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1 / 1884

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[PMID]: 27771387 [Au] Autor: Alfaiate D; Lucifora J; Abeywickrama-Samarakoon N; Michelet M; Testoni B; Cortay JC; Sureau C; Zoulim F; Dény P; Durantel D [Ad] Endereço: INSERM U1052, CNRS UMR-5286, Cancer Research Center of Lyon (CRCL), 69008 Lyon, France; University of Lyon, Université Claude-Bernard (UCBL), 69008 Lyon, France. [Ti] Título: HDV RNA replication is associated with HBV repression and interferon-stimulated genes induction in super-infected hepatocytes. [So] Source: Antiviral Res;136:19-31, 2016 12. [Is] ISSN: 1872-9096 [Cp] País de publicação: Netherlands [La] Idioma: eng [Ab] Resumo: Hepatitis D virus (HDV) super-infection of Hepatitis B virus (HBV)-infected patients is the most aggressive form of viral hepatitis. HDV infection is not susceptible to direct anti-HBV drugs, and only suboptimal antiviral responses are obtained with interferon (IFN)-alpha-based therapy. To get insights on HDV replication and interplay with HBV in physiologically relevant hepatocytes, differentiated HepaRG (dHepaRG) cells, previously infected or not with HBV, were infected with HDV, and viral markers were extensively analyzed. Innate and IFN responses to HDV were monitored by measuring pro-inflammatory and interferon-stimulated gene (ISG) expression. Both mono- and super-infected dHepaRG cells supported a strong HDV intracellular replication, which was accompanied by a strong secretion of infectious HDV virions only in the super-infection setting and despite the low number of co-infected cells. Upon HDV super-infection, HBV replication markers including HBeAg, total HBV-DNA and pregenomic RNA were significantly decreased, confirming the interference of HDV on HBV. Yet, no decrease of circular covalently closed HBV DNA (cccDNA) and HBsAg levels was evidenced. At the peak of HDV-RNA accumulation and onset of interference on HBV replication, a strong type-I IFN response was observed, with interferon stimulated genes, RSAD2 (Viperin) and IFI78 (MxA) being highly induced. We established a cellular model to characterize in more detail the direct interference of HBV and HDV, and the indirect interplay between the two viruses via innate immune responses. This model will be instrumental to assess molecular and immunological mechanisms of this viral interference. [Mh] Termos MeSH primário: Vírus da Hepatite B/fisiologia Vírus Delta da Hepatite/fisiologia Hepatócitos/virologia Imunidade Inata Interferons/imunologia Interferência Viral Replicação Viral [Mh] Termos MeSH secundário: Células Cultivadas Coinfecção Replicação do DNA DNA Circular Hepatite B/virologia Antígenos E da Hepatite B/genética Hepatite D/virologia Vírus Delta da Hepatite/genética Seres Humanos Interferon Tipo I/imunologia Proteínas de Resistência a Myxovirus/genética Proteínas/genética RNA Viral/biossíntese RNA Viral/genética [Pt] Tipo de publicação: JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T [Nm] Nome de substância: 0 (DNA, Circular); 0 (Hepatitis B e Antigens); 0 (Interferon Type I); 0 (MX1 protein, human); 0 (Myxovirus Resistance Proteins); 0 (Proteins); 0 (RNA, Viral); 0 (RSAD2 protein, human); 9008-11-1 (Interferons) [Em] Mês de entrada: 1711 [Cu] Atualização por classe: 180213 [Lr] Data última revisão: 180213 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 161107 [St] Status: MEDLINE

