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Chen J, Yin Q, Xu S, Tan X, Liang Y, Chen C, Li L, Zhang T, Shen T. IFN-treated macrophage-derived exosomes prevents HBV-HCC migration and invasion via regulating miR-106b-3p/PCGF3/PI3K/AKT signaling axis. Front Cell Infect Microbiol 2024; 14:1421195. [PMID: 39529637 PMCID: PMC11551115 DOI: 10.3389/fcimb.2024.1421195] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2024] [Accepted: 09/05/2024] [Indexed: 11/16/2024] Open
Abstract
BACKGROUND Studies revealed that exosomes from IFN-α-treated liver non-parenchymal cells (IFN-exo) mediate antiviral activity. MiR-106b-3p has been shown to play a paradoxical role in disease progressing from different studies. However, its specific role in HBV-related hepatocellular carcinoma (HBV-HCC) and the underlying mechanism remains unclear. METHOD Huh7 cells transient transfected with plasmids of HBV-C2 and B3 were co-cultured with IFN-exo. Cell supernatants were collected to detect miR-106b-3p, HBsAg, HBeAg and HBV DNA levels. Cell proliferation, apoptosis, migration and invasion were analyzed. The putative targets of miR-106b-3p were identified by a dual-luciferase reporter system. The expression of PCGF3, migratory proteins(MMP2/9), and the PI3K/AKT signaling pathway-related proteins were assessed by western blot. The expression of PCGF3 mRNA was quantitative analyzed by using 52 pairs of paraffin-embedded tissues from HCC patients. siRNAs-PCGF3 were used to knocked-down PCGF3 expression. RESULTS The expression of miR-106b-3p was significantly higher in THP-1 cells and supernatants treated with IFN-exo than those untreated. Significantly increased expression of miR-106b-3p and decreased expression of HBsAg and HBV DNA were observed in Huh7-C2/B3 cells treated with IFN-exo. In addition, miR-106b-3p was directly target to PCGF3. Scratch healing assay and transwell assay showed that either IFN-exo or miRNA-106-3p over-expression, or siRNAs-PCGF3 inhibited migration and invasion of Huh7-C2/B3 cells, and subsequently resulted in suppression of p-AKT/AKT and p-PI3K/PI3K. Notably, the expression level of PCGF3 was significantly lower in HBeAg (+)-HCC tumor tissues than HBeAg (-)-HCC tumor. CONCLUSION IFN-α-induced macrophage-derived miR-106b-3p inhibits HBV replication, HBV- Huh7 cells migration and invasion via regulating PCGF3/PI3K/AKT signaling axis. miR-106b-3p and PCGF3 were potential biomarkers in the prevention and treatment of HBV-HCC.
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Affiliation(s)
- Jing Chen
- Department of Pulmonary and Critical Care Medicine, Yunnan Provincial Key Laboratory for Clinical Virology, Institute of Basic and Clinical Medicine, The First People’s Hospital of Yunnan Province, Kunming, China
- Medical School, Kunming University of Science and Technology, Kunming, China
- Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming, China
| | - Qi Yin
- Medical School, Kunming University of Science and Technology, Kunming, China
- Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming, China
| | - Shiheng Xu
- Medical School, Kunming University of Science and Technology, Kunming, China
| | - Xiaoqing Tan
- Medical School, Kunming University of Science and Technology, Kunming, China
| | - Yu Liang
- Medical School, Kunming University of Science and Technology, Kunming, China
| | - Chaohui Chen
- Medical School, Kunming University of Science and Technology, Kunming, China
| | - Li Li
- Department of Pulmonary and Critical Care Medicine, Yunnan Provincial Key Laboratory for Clinical Virology, Institute of Basic and Clinical Medicine, The First People’s Hospital of Yunnan Province, Kunming, China
- Department of Infectious Diseases and Hepatic Disease, Yunnan Province Innovation Team of Intestinal Microecology Related Disease Research and Technological Transformation, The First People’s Hospital of Yunnan Province, Kunming, China
| | - Tao Zhang
- Medical School, Kunming University of Science and Technology, Kunming, China
| | - Tao Shen
- Department of Pulmonary and Critical Care Medicine, Yunnan Provincial Key Laboratory for Clinical Virology, Institute of Basic and Clinical Medicine, The First People’s Hospital of Yunnan Province, Kunming, China
- Medical School, Kunming University of Science and Technology, Kunming, China
- Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming, China
- Department of Infectious Diseases and Hepatic Disease, Yunnan Province Innovation Team of Intestinal Microecology Related Disease Research and Technological Transformation, The First People’s Hospital of Yunnan Province, Kunming, China
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Assefa A, Getie M, Getie B, Yazie T, Enkobahry A. Molecular epidemiology of hepatitis B virus (HBV) in Ethiopia: A review article. INFECTION, GENETICS AND EVOLUTION : JOURNAL OF MOLECULAR EPIDEMIOLOGY AND EVOLUTIONARY GENETICS IN INFECTIOUS DISEASES 2024; 122:105618. [PMID: 38857639 DOI: 10.1016/j.meegid.2024.105618] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/15/2024] [Revised: 06/06/2024] [Accepted: 06/07/2024] [Indexed: 06/12/2024]
Abstract
Hepatitis B virus (HBV) belongs to the family Hepadnaviridae and is the smallest human DNA virus, with a genome that is only 3200 nucleotides long. The absence of proofreading function in HBV reverse transcriptase provides a wide range of genetic variants for targeted outgrowth at different stages of infection. A number of sub genotypes and ten HBV genotypes (A through J) have been identified through analyses of the divergence of HBV genomic sequences. Numerous clinical outcomes, including the emergence of chronicity, the course of the disease, the effectiveness of treatment, and the response to vaccination, have been related to differences in genotype between HBV isolates. There are just seven studies that have been done in Ethiopia that examine the molecular epidemiology of HBV. Moreover, these studies haven't been compiled and reviewed yet. In this review, we looked at the genetic diversity and molecular epidemiology of HBV, the relationship between HBV genotypes and clinical outcomes, the immunopathogenesis of HBV, and finally the molecular epidemiology of HBV in Ethiopia. PubMed, Embase, and Google Scholar search engines were used to find relevant articles for the review. By using HBV genotyping, clinicians can better tailor vaccination decisions and antiviral therapy for patients with chronic hepatitis B who are more likely to experience the disease's progression.
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Affiliation(s)
- Ayenew Assefa
- Unit of Immunology, Department of Medical Laboratory Science, Debre Tabor University, Debre Tabor, Ethiopia.
| | - Molla Getie
- College of Medicine and Health Science, Medical Laboratory Science Department, Injibara University, Injibara, Ethiopia
| | - Birhanu Getie
- Unit of Medical Microbiology, Department of Medical Laboratory Science, Debre Tabor University, Debre Tabor, Ethiopia
| | - Takilosimeneh Yazie
- College of Health Science, Department of Pharmacy, Debre Tabor University, Debre Tabor, Ethiopia
| | - Aklesya Enkobahry
- College of Medicine and Health Science, Department of Biomedical Science, Injibara University, Injibara, Ethiopia
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Hossain MG, Islam M, Araf Y, Paul SK, Akter S, Khan MK, Ahmed MU, Khan S, Akbar SMF, Debnath CR. Comprehensive analysis of antigenic variations and genomic properties of hepatitis B virus in clinical samples in the mid-north east region of Bangladesh. INFECTION, GENETICS AND EVOLUTION : JOURNAL OF MOLECULAR EPIDEMIOLOGY AND EVOLUTIONARY GENETICS IN INFECTIOUS DISEASES 2024; 119:105572. [PMID: 38367678 DOI: 10.1016/j.meegid.2024.105572] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/11/2024] [Revised: 02/12/2024] [Accepted: 02/13/2024] [Indexed: 02/19/2024]
Abstract
This investigation delineates an exhaustive analysis of the clinical, immunological, and genomic landscapes of hepatitis B virus (HBV) infection across a cohort of 22 verified patients. The demographic analysis unveiled a pronounced male bias (77.27%), with patient ages spanning 20 to 85 years and durations of illness ranging from 10 days to 4 years. Predominant clinical manifestations included fever, fatigue, anorexia, abdominal discomfort, and arthralgia, alongside observed co-morbidities such as chronic renal disorders and hepatocellular carcinoma. Antigenic profiling of the HBV envelope proteins elucidated significant heterogeneity among the infected subjects, particularly highlighted by discordances in the detection capabilities of small and large HBsAg assays, suggesting antigenic diversity. Quantitative assessment of viral loads unveiled a broad spectrum, accompanied by atypical HBeAg reactivity patterns, challenging the reliability of existing serological markers. Correlative studies between viral burden and antigenicity of the envelope proteins unearthed phenomena indicative of diagnostic evasion. Notably, samples demonstrating robust viral replication were paradoxically undetectable by the large HBsAg ELISA kit, advocating for more sophisticated diagnostic methodologies. Genotypic examination of three HBV isolates classified them as genotype D (D2), with phylogenetic alignment to strains from various global origins. Mutational profiling identified pivotal mutations within the basic core promoter and preS2/S1 regions, associated with an augmented risk of hepatocellular carcinoma. Further, mutations discerned in the small HBsAg and RT/overlap regions were recognized as contributors to vaccine and/or diagnostic escape mechanisms. In summation, this scholarly discourse elucidates the intricate interplay of clinical presentations, antigenic diversity, and genomic attributes in HBV infection, accentuating the imperative for ongoing investigative endeavors to refine diagnostic and therapeutic modalities.
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Affiliation(s)
- Md Golzar Hossain
- Department of Microbiology and Hygiene, Bangladesh Agricultural University, Mymensingh 2202, Bangladesh.
| | - Mahfuz Islam
- Department of Microbiology, Mymensingh Medical College, Mymensingh, Bangladesh
| | - Yusha Araf
- Department of Microbiology and Hygiene, Bangladesh Agricultural University, Mymensingh 2202, Bangladesh
| | - Shyamal Kumar Paul
- Department of Microbiology, Mymensingh Medical College, Mymensingh, Bangladesh
| | - Sharmin Akter
- Department of Physiology, Bangladesh Agricultural University, Mymensingh 2202, Bangladesh
| | | | - Muzahed Uddin Ahmed
- Department of Medicine, Bangladesh Agricultural University, Mymensingh 2202, Bangladesh
| | - Sakirul Khan
- Research Center for Global and Local Infectious Diseases, Oita University, Oita, Japan; Department of Microbiology, Faculty of Medicine, Oita University, Oita, Japan
| | - Sheikh Mohammad Fazle Akbar
- Research Center for Global and Local Infectious Diseases, Oita University, Oita, Japan; Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Ehime, Japan; Miyakawa Memorial Research Foundation, Tokyo, Japan
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Jose-Abrego A, Roman S, Laguna-Meraz S, Panduro A. Host and HBV Interactions and Their Potential Impact on Clinical Outcomes. Pathogens 2023; 12:1146. [PMID: 37764954 PMCID: PMC10535809 DOI: 10.3390/pathogens12091146] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2023] [Revised: 08/27/2023] [Accepted: 09/06/2023] [Indexed: 09/29/2023] Open
Abstract
Hepatitis B virus (HBV) is a challenge for global health services, affecting millions and leading thousands to end-stage liver disease each year. This comprehensive review explores the interactions between HBV and the host, examining their impact on clinical outcomes. HBV infection encompasses a spectrum of severity, ranging from acute hepatitis B to chronic hepatitis B, which can potentially progress to cirrhosis and hepatocellular carcinoma (HCC). Occult hepatitis B infection (OBI), characterized by low HBV DNA levels in hepatitis B surface antigen-negative individuals, can reactivate and cause acute hepatitis B. HBV genotyping has revealed unique geographical patterns and relationships with clinical outcomes. Moreover, single nucleotide polymorphisms (SNPs) within the human host genome have been linked to several clinical outcomes, including cirrhosis, HCC, OBI, hepatitis B reactivation, and spontaneous clearance. The immune response plays a key role in controlling HBV infection by eliminating infected cells and neutralizing HBV in the bloodstream. Furthermore, HBV can modulate host metabolic pathways involved in glucose and lipid metabolism and bile acid absorption, influencing disease progression. HBV clinical outcomes correlate with three levels of viral adaptation. In conclusion, the clinical outcomes of HBV infection could result from complex immune and metabolic interactions between the host and HBV. These outcomes can vary among populations and are influenced by HBV genotypes, host genetics, environmental factors, and lifestyle. Understanding the degrees of HBV adaptation is essential for developing region-specific control and prevention measures.
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Affiliation(s)
- Alexis Jose-Abrego
- Department of Genomic Medicine in Hepatology, Civil Hospital of Guadalajara, “Fray Antonio Alcalde”, Guadalajara 44280, Mexico; (A.J.-A.); (S.R.); (S.L.-M.)
- Health Sciences Center, University of Guadalajara, Guadalajara 44340, Mexico
| | - Sonia Roman
- Department of Genomic Medicine in Hepatology, Civil Hospital of Guadalajara, “Fray Antonio Alcalde”, Guadalajara 44280, Mexico; (A.J.-A.); (S.R.); (S.L.-M.)
- Health Sciences Center, University of Guadalajara, Guadalajara 44340, Mexico
| | - Saul Laguna-Meraz
- Department of Genomic Medicine in Hepatology, Civil Hospital of Guadalajara, “Fray Antonio Alcalde”, Guadalajara 44280, Mexico; (A.J.-A.); (S.R.); (S.L.-M.)
- Health Sciences Center, University of Guadalajara, Guadalajara 44340, Mexico
| | - Arturo Panduro
- Department of Genomic Medicine in Hepatology, Civil Hospital of Guadalajara, “Fray Antonio Alcalde”, Guadalajara 44280, Mexico; (A.J.-A.); (S.R.); (S.L.-M.)
- Health Sciences Center, University of Guadalajara, Guadalajara 44340, Mexico
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Anabire NG, Quaye O, Helegbe GK. Circulation of multiple hepatitis B virus genotypes in individual pregnant women seeking antenatal care in northern Ghana. Virol J 2023; 20:149. [PMID: 37443015 PMCID: PMC10347747 DOI: 10.1186/s12985-023-02110-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2023] [Accepted: 06/30/2023] [Indexed: 07/15/2023] Open
Abstract
BACKGROUND Identification and monitoring of HBV genotype variations is important, since that can help forecast the likelihood of developing serious liver disease and how well patients respond to antiviral medication. Given that HBV genotyping tests are not widely available in our healthcare system, this study characterized HBV genotypes in pregnant women seeking prenatal treatment in northern Ghana. METHOD By a cross-sectional approach, 2071 pregnant women seeking antenatal care in health facilities in northern Ghana were screened for HBV infection using hepatitis B surface antigen (HBsAg) rapid diagnostic test kit. The women were aged between 17 and 41 years, were of varying gravidae (primigravidae and multigravidae) and gestational age (first, second and third trimesters). A confirmatory PCR assay was used to detect HBsAg, and the distribution of HBV genotypes was determined using a nested PCR assay. RESULTS Three HBV genotypes (A, D and E) were detected among the pregnant women, of which 175 (91.6%) had genotype E, 9 (4.7%) had mixed genotypes A and E, 5 (2.6%) had mixed genotypes D and E, and 2 (1.1) had mixed genotypes A, D and E. The proportions of women with the different HBV genotypes were independent of age (p = 0.925), gravidity (p = 0.193, χ2 = 4.729) and gestational age (p = 0.227, χ2 = 8.152). CONCLUSION This study for the first-time characterized circulating HBV genotypes in pregnant women in northern Ghana, which reveals genotypes A and D are found in mixed infections with genotype E. The findings have clinical implications on the management of chronic HBV infection among pregnant women in northern Ghana.
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Affiliation(s)
- Nsoh Godwin Anabire
- West African Centre for Cell Biology of Infectious Pathogens (WACCBIP), Department of Biochemistry, Cell & Molecular Biology, University of Ghana, P. O. Box LG 54, Legon- Accra, Ghana
- Department of Biochemistry & Molecular Medicine, School of Medicine, University for Development studies, P. O. Box TL 1883, Tamale, Ghana
| | - Osbourne Quaye
- West African Centre for Cell Biology of Infectious Pathogens (WACCBIP), Department of Biochemistry, Cell & Molecular Biology, University of Ghana, P. O. Box LG 54, Legon- Accra, Ghana
| | - Gideon Kofi Helegbe
- Department of Biochemistry & Molecular Medicine, School of Medicine, University for Development studies, P. O. Box TL 1883, Tamale, Ghana
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Kafeero HM, Ndagire D, Ocama P, Kato CD, Wampande E, Walusansa A, Kajumbula H, Kateete D, Ssenku JE, Sendagire H. Mapping hepatitis B virus genotypes on the African continent from 1997 to 2021: a systematic review with meta-analysis. Sci Rep 2023; 13:5723. [PMID: 37029173 PMCID: PMC10082212 DOI: 10.1038/s41598-023-32865-1] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2022] [Accepted: 04/04/2023] [Indexed: 04/09/2023] Open
Abstract
Hepatitis B virus (HBV) has ten genotypes (A-J) and over 40 sub-genotypes based on the divergence of ≥ 8% and 4 to < 8% in the complete genome respectively. These genotypes and sub-genotypes influence the disease prognosis, response to therapy and route of viral transmission. Besides, infection with mixed genotypes and recombinant genotypes has also been reported. This study aimed at mapping the de novo genotypes and correlate them with the immigration trends in order to inform future research on the underlying reasons for the relative distribution of HBV genotypes from a large sample size pooled from many primary studies. Data was extracted from 59 full research articles obtained from Scopus, PubMed, EMBASE, Willy library, African Journal Online (AJOL) and Google Scholar. Studies that investigated the genotypes, sub-genotypes, mixed genotypes and recombinant were included. The Z-test and regression were used for the analysis. The study protocol is registered with PROSPERO under the registration number CRD42022300220. Overall, genotype E had the highest pooled prevalence significantly higher than all the other genotypes (P < 0.001). By region, genotype A posted the highest pooled prevalence in eastern and southern Africa, E in west Africa and D in north Africa (P < 0.0001). Regarding the emerging genotypes B and C on the African continent, genotype B was significantly higher in south Africa than C (P < 0.001). In contrast, genotype C was significantly higher in east Africa than west Africa (P < 0.0001). The A1 and D/E were the most diverse sub-genotypes and genotype mixtures respectively. Finally, we observed a general progressive decrease in the prevalence of predominant genotypes but a progressive increase in the less dominant by region. Historical and recent continental and intercontinental migrations can provide a plausible explanation for the HBV genotype distribution pattern on the African continent.
