (2005-2013) in eastern China. Sci Rep 2017; 7:6669. [PMID: 28751727 PMCID: PMC5532365 DOI: 10.1038/s41598-017-07085-z] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2017] [Accepted: 06/22/2017] [Indexed: 01/21/2023] Open
Abstract
Limited information is available about the temporal trend in the prevalence and evolution of hepatitis B virus (HBV) S-gene mutations in the post-immunization era in China. From 2005 to 2013, 1077 hepatitis B cases under 15 years of age reported through Chinese National Notifiable Disease Reporting System (NNDRS) were successfully sequenced of S-gene in Shandong province, China. A total of 97 (9.01%) cases had amino acid (aa) substitution in the “α” determinant of HBsAg. The yearly prevalence from 2005 to 2013 maintained at a relatively stable level, and showed no significant change (P > 0.05). Multivariate logistic regression analysis demonstrated that the prevalence of “α” mutations was independently associated with the maternal HBsAg status (P < 0.05), and not with surveillance year and hepatitis B vaccination (P > 0.05). The hottest mutation position was aa126 (I126S/N and T126A, 29.63%), and aa 145 (G145R/A, 25.93%). Mutated residue 126 tended to occur less frequent, while that of residue 145 was more frequent with increasing year. Our data showed that there was no increase in the frequency of HBV “α” mutations over time during the post-immunization period. However, long-term vaccination might enhance the change of HBV mutational pattern, and G145 mutation was becoming dominant.
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20
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Prevalence of S gene mutations within the major hydrophilic region of hepatitis B virus in patients in Dongguan, southern China. Arch Virol 2017; 162:2949-2957. [PMID: 28600703 DOI: 10.1007/s00705-017-3437-7] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2016] [Accepted: 05/18/2017] [Indexed: 12/30/2022]
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Saha D, Pal A, Sarkar N, Das D, Blackard JT, Guha SK, Saha B, Chakravarty R. Occult hepatitis B virus infection in HIV positive patients at a tertiary healthcare unit in eastern India. PLoS One 2017; 12:e0179035. [PMID: 28591184 PMCID: PMC5462430 DOI: 10.1371/journal.pone.0179035] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2017] [Accepted: 05/23/2017] [Indexed: 12/13/2022] Open
Abstract
Occult HBV infection (OBI), defined by the presence of HBV DNA in absence of hepatitis B surface antigen (HBsAg), is a significant concern in the HIV-infected population. Of 441 HIV+/HBsAg- patients analyzed, the overall prevalence of OBI was 6.3% (28/441). OBI was identified in 21 anti-HBc positives (17.8%), as well as among those who lacked any HBV-specific serological markers (2.2%). Comparison with HIV/HBV co-infection revealed that the levels of CD4, ALT, and HBV DNA were significantly lower during occult infection. Discrete differences were also observed with respect to quasispecies divergence. Additionally, subgenotype D1 was most frequent in occult infection, while D2 was widespread during chronic infection. The majority (~90%) of occult D1 sequences had the sQ129R mutation in the surface gene. This study highlights several distinct features of OBI in India and underscores the need for additional HBV DNA screening in HIV-positive individuals.
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Affiliation(s)
- Debraj Saha
- ICMR Virus Unit, Kolkata, ID & BG Hospital Campus, Kolkata, West Bengal, India
| | - Ananya Pal
- ICMR Virus Unit, Kolkata, ID & BG Hospital Campus, Kolkata, West Bengal, India
| | - Neelakshi Sarkar
- ICMR Virus Unit, Kolkata, ID & BG Hospital Campus, Kolkata, West Bengal, India
| | - Dipanwita Das
- ICMR Virus Unit, Kolkata, ID & BG Hospital Campus, Kolkata, West Bengal, India
| | - Jason T. Blackard
- Division of Digestive Diseases, University of Cincinnati College of Medicine, Cincinnati, Ohio, United States of America
| | | | - Bibhuti Saha
- Calcutta School of Tropical Medicine, Kolkata, West Bengal, India
| | - Runu Chakravarty
- ICMR Virus Unit, Kolkata, ID & BG Hospital Campus, Kolkata, West Bengal, India
- * E-mail:
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Alshayea AI, Eid GE, El-Hazmi MM, Alhetheel AF. Prevalence and characterization of occult hepatitis B infection among blood donors in central Saudi Arabia. Saudi Med J 2017; 37:1114-9. [PMID: 27652363 DOI: 10.15537/smj.2016.10.14708] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022] Open
Abstract
OBJECTIVES To evaluate the prevalence of occult hepatitis B viral infections (OBIs) among blood donors considering the clinical and epidemiological importance of identifying OBIs. METHODS A cross-sectional study conducted at King Khalid University Hospital, Riyadh, Saudi Arabia between January 2011 and January 2012. Blood donors (n=8501) were screened for Hepatitis B virus surface antigen (HBsAg) and hepatitis B core antibodies (HBcAb). All HBsAg-negative and HBcAb-positive samples were tested further for hepatitis B surface antibodies (HBsAb), hepatitis B virus (HBV)-DNA, and HBV genotyping. RESULTS Of the 8501 serum samples tested, 56 (0.7%) were positive and 8445 (99.3%) were negative for HBsAg. Among the HBsAg-negative samples, 198 (2.3%) were positive for HBcAb and these patients were suspected to have OBIs. Among the HBcAb-positive samples, 119 (60.1%) were positive while 79 (39.9%) were negative for HBsAb. Analysis of HBV-DNA for the suspected OBIs showed that 17 out of 198 samples (8.6%) yielded positive results, and all of them were HBsAb-negative. The viral load was low (less than 20-186 IU/mL) in all OBIs. Hepatitis B virus genotyping showed that 15 out of 17 samples (88.2%) were genotype D, and the other 2 samples (11.8%) were genotype E. CONCLUSION The prevalence of OBIs among blood donors in Riyadh was 0.2%. Therefore, it is recommended that HBV molecular testing should be incorporated with serological assays for screening of blood donors.
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Affiliation(s)
- Areej I Alshayea
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Khalid University Hospital, King Saud University, Riyadh, Kingdom of Saudi Arabia. E-mail.
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Kim MH, Kang SY, Lee WI. Occult HBV among Anti-HBc Alone: Mutation Analysis of an HBV Surface Gene and Pre-S Gene. Yonsei Med J 2017; 58:557-563. [PMID: 28332361 PMCID: PMC5368141 DOI: 10.3349/ymj.2017.58.3.557] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2016] [Revised: 12/23/2016] [Accepted: 01/26/2017] [Indexed: 12/14/2022] Open
Abstract
PURPOSE The aim of this study is to investigate the molecular characteristics of occult hepatitis B virus (HBV) infection in 'anti-HBc alone' subjects. MATERIALS AND METHODS Twenty-four patients with 'anti-HBc alone' and 20 control patients diagnosed with HBV were analyzed regarding S and pre-S gene mutations. All specimens were analyzed for HBs Ag, anti-HBc, and anti-HBs. For specimens with an anti-HBc alone, quantitative analysis of HBV DNA, as well as sequencing and mutation analysis of S and pre-S genes, were performed. RESULTS A total 24 were analyzed for the S gene, and 14 were analyzed for the pre-S gene through sequencing. A total of 20 control patients were analyzed for S and pre-S gene simultaneously. Nineteen point mutations of the major hydrophilic region were found in six of 24 patients. Among them, three mutations, S114T, P127S/T, M133T, were detected in common. Only one mutation was found in five subjects of the control group; this mutation was not found in the occult HBV infection group, however. Pre-S mutations were detected in 10 patients, and mutations of site aa58-aa100 were detected in 9 patients. A mutation on D114E was simultaneously detected. Although five mutations from the control group were found at the same location (aa58-aa100), no mutations of occult HBV infection were detected. CONCLUSION The prevalence of occult HBV infection is not low among 'anti-HBc alone' subjects. Variable mutations in the S gene and pre-S gene were associated with the occurrence of occult HBV infection. Further larger scale studies are required to determine the significance of newly detected mutations.