2 / 1884

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[PMID]: 28988126 [Au] Autor: Sopena S; Godoy C; Tabernero D; Homs M; Gregori J; Riveiro-Barciela M; Ruiz A; Esteban R; Buti M; Rodríguez-Frías F [Ad] Endereço: Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, 28029 Madrid, Spain; Liver Pathology Unit, Departments of Biochemistry and Microbiology, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona (UAB), 08035 Barc [Ti] Título: Quantitative characterization of hepatitis delta virus genome edition by next-generation sequencing. [So] Source: Virus Res;243:52-59, 2018 01 02. [Is] ISSN: 1872-7492 [Cp] País de publicação: Netherlands [La] Idioma: eng [Ab] Resumo: AIM: To determine the capacity of next-generation sequencing (NGS) for quantifying edited and unedited HDV populations, and to confirm if edition is a general phenomenon taking place along the entire HDV region analyzed, as we previously reported (Homs M et al. PLoS One 2016, 11, e0158557). METHODS: Four serum samples from 4 patients with chronic HDV/HBV infection were included in the study. The region selected for analysis covered 360 nucleotides (nt), positions 910-1270 of the HDV genome, which included the HDAg ORF editing site (nt 1014 within codon 196). Quantification of edited and unedited genomes was performed by molecular cloning and Sanger sequencing and by NGS. To evaluate the reliability of the NGS values obtained, we combined a clone with an edited codon and one with an unedited codon in known percentages in a series of artificial mixtures, which were then analyzed by NGS. In addition, we determined the nt changes occurring over the complete amplified region after excluding the editing codon (196) to evaluate edition along it. RESULTS: In total, 11,208 quality-filtered sequences were obtained in the 4 samples. The 95% confidence intervals for the proportions of unedited populations by molecular cloning and NGS were overlapping, and those of cloning were wider, indicating that they are comparable and that NGS is more precise than cloning. Unedited genomes predominated over edited ones in all 4 samples analyzed by NGS and in 3 of the 4 samples analyzed by molecular cloning. In total, 83,276 quality-filtered sequences were obtained from the artificial mixtures. Percentages of the two viral populations detected by NGS in these mixtures were comparable to the expected percentages. Evaluation of edition along the HDV coding region showed that transitions were more frequent than transversions, accounting for 63.09% and 36.91%, respectively. Interestingly, among the 4 possible transition-type changes, G:A and A:G accounted for 73.86% of the total. CONCLUSION: Next-generation sequencing proved useful to quantify edited and unedited HDV genomes, and provided relevant information on the HDV quasispecies. [Mh] Termos MeSH primário: Genoma Viral Hepatite D/virologia Vírus Delta da Hepatite/genética Vírus Delta da Hepatite/isolamento & purificação Sequenciamento de Nucleotídeos em Larga Escala/métodos [Mh] Termos MeSH secundário: Sequência de Bases Vírus Delta da Hepatite/classificação Seres Humanos Dados de Sequência Molecular Filogenia Replicação Viral [Pt] Tipo de publicação: EVALUATION STUDIES; JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T [Em] Mês de entrada: 1801 [Cu] Atualização por classe: 180209 [Lr] Data última revisão: 180209 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 171009 [St] Status: MEDLINE