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Affiliation(s)
- Hussein Mukasa Kafeero
- Department of Medical Microbiology, College of Health Sciences, Makerere University, P. O Box 7062, Kampala, Uganda.
- Department of Medical Microbiology, Habib Medical School, Faculty of Health Sciences, Islamic University in Uganda, P. O Box 7689, Kampala, Uganda.
| | - Dorothy Ndagire
- Department of Plant Sciences, Microbiology and Biotechnology, College of Natural Sciences, Makerere University, P. O Box 7062, Kampala, Uganda
| | - Ponsiano Ocama
- Department of Medicine, College of Health Sciences, Makerere University, P. O Box 7062, Kampala, Uganda
| | - Charles Drago Kato
- Department of Biomolecular Resources and Biolab Sciences, College of Veterinary Medicine, Animal Resources and Biosecurity, Makerere University, P. O Box 7062, Kampala, Uganda
| | - Eddie Wampande
- Department of Biomolecular Resources and Biolab Sciences, College of Veterinary Medicine, Animal Resources and Biosecurity, Makerere University, P. O Box 7062, Kampala, Uganda
| | - Abdul Walusansa
- Department of Medical Microbiology, Habib Medical School, Faculty of Health Sciences, Islamic University in Uganda, P. O Box 7689, Kampala, Uganda
| | - Henry Kajumbula
- Department of Medical Microbiology, College of Health Sciences, Makerere University, P. O Box 7062, Kampala, Uganda
| | - David Kateete
- Department of Molecular Biology and Immunology, College of Health Sciences, Makerere University, P. O Box 7062, Kampala, Uganda
| | - Jamilu E Ssenku
- Department of Plant Sciences, Microbiology and Biotechnology, College of Natural Sciences, Makerere University, P. O Box 7062, Kampala, Uganda
| | - Hakim Sendagire
- Department of Medical Microbiology, College of Health Sciences, Makerere University, P. O Box 7062, Kampala, Uganda
- Department of Medical Microbiology, Habib Medical School, Faculty of Health Sciences, Islamic University in Uganda, P. O Box 7689, Kampala, Uganda
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Anejo-Okopi J, Okeke E, Davwar PM, Onwuamah C, Onywera H, Omaiye P, Duguru M, Okojokwu OJ, Ujah OI, Jonathan B, George CA, Crown RS, Yakubu FB, Sokei JO, Okoli LC, Audu O, Inzaule SC, Abah IO, Agaba P, Agbaji OO, Sagay AS, Hawkins C. Molecular detection of hepatitis B virus genotype E with immune escape mutations in chronic hepatitis B patients on long-term antiviral therapy in Jos, Nigeria. Afr J Lab Med 2022; 11:1677. [PMID: 36337771 PMCID: PMC9634812 DOI: 10.4102/ajlm.v11i1.1677] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2021] [Accepted: 04/28/2022] [Indexed: 12/26/2022] Open
Abstract
Background Previous studies in Nigeria have reported the presence of hepatitis B virus (HBV) genotype E and the availability of immune escape mutants. There is a paucity of data on chronic patients on long-term antiviral therapy for HBV infection. Objective This study assessed HBV genotypes and drug resistance variants among patients with chronic HBV infection receiving tenofovir in Jos, Nigeria. Methods This cross-sectional study consecutively enrolled 101 patients (51 with HIV/HBV co-infection and 50 with HBV infection only) on antiviral therapy from February 2018 to May 2019 at four hospitals in Jos, Nigeria. DNA quantification of HBV was performed on all samples; 30 samples with detectable viral load were selected for genotyping using Sanger sequencing by targeting the full-length sequences of reverse transcriptase gene of the HBV genome. Phylogenetic analysis was performed with reference sequences from GenBank. Escape mutant and drug resistance analysis were performed using HBV drug resistance interpretation and Geno2pheno. Results Only 30 (29.7%) of the 101 study participants had detectable HBV DNA. Of these, six (20.0%) isolates were successfully amplified and sequenced. The identified genotype was E, including escape mutations L127R (16.7%) and G145A (16.7%). Conclusion This study revealed exclusive dominance of genotype E in Nigeria. The S gene mutations G145A and L271R are known to be associated with modified antigenicity and impaired serologic assays, which may cause false negatives in the detection of anti-HBV surface antigen. The presence of mutants that are associated with vaccine immune escape may also have diagnostic and vaccine immune response implications.
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Affiliation(s)
- Joseph Anejo-Okopi
- Department of Microbiology, University of Jos, Jos, Nigeria
- AIDS Prevention Initiative in Nigeria, Jos University Teaching Hospital, Jos, Nigeria
| | - Edith Okeke
- Department of Internal Medicine, University of Jos, Jos University Teaching Hospital, Jos, Nigeria
| | - Pantong M. Davwar
- Department of Internal Medicine, University of Jos, Jos University Teaching Hospital, Jos, Nigeria
| | - Chika Onwuamah
- Center for Human Virology and Genomics Nigeria Institute of Medical Research, Lagos, Nigeria
| | - Harris Onywera
- Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa
- Division of Medical Virology, Department of Pathology, University of Cape Town, Cape Town, South Africa
- Research, Innovations, and Academics Unit, Tunacare Services Health Providers Limited, Nairobi, Kenya
| | - Patience Omaiye
- Department of Internal Medicine, University of Jos, Jos University Teaching Hospital, Jos, Nigeria
| | - Mary Duguru
- Department of Internal Medicine, University of Jos, Jos University Teaching Hospital, Jos, Nigeria
| | | | - Otobo I. Ujah
- Department of Community and Family Health, College of Public Health, University of South Florida, Tampa, Florida, United States
| | - Bulus Jonathan
- Department of Family Medicine, Plateau State Specialist Hospital, Jos, Nigeria
| | - Chima A. George
- Department of Family Medicine, Bingham University Teaching Hospital, Jos, Nigeria
| | - Ramyil S. Crown
- Department of Medical Microbiology and Parasitology, Bingham University Teaching Hospital, Jos, Nigeria
| | - Fiyaktu B. Yakubu
- Department of Chemical Pathology, Jos University Teaching Hospital, Jos, Nigeria
| | - Judith O. Sokei
- Center for Human Virology and Genomics Nigeria Institute of Medical Research, Lagos, Nigeria
| | - Leona C. Okoli
- Center for Human Virology and Genomics Nigeria Institute of Medical Research, Lagos, Nigeria
| | - Onyemocho Audu
- Department of Epidemiology and Community Health, Benue State University, Makurdi, Nigeria
| | - Seth C. Inzaule
- Department of HIV and Global Hepatitis Program, World Health Organization, Geneva, Switzerland
| | - Isaac O. Abah
- Department of Pharmacology, University of Jos, Jos University Teaching Hospital, Jos, Nigeria
| | - Patricia Agaba
- AIDS Prevention Initiative in Nigeria, Jos University Teaching Hospital, Jos, Nigeria
- Department of Family Medicine, University of Jos, Jos University Teaching Hospital, Jos, Nigeria
| | - Oche O. Agbaji
- Department of Internal Medicine, University of Jos, Jos University Teaching Hospital, Jos, Nigeria
| | - Atiene S. Sagay
- Department of Obstetrics and Gynaecology, University of Jos, Jos University Teaching Hospital, Jos, Nigeria
| | - Claudia Hawkins
- Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States
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Kumar R. Review on hepatitis B virus precore/core promoter mutations and their correlation with genotypes and liver disease severity. World J Hepatol 2022; 14:708-718. [PMID: 35646275 PMCID: PMC9099108 DOI: 10.4254/wjh.v14.i4.708] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/14/2021] [Revised: 09/04/2021] [Accepted: 03/27/2022] [Indexed: 02/06/2023] Open
Abstract
Of 350 million people worldwide are chronically infected with hepatitis B virus (HBV) and are at risk of developing cirrhosis and hepatocellular carcinoma (HCC) later in life. HBV is the most diverse DNA virus, and its genome is composed of four open reading frames: Presurface antigen/surface antigen gene (preS/S), precore/core gene (preC/C), polymerase gene (P), and the X gene (X). HBV produces quasispecies naturally or in response to antiviral agents because of the absence of proofreading activity amid reverse transcription and a high replication rate. The virus has 10 genotypes (A to J) with different geographical distributions. There are various HBV mutations in the HBV genome, including preC/C mutations, preS/S mutations, P gene mutations, and X gene mutations. The core promoter region plays a vital part in the replication, morphogenesis and pathogenesis of the virus. The precore region also plays a crucial role in viral replication. Both core promoter and precore mutations rescue the virus from host immune surveillance and result in the formation of mutated strains that may have altered pathogenicity. preC/C mutations are associated with liver disease progression. Precore mutations stop hepatitis B e antigen (HBeAg) production and basal core promoter mutations downregulate HBeAg production. Mutations in the basal core promoter are also associated with increased HBV replication and an increased incidence of advanced liver diseases such as cirrhosis and HCC. The emergence of antiviral-resistant mutations is the main reason for treatment failure. This review focuses mainly on preC/C promoter mutations and their correlation with genotypes and liver disease severity. Thorough perception and knowledge of HBV genetic variety and mutants could be vital to discover techniques for the prognosis and control of HBV infection.
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Affiliation(s)
- Rajesh Kumar
- Department of School Education, Haryana Government, Panchkula 134109, Haryana, India
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Xu R, Song D, Wang M, Huang J, Liao Q, Shan Z, Rong X, Fu Y. Molecular Epidemiological Characteristics and Risk Factors for Acquiring HBV Among Li Ethnic in Baisha County, Hainan Island-Subgenotype D3 Was First Discovered in China. Front Microbiol 2022; 13:837746. [PMID: 35197959 PMCID: PMC8859303 DOI: 10.3389/fmicb.2022.837746] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2021] [Accepted: 01/14/2022] [Indexed: 12/02/2022] Open
Abstract
The residents of Baisha, a county of Hainan Island, mainly composed of Li ethnic population and relatively closed living environment with its unique geographical location. Our previous study showed that Li ethnic population of Baisha is an endemic center for hepatitis C virus, with significantly higher rates than in other parts of China. However, the epidemiology of HBV in this region remains unclear. Therefore, we conducted a comprehensive epidemiological survey of HBV in Baisha County, including 1,682 Li ethnic residents. The total seropositive rate for HBsAg was 10.2% and was higher than other parts of China. HBV-positive status was associated with the 20–40-year-old group (OR = 1.27, 95%CI 1.04–1.39, P < 0.01) and alcohol consumption (OR = 2.17, 95%CI 1.58–2.99, P < 0.01). Phylogenetic analysis showed that HBV subgenotype D3 was predominant in Baisha County which was first discovered in China, followed by C5, C1, B2, and undetermined subgenotypes which were significantly different from other geographical distribution of main genotypes in China. The most recent common ancestor (tMRCA) of the HBV genotype C in the Li ethnic of Baisha County was 1846 (95%CI: 1739–1932), and Baisha-C5 was earlier than Baisha-C1 and Baisha-C2. Most Baisha-D3 sequences were concentrated in one bundle and unrelated to those D3 genome sequences elsewhere in the world. According to the phylogenetic tree, D3 was introduced into Baisha County in 1884 (95%CI: 1816–1993) and became a local endemic virus. In conclusion, HBV infection in the Li ethnic group is characterized by a high prevalence rate in 20–40-year-old individuals and a unique genotype distribution which were significantly different from other geographical distribution of main genotypes in China, and subgenotype D3 was first discovered in China.
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Affiliation(s)
- Ru Xu
- Institute of Clinical Blood Transfusion, Guangzhou Blood Center, Guangzhou, China
- The Key Medical Laboratory of Guangzhou, Guangzhou, China
| | - Dandan Song
- Department of Clinical Laboratory, The Fifth People’s Hospital of Zhuhai, Zhuhai, China
| | - Min Wang
- Institute of Clinical Blood Transfusion, Guangzhou Blood Center, Guangzhou, China
- The Key Medical Laboratory of Guangzhou, Guangzhou, China
| | - Jieting Huang
- Institute of Clinical Blood Transfusion, Guangzhou Blood Center, Guangzhou, China
- The Key Medical Laboratory of Guangzhou, Guangzhou, China
| | - Qiao Liao
- Institute of Clinical Blood Transfusion, Guangzhou Blood Center, Guangzhou, China
- The Key Medical Laboratory of Guangzhou, Guangzhou, China
| | - Zhengang Shan
- Institute of Clinical Blood Transfusion, Guangzhou Blood Center, Guangzhou, China
- The Key Medical Laboratory of Guangzhou, Guangzhou, China
| | - Xia Rong
- Institute of Clinical Blood Transfusion, Guangzhou Blood Center, Guangzhou, China
- The Key Medical Laboratory of Guangzhou, Guangzhou, China
- School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, China
- *Correspondence: Xia Rong,
| | - Yongshui Fu
- Institute of Clinical Blood Transfusion, Guangzhou Blood Center, Guangzhou, China
- The Key Medical Laboratory of Guangzhou, Guangzhou, China
- School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, China
- Zhujiang Hospital of Southern Medical University, Guangzhou, China
- Yongshui Fu,
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10
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Bezerra CS, Portilho MM, Barbosa JR, de Azevedo CP, Mendonça ACDF, da Cruz JNM, Frota CC, do Lago BV, Villar LM. Dried blood spot sampling for hepatitis B virus quantification, sequencing and mutation detection. Sci Rep 2022; 12:1651. [PMID: 35102169 PMCID: PMC8803841 DOI: 10.1038/s41598-022-05264-1] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2021] [Accepted: 01/10/2022] [Indexed: 02/06/2023] Open
Abstract
Hepatitis B virus (HBV) diagnosis is performed on serum samples, but the access to this diagnosis is difficult in low-income regions. The use of dried blood spot (DBS) samples does not require special structure for collection, storage or transport. This study evaluates the use of DBS for detection, quantification and sequencing of HBV DNA using in-house techniques. Two study groups were included: 92 HBsAg + individuals and 49 negative controls. Serum and DBS samples were submitted to quantitative and qualitative in-house PCR for S/pol genes, sequencing and phylogenetic analyses. Total of 84 serum samples were successfully amplified. Of them, 63 paired DBS were also positive in qualitative PCR. Qualitative PCR in DBS presented a sensitivity of 75% and specificity of 100% (Kappa = 0.689). Quantitative PCR in DBS presented a detection limit of 852.5 copies/mL (250 IU/mL), sensitivity of 77.63% and specificity of 100% (Kappa = 0.731). A total of 63 serum samples and 36 DBS samples were submitted to sequencing, revealing the circulation of genotypes A (65.08%), D (4.8%), E (3.2%) and F (27%) with 100% of correspondence between serum and DBS. All sequenced samples displayed polymorphisms in HBsAg gene. An HIV-coinfected patient presented the rtM204V/I-rtL180M double resistance mutation in serum and DBS. In conclusion, DBS is an alternative to detect, quantify and characterize HBV DNA, being a possibility of increasing diagnosis in low-income settings, closing gaps in HBV control.