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Affiliation(s)
- Myeong Hee Kim
- Department of Laboratory Medicine, Kyung Hee University School of Medicine and Kyung Hee University Hospital at Gangdong, Seoul, Korea
| | - So Young Kang
- Department of Laboratory Medicine, Kyung Hee University School of Medicine and Kyung Hee University Hospital at Gangdong, Seoul, Korea.
| | - Woo In Lee
- Department of Laboratory Medicine, Kyung Hee University School of Medicine and Kyung Hee University Hospital at Gangdong, Seoul, Korea
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Guarino M, Picardi M, Vitiello A, Pugliese N, Rea M, Cossiga V, Pane F, Caporaso N, Morisco F. Viral Outcome in Patients with Occult HBV Infection or HCV-Ab Positivity Treated for Lymphoma. Ann Hepatol 2017. [DOI: 10.5604/16652681.1231579] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/26/2023]
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Kolou M, Katawa G, Salou M, Gozo-Akakpo KS, Dossim S, Kwarteng A, Prince-David M. High Prevalence of Hepatitis B Virus Infection in the Age Range of 20-39 Years Old Individuals in Lome. Open Virol J 2017; 11:1-7. [PMID: 28217218 PMCID: PMC5301296 DOI: 10.2174/1874357901710011001] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2015] [Revised: 10/18/2016] [Accepted: 11/07/2016] [Indexed: 12/22/2022] Open
Abstract
BACKGROUND Hepatitis B is a liver infection caused by the hepatitis B virus (HBV). It affects all women and men irrespective of age. Although sub-Saharan Africa is an area of high prevalence of this disease, data on the prevalence of acute and chronic HBV infections in this region remain to be widely documented. OBJECTIVE This study aimed to investigate the prevalence of HBV in relation to age in Centre Hospitalier Universitaire Campus (CHU-C), one of the two teaching hospitals of Lome, Togo. METHOD The present study is a cross-sectional study about the prevalence of hepatitis B surface antigen (HBsAg) carriage from 2009 to 2011. All study participants were screened for HBsAg at the Immunology laboratory of CHU Campus of Lome. RESULTS One thousand two hundred individuals were screened for HBsAg from 2009-2011. The overall prevalence of HBV infection was 19.08%. This prevalence was significantly higher in men (25.00%) than women (14.80%). The highest prevalence of HBV was observed in age range of 20-29 years and 30-39 years with respectively 26.33% and 21.67%. The lowest prevalence was 6.08%, found in people over 50 years. Concerning the clinical indication of the test, the prevalence during the clinical abnormalities related to liver (CARL) was the highest (26.21%), followed by the systematic screening (SS) with 20.25% while the pre-operative assessment (POA) showed the lowest prevalence with 5.56%. CONCLUSION The study shows the high prevalence of HBsAg carriage in young people. This could be used to enhance prevention and treatment of HBV infection in Togo.
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Affiliation(s)
- Malewe Kolou
- Centre Hospitalier Universitaire (CHU) Campus, Lome, Togo; Faculte des Sciences de la Santé (FSS), Universite de Lome, Togo
| | - Gnatoulma Katawa
- Ecole Superieure des Techniques Biologiques et Alimentaires (ESTBA), Universite de Lome, Togo
| | - Mounerou Salou
- Faculte des Sciences de la Santé (FSS), Universite de Lome, Togo
| | | | - Sika Dossim
- Faculte des Sciences de la Santé (FSS), Universite de Lome, Togo
| | - Alexander Kwarteng
- Institute of Medical Microbiology, Immunology and Parasitology (IMMIP), University Hospital of Bonn, Germany
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Zinserling VA, Esaulenko EV, Karev VE, Bubochkin AB, Sukhoruk AA, Shibaeva EO, Ponyatishina MV. [Clinical and morphological correlations in occult hepatitis B]. Arkh Patol 2017; 79:8-13. [PMID: 29265072 DOI: 10.17116/patol20177968-13] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/07/2023]
Abstract
UNLABELLED Occult hepatitis B (ОHB) characterized by the absence of blood HBsAg attracts the attention of specialists of different profiles; however, its clinical morphological aspects have not been practically studied. AIM to estimate the proportion of OHB in the structure of fatal outcomes in chronic viral hepatitis (CVH) and to characterize its clinical course and structural changes on autopsy materials. MATERIAL AND METHODS A total of 455 autopsy cases of CVH were examined for its etiology in the S.P. Botkin Clinical Hospital of Infectious Diseases in 2014-2016. An in-depth prospective clinical analysis was made to investigate 28 cases of OHB in the stage of decompensated liver cirrhosis, which had subsequently culminated in death. The criteria of inclusion were history data and clinical symptoms of CVH in the detection of markers for hepatitis A, C, and D and HIV in serum HBcAb in the absence of HBsAg. HBsAbs were also determined. Along with the traditional morphological examination, immunohistochemistry (IHC) for HBsAg and HBcAg was carried out. RESULTS There were 108 CVHB cases (23.7% of the total cases of CVH), including 77 OHB cases (71.3% of those of CVHB) while HBsAg was not determined. HBsAb-negative patients were more often observed to have clinical signs of jaundice (p<0.05) and skin itching (p<0.05). Dyspepsia and hemorrhagic manifestations prevailed in patients with HBsAb (more than 10 IU/l) (p<0.05). All the cases were found to have characteristic morphological signs of CVH, including intranuclear inclusions and nuclear polymorphism in 10.7% of deaths. There was an IHC-positive reaction to VHB antigens in 28.6% of the patients and a doubtful reaction in 25.0%. CONCLUSION Serum НВсAb may serve as a diagnostic marker for HBV infection. Clinical and morphological correlations enabled the authors to state that CVHB was present in all cases in the absence of serum HBsAg in the patients.
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Affiliation(s)
- V A Zinserling
- Institute of Experimental Medicine, V.A. Almazov North-Western Federal Research Center, Saint Petersburg, Russia; S.P. Botkin Clinical Hospital of Infectious Diseases, Saint Petersburg, Russia; Saint Petersburg State University, Saint-Petersburg, Russia
| | - E V Esaulenko
- Saint Petersburg State Pediatric Medical University, Ministry of Health of Russia, Saint Petersburg, Russia
| | - V E Karev
- Pediatric Research and Clinical Center for Infectious Diseases, Federal Biomedical Agency, Saint Petersburg, Russia
| | - A B Bubochkin
- S.P. Botkin Clinical Hospital of Infectious Diseases, Saint Petersburg, Russia
| | - A A Sukhoruk
- Saint Petersburg State Pediatric Medical University, Ministry of Health of Russia, Saint Petersburg, Russia
| | - E O Shibaeva
- Saint Petersburg State Pediatric Medical University, Ministry of Health of Russia, Saint Petersburg, Russia
| | - M V Ponyatishina
- Saint Petersburg State Pediatric Medical University, Ministry of Health of Russia, Saint Petersburg, Russia
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Abstract
Hepatitis B virus (HBV) infection is a major global health challenge. HBV can cause significant morbidity and mortality by establishing acute and chronic hepatitis. Approximately 250 million people worldwide are chronically infected, and more than 2 billion people have been exposed to HBV. Since the discovery of HBV, the advances in our understanding of HBV virology and immunology have translated into effective vaccines and therapies for HBV infection. Although current therapies successfully suppress viral replication but rarely succeed in viral eradication, recent discoveries in HBV virology and immunology provide exciting rationales for novel treatment strategies aiming at HBV cure.