3 / 1884

MEDLINE

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[PMID]: 27770553 [Au] Autor: Wranke A; Serrano BC; Heidrich B; Kirschner J; Bremer B; Lehmann P; Hardtke S; Deterding K; Port K; Westphal M; Manns MP; Cornberg M; Wedemeyer H [Ad] Endereço: Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany. [Ti] Título: Antiviral treatment and liver-related complications in hepatitis delta. [So] Source: Hepatology;65(2):414-425, 2017 02. [Is] ISSN: 1527-3350 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: Hepatitis delta virus (HDV) is the most severe form of viral hepatitis. Pegylated interferon alfa (PEG-IFNα) is effective in only 25%-30% of patients and is associated with frequent side effects. The aim of this study was to analyze the clinical long-term outcome of hepatitis delta in relation to different antiviral treatment strategies. We studied 136 anti-HDV-positive patients who were followed for at least 6 months in a retrospective single-center cohort (mean time of follow-up, 5.2 years; range, 0.6-18.8). Liver cirrhosis was already present in 62 patients at first presentation. Twenty-nine percent of patients did not receive any antiviral treatment, 38% were treated with interferon alfa (IFNα)-based therapies, and 33% received nucleos(t)ide analogues (NAs) only. Clinical endpoints defined as hepatic decompensation (ascites, encephalopathy, and variceal bleeding), hepatocellular carcinoma, liver transplantation, and liver-related death developed in 55 patients (40%). Patients who received IFNα-based therapies developed clinical endpoints less frequently than those treated with NA (P = 0.02; HR, 4.0) or untreated patients (P = 0.05; HR, 2.2; 17%, 64%, and 44%), respectively, which was significant in both chi-square and Kaplan-Meier analysis. In addition, considering various clinical and virological parameters, IFNα therapy was independently associated with a more benign clinical long-term outcome in multivariate logistic regression analysis (P = 0.04; odds ratio, 0.25; 95% confidence interval, 0.07-0.9). Loss of HDV RNA during follow-up was more frequent in IFNα-treated patients and strongly linked with a lower likelihood to experience liver-related complications. CONCLUSION: IFNα-based antiviral therapy of hepatitis delta was independently associated with a lower likelihood for clinical disease progression. Durable undetectability of HDV RNA is a valid surrogate endpoint in the treatment of hepatitis delta. (Hepatology 2017;65:414-425). [Mh] Termos MeSH primário: Antivirais/uso terapêutico Hepatite D/tratamento farmacológico Hepatite D/mortalidade Interferon-alfa/uso terapêutico Cirrose Hepática/patologia Neoplasias Hepáticas/patologia [Mh] Termos MeSH secundário: Adolescente Adulto Análise de Variância Antivirais/efeitos adversos Causas de Morte Distribuição de Qui-Quadrado Estudos de Coortes Progressão da Doença Relação Dose-Resposta a Droga Esquema de Medicação Quimioterapia Combinada Feminino Seguimentos Alemanha Hepatite D/diagnóstico Vírus Delta da Hepatite/efeitos dos fármacos Vírus Delta da Hepatite/isolamento & purificação Seres Humanos Interferon-alfa/efeitos adversos Estimativa de Kaplan-Meier Fígado/efeitos dos fármacos Fígado/patologia Cirrose Hepática/etiologia Cirrose Hepática/mortalidade Neoplasias Hepáticas/etiologia Neoplasias Hepáticas/mortalidade Modelos Logísticos Masculino Meia-Idade Análise Multivariada Valores de Referência Estudos Retrospectivos Medição de Risco Índice de Gravidade de Doença Análise de Sobrevida Fatores de Tempo Resultado do Tratamento Adulto Jovem [Pt] Tipo de publicação: COMPARATIVE STUDY; JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T [Nm] Nome de substância: 0 (Antiviral Agents); 0 (Interferon-alpha) [Em] Mês de entrada: 1708 [Cu] Atualização por classe: 180121 [Lr] Data última revisão: 180121 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 161023 [St] Status: MEDLINE [do] DOI: 10.1002/hep.28876