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11
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Disproportionate Distribution of HBV Genotypes A and D and the Recombinant Genotype D/E in the High and Low HBV Endemic Regions of Uganda: A Wake-Up Call for Regional Specific HBV Management. Int J Hepatol 2022; 2022:3688547. [PMID: 35070455 PMCID: PMC8767397 DOI: 10.1155/2022/3688547] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/27/2021] [Revised: 11/08/2021] [Accepted: 12/17/2021] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND Hepatitis B virus (HBV) is the leading cause of liver-related diseases. In Uganda, there is a regional disparity in the HBV burden. Our study was aimed at establishing the circulating genotypes in a low and a high endemic region to give plausible explanations for the differences in regional burden and guide the future management of the disease. METHODS A total of 200 HBsAg-seropositive subjects were recruited into the study by convenience sampling. The HBsAg Rapid Test Strip (Healgen Scientific Limited Liability Company, Houston, TX77047- USA) was used to screen for HBsAg while the Roche machine (Roche, Basel Switzerland/Abbot Technologies (USA)) was used to determine the viral load. The Chemistry Analyzer B120 (Mindray, China) was used for chemistry analysis. For HBV genotyping, total DNA was extracted from whole blood using the QIAamp® DNA extraction kit. Nested PCR amplification was performed using Platinum Taq DNA Polymerase (Invitrogen Corporation, USA) to amplify the 400 bp HBV polymerase gene. Purification of nested PCR products was performed using Purelink PCR product purification kit (Life Technologies, USA). Automated DNA sequencing was performed using BigDye Terminator v3.1 Cycle Sequencing Kit on 3130 Genetic Analyzer (Applied Biosystems, USA). The NCBI HBV genotyping tool (https://www.ncbi.nlm.nih.gov/projects/genotyping/formpage.cgi) was used for determination of genotype for each HBV sequence. Pearson's chi-square, multinomial logistic regression, and Mann-Whitney U tests were used for the analysis. All the analyses were done using SPSS version 26.0 and MedCalc software version 19.1.3 at 95% CI. A p < 0.05 was considered statistically significant. RESULTS Majority of our study subjects were female (64.5%), youth (51.0%), and married (62.0%). Overall, genotype A was the most prevalent (46%). Genotype D and the recombinant genotype D/E were proportionately more distributed in the high endemic (38.2%) and low endemic (36.5%) regions, respectively. Genotype D was significantly more prevalent in the high endemic region and among the elderly (p < 0.05). Genotype D was significantly associated with elevated viral load and direct bilirubin (p < 0.05). The recombinant genotype D/E was significantly associated with elevated viral load (p < 0.05). Similarly, genotype A was significantly associated with elevated AST and GGT, lowered viral load, and normal direct bilirubin levels (p < 0.05). CONCLUSION There is disproportionate distribution of genotypes A and D and the recombinant genotype D/E in the low and high endemic regions of Uganda. This probably could explain the differences in endemicity of HBV in our country signifying the need for regional specific HBV management and control strategies.
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12
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Abstract
Hepatitis B was discovered by researchers who were investigating jaundice associated with blood transfusions as well as parenterally administered medications. Through trial and error, the HBV was identified. There are specific tests that detect HBV infection, whether it is a previous exposure or active infection. The various HBV serologies are reviewed in this work as well. Hepatitis B surface antigen has emerged as a tool in defining treatment endpoint and its significance is reviewed. HBV genotypes are distributed uniquely throughout the world, in particular, genotype C is associated with higher rates of hepatocellular carcinoma. Various HBV genotypes and their impact on the clinical course are discussed. The relationship of HBV serologies and HBV DNA to disease progression is outlined. There are specific recommendations on monitoring those infected with HBV and this is reviewed here. HBV mutations have an impact on the disease course and those of significance are also discussed.
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13
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Menner AS, Kinkel HT, Dixit S, Morrison A, Rieke B, Küpper T. Prevalence and behavioural risk factors for hepatitis B in Upper Dolpo, Nepal. J Public Health (Oxf) 2021. [DOI: 10.1007/s10389-019-01152-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023] Open
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14
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Co-circulation of different genotype, sub-genotype and serotypes of hepatitis B virus (HBV) and its epidemiology in Assam: A north-eastern state of India. Indian J Med Microbiol 2021; 39:352-357. [PMID: 34045082 DOI: 10.1016/j.ijmmb.2021.04.012] [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: 12/12/2020] [Revised: 03/16/2021] [Accepted: 04/30/2021] [Indexed: 11/23/2022]
Abstract
PURPOSE Hepatitis B virus (HBV) infection is a global health problem. HBV has different genotypes and subgenotypes with geographical distinctiveness. AIMS To study the molecular epidemiology and distribution pattern of HBV in Assam; a distinct state of India that may have different genotypic divergence. SETTINGS AND DESIGN Patients attending a tertiary care hospital susceptive of Hepatitis B were included, irrespective of age and sex in different agro-climatic zones of Assam. METHODS Samples positive for Hepatitis B surface antigen test and COBAS®TaqMan® HBV tests were further confirmed by PCR and sequencing followed by phylogenetic analysis. STATISTICAL ANALYSIS USED Chi-square test was used to determine whether there was a significant difference among the results in this study. RESULTS An increase trend of HBV positive cases has been observed in the state. The incidence in female was lower than that of male and age group 26-35 years was most vulnerable. Genotype D, subgenotype D2 and serotype ayw3 were predominant genotype, subgenotype and serotype. The prevalence of subgenotype C3 was a new finding. Phylogenetic analysis showed that the genotypes of HBV prevailing in the state have close relationship with neighboring countries of India which may be due to increased cross border migration of population CONCLUSIONS: This comprehensive study of HBV in Assam described the distribution of HBV genotypes and subgenotypes and serotypes in different agro-climatic zones of Assam. These findings will help to formulate the roadmap for prevention and control of the disease as well as targeted therapy of HBV in this State.
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15
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Aguilera A, Trastoy R, Rodríguez-Frias F, Muñoz-Bellido JL, Melón S, Suárez A, Orduña A, Viciana I, Bernal S, García-Bujalance S, Montiel N, Molina JM, Basaras M, Fernández-Cuenca F, García-Arata I, Reina G, Ocete MD, Fuentes A, Navarro-de la Cruz D, Nieto L, Blazquez de Castro A, Buti M, Álvarez M, García F. GEHEP 010 study: Prevalence and distribution of hepatitis B virus genotypes in Spain (2000-2016). J Infect 2020; 81:600-606. [PMID: 32711039 DOI: 10.1016/j.jinf.2020.07.019] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2019] [Revised: 06/29/2020] [Accepted: 07/17/2020] [Indexed: 02/06/2023]
Abstract
OBJECTIVE To study the prevalence and distribution of HBV genotypes in Spain for the period 2000-2016. METHODS Retrospective study recruiting 2559 patients from 17 hospitals. Distribution of HBV genotypes, as well as sex, age, geographical origin, mode of transmission, HDV-, HIV- and/or HCV-coinfection, and treatment were recorded. RESULTS 1924 chronically HBV native Spanish patients have been recruited. Median age was 54 years (IQR: 41-62), 69.6% male, 6.3% HIV-coinfected, 3.1% were HCV-coinfected, 1.7% HDV-co/superinfected. Genotype distribution was: 55.9% D, 33.5% A, 5.6% F, 0.8% G, and 1.9% other genotypes (E, B, H and C). HBV genotype A was closely associated with male sex, sexual transmission, and HIV-coinfection. In contrast, HBV genotype D was associated with female sex and vertical transmission. Different patterns of genotype distribution and diversity were found between different geographical regions. In addition, HBV epidemiological patterns are evolving in Spain, mainly because of immigration. Finally, similar overall rates of treatment success across all HBV genotypes were found. CONCLUSIONS We present here the most recent data on molecular epidemiology of HBV in Spain (GEHEP010 Study). This study confirms that the HBV genotype distribution in Spain varies based on age, sex, origin, HIV-coinfection, geographical regions and epidemiological groups.
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Affiliation(s)
- Antonio Aguilera
- Complexo Hospitalario Universitario de Santiago, Santiago de Compostela, Instituto de Investigación Sanitaria de Santiago IDIS, Spain
| | - Rocío Trastoy
- Hospital Universitario Vall d'Hebrón, Barcelona, Spain
| | | | | | - Santiago Melón
- Hospital Universitario Central de Asturias, Oviedo, Spain
| | - Avelina Suárez
- Hospital Clínico Universitario San Carlos, Madrid, Spain
| | - Antonio Orduña
- Hospital Clínico Universitario de Valladolid, Valladolid, Spain
| | - Isabel Viciana
- Hospital Universitario Virgen de la Victoria, Málaga, Spain
| | - Samuel Bernal
- Hospital Universitario Virgen de Valme, Sevilla, Spain
| | | | | | | | | | | | | | | | | | - Ana Fuentes
- Hospital Universitario San Cecilio, Instituto de Investigación Biosanitaria Ibs, Av. de la Innovación S/N, 18016 Granada, Spain
| | | | | | | | - María Buti
- Hospital Universitario Vall d'Hebrón, Barcelona, Spain
| | - Marta Álvarez
- Hospital Universitario San Cecilio, Instituto de Investigación Biosanitaria Ibs, Av. de la Innovación S/N, 18016 Granada, Spain
| | - Federico García
- Hospital Universitario San Cecilio, Instituto de Investigación Biosanitaria Ibs, Av. de la Innovación S/N, 18016 Granada, Spain.
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16
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Choga WT, Anderson M, Zumbika E, Phinius BB, Mbangiwa T, Bhebhe LN, Baruti K, Kimathi PO, Seatla KK, Musonda RM, Bell TG, Moyo S, Blackard JT, Gaseitsiwe S. In Silico Prediction of Human Leukocytes Antigen (HLA) Class II Binding Hepatitis B Virus (HBV) Peptides in Botswana. Viruses 2020; 12:E731. [PMID: 32640609 PMCID: PMC7412261 DOI: 10.3390/v12070731] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2020] [Accepted: 07/03/2020] [Indexed: 02/07/2023] Open
Abstract
Hepatitis B virus (HBV) is the primary cause of liver-related malignancies worldwide, and there is no effective cure for chronic HBV infection (CHB) currently. Strong immunological responses induced by T cells are associated with HBV clearance during acute infection; however, the repertoire of epitopes (epi) presented by major histocompatibility complexes (MHCs) to elicit these responses in various African populations is not well understood. In silico approaches were used to map and investigate 15-mers HBV peptides restricted to 9 HLA class II alleles with high population coverage in Botswana. Sequences from 44 HBV genotype A and 48 genotype D surface genes (PreS/S) from Botswana were used. Of the 1819 epi bindings predicted, 20.2% were strong binders (SB), and none of the putative epi bind to all the 9 alleles suggesting that multi-epitope, genotype-based, population-based vaccines will be more effective against HBV infections as opposed to previously proposed broad potency epitope-vaccines which were assumed to work for all alleles. In total, there were 297 unique epi predicted from the 3 proteins and amongst, S regions had the highest number of epi (n = 186). Epitope-densities (Depi) between genotypes A and D were similar. A number of mutations that hindered HLA-peptide binding were observed. We also identified antigenic and genotype-specific peptides with characteristics that are well suited for the development of sensitive diagnostic kits. This study identified candidate peptides that can be used for developing multi-epitope vaccines and highly sensitive diagnostic kits against HBV infection in an African population. Our results suggest that viral variability may hinder HBV peptide-MHC binding, required to initiate a cascade of immunological responses against infection.
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Affiliation(s)
- Wonderful Tatenda Choga
- Research Laboratory, Botswana Harvard AIDS Institute Partnership, Gaborone 0000, Botswana; (W.T.C.); (M.A.); (B.B.P.); (T.M.); (L.N.B.); (K.B.); (K.K.S.); (R.M.M.); (S.M.)
- Division of Human Genetics, Department of Pathology, Faculty of Health Sciences, University of Cape Town, Cape Town 7925, South Africa
| | - Motswedi Anderson
- Research Laboratory, Botswana Harvard AIDS Institute Partnership, Gaborone 0000, Botswana; (W.T.C.); (M.A.); (B.B.P.); (T.M.); (L.N.B.); (K.B.); (K.K.S.); (R.M.M.); (S.M.)
| | - Edward Zumbika
- Department of Applied Biology and Biochemistry, Faculty of Applied Sciences, National University of Science and Technology, Bulawayo 0000, Zimbabwe;
| | - Bonolo B. Phinius
- Research Laboratory, Botswana Harvard AIDS Institute Partnership, Gaborone 0000, Botswana; (W.T.C.); (M.A.); (B.B.P.); (T.M.); (L.N.B.); (K.B.); (K.K.S.); (R.M.M.); (S.M.)
| | - Tshepiso Mbangiwa
- Research Laboratory, Botswana Harvard AIDS Institute Partnership, Gaborone 0000, Botswana; (W.T.C.); (M.A.); (B.B.P.); (T.M.); (L.N.B.); (K.B.); (K.K.S.); (R.M.M.); (S.M.)
- Division of Human Genetics, Department of Pathology, Faculty of Health Sciences, University of Cape Town, Cape Town 7925, South Africa
| | - Lynnette N. Bhebhe
- Research Laboratory, Botswana Harvard AIDS Institute Partnership, Gaborone 0000, Botswana; (W.T.C.); (M.A.); (B.B.P.); (T.M.); (L.N.B.); (K.B.); (K.K.S.); (R.M.M.); (S.M.)
| | - Kabo Baruti
- Research Laboratory, Botswana Harvard AIDS Institute Partnership, Gaborone 0000, Botswana; (W.T.C.); (M.A.); (B.B.P.); (T.M.); (L.N.B.); (K.B.); (K.K.S.); (R.M.M.); (S.M.)
- Department of Biological Sciences, Faculty of Science, University of Botswana, Gaborone 0000, Botswana
| | | | - Kaelo K. Seatla
- Research Laboratory, Botswana Harvard AIDS Institute Partnership, Gaborone 0000, Botswana; (W.T.C.); (M.A.); (B.B.P.); (T.M.); (L.N.B.); (K.B.); (K.K.S.); (R.M.M.); (S.M.)
- Department of Medical Laboratory Sciences, Faculty of Health Sciences, University of Botswana, Gaborone 0000, Botswana
| | - Rosemary M. Musonda
- Research Laboratory, Botswana Harvard AIDS Institute Partnership, Gaborone 0000, Botswana; (W.T.C.); (M.A.); (B.B.P.); (T.M.); (L.N.B.); (K.B.); (K.K.S.); (R.M.M.); (S.M.)
- Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA
| | - Trevor Graham Bell
- Independent Researcher, P.O. Box 497, Wits, Johannesburg 2050, South Africa;
| | - Sikhulile Moyo
- Research Laboratory, Botswana Harvard AIDS Institute Partnership, Gaborone 0000, Botswana; (W.T.C.); (M.A.); (B.B.P.); (T.M.); (L.N.B.); (K.B.); (K.K.S.); (R.M.M.); (S.M.)
- Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA
| | - Jason T. Blackard
- Division of Digestive Diseases, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA;
| | - Simani Gaseitsiwe
- Research Laboratory, Botswana Harvard AIDS Institute Partnership, Gaborone 0000, Botswana; (W.T.C.); (M.A.); (B.B.P.); (T.M.); (L.N.B.); (K.B.); (K.K.S.); (R.M.M.); (S.M.)
- Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA
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17
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Ogawa M, Akine D, Sasahara T. Comparison of hepatitis B vaccine efficacy in Japanese students: a retrospective study. Environ Health Prev Med 2019; 24:80. [PMID: 31878867 PMCID: PMC6933897 DOI: 10.1186/s12199-019-0837-1] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2019] [Accepted: 12/09/2019] [Indexed: 12/18/2022] Open
Abstract
Background Two types of recombinant hepatitis B virus (HBV) vaccines are available in Japan. One type uses the antigen from genotype A (Heptavax-II®) and the other uses the antigen from genotype C (Bimmugen®). Potential differences in productivity of the hepatitis B virus surface (HBs) antibody between vaccines have not been studied in detail. We investigated the acquired level of immunity against HBV in association with two vaccines, their administration routes, and patient sex. We present the appropriate inoculation method based on the characteristics of each vaccine. Methods Data of 1135 medical and nursing students (481 men and 651 women) were used, each of whom was unvaccinated prior to recruitment and subsequently vaccinated three times prior to the study. The vaccine type and administration route differed according to the university department and enrolling year. The students were categorized into the following three groups: Bimmugen®-subcutaneous group, Heptavax-II®-subcutaneous group, and Heptavax-II®-intramuscular group. The total and sex-segregated positive rates of the HBs antibody among the three groups were compared using Pearson’s chi-square test. The effect of time between the HBs antibody test and vaccine administration on the HBs antibody level was also analyzed similarly. Results The Bimmugen®-subcutaneous group showed the highest positive HBs antibody rate (92.0%) among the three groups. In the Heptavax-II® group, the positive rate was 66.3% in the subcutaneous injection group and 89.1% in the intramuscular injection group. There was a significant difference among these three groups. In terms of sex, women showed a significantly higher average positive rate than men in each group. In terms of effect of time between the HBs antibody test and vaccine administration, no significant differences were observed. Conclusions Bimmugen® is associated with more effective HBs antibody production than Heptavax-II® in Japanese students. However, the Heptavax-II® vaccine is an appropriate choice for HBV vaccination in areas where HB is caused predominantly by HBV genotype C. With both vaccines, women tended to acquire more immunogenicity than men. Intramuscular injection may be the preferred administration route due to the possibility of local reactions.