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Affiliation(s)
- Bertram Bengsch
- Department of Microbiology and Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, 331 Biomedical Research Building II/III, 421 Curie Boulevard, Philadelphia, PA 19104, USA
| | - Kyong-Mi Chang
- Medical Research, Philadelphia Corporal Michael J. Crescenz VA Medical Center (CMC VAMC), A424, University and Woodland Avenue, Philadelphia, PA 19104, USA; Division of Gastroenterology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, 421 Curie Boulevard, Philadelphia, PA 19104, USA.
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Keechilot CS, Shenoy V, Kumar A, Biswas L, Vijayrajratnam S, Dinesh K, Nair P. Detection of occult hepatitis B and window period infection among blood donors by individual donation nucleic acid testing in a tertiary care center in South India. Pathog Glob Health 2016; 110:287-291. [PMID: 27788631 DOI: 10.1080/20477724.2016.1248171] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
With the introduction of highly sensitive hepatitis B surface antigen immunoassay, transfusion associated HBV infection have reduced drastically but they still tend to occur due to blood donors with occult hepatitis B infection (OBI) and window period (WP) infection. Sera from, 24338 healthy voluntary blood donors were screened for HBsAg, HIV and HCV antibody using Vitros Enhanced Chemiluminescent Immunoassay. The median age of the donor population was 30 (range 18-54) with male preponderance (98%). All serologically negative samples were screened by nucleic acid testing (NAT) for viral DNA and RNA. NAT-positive samples were subjected to discriminatory NAT for HBV, HCV, and HIV and all samples positive for HBV DNA were tested for anti-HBc, anti-HBs, HBeAg. Viral load was determined using artus HBV RG PCR Kit. Of the 24,338 donors screened, 99.81% (24292/24338) were HBsAg negative of which NAT was positive for HBV DNA in 0.0205% (5/24292) donors. Four NAT positive donors had viral load of <200 IU/ml making them true cases of OBI. One NAT positive donor was negative for all antibodies making it a case of WP infection. Among OBI donors, 75% (3/4) were immune and all were negative for HBeAg. Precise HBV viral load could not be determined in all (5/5) NAT positive donors due to viral loads below the detection limit of the artus HBV RG PCR Kit. The overall incidence of OBI and WP infections was found to be low at 1 in 6503 and 1 in 24214 donations, respectively. More studies are needed to determine the actual burden of WP infections in Indian blood donors.
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Affiliation(s)
- Cinzia S Keechilot
- a Amrita Institute of Medical Sciences and Research Center , Amrita Vishwa Vidyapeetham (Amrita University) , Ponekkara, Cochin , Kerala , India
| | - Veena Shenoy
- b Department of Transfusion Medicine , Amrita Institute of Medical Sciences and Research Center, Amrita Vishwa Vidyapeetham (Amrita University) , Ponekkara, Cochin , Kerala , India
| | - Anil Kumar
- c Department of Microbiology , Amrita Institute of Medical Sciences and Research Center, Amrita Vishwa Vidyapeetham (Amrita University) , Ponekkara, Cochin , Kerala , India
| | - Lalitha Biswas
- d Department of Molecular Biology , Amrita Institute of Medical Sciences and Research Center, Amrita Vishwa Vidyapeetham (Amrita University) , Ponekkara, Cochin , Kerala , India
| | - Sukhithasri Vijayrajratnam
- e Center for Nanoscience and Molecular medicine , Amrita Institute of Medical Sciences and Research Center, Amrita Vishwa Vidyapeetham (Amrita University) , Ponekkara, Cochin , Kerala , India
| | - Kavitha Dinesh
- c Department of Microbiology , Amrita Institute of Medical Sciences and Research Center, Amrita Vishwa Vidyapeetham (Amrita University) , Ponekkara, Cochin , Kerala , India
| | - Prem Nair
- f Department of Gastroenterology , Amrita Institute of Medical Sciences and Research Center, Amrita Vishwa Vidyapeetham (Amrita University) , Ponekkara, Cochin , Kerala , India
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Makvandi M. Update on occult hepatitis B virus infection. World J Gastroenterol 2016; 22:8720-8734. [PMID: 27818588 PMCID: PMC5075547 DOI: 10.3748/wjg.v22.i39.8720] [Citation(s) in RCA: 102] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2016] [Revised: 06/13/2016] [Accepted: 07/20/2016] [Indexed: 02/06/2023] Open
Abstract
The event of mutations in the surface antigen gene of hepatitis B virus (HBV) results in undetectable hepatitis B surface antigen with positive/negative anti-hepatitis B core (anti-HBc) antibody status in serum and this phenomenon is named occult hepatitis B infection (OBI). The presence of anti-HBc antibody in serum is an important key for OBI tracking, although about 20% of OBI cases are negative for anti-HBc antibody. The diagnosis of OBI is mainly based on polymerase chain reaction (PCR) and real-time PCR assays. However, real-time PCR is a more reliable method than PCR. OBI is a great issue for the public health problem and a challenge for the clinical entity worldwide. The persistence of OBI may lead to the development of cirrhosis and hepatocellular carcinoma. With regard to OBI complications, the screening of HBV DNA by the highly sensitive molecular means should be implemented for: (1) patients with a previous history of chronic or acute HBV infection; (2) patients co-infected with hepatitis C virus/human immunodeficiency virus; (3) patients undergoing chemotherapy or anti-CD20 therapy; (4) recipients of organ transplant; (5) blood donors; (6) organ transplant donors; (7) thalassemia and hemophilia patients; (8) health care workers; (9) patients with liver related disease (cryptogenic); (10) hemodialysis patients; (11) patients undergoing lamivudine or interferon therapy; and (12) children in time of HBV vaccination especially in highly endemic areas of HBV. Active HBV vaccination should be implemented for the close relatives of patients who are negative for OBI markers. Thus, the goal of this review is to evaluate the rate of OBI with a focus on status of high risk groups in different regions of the world.
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Chen Y, Bai X, Zhang Q, Wen L, Su W, Fu Q, Sun X, Lou Y, Yang J, Zhang J, Chen Q, Wang J, Liang T. The hepatitis B virus X protein promotes pancreatic cancer through modulation of the PI3K/AKT signaling pathway. Cancer Lett 2016; 380:98-105. [DOI: 10.1016/j.canlet.2016.06.011] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2016] [Revised: 06/12/2016] [Accepted: 06/14/2016] [Indexed: 02/07/2023]
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Hepatitis B virus infection in blood donors in Argentina: prevalence of infection, genotype distribution and frequency of occult HBV infection. Arch Virol 2016; 161:2813-7. [PMID: 27383207 DOI: 10.1007/s00705-016-2960-2] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2015] [Accepted: 06/28/2016] [Indexed: 12/13/2022]
Abstract
This study describes the prevalence of HBV infection based on detection of HBsAg and HBV-DNA by NAT in 70,102 blood donors in Argentina (Córdoba province) and shows the viral genotype distribution and frequency of occult HBV infection (OBI) in this population. Forty-two donors were confirmed positive for HBV infection (0.06 %), and four had OBI. Genotype F was the most prevalent (71.4 %), followed by A (14.3 %), C (7.1 %) and D (7.1 %). This is the first report of the prevalence of confirmed HBV infection and the high frequency of occult HBV infection in a blood bank in Argentina.