4 / 1884

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[PMID]: 28730878 [Au] Autor: Rizzetto M [Ad] Endereço: a Department of Medicine , University of Torino , Torino , Italy. [Ti] Título: Investigational drugs in development for Hepatitis D. [So] Source: Expert Opin Investig Drugs;26(9):999-1005, 2017 Sep. [Is] ISSN: 1744-7658 [Cp] País de publicação: England [La] Idioma: eng [Ab] Resumo: INTRODUCTION: Treatment of chronic hepatitis D still relies on Interferon. To improve efficacy, new therapeutic strategies are in development which aim to deprive the Hepatitis D Virus (HDV) of functions of the Hepatitis B Virus and of the host required for its life-cycle. Areas covered: The therapeutic options are; 1) The inhibition of the farnesylation of the large HD-protein permissive of virion assembly with Lonafarnib, 2) The blocking of HBsAg entry into cells with Myrcludex B via the inhibition of the Sodium Taurocholate Cotransporting Receptor, to prevent the spreading of HDV to uninfected hepatocytes, 3) The reduction of subviral HBsAg particles by REP 2139, leading to diminished virion morphogenesis . Expert opinion: Lonafarnib and Myrcludex reduced serum HVD-RNA; neither diminished serum HBsAg. NAP REP-2139 diminished both HDV-RNA and HBsAg in serum; a full report is awaited. In combination with Peg-Interferon, these new drugs may provide additional efficacy. [Mh] Termos MeSH primário: Antivirais/uso terapêutico Drogas em Investigação/uso terapêutico Hepatite D Crônica/tratamento farmacológico [Mh] Termos MeSH secundário: Animais Antivirais/administração & dosagem Antivirais/farmacologia Desenho de Drogas Quimioterapia Combinada Drogas em Investigação/farmacologia Vírus da Hepatite B/efeitos dos fármacos Hepatite D Crônica/virologia Vírus Delta da Hepatite/efeitos dos fármacos Seres Humanos Interferons/administração & dosagem Interferons/farmacologia Interferons/uso terapêutico Lipopeptídeos/administração & dosagem Lipopeptídeos/farmacologia Lipopeptídeos/uso terapêutico Piperidinas/administração & dosagem Piperidinas/farmacologia Piperidinas/uso terapêutico Piridinas/administração & dosagem Piridinas/farmacologia Piridinas/uso terapêutico [Pt] Tipo de publicação: JOURNAL ARTICLE; REVIEW [Nm] Nome de substância: 0 (Antiviral Agents); 0 (Drugs, Investigational); 0 (Lipopeptides); 0 (Piperidines); 0 (Pyridines); 0 (myrcludex-B); 9008-11-1 (Interferons); IOW153004F (lonafarnib) [Em] Mês de entrada: 1709 [Cu] Atualização por classe: 170904 [Lr] Data última revisão: 170904 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170722 [St] Status: MEDLINE [do] DOI: 10.1080/13543784.2017.1357695

5 / 1884

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[PMID]: 28676076 [Au] Autor: Coffie PA; Tchounga BK; Bado G; Kabran M; Minta DK; Wandeler G; Gottlieb GS; Dabis F; Eholie SP; Ekouevi DK [Ad] Endereço: Département de Dermatologie et d'Infectiologie, UFR des Sciences Médicales, Université Félix Houphouët Boigny, BP V3 Abidjan, CHU de Treichville, Abidjan, Côte d'Ivoire. ahuatchi@gmail.com. [Ti] Título: Prevalence of hepatitis B and delta according to HIV-type: a multi-country cross-sectional survey in West Africa. [So] Source: BMC Infect Dis;17(1):466, 2017 Jul 04. [Is] ISSN: 1471-2334 [Cp] País de publicação: England [La] Idioma: eng [Ab] Resumo: BACKGROUND: In West Africa where HIV-1 and HIV-2 co-circulate, the co-infection with hepatitis B virus (HBV) and hepatitis Delta virus (HDV) is not well described. This study aimed at estimating the prevalence of HBV and HBV/HDV co-infection according to HIV types and risk factors for HBV infection among West African HIV-infected patients. METHOD: A cross-sectional survey was conducted within the IeDEA West Africa cohort from March to December 2012 in Côte d'Ivoire (three sites), Burkina Faso and Mali (one site each). All HIV-infected adult patients on antiretroviral therapy (ART) or not who attended one of the participating HIV clinics during the study period and agreed to participate were included. Blood samples were collected and re-tested for HIV type discrimination, HBV and HDV serology as well as HBV viral load. Logistic regression was used to identify risk factors for HBV infection. RESULTS: A total of 791 patients were included: 192 HIV-1, 447 HIV-2 and 152 HIV-1&2 dually reactive. At time of sampling, 555 (70.2%) were on ART and median CD4+ cell count was 472/mm (inter-quartile range [IQR]: IQR: 294-644). Sixty-seven (8.5%, 95% CI 6.6-10.6) patients were HBsAg positive without any difference according to HIV type (7.9% in HIV-1, 7.2% in HIV-1&2 dually reactive and 9.4% in HIV-2; p = 0.61). In multivariate logistic analysis, age ≤ 30 years old (adjusted odds ratio [aOR] 5.00, 95% CI 1.96-12.76), age between 31 and 49 years old (aOR 1.78, 95% CI 1.00-2.21) and male gender (aOR 2.15, 95% CI 1.25-3.69) were associated with HBsAg positivity. HBV DNA testing was performed in 36 patients with blood sample available (25 on ART) and 8 (22.2%) had detectable HBV DNA. Among the HBsAg-positive individuals, 14.9% (95% CI 7.4-25.7) were also positive for anti-HDV antibody without any difference according to HIV type (28.6% in HIV-1, 14.3% in HIV-2 and 0.0% in HIV-1&2 dually reactive; p = 0.15). CONCLUSION: HBV and HBV/HDV co-infection are common in West Africa, irrespective of HIV type. Therefore, screening for both viruses should be systematically performed to allow a better management of HIV-infected patients. Follow-up studies are necessary to determine the impact of these two viruses on HIV infection. [Mh] Termos MeSH primário: Infecções por HIV/virologia Hepatite B/epidemiologia Hepatite B/virologia [Mh] Termos MeSH secundário: Infecções Oportunistas Relacionadas com a AIDS/epidemiologia Adulto Burkina Faso/epidemiologia Contagem de Linfócito CD4 Coinfecção/epidemiologia Costa do Marfim/epidemiologia Estudos Transversais Feminino Seguimentos Infecções por HIV/epidemiologia HIV-1/patogenicidade HIV-2/patogenicidade Vírus da Hepatite B/genética Vírus da Hepatite B/patogenicidade Vírus Delta da Hepatite/genética Vírus Delta da Hepatite/patogenicidade Seres Humanos Masculino Mali/epidemiologia Meia-Idade Prevalência Fatores de Risco [Pt] Tipo de publicação: JOURNAL ARTICLE [Em] Mês de entrada: 1710 [Cu] Atualização por classe: 171002 [Lr] Data última revisão: 171002 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170706 [St] Status: MEDLINE [do] DOI: 10.1186/s12879-017-2568-5