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Affiliation(s)
- Masanori Ogawa
- Health Service Center, Jichi Medical University, 3311-1, Yakushiji, Shimotsuke, 329-0498, Japan.
| | - Dai Akine
- Health Service Center, Jichi Medical University, 3311-1, Yakushiji, Shimotsuke, 329-0498, Japan
| | - Teppei Sasahara
- Division of Clinical Infectious Diseases, Department of Infection and Immunity, Jichi Medical University, 3311-1, Yakushiji, Shimotsuke, 329-0498, Japan
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18
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Akinbami A, Badiru M, Uche E, Onyekwere C, Ismail K, Olowoselu O, Oluwole E, Suleiman A, Augustine B, Olaosebikan H. The Prevalence of Occult Hepatitis B Infection among Blood Donors in Lagos, Nigeria. Niger Med J 2019; 60:22-26. [PMID: 31413431 PMCID: PMC6677000 DOI: 10.4103/nmj.nmj_29_19] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022] Open
Abstract
Background: In occult hepatitis B virus (HBV) infection, the HBV DNA is present in the blood or liver tissue in patients negative for hepatitis B surface antigen (HBsAg) with or without anti-HBV antibodies. Thus, the absence of HBsAg in the blood only reduces the risk of transmission and is not sufficient enough to ensure the absence of HBV infection. Aim: This study was aimed at determining the prevalence of occult HBV infection among blood donors in Lagos. Study Designs: A cross-sectional study was done among 101 consenting blood donors at Lagos State University Teaching Hospital, Ikeja, between November 2016 and January 2017. Materials and Methods: HBV DNA analysis and viral load were done at the Molecular Laboratory of National Sickle Cell Centre, Idi Araba, Lagos, for all the HBsAg negative blood donors screened by rapid kit at Ikeja. Results: The prevalence of occult HBV DNA among the participants was 3% consisting of 3% prevalence of HBV DNA surface antigen and 0% prevalence for precore and core of the HBV DNA. Conclusion: The low prevalence (3%) of occult HBV seen in our study does not make it cost-effective to routinely screen blood donors or the general population for HBV infection using DNA polymerase chain reaction.
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Affiliation(s)
- Akinsegun Akinbami
- Department of Haematology and Blood Transfusion, Lagos State University College of Medicine, Lagos, Nigeria
| | - Mulikat Badiru
- Department of Haematology and Blood Transfusion, Lagos State University College of Medicine, Lagos, Nigeria
| | - Ebele Uche
- Department of Haematology and Blood Transfusion, Lagos State University College of Medicine, Lagos, Nigeria
| | - Charles Onyekwere
- Department of Internal Medicine, Lagos State University College of Medicine, Lagos, Nigeria
| | - Kamal Ismail
- Department of Haematology and Blood Transfusion, Lagos State University College of Medicine, Lagos, Nigeria
| | - Olusola Olowoselu
- Department of Haematology and Blood Transfusion, Faculty of Clinical Sciences, College of Medicine, University of Lagos, Lagos, Nigeria
| | - Esther Oluwole
- Department of Community Health and Primary Care, Faculty of Clinical Sciences, College of Medicine, University of Lagos, Lagos, Nigeria
| | - Aisha Suleiman
- Department of Haematology and Blood Transfusion, Faculty of Basic Clinical Sciences, Ahmadu Bello University, Zaria, Nigeria
| | - Benjamin Augustine
- Department of Haematology and Blood Transfusion, Faculty of Basic Clinical Sciences, Ahmadu Bello University, Zaria, Nigeria
| | - Hakeem Olaosebikan
- Department of Internal Medicine, Lagos State University College of Medicine, Lagos, Nigeria
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19
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Zhang X, Chen X, Wei M, Zhang C, Xu T, Liu L, Xu Z. Potential resistant mutations within HBV reverse transcriptase sequences in nucleos(t)ide analogues-experienced patients with hepatitis B virus infection. Sci Rep 2019; 9:8078. [PMID: 31147594 PMCID: PMC6542804 DOI: 10.1038/s41598-019-44604-6] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2019] [Accepted: 05/16/2019] [Indexed: 12/17/2022] Open
Abstract
This study was performed to analyze the potential resistant mutations within HBV reverse transcriptase (RT) sequences against nucleos(t)ide analogues (NA). HBV DNA RT region spanning from amino acid 169 to 250 was amplified and sequenced from 435 HBV patients who experienced NA treatment. Among study’s cohort, genotypes B and C infected patients were 55.9% and 44.1%, respectively. Mutations were recorded in 54.7% (238/435) patients at 22 positions. Genotype C displayed significant higher frequency of potential NA resistant mutations than genotype B (63.0% vs. 48.1%, P = 0.003). Moreover, eight mutation sites, including 180, 181, 191, 200, 202, 221, 229 and 224, in genotype C showed significant higher frequencies than in genotype B. In contrast, mutation at site 236 was more common in genotype B. Notably, 11 mutations at position 169, 202, 250, 173, 180, 200, 207, 214, 237, 242 and 245 coexisted with M204I or V. Substitutions at nine non-classical mutation sites (191, 207, 213, 218, 221, 224, 229, 238 and 242) were detected in patients with virological breakthrough. Particularly, tenofovir (TDF) resistance was observed in one patient undergoing TDF monotherapy and experienced several NA treatment before. These results might provide clinical useful information under antiviral therapy.
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Affiliation(s)
- Xiaoman Zhang
- Clinical Liver Center, the 910th hospital of People's Liberation Army, Quanzhou, 362000, China
| | - Xianli Chen
- Department of Infectious and Liver Disease, Xiang'an hospital of Xiamen University, Xiamen, 361000, China
| | - Meijuan Wei
- Clinical Liver Center, the 910th hospital of People's Liberation Army, Quanzhou, 362000, China.,Clinical Liver Center, Decheng hospital of Quanzhou Affiliated of Huaqiao University, Quanzhou, 362000, China
| | - Chunyu Zhang
- Clinical Liver Center, the 910th hospital of People's Liberation Army, Quanzhou, 362000, China
| | - Tao Xu
- Clinical Liver Center, the 910th hospital of People's Liberation Army, Quanzhou, 362000, China
| | - Liguan Liu
- Clinical Liver Center, the 910th hospital of People's Liberation Army, Quanzhou, 362000, China
| | - Zhengju Xu
- Clinical Liver Center, the 910th hospital of People's Liberation Army, Quanzhou, 362000, China.
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20
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Matlou MK, Gaelejwe LR, Musyoki AM, Rakgole JN, Selabe SG, Amponsah-Dacosta E. A novel hepatitis B virus recombinant genotype D4/E identified in a South African population. Heliyon 2019; 5:e01477. [PMID: 31008405 PMCID: PMC6453802 DOI: 10.1016/j.heliyon.2019.e01477] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2018] [Revised: 03/08/2019] [Accepted: 04/01/2019] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Genetic diversity is a characteristic trait of the hepatitis B virus (HBV) and has been associated with different clinical outcomes. In South Africa, HBV infection is a major public health concern. Most HBV infections are caused by genotype A strains. However rare cases of infection with HBV genotype D have been reported. The purpose of this study was to investigate the molecular characteristics of a rare HBV subgenotype D4 isolate. METHODS The full-length genome of isolate ZADGM6964 was amplified in a one-step polymerase chain reaction. The amplified product was purified and cloned into a pGEM®-T Easy Vector System to investigate the genetic diversity of the viral quasi-populations. The primary isolate and clones were then directly sequenced and analysed using an array of bioinformatics software. RESULTS Phylogenetic analysis showed that the primary isolate and cloned sequences formed a monophyletic cluster away from subgenotype D4 reference strains. Further recombination analysis revealed that isolate ZADGM6964 was in fact a D4/E recombinant strain with breakpoints identified within the X and overlapping pre-Core/Core open reading frames with a >70% bootstrap confidence level. The recombinant genotype D4/E was found to be unique from other D/E strains archived in the genetic database, GenBank. CONCLUSION This study represents the first ever report on the isolation and molecular characterization of an HBV D4/E recombinant strain in South Africa. The findings provide evidence of further HBV genetic diversity in South Africa than has been previously reported.
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Affiliation(s)
- Mmatsatsi K. Matlou
- HIV and Hepatitis Research Unit, Department of Virology, Sefako Makgatho Health Sciences University and National Health Laboratory Services, Pretoria, South Africa
| | - Lucinda R. Gaelejwe
- HIV and Hepatitis Research Unit, Department of Virology, Sefako Makgatho Health Sciences University and National Health Laboratory Services, Pretoria, South Africa
| | - Andrew M. Musyoki
- HIV and Hepatitis Research Unit, Department of Virology, Sefako Makgatho Health Sciences University and National Health Laboratory Services, Pretoria, South Africa
- Department of Microbiological Pathology, Sefako Makgatho Health Sciences University, Pretoria, South Africa
| | - J. Nare Rakgole
- HIV and Hepatitis Research Unit, Department of Virology, Sefako Makgatho Health Sciences University and National Health Laboratory Services, Pretoria, South Africa
| | - Selokela G. Selabe
- HIV and Hepatitis Research Unit, Department of Virology, Sefako Makgatho Health Sciences University and National Health Laboratory Services, Pretoria, South Africa
| | - Edina Amponsah-Dacosta
- HIV and Hepatitis Research Unit, Department of Virology, Sefako Makgatho Health Sciences University and National Health Laboratory Services, Pretoria, South Africa
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21
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Torres MC, Civetta E, D'amico C, Barbini L. Hepatitis B virus in Mar del Plata, Argentina: Genomic characterization and evolutionary analysis of subgenotype F1b. J Med Virol 2019; 91:791-802. [PMID: 30570771 DOI: 10.1002/jmv.25383] [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: 07/13/2018] [Accepted: 12/14/2018] [Indexed: 11/07/2022]
Abstract
The aim is to describe the molecular epidemiology and perform a genomic characterization of hepatitis B virus (HBV) circulating in Mar del Plata and to identify the origin and diversification patterns of the most prevalent genotype. The S gene and the region encompassing the X gene, basal core promoter (BCP), and precore (preC) was analyzed in 56 samples. They were genotyped as: 80% F1b, 9% A2, 7% D3, and 2% D1. A recombinant F4/D2 genome was detected. The double substitution G1764A/A1762T at the BCP (reduced HBeAg expression) was found in 20% F1b, 2% A2, 2% D1, and 2% D3 samples. A unique D3 presented the G1896A substitution at the preC (HBeAg negative phenotype). A 13% of the samples showed mutations at the HBsAg "a" immunodeterminant (escape from neutralizing antibodies). Mutations at the polymerase (antiviral resistance) were found in 52% of the samples. Coalescent analysis of subgenotype F1b, the most prevalent in the city, showed that viral diversification in Mar del Plata started by year 2000. F1b was the most prevalent genotype detected, being a characteristic of actual HBV infections in Mar del Plata. Local HBV exhibit clinically relevant mutations, but a minority of them was shown to be associated to potential vaccination escape or antiviral resistance. Nevertheless, further studies are needed to determine whether any of these mutants could pose a threat to prevention, diagnosis, or treatment.
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Affiliation(s)
| | - Elida Civetta
- Unidad de Hepatología y Alcoholismo, HIGA Dr. O. Alende, Mar del Plata, Argentina
| | - Claudia D'amico
- Centro de Especialidades Médicas Ambulatorias, Unidad de Hepatología, Mar del Plata, Argentina
| | - Luciana Barbini
- Departamento de Química, FCEyN, UNMdP, Buenos Aires, Argentina
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22
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Catanach TA, Sweet AD, Nguyen NPD, Peery RM, Debevec AH, Thomer AK, Owings AC, Boyd BM, Katz AD, Soto-Adames FN, Allen JM. Fully automated sequence alignment methods are comparable to, and much faster than, traditional methods in large data sets: an example with hepatitis B virus. PeerJ 2019; 7:e6142. [PMID: 30627489 PMCID: PMC6321758 DOI: 10.7717/peerj.6142] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2018] [Accepted: 11/14/2018] [Indexed: 01/05/2023] Open
Abstract
Aligning sequences for phylogenetic analysis (multiple sequence alignment; MSA) is an important, but increasingly computationally expensive step with the recent surge in DNA sequence data. Much of this sequence data is publicly available, but can be extremely fragmentary (i.e., a combination of full genomes and genomic fragments), which can compound the computational issues related to MSA. Traditionally, alignments are produced with automated algorithms and then checked and/or corrected "by eye" prior to phylogenetic inference. However, this manual curation is inefficient at the data scales required of modern phylogenetics and results in alignments that are not reproducible. Recently, methods have been developed for fully automating alignments of large data sets, but it is unclear if these methods produce alignments that result in compatible phylogenies when compared to more traditional alignment approaches that combined automated and manual methods. Here we use approximately 33,000 publicly available sequences from the hepatitis B virus (HBV), a globally distributed and rapidly evolving virus, to compare different alignment approaches. Using one data set comprised exclusively of whole genomes and a second that also included sequence fragments, we compared three MSA methods: (1) a purely automated approach using traditional software, (2) an automated approach including by eye manual editing, and (3) more recent fully automated approaches. To understand how these methods affect phylogenetic results, we compared resulting tree topologies based on these different alignment methods using multiple metrics. We further determined if the monophyly of existing HBV genotypes was supported in phylogenies estimated from each alignment type and under different statistical support thresholds. Traditional and fully automated alignments produced similar HBV phylogenies. Although there was variability between branch support thresholds, allowing lower support thresholds tended to result in more differences among trees. Therefore, differences between the trees could be best explained by phylogenetic uncertainty unrelated to the MSA method used. Nevertheless, automated alignment approaches did not require human intervention and were therefore considerably less time-intensive than traditional approaches. Because of this, we conclude that fully automated algorithms for MSA are fully compatible with older methods even in extremely difficult to align data sets. Additionally, we found that most HBV diagnostic genotypes did not correspond to evolutionarily-sound groups, regardless of alignment type and support threshold. This suggests there may be errors in genotype classification in the database or that HBV genotypes may need a revision.
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Affiliation(s)
- Therese A. Catanach
- Ornithology Department, Academy of Natural Sciences of Drexel University, Philadelphia, PA, United States of America
- Illinois Natural History Survey, University of Illinois at Urbana-Champaign, Champaign, IL, United States of America
- Department of Wildlife and Fisheries Sciences, Texas A&M University, College Station, TX, United States of America
| | - Andrew D. Sweet
- Illinois Natural History Survey, University of Illinois at Urbana-Champaign, Champaign, IL, United States of America
- Department of Entomology, Purdue University, West Lafayette, IN, United States of America
| | - Nam-phuong D. Nguyen
- Computer Science and Engineering, University of San Diego, California, La Jolla, CA, United States of America
| | - Rhiannon M. Peery
- Department of Biology, University of Alberta, Edmonton, Alberta, Canada
- Department of Plant Biology, University of Illinois at Urbana-Champaign, Champaign, IL, United States of America
| | - Andrew H. Debevec
- School of Integrative Biology, University of Illinois at Urbana-Champaign, Champaign, IL, United States of America
| | - Andrea K. Thomer
- School of Information, University of Michigan—Ann Arbor, Ann Arbor, MI, United States of America
| | - Amanda C. Owings
- Program in Ecology, Evolution, and Conservation Biology, University of Illinois at Urbana-Champaign, Urbana, IL, United States of America
| | - Bret M. Boyd
- Illinois Natural History Survey, University of Illinois at Urbana-Champaign, Champaign, IL, United States of America
- Department of Entomology, University of Georga, Athens, GA, United States of America
| | - Aron D. Katz
- Illinois Natural History Survey, University of Illinois at Urbana-Champaign, Champaign, IL, United States of America
- Department of Entomology, University of Illinois at Urbana-Champaign, Champaign, IL, United States of America
| | - Felipe N. Soto-Adames
- Florida State Collection of Arthropods, Florida Department of Agriculture and Consumer Services, Gainesville, FL, United States of America
- Department of Entomology and Nematology, University of Florida, Gainesville, FL, United States of America
| | - Julie M. Allen
- Biology Department, University of Nevada, Reno, Reno, NV, United States of America
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23
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Assih M, Ouattara AK, Diarra B, Yonli AT, Compaore TR, Obiri-Yeboah D, Djigma FW, Karou S, Simpore J. Genetic diversity of hepatitis viruses in West-African countries from 1996 to 2018. World J Hepatol 2018; 10:807-821. [PMID: 30533182 PMCID: PMC6280160 DOI: 10.4254/wjh.v10.i11.807] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/02/2018] [Revised: 09/10/2018] [Accepted: 10/23/2018] [Indexed: 02/06/2023] Open
Abstract
The severity of hepatic pathology and the response to treatment depend on the hepatitis virus genotype in the infected host. The objective of this review was to determine the distribution of hepatitis virus genotypes in West African countries. A systematic review of the literature in PubMed, Google Scholar and Science Direct was performed to identify 52 relevant articles reporting hepatitis A, B, C, D, E and G viruses genotypes. Hepatitis B virus (HBV) genotype E with a prevalence of 90.6% (95%CI: 0.891-0.920) found in this review, is characterized by low genetic diversity. Hepatitis C virus (HCV) genotypes 1 and 2 represented 96.4% of HCV infections in West African countries, while hepatitis delta virus, hepatitis A virus, hepatitis G virus genotypes 1 and HEV genotype 3 were reported in some studies in Ghana and Nigeria. HBV genotype E is characterized by high prevalence, low genetic diversity and wide geographical distribution. Further studies on the clinical implications of HBV genotype E and HCV genotypes 1 and 2 are needed for the development of an effective treatment against this viral hepatitis in West African countries. Surveillance of the distribution of different genotypes is also needed to reduce recombination rates and prevent the emergence of more virulent viral strains.