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Salehi-Vaziri M, Sadeghi F, Almasi Hashiani A, Gholami Fesharaki M, Alavian SM. Hepatitis B Virus Infection in the General Population of Iran: An Updated Systematic Review and Meta-Analysis. HEPATITIS MONTHLY 2016; 16:e35577. [PMID: 27257428 PMCID: PMC4888501 DOI: 10.5812/hepatmon.35577] [Citation(s) in RCA: 64] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/17/2015] [Revised: 02/02/2016] [Accepted: 02/07/2016] [Indexed: 12/11/2022]
Abstract
CONTEXT The hepatitis B virus (HBV) is a major global public health problem, affecting more than 2 billion people worldwide. Accurate and updated data on HBV prevalence is important for further planning to control the infection. The aim of this study was to update the prevalence estimate of HBV infection in the general population of Iran. EVIDENCE ACQUISITION A systematic review was done for data on the prevalence of HBV infection in the general Iranian population published between Jan. 1, 1990, and Jan. 1, 2016, in both international and national databases, including PubMed, Scopus, Web of Science, Scientific Information Database, IranMedex, and Magiran. All papers with clearly described time and location of the study, proper sampling strategies, and proper analysis methods were included in the present study. Data were extracted by two independent reviewers. Prevalence of HBV infection with a 95% confidence interval (CI) was calculated using Stata software, version 13. RESULTS The polled estimated prevalence of HBV infection in the general population of Iran was 2.2 % (95% CI: 1.9% - 2.6%). The highest prevalence of HBV infection (8.9%, 95% CI: 7.6% - 10.2%) was reported from Golestan province, and the lowest prevalence (0.7%, 95% CI: 0.4% - 1.1%) was seen in Kermanshah province. The prevalence of HBV infection was estimated at 3% (95% CI: 2.2% - 3.8%) for Iranian males and 1.7% (95% CI: 1.2% - 2.3%) for Iranian females. The prevalence of HBV infection in the general population of Iran was 2.9% (95% CI: 2.5% - 3.4%) before 2010 and 1.3% (95% CI: 0.9% - 1.7%) after 2010. CONCLUSIONS In total, Iran was classified within the low-intermediate HBV prevalence areas (2% - 4%), while according to recent data (after 2010), Iran was classified within the low HBV prevalence areas (< 2%), indicating that preventive measures conducted in Iran have been effective.
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Affiliation(s)
- Mostafa Salehi-Vaziri
- Department of Arboviruses and Viral Hemorrhagic Fevers, Pasteur Institute of Iran, Tehran, IR Iran
| | - Farzin Sadeghi
- Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, IR Iran
| | - Amir Almasi Hashiani
- Medical Ethics and Law Research Center, Shahid Beheshti University of Medical Sciences, Tehran, IR Iran
| | | | - Seyed Moayed Alavian
- Baqiyatallah Research Center for Gastroenterology and Liver Diseases, Baqiyatallah University of Medical Sciences Tehran, IR Iran
- Corresponding Author: Seyed Moayed Alavian, Baqiyatallah Research Center for Gastroenterology and Liver Diseases, Baqiyatallah University of Medical Sciences Tehran, IR Iran. Tel/Fax: +98-2188945186, E-mail:
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Samadi Kochaksaraei G, Castillo E, Osman M, Simmonds K, Scott AN, Oshiomogho JI, Lee SS, Myers RP, Martin SR, Coffin CS. Clinical course of 161 untreated and tenofovir-treated chronic hepatitis B pregnant patients in a low hepatitis B virus endemic region. J Viral Hepat 2016; 23:15-22. [PMID: 26192022 DOI: 10.1111/jvh.12436] [Citation(s) in RCA: 48] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/04/2015] [Accepted: 06/01/2015] [Indexed: 12/11/2022]
Abstract
Hepatitis B immunoprophylaxis failure is linked to high maternal viraemia. There is limited North American data on hepatitis B outcomes in pregnancy. Pregnant hepatitis B carriers were enrolled January 2011-December 2014 and offered tenofovir in the 3rd trimester if hepatitis B virus (HBV)-DNA was >7-log IU/mL. Outcomes were determined in treated vs untreated patients. In total, 161 women with 169 pregnancies (one twin, 170 infants; median age 32 years), 18% (29/161) HBeAg+ and median HBV-DNA 2.51 log IU/mL (IQR 1.66-3.65; range 0.8-8.1) were studied. 14.3% (23/161) received tenofovir due to high viral load (16/23, median 74 days, IQR 59-110) or due to liver disease (7/23). In 10/16 treated due to high viraemia, with confirmed adherence, follow-up HBV-DNA showed a 5.49 log decline (P = 0.003). In treatment naïve mothers, median alanine aminotransferase (ALT) increased from 17 IU/L (IQR 12-24) to 29 (IQR 18-36) post-partum (P = 1.5e-7). In seven highly viraemic mothers who declined therapy (HBV-DNA >8-log IU/mL); median ALT increased ~3X from baseline (P < 0.01). 26% (44/169) had Caesarean section with no difference in treated vs untreated subjects. No tenofovir-treated mothers had renal dysfunction. Data were available on 167/170 infants; in 50.8% (85/167) who completed immunoprophylaxis, 98.8% (84/85, including 12 exposed to tenofovir in utero) were HBV immune. One infant born to an HBeAg+ mother with HBV-DNA >8-log IU/mL failed immunoprophylaxis. In this prospective Canadian cohort study, most untreated mothers experienced mild HBV flares. Tenofovir in pregnancy is well tolerated and reduces viral load prior to parturition.
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Affiliation(s)
- G Samadi Kochaksaraei
- Calgary Liver Unit, Division of Gastroenterology and Hepatology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
| | - E Castillo
- Medical Disorders in Pregnancy, Division of Internal Medicine, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
| | - M Osman
- Alberta Health, Government of Alberta, Edmonton, AB, Canada
| | - K Simmonds
- Alberta Health, Government of Alberta, Edmonton, AB, Canada
| | - A N Scott
- Alberta Health, Government of Alberta, Edmonton, AB, Canada
| | - J I Oshiomogho
- Calgary Liver Unit, Division of Gastroenterology and Hepatology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
| | - S S Lee
- Calgary Liver Unit, Division of Gastroenterology and Hepatology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
| | - R P Myers
- Calgary Liver Unit, Division of Gastroenterology and Hepatology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
| | - S R Martin
- Department of Paediatrics, Alberta Children's Hospital, Calgary, AB, Canada
| | - C S Coffin
- Calgary Liver Unit, Division of Gastroenterology and Hepatology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
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Mori S, Fujiyama S. Hepatitis B virus reactivation associated with antirheumatic therapy: Risk and prophylaxis recommendations. World J Gastroenterol 2015; 21:10274-10289. [PMID: 26420955 PMCID: PMC4579875 DOI: 10.3748/wjg.v21.i36.10274] [Citation(s) in RCA: 66] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/01/2015] [Revised: 06/20/2015] [Accepted: 08/25/2015] [Indexed: 02/06/2023] Open
Abstract
Accompanying the increased use of biological and non-biological antirheumatic drugs, a greater number of cases of hepatitis B virus (HBV) reactivation have been reported in inactive hepatitis B surface antigen (HBsAg) carriers and also in HBsAg-negative patients who have resolved HBV infection. The prevalence of resolved infection varies in rheumatic disease patients, ranging from 7.3% to 66%. Through an electronic search of the PubMed database, we found that among 712 patients with resolved infection in 17 observational cohort studies, 12 experienced HBV reactivation (1.7%) during biological antirheumatic therapy. Reactivation rates were 2.4% for etanercept therapy, 0.6% for adalimumab, 0% for infliximab, 8.6% for tocilizumab, and 3.3% for rituximab. Regarding non-biological antirheumatic drugs, HBV reactivation was observed in 10 out of 327 patients with resolved infection from five cohort studies (3.2%). Most of these patients received steroids concomitantly. Outcomes were favorable in rheumatic disease patients. A number of recommendations have been established, but most of the supporting evidence was derived from the oncology and transplantation fields. Compared with patients in these fields, rheumatic disease patients continue treatment with multiple immunosuppressants for longer periods. Optimal frequency and duration of HBV-DNA monitoring and reliable markers for discontinuation of nucleoside analogues should be clarified for rheumatic disease patients with resolved HBV infection.