6 / 1884

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[PMID]: 28485924 [Au] Autor: Frankel EA; Strulson CA; Keating CD; Bevilacqua PC [Ad] Endereço: Department of Chemistry, Pennsylvania State University , University Park, Pennsylvania 16802, United States. [Ti] Título: Cooperative Interactions in the Hammerhead Ribozyme Drive pK Shifting of G12 and Its Stacked Base C17. [So] Source: Biochemistry;56(20):2537-2548, 2017 May 23. [Is] ISSN: 1520-4995 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: General acid-base catalysis is a key mechanistic strategy in protein and RNA enzymes. Ribozymes use hydrated metal ions, nucleobases, and organic cofactors to carry this out. In most small ribozymes, a guanosine is positioned to participate in proton transfer with the nucleophilic 2'-OH. The unshifted pK values for nucleobases and solvated metal ions are far from neutrality, however, and thus nonideal for general acid-base catalysis. Herein, evidence is provided for cooperative interaction in the hammerhead ribozyme among the guanine that interacts with the nucleophilic 2'-OH, G12, the -1 nucleobase C17, and Mg ions. We introduce global fitting for analyzing ribozyme rate-pH data parametric in Mg concentration and benchmark this method on data from the hepatitis delta virus ribozyme. We then apply global fitting to new rate-pH data for the hammerhead ribozyme using a minimal three-dimensional, four-channel cooperative model. The value for the pK of G12 that we obtain is channel-dependent and varies from 8.1 to 9.9, shifting closest toward neutrality in the presence of two cationic species: C17H and a Mg ion. The value for the pK of the -1 nucleotide, C17, is increased a remarkable 3.5-5 pK units toward neutrality. Shifting of the pK of C17 appears to be driven by an electrostatic sandwich of C17 between carbonyl groups of the 5'-neighboring U and of G12 and involves cation-π interactions. Rate-pH profiles reveal that the major reactive channel under biological Mg and pH involves a cationic C17 rather than a second metal ion. Substitution of a cationic base for a metal underscores the versatility of RNA. [Mh] Termos MeSH primário: Vírus Delta da Hepatite/enzimologia RNA Catalítico/química [Mh] Termos MeSH secundário: Catálise Concentração de Íons de Hidrogênio Magnésio/química Modelos Moleculares Ligação Proteica Estrutura Secundária de Proteína [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (RNA, Catalytic); 0 (hammerhead ribozyme); I38ZP9992A (Magnesium) [Em] Mês de entrada: 1706 [Cu] Atualização por classe: 170626 [Lr] Data última revisão: 170626 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170510 [St] Status: MEDLINE [do] DOI: 10.1021/acs.biochem.7b00174