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Affiliation(s)
- Maléki Assih
- Biochemistry-Microbiology, CERBA/LABIOGENE, Ouagadougou 02006, Burkina Faso
- Laboratory of Molecular Biology and Molecular Genetics (LABIOGENE) UFR/SVT, University Ouaga I Prof Joseph KI-ZERBO, Ouagadougou 00226, Burkina Faso
| | - Abdoul Karim Ouattara
- Biochemistry-Microbiology, CERBA/LABIOGENE, Ouagadougou 02006, Burkina Faso
- Laboratory of Molecular Biology and Molecular Genetics (LABIOGENE) UFR/SVT, University Ouaga I Prof Joseph KI-ZERBO, Ouagadougou 00226, Burkina Faso.
| | - Birama Diarra
- Biochemistry-Microbiology, CERBA/LABIOGENE, Ouagadougou 02006, Burkina Faso
- Laboratory of Molecular Biology and Molecular Genetics (LABIOGENE) UFR/SVT, University Ouaga I Prof Joseph KI-ZERBO, Ouagadougou 00226, Burkina Faso
| | - Albert Theophane Yonli
- Biochemistry-Microbiology, CERBA/LABIOGENE, Ouagadougou 02006, Burkina Faso
- Laboratory of Molecular Biology and Molecular Genetics (LABIOGENE) UFR/SVT, University Ouaga I Prof Joseph KI-ZERBO, Ouagadougou 00226, Burkina Faso
| | - Tegwindé Rebeca Compaore
- Biochemistry-Microbiology, CERBA/LABIOGENE, Ouagadougou 02006, Burkina Faso
- Laboratory of Molecular Biology and Molecular Genetics (LABIOGENE) UFR/SVT, University Ouaga I Prof Joseph KI-ZERBO, Ouagadougou 00226, Burkina Faso
| | - Dorcas Obiri-Yeboah
- Department of Microbiology and Immunology, School of Medical Sciences, University of Cape Coast, Cape Coast 00233, Ghana
| | - Florencia Wendkuuni Djigma
- Biochemistry-Microbiology, CERBA/LABIOGENE, Ouagadougou 02006, Burkina Faso
- Laboratory of Molecular Biology and Molecular Genetics (LABIOGENE) UFR/SVT, University Ouaga I Prof Joseph KI-ZERBO, Ouagadougou 00226, Burkina Faso
| | - Simplice Karou
- Ecole Supérieure des Techniques Biologiques et Alimentaires (ESTBA-UL), Universite de Lome, Lome 00229, Togo
| | - Jacques Simpore
- Biochemistry-Microbiology, CERBA/LABIOGENE, Ouagadougou 02006, Burkina Faso
- Laboratory of Molecular Biology and Molecular Genetics (LABIOGENE) UFR/SVT, University Ouaga I Prof Joseph KI-ZERBO, Ouagadougou 00226, Burkina Faso
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24
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Batsis ID, Wasuwanich P, Karnsakul WW. The management of hepatitis B and hepatitis C in children. Minerva Pediatr 2018; 71:59-75. [PMID: 30334626 DOI: 10.23736/s0026-4946.18.05410-5] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
In the present paper, we review the increased disease burden of hepatitis B (HBV) and hepatitis C (HCV) infection that is recognized worldwide; especially in children when the most common mode of transmission is vertically from infected mothers. In children with HBV and HCV infection, spontaneous clearance of the virus in the first years of life is not common, in contrast with adults, but these patients often stay asymptomatic until early adulthood, when disease has progressed to chronic hepatitis with increased risk of cirrhosis and its complication, and hepatocellular carcinoma. Due to limited treatment options of HBV infection in the pediatric population, clinicians focus on primary prevention, by vaccinating all infants during their first days of life. Infants born to infected mothers, receive intravenous immunoglobulin on top of the vaccine, and thus preventing transmission in 95% of the infants. While for HCV infection, since there is no vaccine to prevent HCV disease, providers focus primarily on treatment. The treatment landscape of HCV infection in children rapidly evolves, away from interferon regimens, and towards direct-acting antiviral agents that have a safer and more efficacious drug profile. Currently, there are ongoing clinical trials investigating the efficacy and tolerance of direct-acting agents in children below 12 years of age.
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Affiliation(s)
- Irini D Batsis
- Division of Pediatric Gastroenterology, Nutrition, and Hepatology, Department of Pediatrics, Johns Hopkins School of Medicine, Baltimore, MD, USA
| | - Paul Wasuwanich
- Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN, USA
| | - Wikrom W Karnsakul
- Division of Pediatric Gastroenterology, Nutrition, and Hepatology, Department of Pediatrics, Johns Hopkins School of Medicine, Baltimore, MD, USA -
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25
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Matsumoto A, Nishiguchi S, Enomoto H, Kang JH, Tanaka Y, Shinkai N, Kurosaki M, Enomoto M, Kanda T, Yokosuka O, Yatsuhashi H, Nagaoka S, Okuse C, Kagawa T, Mine T, Takaguchi K, Saito S, Hino K, Ikeda F, Sakisaka S, Morihara D, Miyase S, Tsuge M, Chayama K, Hiramatsu N, Suzuki Y, Murata K, Tanaka E. Combinational use of hepatitis B viral antigens predicts responses to nucleos(t)ide analogue/peg-interferon sequential therapy. J Gastroenterol 2018; 53:247-257. [PMID: 28634723 DOI: 10.1007/s00535-017-1360-z] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/18/2017] [Accepted: 06/04/2017] [Indexed: 02/04/2023]
Abstract
BACKGROUND This prospective cohort study searched for factors associated with a response to nucleos(t)ide analogue/peg-interferon (NUC/peg-IFN) sequential therapy. METHODS A total of 95 patients with chronic hepatitis B being treated with NUCs were enrolled. Immediately following NUC cessation, peg-IFN was administered at 180 µg/dose weekly for 48 weeks. RESULTS Twenty-six patients (27%) were judged to be responders at 48 weeks after the completion of peg-IFN. Analysis of baseline factors revealed that hepatitis B surface antigen (HBsAg) <3.1 log IU/ml and HB core-related antigen (HBcrAg) <3.9 log U/ml were significant indicators of a treatment response. The levels of the markers decreased in both responders and non-responders during peg-IFN therapy but continued falling in responders only after halting peg-IFN. Lower HBsAg (<2.0 log IU/ml) and HBcrAg (<3.8 log U/ml) levels at the time of response judgment were also significantly associated with a favorable response. While lower HBcrAg at baseline was the sole predictor of decreased HBcrAg levels at judgment, lower HBsAg, lower HBcrAg, and the use of adefovir dipivoxil at baseline predicted decreased HBsAg levels at the study endpoint. The use of adefovir dipivoxil was also associated with higher serum IFN-λ3, which might have contributed to the reduction in patient HBsAg levels. CONCLUSIONS The combinational use of HBsAg and HBcrAg levels at baseline and their changes throughout sequential therapy may be useful for predicting a response to NUC/peg-IFN sequential therapy.
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Affiliation(s)
- Akihiro Matsumoto
- Department of Medicine, Shinshu University School of Medicine, Asahi 3-1-1, Matsumoto, 390-8621, Japan
| | - Shuhei Nishiguchi
- Division of Hepatobiliary and Pancreatic Disease, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan
| | - Hirayuki Enomoto
- Division of Hepatobiliary and Pancreatic Disease, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan
| | - Jong-Hon Kang
- Center for Gastroenterology, Teine Keijinkai Hospital, Sapporo, Japan
| | - Yasuhito Tanaka
- Department of Virology and Liver Unit, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Noboru Shinkai
- Department of Virology and Liver Unit, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Masayuki Kurosaki
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Masaru Enomoto
- Department of Hepatology, Osaka City University Medical School, Osaka, Japan
| | - Tatsuo Kanda
- Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Osamu Yokosuka
- Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Hiroshi Yatsuhashi
- The Clinical Research Center, National Hospital Organization Nagasaki Medical Center, Omura, Japan
| | - Shinya Nagaoka
- The Clinical Research Center, National Hospital Organization Nagasaki Medical Center, Omura, Japan
| | - Chiaki Okuse
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Japan
| | - Tatehiro Kagawa
- Division of Gastroenterology, Department of Internal Medicine, Tokai University School of Medicine, Isehara, Japan
| | - Tetsuya Mine
- Division of Gastroenterology, Department of Internal Medicine, Tokai University School of Medicine, Isehara, Japan
| | - Koichi Takaguchi
- Department of Hepatology, Kagawa Prefectural Central Hospital, Takamatsu, Japan
| | - Satoru Saito
- Department of Gastroenterology and Hepatology, Yokohama City University School of Medicine, Yokohama, Japan
| | - Keisuke Hino
- Department of Hepatology and Pancreatology, Kawasaki Medical School, Kurashiki, Japan
| | - Fusao Ikeda
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan
| | - Shotaro Sakisaka
- Department of Gastroenterology and Medicine, Fukuoka University Faculty of Medicine, Fukuoka, Japan
| | - Daisuke Morihara
- Department of Gastroenterology and Medicine, Fukuoka University Faculty of Medicine, Fukuoka, Japan
| | - Shiho Miyase
- Department of Gastroenterology and Hepatology, Kumamoto Shinto General Hospital, Kumamoto, Japan
| | - Masataka Tsuge
- Department of Gastroenterology and Metabolism, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Kazuaki Chayama
- Department of Gastroenterology and Metabolism, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Naoki Hiramatsu
- Department of Gastroenterology, Osaka Rosai Hospital, Sakai, Japan
| | | | - Kazumoto Murata
- The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Ichikawa, Japan
- Department of Gastroenterology, Graduate School of Medical Sciences, International University of Health and Welfare, Narita, Japan
| | - Eiji Tanaka
- Department of Medicine, Shinshu University School of Medicine, Asahi 3-1-1, Matsumoto, 390-8621, Japan.
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26
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Novel Genetic Variants of Hepatitis B Virus in Fulminant Hepatitis. J Pathog 2017; 2017:1231204. [PMID: 29410920 PMCID: PMC5749291 DOI: 10.1155/2017/1231204] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2017] [Accepted: 11/20/2017] [Indexed: 02/06/2023] Open
Abstract
Fulminant hepatitis (FH) is a life-threatening liver disease characterised by intense immune attack and massive liver cell death. The common precore stop codon mutation of hepatitis B virus (HBV), A1896, is frequently associated with FH, but lacks specificity. This study attempts to uncover all possible viral nucleotides that are specifically associated with FH through a compiled sequence analysis of FH and non-FH cases from acute infection. We retrieved 67 FH and 280 acute non-FH cases of hepatitis B from GenBank and applied support vector machine (SVM) model to seek candidate nucleotides highly predictive of FH. Six best candidates with top predictive accuracy, 92.5%, were used to build a SVM model; they are C2129 (85.3%), T720 (83.0%), Y2131 (82.4%), T2013 (82.1%), K2048 (82.1%), and A2512 (82.1%). This model gave a high specificity (99.3%), positive predictive value (95.6%), and negative predictive value (92.1%), but only moderate sensitivity (64.2%). We successfully built a SVM model comprising six variants that are highly predictive and specific for FH: four in the core region and one each in the polymerase and the surface regions. These variants indicate that intracellular virion/core retention could play an important role in the progression to FH.
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27
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Boyce CL, Ganova-Raeva L, Archampong TNA, Lartey M, Sagoe KW, Obo-Akwa A, Kenu E, Kwara A, Blackard JT. Identification and comparative analysis of hepatitis B virus genotype D/E recombinants in Africa. Virus Genes 2017; 53:538-547. [PMID: 28567562 PMCID: PMC5710801 DOI: 10.1007/s11262-017-1469-4] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2017] [Accepted: 05/25/2017] [Indexed: 12/17/2022]
Abstract
Globally, there are approximately 240 million people chronically infected with hepatitis B virus (HBV)-a major cause of hepatocellular carcinoma. Ten different HBV genotypes (A-J) have been identified with distinct geographic distributions. Novel variants generated by recombination between different HBV genotypes have been documented worldwide and represent an important element of genetic variability with possible clinical implications. Here, the complete genome sequence of an HBV genotype D/E recombinant from Ghana is reported. The full-length sequence was obtained using rolling circle amplification followed by PCR and sequenced using next-generation sequencing (NGS). A consensus sequence was extracted from the NGS data and underwent phylogenetic analysis to determine genotype, as well as the recombination pattern. Subsequently, the sequence was compared to recombinants described previously in Africa. Based on MCMC phylogenetic analysis, SimPlot recombination analyses, and intragroup genetic distance, the isolate 007N full-length genome is unique compared to other reported D/E recombinants in Africa.
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Affiliation(s)
- Ceejay L Boyce
- Division of Digestive Disease, University of Cincinnati College of Medicine, Cincinnati, OH, USA
| | - Lilia Ganova-Raeva
- Division of Viral Hepatitis, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA, USA
| | - Timothy N A Archampong
- Department of Medicine and Therapeutics, School of Medicine and Dentistry, College of Health Sciences, University of Ghana, Accra, Ghana
- Korle-Bu Teaching Hospital, Accra, Ghana
| | - Margaret Lartey
- Department of Medicine and Therapeutics, School of Medicine and Dentistry, College of Health Sciences, University of Ghana, Accra, Ghana
- Korle-Bu Teaching Hospital, Accra, Ghana
| | - Kwamena W Sagoe
- Department of Medical Microbiology, School of Biomedical and Allied Health Sciences, College of Health Sciences, University of Ghana, Accra, Ghana
| | - Adjoa Obo-Akwa
- Department of Medicine and Therapeutics, School of Medicine and Dentistry, College of Health Sciences, University of Ghana, Accra, Ghana
| | - Ernest Kenu
- Korle-Bu Teaching Hospital, Accra, Ghana
- School of Public Health, College of Health Sciences, University of Ghana, Accra, Ghana
| | - Awewura Kwara
- Warren Alpert Medical School of Brown University, Providence, RI, USA
- The Miriam Hospital, Providence, RI, USA
- Division of Infectious Diseases and Global Medicine, University of Florida, Gainesville, FL, USA
| | - Jason T Blackard
- Division of Digestive Disease, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
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Li X, Liu Y, Xin S, Ji D, You S, Hu J, Zhao J, Wu J, Liao H, Zhang XX, Xu D. Comparison of Detection Rate and Mutational Pattern of Drug-Resistant Mutations Between a Large Cohort of Genotype B and Genotype C Hepatitis B Virus-Infected Patients in North China. Microb Drug Resist 2017; 23:516-522. [PMID: 27792585 DOI: 10.1089/mdr.2016.0093] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
The study aimed to investigate the association of prevalent genotypes in China (HBV/C and HBV/B) with HBV drug-resistant mutations. A total of 13,847 nucleos(t)ide analogue (NA)-treated patients with chronic HBV infection from North China were enrolled. HBV genotypes and resistant mutations were determined by direct sequencing and confirmed by clonal sequencing if necessary. HBV/B, HBV/C, and HBV/D occupied 14.3%, 84.9%, and 0.8% across the study population, respectively. NA usage had no significant difference between HBV/B- and HBV/C-infected patients. Lamivudine-resistant mutations were more frequently detected in HBV/C-infected patients, compared with HBV/B-infected patients (31.67% vs. 25.26%, p < 0.01). Adefovir- and entecavir-resistant mutation detection rates were similar, but the mutational pattern was different between the two genotypes. For adefovir-resistant mutations, HBV/C-infected patients had a higher detection rate of rtA181 V (HBV/C 5.29% vs. HBV/B 1.36%, p < 0.01) and a lower detection rate of rtN236T (2.70% vs. 6.54%, p < 0.01). For entecavir-resistant mutations, HBV/C-infected patients had a higher detection rate of rtM204 V/I+T184 substitution or S202G/C (3.66% vs. 2.16%, p < 0.01) and a lower detection rate of rtM204 V/I+M250 V/I/L substitution (0.67% vs. 1.46%, p < 0.01). Multidrug-resistant mutations (defined as coexistence of mutation to nucleoside and nucleotide analogues) were detected in 104 patients. HBV/C-infected patients had a higher detection rate of multidrug-resistant mutation than HBV/B-infected patients (0.83% vs. 0.35%, p < 0.05). The study for the first time clarified that HBV/C-infected patients had a higher risk to develop multidrug-resistant mutations, compared with HBV/B-infected patients; and HBV/C- and HBV/B-infected patients had different inclinations in the ETV-resistant mutational pattern.