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Elbahrawy A, Alaboudy A, El Moghazy W, Elwassief A, Alashker A, Abdallah AM. Occult hepatitis B virus infection in Egypt. World J Hepatol 2015; 7:1671-1678. [PMID: 26140086 PMCID: PMC4483548 DOI: 10.4254/wjh.v7.i12.1671] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/29/2014] [Revised: 01/27/2015] [Accepted: 05/08/2015] [Indexed: 02/06/2023] Open
Abstract
The emerging evidence of the potentially clinical importance of occult hepatitis B virus (HBV) infection (OBI) increases the interest in this topic. OBI may impact in several clinical contexts, which include the possible transmission of the infection, the contribution to liver disease progression, the development of hepatocellular carcinoma, and the risk of reactivation. There are several articles that have published on OBI in Egyptian populations. A review of MEDLINE database was undertaken for relevant articles to clarify the epidemiology of OBI in Egypt. HBV genotype D is the only detectable genotype among Egyptian OBI patients. Higher rates of OBI reported among Egyptian chronic HCV, hemodialysis, children with malignant disorders, and cryptogenic liver disease patients. There is an evidence of OBI reactivation after treatment with chemotherapy. The available data suggested that screening for OBI must be a routine practice in these groups of patients. Further studies needed for better understand of the epidemiology of OBI among Egyptian young generations after the era of hepatitis B vaccination.
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Affiliation(s)
- Ashraf Elbahrawy
- Ashraf Elbahrawy, Ahmed Elwassief, Ahmed Alashker, Abdallah Mahmoud Abdallah, Department of Internal Medicine, Al-Azhar School of Medicine, Al-Azhar University, Cairo 11884, Egypt
| | - Alshimaa Alaboudy
- Ashraf Elbahrawy, Ahmed Elwassief, Ahmed Alashker, Abdallah Mahmoud Abdallah, Department of Internal Medicine, Al-Azhar School of Medicine, Al-Azhar University, Cairo 11884, Egypt
| | - Walid El Moghazy
- Ashraf Elbahrawy, Ahmed Elwassief, Ahmed Alashker, Abdallah Mahmoud Abdallah, Department of Internal Medicine, Al-Azhar School of Medicine, Al-Azhar University, Cairo 11884, Egypt
| | - Ahmed Elwassief
- Ashraf Elbahrawy, Ahmed Elwassief, Ahmed Alashker, Abdallah Mahmoud Abdallah, Department of Internal Medicine, Al-Azhar School of Medicine, Al-Azhar University, Cairo 11884, Egypt
| | - Ahmed Alashker
- Ashraf Elbahrawy, Ahmed Elwassief, Ahmed Alashker, Abdallah Mahmoud Abdallah, Department of Internal Medicine, Al-Azhar School of Medicine, Al-Azhar University, Cairo 11884, Egypt
| | - Abdallah Mahmoud Abdallah
- Ashraf Elbahrawy, Ahmed Elwassief, Ahmed Alashker, Abdallah Mahmoud Abdallah, Department of Internal Medicine, Al-Azhar School of Medicine, Al-Azhar University, Cairo 11884, Egypt
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Gao S, Duan ZP, Coffin CS. Clinical relevance of hepatitis B virus variants. World J Hepatol 2015; 7:1086-1096. [PMID: 26052397 PMCID: PMC4450185 DOI: 10.4254/wjh.v7.i8.1086] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2014] [Revised: 01/28/2015] [Accepted: 02/12/2015] [Indexed: 02/06/2023] Open
Abstract
The hepatitis B virus (HBV) is a global public health problem with more than 240 million people chronically infected worldwide, who are at risk for end-stage liver disease and hepatocellular carcinoma. There are an estimated 600000 deaths annually from complications of HBV-related liver disease. Antiviral therapy with nucleos/tide analogs (NA) targeting the HBV polymerase (P) can inhibit disease progression by long-term suppression of HBV replication. However, treatment may fail with first generation NA therapy due to the emergence of drug-resistant mutants, as well as incomplete medication adherence. The HBV replicates via an error-prone reverse transcriptase leading to quasispecies. Due to overlapping open reading frames mutations within the HBV P can cause concomitant changes in the HBV surface gene (S) and vice versa. HBV quasispecies diversity is associated with response to antiviral therapy, disease severity and long-term clinical outcomes. Specific mutants have been associated with antiviral drug resistance, immune escape, liver fibrosis development and tumorgenesis. An understanding of HBV variants and their clinical relevance may be important for monitoring chronic hepatitis B disease progression and treatment response. In this review, we will discuss HBV molecular virology, mechanism of variant development, and their potential clinical impact.
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Kwak MS, Kim YJ. Occult hepatitis B virus infection. World J Hepatol 2014; 6:860-869. [PMID: 25544873 PMCID: PMC4269905 DOI: 10.4254/wjh.v6.i12.860] [Citation(s) in RCA: 71] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/13/2014] [Revised: 09/23/2014] [Accepted: 10/29/2014] [Indexed: 02/06/2023] Open
Abstract
Occult hepatitis B virus (HBV) infection (OBI) refers to the presence of HBV DNA in the absence of detectable hepatitis B surface antigen. Since OBI was first described in the late 1970s, there has been increasing interest in this topic. The prevalence of OBI varies according to the different endemicity of HBV infection, cohort characteristics, and sensitivity and specificity of the methods used for detection. Although the exact mechanism of OBI has not been proved, intra-hepatic persistence of viral covalently closed circular DNA under the host’s strong immune suppression of HBV replication and gene expression seems to be a cause. OBI has important clinical significance in several conditions. First, OBI can be transmitted through transfusion, organ transplantation including orthotopic liver transplantation, or hemodialysis. Donor screening before blood transfusion, prophylaxis for high-risk organ transplantation recipients, and dialysis-specific infection-control programs should be considered to reduce the risk of transmission. Second, OBI may reactivate and cause acute hepatitis in immunocompromised patients or those receiving chemotherapy. Close HBV DNA monitoring and timely antiviral treatment can prevent HBV reactivation and consequent clinical deterioration. Third, OBI may contribute to the progression of hepatic fibrosis in patients with chronic liver disease including hepatitis C. Finally, OBI seems to be a risk factor for hepatocellular carcinoma by its direct proto-oncogenic effect and by indirectly causing persistent hepatic inflammation and fibrosis. However, this needs further investigation. We review published reports in the literature to gain an overview of the status of OBI and emphasize the clinical importance of OBI.
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Nakamoto S, Kanda T, Nakaseko C, Sakaida E, Ohwada C, Takeuchi M, Takeda Y, Mimura N, Iseki T, Wu S, Arai M, Imazeki F, Saito K, Shirasawa H, Yokosuka O. Reactivation of hepatitis B virus in hematopoietic stem cell transplant recipients in Japan: efficacy of nucleos(t)ide analogues for prevention and treatment. Int J Mol Sci 2014; 15:21455-21467. [PMID: 25421241 PMCID: PMC4264235 DOI: 10.3390/ijms151121455] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2014] [Revised: 11/11/2014] [Accepted: 11/18/2014] [Indexed: 01/17/2023] Open
Abstract
We retrospectively reviewed 413 recipients with hematologic malignancies who underwent hematopoietic stem cell transplantation (HSCT) between June 1986 and March 2013. Recipients with antibody to hepatitis B core antigen (anti-HBc) and/or to hepatitis B surface antigen (anti-HBs) were regarded as experiencing previous hepatitis B virus (HBV) infection. Clinical data of these recipients were reviewed from medical records. We defined ≥1 log IU/mL increase in serum HBV DNA from nadir as HBV reactivation in hepatitis B surface antigen (HBsAg)-positive recipients, and also defined ≥1 log IU/mL increase or re-appearance of HBV DNA and/or HBsAg as HBV reactivation in HBsAg-negative recipients. In 5 HBsAg-positive recipients, 2 recipients initially not administered with nucleos(t)ide analogues (NUCs) experienced HBV reactivation, but finally all 5 were successfully controlled with NUCs. HBV reactivation was observed in 11 (2.7%) of 408 HBsAg-negative recipients; 8 of these were treated with NUCs, and fortunately none developed acute liver failure. In 5 (6.0%) of 83 anti-HBc and/or anti-HBs-positive recipients, HBV reactivation occurred. None of 157 (0%) recipients without HBsAg, anti-HBs or anti-HBc experienced HBV reactivation. In HSCT recipients, HBV reactivation is a common event in HBsAg-positive recipients, or in HBsAg-negative recipients with anti-HBc and/or anti-HBs. Further attention should be paid to HSCT recipients with previous exposure to HBV.