7 / 1884

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[PMID]: 28403190 [Au] Autor: Nguyen HM; Sy BT; Trung NT; Hoan NX; Wedemeyer H; Velavan TP; Bock CT [Ad] Endereço: Center for Molecular Biology, Institute of Research and Development, Duy Tan University, Da Nang, Vietnam. [Ti] Título: Prevalence and genotype distribution of hepatitis delta virus among chronic hepatitis B carriers in Central Vietnam. [So] Source: PLoS One;12(4):e0175304, 2017. [Is] ISSN: 1932-6203 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: Hepatitis D virus (HDV) infection plays an important role in liver diseases. However, the molecular epidemiology and impact of HDV infection in chronic hepatitis B (CHB) remain uncertain in Vietnam. This cross-sectional study aimed to investigate the prevalence and genotype distribution of HDV among HBsAg-positive patients in Central Vietnam. 250 CHB patients were tested for HDV using newly established HDV-specific RT-PCR techniques. HDV genotypes were determined by direct sequencing. Of the 250 patients 25 (10%) had detectable copies of HDV viral RNA. HDV-2 was predominant (20/25; 80%) followed by HDV-1 (5/25; 20%). Proven HDV genotypes share the Asian nomenclature. Chronic hepatitis B patients with concomitant HDV-1 showed higher HBV loads as compared to HDV-2 infected patients [median log10 (HBV-DNA copies/ml): 8.5 vs. 4.4, P = 0.036]. Our findings indicate that HDV infection is highly prevalent and HDV-2 is predominant in Central Vietnam. The data will add new information to the management of HBsAg-positive patients in a highly HBV endemic region to in- or exclude HDV infection in terms of diagnostic and treatment options. [Mh] Termos MeSH primário: Coinfecção/epidemiologia Vírus da Hepatite B/isolamento & purificação Hepatite B Crônica/epidemiologia Hepatite D/epidemiologia Vírus Delta da Hepatite/isolamento & purificação [Mh] Termos MeSH secundário: Adolescente Adulto Idoso Criança Coinfecção/virologia Estudos Transversais Feminino Genótipo Vírus da Hepatite B/genética Hepatite B Crônica/virologia Hepatite D/virologia Vírus Delta da Hepatite/genética Seres Humanos Masculino Meia-Idade Filogenia Prevalência Vietnã/epidemiologia Adulto Jovem [Pt] Tipo de publicação: JOURNAL ARTICLE [Em] Mês de entrada: 1704 [Cu] Atualização por classe: 170504 [Lr] Data última revisão: 170504 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170414 [St] Status: MEDLINE [do] DOI: 10.1371/journal.pone.0175304