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Affiliation(s)
- Xiaodong Li
- 1 Research Center for Clinical and Translational Medicine , Beijing 302 Hospital, Beijing, China
| | - Yan Liu
- 1 Research Center for Clinical and Translational Medicine , Beijing 302 Hospital, Beijing, China
| | - Shaojie Xin
- 2 Medical Center for Liver Failure , Beijing 302 Hospital, Beijing, China
| | - Dong Ji
- 2 Medical Center for Liver Failure , Beijing 302 Hospital, Beijing, China
| | - Shaoli You
- 2 Medical Center for Liver Failure , Beijing 302 Hospital, Beijing, China
| | - Jinhua Hu
- 2 Medical Center for Liver Failure , Beijing 302 Hospital, Beijing, China
| | - Jun Zhao
- 2 Medical Center for Liver Failure , Beijing 302 Hospital, Beijing, China
| | - Jingjing Wu
- 1 Research Center for Clinical and Translational Medicine , Beijing 302 Hospital, Beijing, China
| | - Hao Liao
- 1 Research Center for Clinical and Translational Medicine , Beijing 302 Hospital, Beijing, China
| | - Xin-Xin Zhang
- 3 Department of Infectious Diseases, Rui Jin Hospital, Shanghai Jiao Tong University , Shanghai, China
| | - Dongping Xu
- 1 Research Center for Clinical and Translational Medicine , Beijing 302 Hospital, Beijing, China
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Early childhood transmission of hepatitis B prior to the first hepatitis B vaccine dose is rare among babies born to HIV-infected and non-HIV infected mothers in Gulu, Uganda. Vaccine 2017; 35:2937-2942. [PMID: 28434689 DOI: 10.1016/j.vaccine.2017.04.020] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2016] [Revised: 03/25/2017] [Accepted: 04/10/2017] [Indexed: 12/19/2022]
Abstract
BACKGROUND Hepatitis B (HBV) in sub-Saharan Africa is believed to be horizontally acquired. However, because of the high HBV prevalence in northern Uganda, no hepatitis B vaccination at birth and no access to HBV immunoglobulin, we hypothesize that vertical transmission also could also play an important role. We therefore investigated the incidence of HBV among babies presenting for their first HBV vaccine dose in Gulu, Uganda. METHODS We recruited mothers and their babies (at least 6-week old) presenting for their postnatal care and first HBV vaccine dose respectively. Socio-demographic and risk factors for HBV transmission were recorded. Mothers were tested for Hepatitis B core antibody (anti-HBc-IgG) and hepatitis B surface antigen (HBsAg). HBsAg-positive sera were tested for hepatitis B e antigen (HBeAg) and HBV viral load (HBVDNA). Babies were tested for HBsAg at presentation and at the last immunization visit. A sample of HBsAg-negative babies were tested for HBVDNA. Incident HBV infection was defined by either a positive HBsAg or HBVDNA test. Chi-square or fisher's exact tests were utilized to investigate associations and t-tests or Wilcoxon rank-sum test for continuous differences. RESULTS We recruited 612 mothers, median age 23years (IQR 20-28). 53 (8.7%) were HBsAg-positive and 339 (61.5%) were anti-HBc-IgG-positive. Ten (18.9%) of the HBsAg-positive mothers were HBeAg-positive. Median HBVDNA levels of HBV-infected mothers was 5.7log (IQR 4.6-7.0) IU/mL with 9 (17.6%) having levels≥105IU/mL. Eighty (13.3%) mothers were HIV-infected of whom 9 (11.5%) were co-infected with HBV. No baby tested HBsAg or HBVDNA positive. CONCLUSION Vertical transmission does not seem to contribute substantially to the high HBV endemicity in northern Uganda. The current practice of administering the first HBV vaccine to babies in Uganda at six weeks of age may be adequate in control of HBV transmission.
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Yanag Y, Du D, Jin L, Tian Z, Li Q, Yi R, Qiu T, Yang D, He Y, Liu J, Chen T, Zhao Y. A molecular epidemiology study investigating familial clustering of hepatitis B virus infection in families with unfavorable prognoses in Northwest China. J Med Virol 2017; 89:1427-1434. [PMID: 28198546 DOI: 10.1002/jmv.24783] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2016] [Revised: 01/20/2017] [Accepted: 01/26/2017] [Indexed: 12/23/2022]
Abstract
Hepatitis B virus (HBV) infections and adverse outcome have been demonstrated to show characteristics of familial clustering. The aim of this study was to investigate the prevalence of different HBV genotypes, HBV sub-genotypes, and Pre-S mutations associated with familial HBV infection clusters with unfavorable prognoses. Families presenting with clustered HBV infections and unfavorable prognoses were enrolled in this study. Non-clustered HBV-infected individuals were used as the control group. DNA extracted from patient serum samples was used to facilitate characterization of the HBV genotypes, HBV sub-genotypes, and Pre-S mutations by phylogenetic analysis. The Pre-S/S gene was successfully amplified in 83 patients from the clustering group and 105 patients from the sporadic group. The prevalence of genotype C in the clustering group (71/83, 85.54%) was significantly higher than in the sporadic group (77/105, 73.33%) (P = 0.042). The prevalence of sub-genotype C2 in the clustering group (33/83, 39.76%) was also higher than in the sporadic group (21/105, 20%) (P = 0.003). Analyses of functional mapping of pre-S sequences showed that the prevalence of the mutation in the S promoter site (nt 3045-3189 of pre-S1 domain) was significantly increased in the clustering group compared with the sporadic group (15.7% vs. 3.8%) (P = 0.009). This study suggests that genotype C, especially sub-genotype C2, may be associated with the progression of HBV infection in familial clustering infection cohorts with unfavorable prognoses. We also observed that the natural occurrence of S promoter mutations in the clustering group was significantly prevalent.
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Affiliation(s)
- Yuan Yanag
- Department of Infectious Disease, The First Affiliated Hospital, Xi'an Jiao Tong University, Xi'an, Shaanxi, China
| | - Dan Du
- Department of Infectious Disease, The First Affiliated Hospital, Xi'an Jiao Tong University, Xi'an, Shaanxi, China
| | - Li Jin
- Department of Infectious Disease, The First Affiliated Hospital, Xi'an Jiao Tong University, Xi'an, Shaanxi, China
| | - Zhen Tian
- Department of Infectious Disease, The First Affiliated Hospital, Xi'an Jiao Tong University, Xi'an, Shaanxi, China
| | - Qian Li
- Xian Center for Disease Control and Prevention, Xi'an, Shaanxi, China
| | - Ruitian Yi
- Department of Infectious Disease, The First Affiliated Hospital, Xi'an Jiao Tong University, Xi'an, Shaanxi, China
| | - Ting Qiu
- Department of Gastroenterology, Shaanxi People's Hospital, Xi'an, Shaanxi, China
| | - Daokun Yang
- Department of Infectious Disease, Xinxiang Medical University, Xinxiang, Henan, China
| | - Yingli He
- Department of Infectious Disease, The First Affiliated Hospital, Xi'an Jiao Tong University, Xi'an, Shaanxi, China
| | - Jinfeng Liu
- Department of Infectious Disease, The First Affiliated Hospital, Xi'an Jiao Tong University, Xi'an, Shaanxi, China
| | - Tianyan Chen
- Department of Infectious Disease, The First Affiliated Hospital, Xi'an Jiao Tong University, Xi'an, Shaanxi, China
| | - Yingren Zhao
- Department of Infectious Disease, The First Affiliated Hospital, Xi'an Jiao Tong University, Xi'an, Shaanxi, China
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Dongdem AZ, Dzodzomenyo M, Asmah RH, Nyarko KM, Nortey P, Agyei A, Adjei DN, Kenu E, Adjei AA. Hepatitis B virus genotypes among chronic hepatitis B patients reporting at Korle-Bu teaching hospital, Accra, Ghana. Pan Afr Med J 2016; 25:5. [PMID: 28210373 PMCID: PMC5292115 DOI: 10.11604/pamj.supp.2016.25.1.6170] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2015] [Accepted: 05/29/2015] [Indexed: 12/17/2022] Open
Abstract
Introduction Knowledge of hepatitis B virus (HBV) genotype is an important predictive variable which might have an impact in management and treatment of patients with chronic hepatitis B infection. In Ghana very little information is available on hepatitis B genotypes. This study was conducted to determine the distribution of HBV genotypes circulating among chronic hepatitis B patients reporting at the Korle-Bu Teaching Hospital (KBTH), Accra, Ghana. Methods Blood samples (10 ml) were collected from 250 consenting patients. DNA was extracted and amplified using polymerase chain reaction technique. Restriction fragment length polymorphism (RFLP) was used for the detection of genotypes. Results Out of the 250 chronic hepatitis B patients who were HBsAg positive, 91 (36.4%) were males aged 29.8 ± 9.1 and 159 (63.6%) females aged 33± 12.1 years. HBV DNA was detected in 111 (44.4%) but only 58 (52%) of these were typeable. These were classified as genotype A, 8 (7.2%); genotype D, 3 (2.7%) and genotype E, 47 (42.3%). Our results did not show any association between the infecting genotype and age (X2= 0.923; p-value=0.623) or gender (X2= 0.283, p= 0.579). Conclusion Consistent with similar studies worldwide, the results suggest that genotypes A, D and E were the genotypes circulating among chronic hepatitis B patients who reported to the Korle-Bu Teaching Hospital with genotype E being the most predominant and therefore constitutes an important public health concern. We recommend further epidemiological studies to understand the implication of genotype E in terms of disease progression and treatment.
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Affiliation(s)
- Anthony Zunuo Dongdem
- Ghana Field Epidemiology and Laboratory Training Program, School of Public Health, College of Health Sciences, University of Ghana, Legon, Ghana; Department of Epidemiology and Biostatistics, School of Public Health, University of Health and Allied Sciences, Ho, Volta Region, Ghana
| | - Mawuli Dzodzomenyo
- Department of Biological, Environmental and Occupational Health, School of Public Health, College of Health Sciences, University of Ghana, Legon, Ghana
| | - Richard Harry Asmah
- School of Biomedical and Allied Health Sciences, College of Health Sciences, Korle-Bu, Accra, Ghana
| | - Kofi Mensah Nyarko
- Ghana Field Epidemiology and Laboratory Training Program, School of Public Health, College of Health Sciences, University of Ghana, Legon, Ghana
| | - Priscillia Nortey
- Ghana Field Epidemiology and Laboratory Training Program, School of Public Health, College of Health Sciences, University of Ghana, Legon, Ghana
| | - Adwoa Agyei
- Department of Medicine, Korle-bu Teaching Hospital, Accra, Ghana
| | - David Nana Adjei
- School of Biomedical and Allied Health Sciences, College of Health Sciences, Korle-Bu, Accra, Ghana
| | - Ernest Kenu
- Ghana Field Epidemiology and Laboratory Training Program, School of Public Health, College of Health Sciences, University of Ghana, Legon, Ghana
| | - Andrew Anthony Adjei
- Department of Pathology, University of Ghana Medical School, College of Health Sciences, Korle-Bu, Accra, Ghana
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Abstract
Hepatitis B virus (HBV) infection is a major global health problems leading to severe liver disease such as cirrhosis and hepatocellular carcinoma (HCC). HBV is a circular, partly double-stranded DNA virus with various serological markers: hepatitis B surface antigen (HBsAg) and anti-HBs, anti-HBc IgM and IgG, and hepatitis B e antigen (HBeAg) and anti-HBe. It is transmitted by sexual, parenteral and vertical route. One significant method to diminish the burden of this disease is timely diagnosis of acute, chronic and occult cases of HBV. First step of HBV diagnosis is achieved by using serological markers for detecting antigens and antibodies. In order to verify first step of diagnosis, to quantify viral load and to identify genotypes, quantitative or qualitative molecular tests are used. In this article, the serological and molecular tests for diagnosis of HBV infection will be reviewed.
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Affiliation(s)
- Jeong Eun Song
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Do Young Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
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33
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Liao H, Li X, Liu Y, Xu Z, Huang P, Nian X, Liu X, Xu D. Intergenotype recombinant analysis of full-length hepatitis B virus genomes from 516 Chinese patients with different illness categories. J Med Virol 2016; 89:139-145. [PMID: 27328656 DOI: 10.1002/jmv.24609] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/20/2016] [Indexed: 01/05/2023]
Abstract
This study aimed to reveal characteristics and clinical relevance of HBV intergenotypic recombinants. Serum samples of 516 patients from Northern China were collected, including 131 with acute hepatitis B (AHB), 239 with chronic hepatitis B (CHB), and 146 with acute-on-chronic liver failure (ACLF). Full-length HBV genomes were sequenced and HBV genotypes were analyzed. Genotypes C, B, D, and intergenotypic recombinants were detected in 71.12% (367/516), 19.96% (103/516), 0.78% (4/516), and 8.14% (42/516) of the patients. The latter comprised 21 with AHB, 10 with CHB, and 11 with ACLF; and the occupations of intergenotypic recombinants in AHB, CHB, and ACLF groups were 16.03%, 4.18%, and 7.53% (P < 0.01), respectively. HBV B/C and C/D hybrids accounted for 85.71% (36/42) and 14.29% (6/42) of the intergenotypic recombinants. In AHB and CHB groups, serum HBV DNA levels were significantly lower in patients with intergenotypic recombinants than those without intergenotypic recombinants. Difference in basal core promoter A1762T/G1764A mutations and precore G1896A mutation incidences was not significant between B/C recombinant and genotypes B or C virus, although the significance was there between genotypes B and C viruses. Clonal sequence analysis showed that intergenotypic recombinant viral strains existed in single or in concomitance with other genotype virus. Phenotypic analysis showed that viral replication capacity was similar between recombinant and non-recombinant strains in tested samples. Taken together, the occurrence of intergenotypic recombinant HBV is relatively low in HBV-infected patients in Northern China, and intergenotypic recombinant HBV infection is likely favorable to induce an acute course of disease. J. Med. Virol. 89:139-145, 2017. © 2016 Wiley Periodicals, Inc.
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Affiliation(s)
- Hao Liao
- Research Center for Clinical and Translational Medicine, Beijing 302 Hospital, Beijing, China
| | - Xiaodong Li
- Research Center for Clinical and Translational Medicine, Beijing 302 Hospital, Beijing, China
| | - Yan Liu
- Research Center for Clinical and Translational Medicine, Beijing 302 Hospital, Beijing, China
| | - Zhihui Xu
- Research Center for Clinical and Translational Medicine, Beijing 302 Hospital, Beijing, China
| | - Pengyu Huang
- Institute of Biochemistry and Molecular Biology, Guangdong Medical College, Guangdong, China
| | - Xueyuan Nian
- Research Center for Clinical and Translational Medicine, Beijing 302 Hospital, Beijing, China
| | - Xinguang Liu
- Institute of Biochemistry and Molecular Biology, Guangdong Medical College, Guangdong, China. .,Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Guangdong, China.
| | - Dongping Xu
- Research Center for Clinical and Translational Medicine, Beijing 302 Hospital, Beijing, China. .,Institute of Biochemistry and Molecular Biology, Guangdong Medical College, Guangdong, China.
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34
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Hepatitis B virus genotypes: epidemiological and clinical relevance in Asia. Hepatol Int 2016; 10:854-860. [PMID: 27300749 DOI: 10.1007/s12072-016-9745-2] [Citation(s) in RCA: 47] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/15/2016] [Accepted: 05/27/2016] [Indexed: 02/08/2023]
Abstract
Hepatitis B virus (HBV) is characterized by a high genetic heterogeneity since it replicates via a reverse transcriptase that lacks proofreading ability. Up to now, ten genotypes (A-J) have been described, with genotype A and D being ubiquitous but most prevalent in Europe and Africa, genotype B and C being confined to Asia and Oceania. Infections with other genotypes such as E, F, G and H are also occasionally observed in Asia. Genotype I is rare and can be found in Laos, Vietnam, India and China, whereas genotype J has been described in Japan and Ryukyu. Novel variants generated by recombination and co-infection with other genotypes have gradually gotten worldwide attention and may be correlated with certain clinical features. There are substantial differences in HBV infection regarding prevalence, clinical manifestation, disease progression and response to antiviral therapy. Due to the complex interplay among viral, host and environmental factors, the relationship between HBV genotypes and clinical profiles remains incompletely revealed. In general, genotype A is associated with better response to interferon therapy; genotype C, and to lesser extent B, usually represent a risk factor for perinatal infection and are associated with advanced liver diseases such as cirrhosis and hepatocellular carcinoma; genotype D may be linked with poor response to interferon therapy. Future studies with better design and larger sample size are warranted to further clarify the controversial issues and guide the day-to-day clinical practice.
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35
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Gededzha MP, Muzeze M, Burnett RJ, Amponsah-Dacosta E, Mphahlele MJ, Selabe SG. Complete genome analysis of hepatitis B virus in human immunodeficiency virus infected and uninfected South Africans. J Med Virol 2016; 88:1560-6. [PMID: 26890489 DOI: 10.1002/jmv.24502] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/14/2016] [Indexed: 12/21/2022]
Abstract
Hepatitis B virus (HBV) and human immunodeficiency virus (HIV) infections are highly endemic in South Africa. Data on the complete genome sequences of HBV in HIV-positive patients in South Africa are scanty. This study characterized the complete HBV genome isolated from both HIV-positive and negative patients at the Dr George Mukhari Academic Hospital (DGMAH), Pretoria. Serum samples from nine (five HIV-positive and four HIV-negative) patients attending the DGMAH from 2007 to 2011 were serologically tested, amplified, and sequenced for complete genome. Phylogenetic tree was constructed using MEGA6.0. Mutations were analyzed by comparing the sequences with genotype-matched GenBank references. Eight patients were HBsAg positive, with only one from the HIV positive group being negative. Phylogenetic analysis of the complete genome sequences classified them into five genotypes; A1 (n = 4), A2 (n = 1), C1 (n = 2), D1 (n = 1), and D3 (n = 1). Deletions up to 35 nucleotides in length were identified in this study. No drug resistance mutations were identified in the P ORF, while the L217R mutation was identified in one subgenotype A2 sequence. The double (A1762T/G1764A) and triple (T1753C/A1762T/G1764A) mutations in the Basal core promoter were identified in four and two sequences, respectively. In the core region, mutation G1888A was identified in four of the subgenotype A1 sequences. In conclusion, this study has added to the limited South African data on HBV genotypes and mutations in HBV/HIV co-infected and HBV mono-infected patients, based on complete HBV genome analysis. Subgenotype A1 was predominant, and no drug-resistant mutants were detected in the study. J. Med. Virol. 88:1560-1566, 2016. © 2016 Wiley Periodicals, Inc.