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Affiliation(s)
- Shingo Nakamoto
- Department of Molecular Virology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8677, Japan.
| | - Tatsuo Kanda
- Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8677, Japan.
| | - Chiaki Nakaseko
- Department of Hematology, Chiba University Hospital, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
| | - Emiko Sakaida
- Department of Hematology, Chiba University Hospital, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
| | - Chikako Ohwada
- Department of Hematology, Chiba University Hospital, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
| | - Masahiro Takeuchi
- Department of Hematology, Chiba University Hospital, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
| | - Yusuke Takeda
- Department of Hematology, Chiba University Hospital, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
| | - Naoya Mimura
- Department of Hematology, Chiba University Hospital, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
| | - Tohru Iseki
- Department of Hematology, Chiba University Hospital, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
| | - Shuang Wu
- Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8677, Japan.
| | - Makoto Arai
- Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8677, Japan.
| | - Fumio Imazeki
- Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8677, Japan.
| | - Kengo Saito
- Department of Molecular Virology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8677, Japan.
| | - Hiroshi Shirasawa
- Department of Molecular Virology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8677, Japan.
| | - Osamu Yokosuka
- Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8677, Japan.
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Occult hepatitis B virus infection in Chinese cryptogenic intrahepatic cholangiocarcinoma patient population. J Clin Gastroenterol 2014; 48:878-82. [PMID: 24356457 DOI: 10.1097/mcg.0000000000000058] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
BACKGROUND There is no information available about occult hepatitis B virus (HBV) infection (OBI) in individuals with intrahepatic cholangiocarcinoma (ICC). GOALS To investigate the correlation between OBI and ICC. STUDY A retrospective case-control study was conducted. The cases were 183 cryptogenic ICC patients (group I), and the controls were 549 healthy individuals (group II). The cases and controls were matched for age, sex, and inhabitancy. Adjusted odds ratios and 95% confidence intervals were calculated. Intrahepatic total HBV DNA in 63 paraffin-embedded samples was collected from patients in group I (n=44), HBV-associated ICC patients (n=3), and hepatic cavernous hemangioma patients with seronegative HBsAg (hepatitis B S antigen) (group III; n=16). We determined the levels of serum and intrahepatic HBV DNA and compared the level of intrahepatic HBV DNA in 44 cryptogenic patients from group I with the level in the patients from group III. RESULTS Compared with group II, group I had a lower prevalence of anti-HBs (antibody against HBsAg) and a higher prevalence of anti-HBe (antibody against hepatitis B e antigen) and anti-HBc (antibody against hepatitis B c antigen). Multivariate analysis confirmed that anti-HBe and anti-HBc positivity were associated with ICC. The odds ratios and 95% confidence intervals for anti-HBe and anti-HBc were 2.482 and 1.482-4.158, 4.556 and 2.938-7.066, respectively. Compared with group III, cryptogenic ICC cases showed more frequent detection of intrahepatic total HBV DNA (63.64% vs. 18.75%, P=0.002). CONCLUSIONS OBI may represent an important risk factor for ICC. HBsAg seroclearance does not signify eradication of HBV and may not entirely prevent the development of ICC.
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Alvarez-Muñoz MT, Maldonado-Rodriguez A, Rojas-Montes O, Torres-Ibarra R, Gutierrez-Escolano F, Vazquez-Rosales G, Gomez A, Muñoz O, Torres J, Lira R. Occult hepatitis B virus infection among Mexican human immunodeficiency virus-1-infected patients. World J Gastroenterol 2014; 20:13530-13537. [PMID: 25309083 PMCID: PMC4188904 DOI: 10.3748/wjg.v20.i37.13530] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2014] [Revised: 04/30/2014] [Accepted: 05/26/2014] [Indexed: 02/06/2023] Open
Abstract
AIM: To determine the frequency of occult hepatitis B infection (OHBI) in a group of human immunodeficiency virus (HIV)-1+/ hepatitis B surface antigen negative (HBsAg)- patients from Mexico.
METHODS: We investigated the presence of OHBI in 49 HIV-1+/HBsAg- patients. Hepatitis B virus (HBV) DNA was analyzed using nested PCR to amplify the Core (C) region and by real-time PCR to amplify a region of the S and X genes. The possible associations between the variables and OHBI were investigated using Pearson’s χ2 and/or Fisher’s exact test.
RESULTS: We found that the frequency of OHBI was 49% among the group of 49 HIV-1+/HBsAg- patients studied. The presence of OHBI was significantly associated with the HIV-1 RNA viral load [odds ratio (OR) = 8.75; P = 0.001; 95%CI: 2.26-33.79] and with HIV-antiretroviral treatment with drugs that interfere with HBV replication (lamivudine, tenofovir or emtricitabine) (OR = 0.25; P = 0.05; 95%CI: 0.08-1.05).
CONCLUSION: The OHBI frequency is high among 49 Mexican HIV-1+/HBsAg- patients and it was more frequent in patients with detectable HIV RNA, and less frequent in patients who are undergoing HIV-ARV treatment with drugs active against HBV.
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Xie KL, Zhang YG, Liu J, Zeng Y, Wu H. MicroRNAs associated with HBV infection and HBV-related HCC. Theranostics 2014; 4:1176-92. [PMID: 25285167 PMCID: PMC4183996 DOI: 10.7150/thno.8715] [Citation(s) in RCA: 60] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2014] [Accepted: 08/10/2014] [Indexed: 02/05/2023] Open
Abstract
Hepatitis B virus (HBV) infection is a global problem and a major risk factor for hepatocellular carcinoma (HCC). microRNAs (miRNAs) comprise a group of small noncoding RNAs regulating gene expression at the posttranslational level, thereby participating in fundamental biological processes, including cell proliferation, differentiation, and apoptosis. In this review, we summarize the roles of miRNAs in HBV infection, the recently identified mechanism underlying dysregulation of miRNAs in HBV-associated HCC, and their association with hepatocarcinogenesis. Moreover, we discuss the recent advances in the use of circulating miRNAs in the early diagnosis of HCC as well as therapies based on these aberrantly expressed miRNAs.
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Yang HC, Kao JH. Persistence of hepatitis B virus covalently closed circular DNA in hepatocytes: molecular mechanisms and clinical significance. Emerg Microbes Infect 2014; 3:e64. [PMID: 26038757 PMCID: PMC4185362 DOI: 10.1038/emi.2014.64] [Citation(s) in RCA: 101] [Impact Index Per Article: 9.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2014] [Revised: 07/17/2014] [Accepted: 07/21/2014] [Indexed: 02/06/2023]
Abstract
Covalently closed circular DNA (cccDNA) is the transcriptional template of hepatitis B virus (HBV). Extensive research over the past decades has unveiled the important role of cccDNA in the natural history and antiviral treatment of chronic HBV infection. cccDNA can persist in patients recovering from acute HBV infection for decades. This explains why HBV reactivation occasionally occurs in patients with resolved hepatitis B receiving intensive immunosuppressive agents. In addition, although advances in antiviral treatment dramatically improve the adverse outcomes of chronic hepatitis B (CHB), accumulating evidence demonstrates that current antiviral treatments alone, be they nucleos(t)ide analogs (NAs) or interferon (IFN), fail to cure most CHB patients because of the persistent cccDNA. NA suppresses HBV replication by directly inhibiting viral polymerase, while IFN enhances host immunity against HBV infection. Viral rebound often occurs after discontinuation of antiviral treatment. The loss of cccDNA can be induced by non-cytolytic destruction of cccDNA or immune-mediated killing of infected hepatocytes. It is known that NA has no direct effect on viral transcription or cccDNA stability. Therefore, the long half-life of hepatocytes leads to a very slow decline in cccDNA in patients under antiviral therapy. Novel antiviral agents targeting cccDNA or cccDNA-containing hepatocytes are thus required for curing chronic HBV infection.