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Affiliation(s)
- Maemu P Gededzha
- Department of Virology, HIV and Hepatitis Research Unit, Sefako Makgatho Health Sciences University and National Health Laboratory Service, Pretoria, South Africa
| | - Muxe Muzeze
- Department of Virology, HIV and Hepatitis Research Unit, Sefako Makgatho Health Sciences University and National Health Laboratory Service, Pretoria, South Africa
| | - Rosemary J Burnett
- Department of Virology, HIV and Hepatitis Research Unit, Sefako Makgatho Health Sciences University and National Health Laboratory Service, Pretoria, South Africa
| | - Edina Amponsah-Dacosta
- Department of Virology, HIV and Hepatitis Research Unit, Sefako Makgatho Health Sciences University and National Health Laboratory Service, Pretoria, South Africa
| | | | - Selokela G Selabe
- Department of Virology, HIV and Hepatitis Research Unit, Sefako Makgatho Health Sciences University and National Health Laboratory Service, Pretoria, South Africa
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Rahman MA, Hakim F, Ahmed M, Ahsan CR, Nessa J, Yasmin M. Prevalence of genotypes and subtypes of hepatitis B viruses in Bangladeshi population. SPRINGERPLUS 2016; 5:278. [PMID: 27006886 PMCID: PMC4779089 DOI: 10.1186/s40064-016-1840-2] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/14/2015] [Accepted: 02/15/2016] [Indexed: 12/18/2022]
Abstract
The genetic variability of hepatitis B virus (HBV) represents a challenge for the sensitivity of immunologic and molecular based assays. Based on sequence divergences in the entire genome of >8 %, HBV genomes have been classified into ten genotypes designated as A to J. The aim of this study was to determine HBV genotypes and subtype in samples of HBV infected patients in Bangladesh. The sera samples were collected from chronically infected HBV patients. At first the DNA positive HBV samples were screened by EIA in our laboratory and the 1063 bp region of surface gene was amplified, sequenced and genotyped by sequence analysis. The same sequences were also used for subtypes and mutational analyses. After that, genotyping was also carried out by nested PCR using genotype specific primers in the same region of HBV surface gene. A total of 39 samples were sequencing to find out the genotypes and subtypes. It was found that the prevalent genotype was genotype C (subgenotype C1) which accounted for 48.7 %. The other genotypes found were genotype A (23.1 %) and genotype D (28.2 %). Predominant subtypes in Bangladesh were adr (41 %) followed by subtype adw2 (28.2 %), ayw3 (25.6 %), and others. Additionally, genotyping was also done by nested PCR using type-specific primers. In this method, out of 17 samples 6 were found to be genotype C, followed by genotype D (4 of 17) and genotype A (3 of 17). In PCR-based genotyping system we also observed the mix genotypes; 3 samples contained both genotype A and D, and 2 samples contained both C and D. The genetic diversity of HBV and distribution of its genotypes and subtypes amongst Bangladeshi population were done in this study, which will help us to provide information regarding circulating genotypes in this region and also help physicians to prescribe proper antiviral/interferon therapy.
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Affiliation(s)
- Md Arifur Rahman
- Department of Microbiology, University of Dhaka, Dhaka, 1000 Bangladesh ; Department of Microbiology, Noakhali Science and Technology University, Sonapur, Noakhali, 3814 Bangladesh
| | - Farzana Hakim
- Department of Microbiology, University of Dhaka, Dhaka, 1000 Bangladesh
| | - Mamun Ahmed
- Department of Biochemistry and Molecular Biology, University of Dhaka, Dhaka, Bangladesh
| | | | - Jamalun Nessa
- Department of Microbiology, University of Dhaka, Dhaka, 1000 Bangladesh
| | - Mahmuda Yasmin
- Department of Microbiology, University of Dhaka, Dhaka, 1000 Bangladesh
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Esmail MA, Mahdi WKM, Khairy RM, Abdalla NH. Genotyping of occult hepatitis B virus infection in Egyptian hemodialysis patients without hepatitis C virus infection. J Infect Public Health 2016; 9:452-7. [PMID: 26778093 DOI: 10.1016/j.jiph.2015.11.018] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2015] [Revised: 10/21/2015] [Accepted: 11/10/2015] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND Occult hepatitis B viral infection is the presence of hepatitis B viral nucleic acids in the serum and/or liver in the absence of hepatitis B surface antigen. AIM The study aimed to determine the prevalence of occult hepatitis B virus infection among hepatitis C virus-negative hemodialysis patients and to identify their genotypes. METHODS of 144 patients on maintenance hemodialysis, 50 hepatitis B surface antigen and hepatitis C virus nucleic acid-negative patients were selected according to strict inclusion criteria to avoid the effect of confounding variables. The following investigations were done: serum AST and ALT; HBsAg; HBcAb; HCV-Ab; HCV-RNA; and HBV-DNA. RESULTS Positive hepatitis B viral nucleic acid was confirmed in 12/144 (8.3%) hemodialysis patients and 12/50 (24%) in our study group (occult infection). Mean hemodialysis periods for negative patients and occult hepatitis B virus patients were 27.3±18.8 and 38.4±8.14 months, respectively, and this difference was significant (p-value=0.02). Mean alanine transaminase levels were 20.27±5.5IU/L and 25.3±9.6 in negative patients and occult infection patients, respectively. This difference was non-significant. Aspartate transaminase levels were 21.4±10.2IU/L and 27.3±4.6IU/L, respectively, in negative patients and infected patients; this difference was significant (p-value=0.03). Half (6/12) of the positive samples belonged to genotype 'B', 33.3% (4/12) to 'C', and 16.6% (2/12) to genotype 'D'. CONCLUSION OBI is likely among hemodialysis patients even without HCV coinfection (24%). Genotype D cannot be the only genotype distributed in Upper Egypt, as the current study reported relatively new results that 50% of the patients with occult B carry genotype B, 33.3% carry genotype C and only 16.6% carry genotype D.
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Affiliation(s)
- Mona A Esmail
- Microbiology and Immunology Department, Faculty of Medicine, Minia University, El Minia 61519, Egypt.
| | - Wafaa K M Mahdi
- Microbiology and Immunology Department, Faculty of Medicine, Minia University, El Minia 61519, Egypt
| | - Rasha M Khairy
- Microbiology and Immunology Department, Faculty of Medicine, Minia University, El Minia 61519, Egypt.
| | - Nilly H Abdalla
- Internal Medicine Department, Faculty of Medicine, Beni Suif University, Egypt.
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Martin P, Lau DTY, Nguyen MH, Janssen HLA, Dieterich DT, Peters MG, Jacobson IM. A Treatment Algorithm for the Management of Chronic Hepatitis B Virus Infection in the United States: 2015 Update. Clin Gastroenterol Hepatol 2015; 13:2071-87.e16. [PMID: 26188135 DOI: 10.1016/j.cgh.2015.07.007] [Citation(s) in RCA: 83] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2015] [Revised: 07/01/2015] [Accepted: 07/09/2015] [Indexed: 02/07/2023]
Abstract
Chronic hepatitis B (CHB) continues to be an important public health problem worldwide, including in the United States. An algorithm for managing CHB was developed by a panel of United States hepatologists in 2004 and subsequently updated in 2006 and 2008. Since 2008, additional data on long-term safety and efficacy of licensed therapies have become available and have better defined therapeutic options for CHB. The evidence indicates that potent antiviral therapy can lead to regression of extensive fibrosis or even cirrhosis, thus potentially altering the natural history of CHB. In addition, appropriate choice of antiviral agent can minimize the risk of resistance. This updated algorithm for managing CHB is based primarily on evidence from the scientific literature. Where data were lacking, the panel relied on clinical experience and consensus expert opinion. The primary aim of antiviral therapy for CHB is durable suppression of serum hepatitis B virus (HBV) DNA to low or undetectable levels. CHB patients who have HBV DNA >2000 IU/mL, elevated alanine aminotransferase level, and any degree of fibrosis should receive antiviral therapy regardless of their hepatitis B e antigen status. CHB patients with HBV DNA >2000 IU/mL and elevated alanine aminotransferase level but no evidence of fibrosis may also be considered for antiviral therapy. Approved antiviral therapies for CHB are interferon alfa-2b, peginterferon alfa-2a, lamivudine, adefovir, entecavir, telbivudine, and tenofovir, although the preferred first-line treatment choices are peginterferon alfa-2a, entecavir, and tenofovir. In determining choice of therapy, considerations include efficacy, safety, rate of resistance, method of administration, duration, and cost.
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Affiliation(s)
- Paul Martin
- Division of Hepatology, University of Miami School of Medicine, Miami, Florida.
| | - Daryl T-Y Lau
- Liver Center, Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
| | - Mindie H Nguyen
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Stanford, California
| | - Harry L A Janssen
- Toronto Centre for Liver Diseases, University Health Network, Toronto, Canada
| | | | - Marion G Peters
- Division of Gastroenterology, University of California, San Francisco, San Francisco, California
| | - Ira M Jacobson
- Department of Medicine, Mount Sinai Beth Israel, Icahn School of Medicine at Mount Sinai, New York, New York
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Molecular characterisation of hepatitis B virus in HIV-1 subtype C infected patients in Botswana. BMC Infect Dis 2015; 15:335. [PMID: 26268355 PMCID: PMC4535680 DOI: 10.1186/s12879-015-1096-4] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2015] [Accepted: 08/06/2015] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Hepatitis B virus (HBV) is a major global health problem especially in sub-Saharan Africa and in East Asia. Ten hepatitis B virus genotypes have been described that differ by geographic distribution, disease progression, and response to treatment. Escape mutations within the surface open reading frame (ORF) affect HBV antigenicity leading to failures in diagnosis, vaccine and hepatitis B immunoglobulin therapy. However, the molecular characteristics of HBV in Botswana, a highly endemic country, are unknown. We describe the molecular characteristics of HBV and prevalence of escape mutants among HIV/HBV coinfected individuals Botswana. METHODS DNA was extracted from archived plasma samples from 81 HIV/HBV co-infected participants from various clinical studies at the Botswana Harvard AIDS Institute Partnership. A 415 base pair (bp) fragment of the polymerase gene was amplified by semi-nested PCR. In a subset of samples, a 2100 bp fragment was amplified. The PCR product was genotyped using Big Dye sequencing chemistry and the sequences were analysed for genotypes and mutations. RESULTS Of the 81 samples included, 70 (86 %) samples were successfully genotyped. Genotype A was found in 56 (80 %) participants, D in 13 (18.6 %), and 1 (1.4 %) was genotype E. Escape mutations previously linked with failure of diagnosis or escaping active vaccination and passive immunoglobulin therapy were detected in 12 (17.1 %) participants at positions 100, 119, 122, 123, 124, 126, 129, 130, 133, 134 and 140 of the S ORF. Genotypes and escape mutations were not significantly associated with aspartate aminotransferase (AST), alanine aminotransferase (ALT) and AST platelet ratio index (APRI). CONCLUSION Genotypes A, D and E were found in this cohort of HIV coinfected patients in Botswana, consistent with the findings from the sub-Saharan Africa region. Some escape mutations which have previously been associated with diagnosis failure, escaping vaccine and immunoglobulin therapy were also observed and are important in guiding future policies related to vaccine implementation, therapeutic guidelines, and diagnostic guidelines. They are also important for identifying patients who are at an increased risk of disease progression and to choose optimal therapy. Future research should focus on determining the clinical significance of the different HBV genotypes and mutations found in this population.
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Brinck-Jensen NS, Erichsen P, Tarp B, Lindberg J, Kristensen LH, Erlandsen M, Petersen E, Leutscher PDC. Clinical findings in a multi-ethnic adult hepatitis B virus patient population in Denmark with emphasis on genotypic characteristics. Scand J Gastroenterol 2015; 50:1032-8. [PMID: 25861877 DOI: 10.3109/00365521.2014.974202] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVE Most knowledge about chronic hepatitis B virus (HBV) infection is based upon studies in high-endemic areas with one or two predominant genotype(s). The aim of the study was to describe clinical characteristics of a heterogeneous genotypic HBV patient population in a low-endemic European country. METHODS Data from HBV patients currently followed in a Danish university hospital and affiliated regional clinics were reviewed in accordance to genotype status. RESULTS Of 540 HBV patients, 462 (86%) were of non-Danish ethnicity originating from 43 different countries. HBV genotype was known in 37% of the patients: A (11%), B (25%), C (25%), D (37%) and E (2%). Logistic regression analysis of pre-treatment data among genotype A-D patients receiving nucleos(t)ide analogue (NA) therapy revealed a decreased HBeAg rate by age (OR = 0.93; CI: 0.89-0.97; p < 0.01) and an increased rate in genotype C patients (OR = 20.5; CI: 3.3-129; p < 0.01). Among untreated patients HBeAg rate was also significantly decreased by age (OR = 0.90 (0.85:0.95; p < 0.0001), whereas the rate was increased in both genotype B and C patients (OR = 7.5; CI: 1.8-30.5; p < 0.01 and OR = 12.2; CI: 3.2-46.6; p < 0.001, respectively). No significant variation was found in HBV DNA level in any of the two groups when adjusting for age, gender, genotype and HBeAg. Increased liver pathology prevalence was, irrespectively of treatment status, associated to age and male gender, but not to any genotype. CONCLUSION In this study population, genotype B and C was found associated with higher HBeAg rate but not with increased liver pathology.
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Pollack HJ, Kwon SC, Wang SH, Wyatt LC, Trinh-Shevrin C. Chronic hepatitis B and liver cancer risks among Asian immigrants in New York City: Results from a large, community-based screening, evaluation, and treatment program. Cancer Epidemiol Biomarkers Prev 2015; 23:2229-39. [PMID: 25368398 DOI: 10.1158/1055-9965.epi-14-0491] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND Hepatitis B virus (HBV) infection, the predominant cause of hepatocellular carcinoma (HCC) worldwide, disproportionately affects Asian Americans. Limited data exist on the variability and characteristics of infection that determine disease progression risk within U.S. Asian ethnic subgroups. METHODS Retrospective analyses were conducted on a large, community-based HBV screening and treatment program in New York City (NYC). From 2004 to 2008, the program enrolled 7,272 Asian-born individuals. Determinants of HBV seroprevalence were calculated and risk factors for HCC progression were compared across Asian subgroups. RESULTS Among newly tested individuals, 13% were HBV positive. Seroprevalence varied significantly with age, gender, education, birthplace, and family history of infection. Chinese-born individuals, particularly from the Fujian province, had the highest seroprevalence (23.2% and 33.1%, respectively). Clinical and virologic characteristics placed HBV-infected individuals at significant risk for HCC. Significant differences in HCC risk existed among Asian subgroups in bivariate analysis, including age, gender, HBV viral load, and HBeAg status. Differences in HBV genotype and family history of HCC may further HCC risk among subgroups. CONCLUSIONS Asian immigrants in NYC have a high prevalence of HBV infection and are at significant risk of disease progression and HCC. Although heterogeneity in HBV seroprevalence was found by Asian subgroups, HCC risk among infected individuals was primarily explained by age and gender differences. Country and province of birth, age, and gender may further explain seroprevalence differences. IMPACT Findings provide estimates of HBV burden in Asian ethnic subgroups and identify high-risk groups to target for screening and treatment that can prevent HCC.
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Affiliation(s)
- Henry J Pollack
- Department of Pediatrics, New York University School of Medicine, New York, New York.
| | - Simona C Kwon
- Department of Population Health, New York University School of Medicine, New York, New York
| | - Su H Wang
- Saint Barnabas Medical Center, Center for Asian Health, Livingston, New Jersey. Formerly at Charles B. Wang Community Health Center, New York, New York
| | - Laura C Wyatt
- Department of Population Health, New York University School of Medicine, New York, New York
| | - Chau Trinh-Shevrin
- Department of Population Health, New York University School of Medicine, New York, New York
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Mina T, Amini-Bavil-Olyaee S, Tacke F, Maes P, Van Ranst M, Pourkarim MR. Genomic Diversity of Hepatitis B Virus Infection Associated With Fulminant Hepatitis B Development. HEPATITIS MONTHLY 2015; 15:e29477. [PMID: 26288637 PMCID: PMC4533131 DOI: 10.5812/hepatmon.29477v2] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 04/23/2015] [Accepted: 05/25/2015] [Indexed: 12/11/2022]
Abstract
CONTEXT After five decades of Hepatitis B Virus (HBV) vaccine discovery, HBV is still a major public health problem. Due to the high genetic diversity of HBV and selective pressure of the host immune system, intra-host evolution of this virus in different clinical manifestations is a hot topic of research. HBV infection causes a range of clinical manifestations from acute to chronic infection, cirrhosis and hepatocellular carcinoma. Among all forms of HBV infection manifestations, fulminant hepatitis B infection possesses the highest fatality rate. Almost 1% of the acutely infected patients develop fulminant hepatitis B, in which the mortality rate is around 70%. EVIDENCE ACQUISITION All published papers deposited in Genbank, on the topic of fulminant hepatitis were reviewed and their virological aspects were investigated. In this review, we highlight the genomic diversity of HBV reported from patients with fulminant HBV infection. RESULTS The most commonly detected diversities affect regulatory motifs of HBV in the core and S region, indicating that these alterations may convert the virus to an aggressive strain. Moreover, mutations at T-cell and B-cell epitopes located in pre-S1 and pre-S2 proteins may lead to an immune evasion of the virus, likely favoring a more severe clinical course of infection. Furthermore, point and frame shift mutations in the core region increase the viral replication of HBV and help virus to evade from immune system and guarantee its persistence. CONCLUSIONS Fulminant hepatitis B is associated with distinct mutational patterns of HBV, underlining that genomic diversity of the virus is an important factor determining its pathogenicity.