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Affiliation(s)
- Hung-Chih Yang
- Department of Microbiology, National Taiwan University College of Medicine , Taipei 10002, Taiwan, China ; Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine , Taipei 10002, Taiwan, China ; Department of Internal Medicine, National Taiwan University Hospital , Taipei 10002, Taiwan, China
| | - Jia-Horng Kao
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine , Taipei 10002, Taiwan, China ; Department of Internal Medicine, National Taiwan University Hospital , Taipei 10002, Taiwan, China ; Hepatitis Research Center, National Taiwan University Hospital , Taipei 10002, Taiwan, China ; Department of Medical Research, National Taiwan University Hospital , Taipei 10002, Taiwan, China
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Ferrari TCA, Xavier MAP, Vidigal PVT, Amaral NS, Diniz PA, Resende AP, Miranda DM, Faria AC, Lima AS, Faria LC. Occult hepatitis B virus infection in liver transplant patients in a Brazilian referral center. ACTA ACUST UNITED AC 2014. [PMID: 25296362 PMCID: PMC4230290 DOI: 10.1590/1414-431x20143782] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
Estimates of occult hepatitis B virus (HBV) infection prevalence varies among different studies depending on the prevalence of HBV infection in the study population and on the sensitivity of the assay used to detect HBV DNA. We investigated the prevalence of occult HBV infection in cirrhotic patients undergoing liver transplantation in a Brazilian referral center. Frozen liver samples from 68 adults were analyzed using a nested polymerase chain reaction assay for HBV DNA. The specificity of the amplified HBV sequences was confirmed by direct sequencing of the amplicons. The patient population comprised 49 (72.1%) males and 19 (27.9%) females with a median age of 53 years (range=18-67 years). Occult HBV infection was diagnosed in three (4.4%) patients. The etiologies of the underlying chronic liver disease in these cases were alcohol abuse, HBV infection, and cryptogenic cirrhosis. Two of the patients with cryptic HBV infection also presented hepatocellular carcinoma. Markers of previous HBV infection were available in two patients with occult HBV infection and were negative in both. In conclusion, using a sensitive nested polymerase chain reaction assay to detect HBV DNA in frozen liver tissue, we found a low prevalence of occult HBV infection in cirrhotic patients undergoing liver transplant, probably due to the low prevalence of HBV infection in our population.
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Affiliation(s)
- T C A Ferrari
- Departamento de Clínica Médica, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brasil
| | - M A P Xavier
- Departamento de Anatomia Patológica e Medicina Legal, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brasil
| | - P V T Vidigal
- Departamento de Anatomia Patológica e Medicina Legal, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brasil
| | - N S Amaral
- Laboratório de Genética Molecular, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brasil
| | - P A Diniz
- Departamento de Clínica Médica, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brasil
| | - A P Resende
- Instituto Alfa de Gastroenterologia, Hospital das Clínicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brasil
| | - D M Miranda
- Departamento de Pediatria, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brasil
| | - A C Faria
- Departamento de Clínica Médica, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brasil
| | - A S Lima
- Instituto Alfa de Gastroenterologia, Hospital das Clínicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brasil
| | - L C Faria
- Departamento de Clínica Médica, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brasil
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Makvandi M, Neisi N, Khalafkhany D, Makvandi K, Hajiani E, Shayesteh AA, Masjedi Zadeh A, Sina AH, Hamidifard M, Rasti M, Aryan E, Ahmadi K, Yad Yad MJ. Occult hepatitis B virus among the patients with abnormal alanine transaminase. Jundishapur J Microbiol 2014; 7:e11648. [PMID: 25485052 PMCID: PMC4255214 DOI: 10.5812/jjm.11648] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2013] [Revised: 06/25/2013] [Accepted: 07/14/2013] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND The occult hepatitis B infection (OBI) is defined as the presence of hepatitis B virus (HBV) DNA in the sera or in the liver biopsy and the absence of hepatitis B surface antigen (HBsAg) by serological test. OBJECTIVES The current study aimed to evaluate the occult HBV infection by polymerase chain reaction (PCR) and determine HBV genotyping among the patients with abnormal alanine transaminase (ALT) in Ahvaz city, Iran. PATIENTS AND METHODS The sera of 120 patients, 54 (45%) females and 66 (55%) males, with abnormal ALT 40-152 IU were collected. All the patients were negative for HBsAg for more than one year. The patients` sera were tested by PCR using primers specified for the S region of HBV. Then the positive PCR products were sequenced to determine HBV genotyping and phylogenic tree. RESULTS Of these 120 subjects, 12 (10%) patients including 6 (5%) males and 6 (5%) females were found positive for HBV DNA by PCR, which indicated the presence of occult HBV infection among these patients. The sequencing results revealed that genotype D was predominant with sub-genotyping D1 among OBI patients. CONCLUSIONS Occult hepatitis B infection is remarkably prevalent in Ahvaz, Iran, and should be considered as a potential risk factor for the transmission of Hepatitis B Virus throughout the community by the carriers.
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Affiliation(s)
- Manoochehr Makvandi
- Infectious and Tropical Disease Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, IR Iran
- Research Institute for Infectious Diseases of Digestive System, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, IR Iran
- Virology Department, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, IR Iran
| | - Niloofar Neisi
- Virology Department, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, IR Iran
| | - Davod Khalafkhany
- Virology Department, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, IR Iran
| | - Kamyar Makvandi
- School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, IR Iran
| | - Eskandar Hajiani
- Gastroenterology and Hepatology Department, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, IR Iran
| | - Ali Akbar Shayesteh
- Gastroenterology and Hepatology Department, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, IR Iran
| | - Abdolrahim Masjedi Zadeh
- Gastroenterology and Hepatology Department, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, IR Iran
| | | | - Mojtaba Hamidifard
- Virology Department, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, IR Iran
| | - Mojtaba Rasti
- Virology Department, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, IR Iran
| | - Ehsan Aryan
- Antimicrobial Resistance Research Center, Department of Medical Microbiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, IR Iran
| | - Kambiz Ahmadi
- Department of Statistics, School of Public Health, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, IR Iran
| | - Mohammad Jafar Yad Yad
- Department of Education Development Center, Ahvaz Jundishapur of Medical Sciences, Ahvaz, IR Iran
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Kitab B, Ezzikouri S, Alaoui R, Nadir S, Badre W, Trepo C, Chemin I, Benjelloun S. Occult HBV infection in Morocco: from chronic hepatitis to hepatocellular carcinoma. Liver Int 2014; 34:e144-e150. [PMID: 24502524 DOI: 10.1111/liv.12482] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/02/2013] [Accepted: 01/30/2014] [Indexed: 12/14/2022]
Abstract
BACKGROUND & AIMS Morocco is one of low to intermediate endemic areas for hepatitis B virus (HBV) infection, but no reports have been published on Occult HBV infection (OBI). To determine the prevalence of OBI and its clinical impact among patients with cryptogenic and HCV-related chronic liver disease in Morocco. METHODS A total of 152 HBsAg-negative patients (60 patients with cryptogenic hepatitis and 92 HCV carriers) were enrolled in this study. Sera collected from all patients were tested for anti-HBc and anti-HBs antibodies. OBI was assessed in serum and liver tissue samples using highly sensitive PCR assays targeting Surface, X and core regions of the HBV genome and confirmed by Southern blot hybridization. RESULTS A high rate of anti-HBc positivity was found among patients with HCV infection (57/92, 61.95%) compared to those with cryptogenic hepatitis (24/60, 40%) (P = 0.034). A high prevalence of OBI was found among patients with HCV infection (42/92, 45.65%) compared to those with cryptogenic hepatitis (17/60, 28.3%) (P = 0.013). In both groups, the prevalence of OBI increased in parallel with advancing stage of liver disease (χ2 = 6.73; P = 0.0095). The highest proportion of OBI was reached among HCV-related HCC cases (62.5%). Multivariate Cox regression analysis revealed that older age (≥56 years), positivity for anti-HBc and presence of OBI were independent risk factors for the development of HCC in HCV-infected patients. CONCLUSION This study helps to understand the current status of OBI and its impact on the severity of liver disease in Moroccan patients.