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Affiliation(s)
- Thomas Mina
- Department of Microbiology and Immunology, Laboratory of Clinical and Epidemiological Virology, Rega Institute for Medical Research, KU Leuven, Leuven, Belgium
| | - Samad Amini-Bavil-Olyaee
- Department of Molecular Microbiology and Immunology, Harlyne J. Norris Cancer Research Tower, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
| | - Frank Tacke
- Department of Medicine III, RWTH-University Hospital Aachen, Aachen, Germany
| | - Piet Maes
- Department of Microbiology and Immunology, Laboratory of Clinical and Epidemiological Virology, Rega Institute for Medical Research, KU Leuven, Leuven, Belgium
| | - Marc Van Ranst
- Department of Microbiology and Immunology, Laboratory of Clinical and Epidemiological Virology, Rega Institute for Medical Research, KU Leuven, Leuven, Belgium
| | - Mahmoud Reza Pourkarim
- Department of Microbiology and Immunology, Laboratory of Clinical and Epidemiological Virology, Rega Institute for Medical Research, KU Leuven, Leuven, Belgium
- Blood Transfusion Research Centre, High Institute for Research and Education in Transfusion Medicine, Tehran, IR Iran
- Corresponding Author: Mahmoud Reza Pourkarim, Department of Microbiology and Immunology, Laboratory of Clinical and Epidemiological Virology, Rega Institute for Medical Research, KU Leuven, P. O. Box: BE-3000, Leuven, Belgium. Tel: +32-16332145, Fax: +32-16332141, E-mail:
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Lopez L, Flichman D, Mojsiejczuk L, Gonzalez MV, Uriarte R, Campos R, Cristina J, Garcia-Aguirre L. Genetic variability of hepatitis B virus in Uruguay: D/F, A/F genotype recombinants. Arch Virol 2015; 160:2209-17. [PMID: 26100402 DOI: 10.1007/s00705-015-2477-0] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2014] [Accepted: 05/29/2015] [Indexed: 12/22/2022]
Abstract
Hepatitis B virus (HBV) infection is a serious global health problem. Approximately 2 billion people worldwide have been infected, and approximately 350 million individuals currently suffer from HBV-induced chronic liver infection, which causes 600,000 deaths annually from chronic hepatitis, cirrhosis and hepatocellular carcinoma. HBV is classified in eight genotypes (A-H), and two more have been proposed (I-J). In this paper, complete genome sequences of nine Uruguayan HBV are reported. Five samples belong to genotype F1b and one to genotype A2. Three HBV recombinants were detected: A1/F1b, A2/F1b and D3/F1b. The following mutations were detected: a G1896A substitution, a 33-nucleotide deletion from position 2896 to 2928 in the Pre-S1 region involving Pre-S1 residues 3-13, a 33-nt deletion in the Pre-S1 region involving nt 2913-2945 and Pre-S1 residues 9-19. More F genotypes strains than expected were detected in this study, supporting the hypothesis that there are more people of indigenous origin than declared in our population. Also, one third of the samples analyzed were recombinants. This cannot be explained by the low HBV prevalence in Uruguay, but a high HBV infection rate in drug addicts and dialysis patients could act in favor of multiple-genotype HBV infections that could lead to recombination.
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Affiliation(s)
- L Lopez
- Laboratorio de Virología Molecular, Facultad de Ciencias, Centro de Investigaciones Nucleares, Udelar, Montevideo, Uruguay
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Zhang Q, Han T, Nie CY, Ha FS, Liu L, Liu H. Tenofovir rescue regimen following prior suboptimal response to entecavir and adefovir combination therapy in chronic hepatitis B patients exposed to multiple treatment failures. J Med Virol 2015; 87:1013-21. [PMID: 25716029 DOI: 10.1002/jmv.24153] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/07/2015] [Indexed: 12/16/2022]
Abstract
In clinical practice, establishing a subsequent optimum treatment for chronic hepatitis B patients with a history of multiple NAs treatment failures, including a suboptimal response to a final therapy with combined ETV and ADV, is a complicated but crucial challenge. This study investigated the efficacy and safety of a tenofovir rescue regimen in these patients. A total of six eligible patients were enrolled and were switched to a tenofovir rescue regimen. At baseline, the genotypes and genotypic mutations of the reverse transcriptase and surface gene were determined by ultra-deep pyrosequencing, and further clonal analyses of the reverse transcriptase domain were performed to identify multidrug-resistant HBV strains. In addition, HBV DNA levels, serology, and biochemistry parameters were monitored at baseline and every 3 months, and abdominal ultrasonography was performed at baseline and every 6 months. All patients were confirmed to harbor LAM-related resistant HBV strains. After switching to the tenofovir rescue treatment, all patients had an undetectable level of HBV DNA within 6 months and achieved normalization of the ALT level within 9 months. These virological and biochemical responses persisted until the end of the observation period. None of the patients developed clinical deterioration or any adverse events related to the tenofovir therapy during the median 16.5-month follow-up. In conclusion, the tenofovir rescue regimen can be employed confidently as a highly effective and safe treatment choice following a suboptimal response to ETV plus ADV therapy for a subset of chronic hepatitis B patients with a history of multiple unsuccessful antiviral treatments.
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Affiliation(s)
- Qian Zhang
- The Third Central Clinical College of Tianjin Medical University, Tianjin, China; Department of Hepatology, Tianjin Third Central Hospital, Tianjin, China
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Zhong C, Hou Z, Huang J, Xie Q, Zhong Y. Mutations and CpG islands among hepatitis B virus genotypes in Europe. BMC Bioinformatics 2015; 16:38. [PMID: 25652331 PMCID: PMC4339741 DOI: 10.1186/s12859-015-0481-8] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2014] [Accepted: 01/27/2015] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Hepatitis B virus (HBV) genotypes have a distinct geographical distribution and influence disease progression and treatment outcomes. The purpose of this study was to investigate the distribution of HBV genotypes in Europe, the impact of mutation of different genotypes on HBV gene abnormalities, the features of CpG islands in each genotype and their potential role in epigenetic regulation. RESULTS Of 383 HBV isolates from European patients, HBV genotypes A-G were identified, with the most frequent being genotype D (51.96%) in 12 countries, followed by A (39.16%) in 7 countries, and then E (3.66%), G (2.87%), B (1.57%), F (0.52%) and C (0.26%). A higher rate of mutant isolates were identified in those with genotype D (46.7%) followed by G (45.5%), and mutations were associated with structural and functional abnormalities of HBV genes. Conventional CpG island I was observed in genotypes A, B, C, D and E. Conventional islands II and III were detected in all A-G genotypes. A novel CpG island IV was found in genotypes A, D and E, and island V was only observed in genotype F. The A-G genotypes lacked the novel CpG island VI. "Split" CpG island I in genotypes D and E and "split" island II in genotypes A, D, E, F and G were observed. Two mutant isolates from genotype D and one from E were found to lack both CpG islands I and III. CONCLUSIONS HBV genotypes A-G were identified in European patients. Structural and functional abnormalities of HBV genes were caused by mutations leading to the association of genotypes D and G with increased severity of liver disease. The distribution, length and genetic traits of CpG islands were different between genotypes and their biological and clinical significances warrant further study, which will help us better understand the potential role of CpG islands in epigenetic regulation of the HBV genome.
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Affiliation(s)
- Chengyao Zhong
- Faculty of Science and Engineering, University Paul Sabatier, Toulouse, 31062, France.
| | - Zhiwei Hou
- Key Laboratory of Birth Defects and Reproductive Health of National Health and Family Planning Commission, Chongqing Research Institute for Population and Family Planning Science and Technology, Chongqing, 400020, China.
| | - Jihua Huang
- Jinxin Research Institute for Reproductive Medicine and Genetics, Chengdu Jinjiang Hospital for Maternal and Child Health Care, Chengdu, 610066, China.
| | - Qingdong Xie
- Research Center for Reproductive Medicine, Shantou University Medical College, Shantou, 515041, China.
| | - Ying Zhong
- Jinxin Research Institute for Reproductive Medicine and Genetics, Chengdu Jinjiang Hospital for Maternal and Child Health Care, Chengdu, 610066, China.
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Epidemiology of HBV subgenotypes D. Clin Res Hepatol Gastroenterol 2015; 39:28-37. [PMID: 25037178 DOI: 10.1016/j.clinre.2014.06.005] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2013] [Revised: 04/09/2014] [Accepted: 06/02/2014] [Indexed: 02/04/2023]
Abstract
The natural history of hepatitis B virus infection is not uniform and affected from several factors including, HBV genotype. Genotype D is a widely distributed genotype. Among genotype D, several subgenotypes differentiate epidemiologically and probably clinically. D1 is predominant in Middle East and North Africa, and characterized by early HBeAg seroconversion and low viral load. D2 is seen in Albania, Turkey, Brazil, western India, Lebanon, and Serbia. D3 was reported from Serbia, western India, and Indonesia. It is a predominant subgenotype in injection drug use-related acute HBV infections in Europe and Canada. D4 is relatively rare and reported from Haiti, Russia and Baltic region, Brazil, Kenya, Morocco and Rwanda. Subgenotype D5 seems to be common in Eastern India. D6 has been reported as a rare subgenotype from Indonesia, Kenya, Russia and Baltic region. D7 is the main genotype in Morocco and Tunisia. D8 and D9 are recently described subgenotypes and reported from Niger and India, respectively. Subgenotypes of genotype D may have clinical and/or viral differences. More subgenotype studies are required to conclude on subgenotype and its clinical/viral characteristics.
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Martínez AA, Zaldivar YY, De Castillo Z, Ortiz AY, Mendoza Y, Cristina J, Pascale JM. High diversity of hepatitis B virus genotypes in Panamanian blood donors: a molecular analysis of new variants. PLoS One 2014; 9:e103545. [PMID: 25093674 PMCID: PMC4122375 DOI: 10.1371/journal.pone.0103545] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2014] [Accepted: 06/29/2014] [Indexed: 02/08/2023] Open
Abstract
Hepatitis B Virus (HBV) is an infectious agent that causes more than half of the cases of liver disease and cancer in the world. Globally there are around 250 million people chronically infected with this virus. Despite 16% of the cases of liver disease in Central America are caused by HBV, the information regarding its genetic diversity, genotypes and circulation is scarce. The purpose of this study was to evaluate the genetic variability of the HBV genotypes from HBV-DNA positive samples obtained from screening blood donors at the Social Security System of Panama and to estimate its possible origin. From 59,696 blood donors tested for HBV infection during 2010-2012, there were 74 HBV-DNA positive subjects. Analysis of the partial PreS2-S region of 27 sequences shows that 21% of the infections were caused by genotype A, 3% by genotype D and 76% by genotype F. In addition, we were able to confirm circulation of six sub-genotypes A1, A2, A3, D4, F3, F1 and a proposed new sub-genotype denominated F5pan. We found a confinement of sub-genotypes F1 and F5pan to the western area of Panama. The tMRCA analysis suggests a simultaneous circulation of previously described sub-genotypes rather than recent introductions of the Panamanian sub-genotypes in the country. Moreover, these results highlight the need of more intensive research of the HBV strains circulating in the region at the molecular level. In conclusion, Panama has a high HBV genotype diversity that includes a new proposed sub-genotype, an elevated number of PreCore-Core mutations, and confinement of these variants in a specific geographical location.
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Affiliation(s)
- Alexander A. Martínez
- Gorgas Memorial Institute for Health Studies, Panama, Panama
- Department of Biotechnology, Acharya Nagarjuna University, Guntur, A.P. India
- INDICASAT-AIP Clayton, City of Knowledge, Panama
| | | | - CSS-NAT Group
- Complejo Hospitalario Dr. Arnulfo Arias Madrid, Caja de Seguro Social, Panama, Panama
| | - Zoila De Castillo
- Complejo Hospitalario Dr. Arnulfo Arias Madrid, Caja de Seguro Social, Panama, Panama
| | - Alma Y. Ortiz
- Gorgas Memorial Institute for Health Studies, Panama, Panama
| | - Yaxelis Mendoza
- Gorgas Memorial Institute for Health Studies, Panama, Panama
- Department of Biotechnology, Acharya Nagarjuna University, Guntur, A.P. India
- INDICASAT-AIP Clayton, City of Knowledge, Panama
| | - Juan Cristina
- Laboratorio de Virología Molecular, Centro de Investigaciones Nucleares, Facultad de Ciencias, Universidad de la República, Montevideo, Uruguay
| | - Juan M. Pascale
- Gorgas Memorial Institute for Health Studies, Panama, Panama
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Bessone F. Re-appraisal of old and new diagnostic tools in the current management of chronic hepatitis B. Liver Int 2014; 34:991-1000. [PMID: 25098191 DOI: 10.1111/liv.12499] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/26/2013] [Accepted: 02/05/2014] [Indexed: 12/11/2022]
Abstract
Hepatitis B virus (HBV) is a very complex and intricate DNA structure associated with a particular genomic organization and replication cycle. However, many years of investigations allowed clarification of the real HBV natural history, through a deeper knowledge of the behavior of HBV antigens and viral structures. Several of the old diagnostic tools, such as HBV surface antigen (HBsAg) and HBV e antigen (HBeAg) determinations, gained prominence now, since the variation of both HBsAg and HBeAg plasma levels was shown to predict treatment response. In addition, the availability of more sensitive methods, such as HBV DNA detection by real-time PCR, has improved the current knowledge of the relationships between HBV replication levels and the natural history of the disease. It is now well established that some HBV genotypes are associated with a better response to treatment with pegylated interferon. Despite the widely accepted value of liver biopsy as a staging tool, transient elastography is being increasingly acknowledged as a non-invasive method to assess liver stiffness, chiefly for detection of advanced fibrosis. Current international guidelines for the management of chronic hepatitis B have provided several accurate biochemical and serological criteria for selecting patients for treatment, allowing a higher number of cases to be enrolled into antiviral therapy. This review describes the different serological markers used for the study of HBV and their clinical significance. It also deals with methods used for detection of genotypes and HBV DNA, emphasizing the effectiveness of such determinations for both patient selection and chronic hepatitis B therapy/monitoring.
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Affiliation(s)
- Fernando Bessone
- Gastroenterology and Hepatology Department, School of Medicine, University of Rosario, Rosario, Santa Fe, Argentina
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Chen X, Chen X, Chen W, Ma X, Huang J, Chen R. Extended peginterferon alfa-2a (Pegasys) therapy in Chinese patients with HBeAg-negative chronic hepatitis B. J Med Virol 2014; 86:1705-13. [PMID: 24980710 DOI: 10.1002/jmv.24013] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/06/2014] [Indexed: 12/12/2022]
Affiliation(s)
- Xuefu Chen
- Department of Infection; Guangdong General Hospital; Guangdong Academy of Medical Sciences; Guangzhou China
| | - Xiaoping Chen
- Department of Infection; Guangdong General Hospital; Guangdong Academy of Medical Sciences; Guangzhou China
| | - Wenli Chen
- Department of Infection; Guangdong General Hospital; Guangdong Academy of Medical Sciences; Guangzhou China
| | - Xiaojun Ma
- Department of Infection; Guangdong General Hospital; Guangdong Academy of Medical Sciences; Guangzhou China
| | - Jing Huang
- Department of Infection; Guangdong General Hospital; Guangdong Academy of Medical Sciences; Guangzhou China
| | - Ren Chen
- Department of Infection; Guangdong General Hospital; Guangdong Academy of Medical Sciences; Guangzhou China
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Panebianco C, Saracino C, Pazienza V. Epithelial-mesenchymal transition: molecular pathways of hepatitis viruses-induced hepatocellular carcinoma progression. Tumour Biol 2014; 35:7307-15. [PMID: 24833096 DOI: 10.1007/s13277-014-2075-x] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2014] [Accepted: 05/07/2014] [Indexed: 12/18/2022] Open
Abstract
Hepatocellular carcinoma is the fifth most common tumor and the third cause of death for cancer in the world. Among the main causative agents of this tumor is the chronic infection by hepatitis viruses B and C, which establish a context of chronic inflammation degenerating in fibrosis, cirrhosis, and, finally, cancer. Recent findings, however, indicate that hepatitis viruses are not only responsible for cancer onset but also for its progression towards metastasis. Indeed, they are able to promote epithelial-mesenchymal transition, a process of cellular reprogramming underlying tumor spread. In this manuscript, we review the currently known molecular mechanisms by which hepatitis viruses induce epithelial-mesenchymal transition and, thus, hepatocellular carcinoma progression.
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Affiliation(s)
- Concetta Panebianco
- Gastroenterology Unit, Fondazione "Casa Sollievo della Sofferenza" IRCCS Hospital, San Giovanni Rotondo, FG, Italy
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