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Affiliation(s)
- Bouchra Kitab
- Viral Hepatitis Laboratory, Pasteur Institute of Morocco, Casablanca, Morocco
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Lee JJ, Kwon OS. [Occult hepatitis B virus infection and hepatocellular carcinoma]. THE KOREAN JOURNAL OF GASTROENTEROLOGY 2014; 62:160-4. [PMID: 24077626 DOI: 10.4166/kjg.2013.62.3.160] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Many studies have suggested that occult HBV infection has a substantial clinical relevance to hepatocellular carcinoma (HCC). Occult HBV infection is an important risk factor for the development of cirrhosis and HCC in patients without HBsAg. As a matter of fact, occult HBV infection is one of the most common causes of crytogenic HCC in endemic areas of HBV. However, there still are controversial issues about the association between occult HBV infection and HCC according to the underlying liver disease. In alcoholic cirrhosis, occult HBV infection may exert synergistic effect on the development of HCC. However, there is insufficient evidence to relate occult HBV infection to hepatocarcinogenesis in non-alcoholic fatty liver disease. In cryptogenic HCC, occult HBV infection may play a direct role in the development of HCC. In order to elucidate the assocciation between occult HBV infection and HCC, underlying liver disease must be specified and larger number of cases must be included in future studies.
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Affiliation(s)
- Jong Joon Lee
- Department of Internal Medicine, Gachon University Gil Medical Center, Gachon University School of Medicine, Incheon, Korea
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48
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Kim YS. [Definition, diagnosis, and prevalence of occult hepatitis B virus infection]. THE KOREAN JOURNAL OF GASTROENTEROLOGY 2014; 62:143-7. [PMID: 24077623 DOI: 10.4166/kjg.2013.62.3.143] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Occult HBV infection is characterized by the absence of serum HBsAg with persistence of low level of intrahepatic HBV DNA. Several suggested mechanisms for the origin of occult HBV infection include strong suppression of viral replication and gene expression, mutation in the regulatory regions of HBV genome, formation of immunoglobulin-bound HBsAg, viral interference, and blockage of HBsAg secretion from infected hepatocytes. Standardized assays are not yet available, and sensitive HBV DNA amplification assay is necessary for the diagnosis of cryptic infection. Detection rate of HBV DNA is highest in IgG anti-HBc positive population. However, neither anti-HBc nor anti-HBs can be detected in a significant proportion of infected persons. Occult HBV infection occurs in a number of clinical settings and is highly prevalent in HCV-infected patients as well as in patients with cryptogenic chronic liver disease including hepatocellular carcinoma.
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Affiliation(s)
- Yun Soo Kim
- Department of Internal Medicine, Gachon University Gil Medical Center, Gachon University School of Medicine, Incheon, Korea
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Tramuto F, Maida CM, Colomba GME, Di Carlo P, Mazzola G, Li Vecchi V, Affronti M, Montalto G, Vitale F. Occult hepatitis B infection in the immigrant population of Sicily, Italy. J Immigr Minor Health 2014; 15:725-31. [PMID: 22875279 DOI: 10.1007/s10903-012-9699-y] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
In Italy, about 7 % of the resident population is represented by immigrants originating from geographic regions at high endemicity for hepatitis B virus infection. This study aims to assess the prevalence of occult HBV infection (OBI) including the identification of HBV-genotypes in a population of immigrants serologically negative for hepatitis B surface antigen (HBsAg). Between May 2006 and May 2010, 339 immigrants were tested for markers of HBV, hepatitis C virus (HCV) and human immunodeficiency virus (HIV) infections. HBV-DNA was tested by using nested-PCR assays on three different genetic region. HBV-DNA was detected in plasma samples of 11/339 (3.2 %) patients. Most of them had no serological markers of HBV infection, 3/58 (5.2 %) were anti-HBc-alone, and 4/13 (30.8 %) were anti-HIV positive. HIV positivity was the only factor independently associated with the higher probability of observing OBI (OR = 16.5, p < 0.001). No HCV co-infected patients were found. Genotype D was detected in 9/11 (81.8 %) OBI cases, while the remaining two (18.2 %) were classified as genotype E. Although OBI was found at lower rate than expected among immigrants from highly endemic countries, anti-HBc alone positivity was confirmed as a sentinel marker of occult HBV infection. Nevertheless, a marked heterogeneity of HBV markers was found among HBV-DNA positive subjects. Our finding evidenced the predominance of HBV-genotype D viral strains among OBI cases, also in those from geographical areas where overt HBV infections are mainly sustained by viral genotypes other than D.
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Affiliation(s)
- Fabio Tramuto
- Department of Sciences for Health Promotion G. D'Alessandro-Hygiene Section, University of Palermo, 133 via del Vespro, 90127, Palermo, Italy.
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Chen XP, Luo ZG, Cao LL, Yang S, Zhang LY, You LY, Yang JH, Tang YM. Diagnostic characteristics and hepatic histopathology in 115 patients with liver injury of unknown reasons. Shijie Huaren Xiaohua Zazhi 2014; 22:1730-1733. [DOI: 10.11569/wcjd.v22.i12.1730] [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] [Indexed: 02/06/2023] Open
Abstract
AIM: To improve the awareness of liver injury of unknown causes by analyzing the diagnostic and pathological features of unexplained liver injury.
METHODS: A total of 115 patients with liver injury of unknown reasons were enrolled in this study. The biochemical and immunological features, as well as virus markers, abdominal imaging findings and hepatic histopathology were analyzed.
RESULTS: A definite diagnosis was achieved by liver biopsy in 109 patients. Among them, 38 were diagnosed with primary biliary cirrhosis (PBC), and the main pathological feature was non-suppurative inflammation in the bile duct; 31 with autoimmune hepatitis (AIH), which showed obvious interface inflammation in liver tissue; 27 with nonalcoholic fatty liver disease (NAFLD), which showed visible hepatic steatosis and ballooning degeneration; 4 with occult hepatitis B, which presented with portal inflammation and infiltration of lymphocytes and were positive for HBcAg and/or HBsAg as revealed by immunohistochemistry; 2 with hepatic amyloidosis, which showed a lot of eosin amyloid deposits reactive with Congo red in liver cells and blood sinus; 2 with hemochromatosis, which showed obvious iron pigment deposition in liver cells; 2 with glycogen storage disease, which showed extensive hyaline degeneration in hepatic cells and was positive for Dpas; 1 with schistosomiasis with schistosome eggs detected microscopically; 1 with toxoplasmosis, and electron microscopy revealed Toxoplasma gondii rhoptry; 1 with Dubin-Johnson syndrome, which showed thick, dark brown pigment particles in liver cells. There were still 6 cases in whom a definite diagnosis could not be achieved after liver biopsy.
CONCLUSION: Autoimmune liver diseases are main causes of liver injury of unknown causes, followed by NAFLD. Liver parasite, genetic diseases and metabolic diseases are rare. Liver biopsy should be emphasized in patients with liver injury of unknown reasons.
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