8 / 1884

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[PMID]: 28329027 [Au] Autor: Couto I; Victoria M; Veloso VG; Rodrigues L; Grinsztejn B; Lacerda M; Victoria F; Perazzo H [Ad] Endereço: Fundação de Medicina Tropical Dr. Heitor Vieira Dourado (FMT HVD), Manaus, Amazonas, Brazil. [Ti] Título: Prevalence and predictors for compensated Advanced Chronic Liver Disease (c-ACLD) in patients with chronic Hepatitis Delta Virus (HDV) infection. [So] Source: PLoS One;12(3):e0174453, 2017. [Is] ISSN: 1932-6203 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: OBJECTIVE: The study aimed to evaluate the prevalence and predictor factors for compensated advanced chronic liver disease (c-ACLD) in patients with hepatitis Delta virus (HDV) infection. METHODS: This cross-sectional study included consecutive HDV-infected patients defined by positive anti-HDV. Patients with hepatitis C coinfection, liver transplantation or presence of conditions that limit liver (LSM) or spleen stiffness measurement (SSM) were excluded. Blood tests, abdominal ultrasound, SSM and LSM by transient elastography (FibroScan®) were performed at the same day. Alcohol consumption was quantified using the AUDIT score and c-ACLD was defined by LSM ≥ 15 kPa performed by an experimented operator blinded for clinical and laboratory data. RESULTS: 101 patients were eligible and few patients were excluded due to negative anti-HDV (n = 7), hepatitis C coinfection (n = 2), liver transplantation (n = 10) and limitation for LSM or SSM (n = 5). Therefore, 77 patients [61% male, age = 43 (IQR,36-52) years] were included. The prevalence of c-ACLD was 57% (n = 44/77). Patients with c-ACLD had a higher rate of detectable HBV viral load (p = 0.039), higher levels of transaminases, GGT, alkaline phosphatases, total bilirubin and INR (p<0.001 for all), as well as lower platelet count and albumin levels (p>0.001 for both) compared to those without c-ACLD. Patients with c-ACLD had higher SSM [65.2 (IQR,33.8-75.0) vs 21.8 (16.5-32.0) kPa; p<0.001] and higher splenic volume [475 (IQR,311-746) vs 154 (112-283) cm3; p<0.001] compared to those without. Detectable HBV viral load (>10 UI/ml), alkaline phosphatase (per IU/L) and GGT levels (per IU/L) were independently associated with c-ACLD in all multivariate models. Splenic volume [per cm3,OR = 1.01 (95%CI,1.01-1.02);p = 0.002], SSM [per kPa, OR = 1.04 (1.01-1.07);p = 0.012] and splenomegaly [yes vs no,OR = 28.45 (4.42-182.95);p<0.001] were independently associated with c-ACLD. CONCLUSIONS: The prevalence of c-ACLD was high in patients with chronic HDV infection in western Amazon basin. HBV viral load, liver enzymes and splenic features can be used to predict severe liver disease in HDV-infected patients. [Mh] Termos MeSH primário: Hepatite D Crônica/epidemiologia Hepatite D Crônica/virologia Hepatopatias/virologia [Mh] Termos MeSH secundário: Adulto Coinfecção/epidemiologia Coinfecção/virologia Estudos Transversais Feminino Hepacivirus/patogenicidade Anticorpos Anti-Hepatite/imunologia Vírus da Hepatite B/patogenicidade Hepatite B Crônica/epidemiologia Hepatite B Crônica/virologia Hepatite C/epidemiologia Hepatite C/virologia Vírus Delta da Hepatite/patogenicidade Seres Humanos Fígado/virologia Testes de Função Hepática/métodos Masculino Meia-Idade Prevalência Carga Viral/métodos [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Hepatitis Antibodies) [Em] Mês de entrada: 1708 [Cu] Atualização por classe: 170822 [Lr] Data última revisão: 170822 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170323 [St] Status: MEDLINE [do] DOI: 10.1371/journal.pone.0174453

9 / 1884

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[PMID]: 28213271 [Au] Autor: Fu L; Hu H; Liu Y; Jing Z; Li W [Ad] Endereço: Graduate School of Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China; National Institute of Biological Sciences, Beijing, China. [Ti] Título: Woodchuck sodium taurocholate cotransporting polypeptide supports low-level hepatitis B and D virus entry. [So] Source: Virology;505:1-11, 2017 May. [Is] ISSN: 1096-0341 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: Sodium taurocholate cotransporting polypeptide (NTCP) is the functional receptor for human hepatitis B virus (HBV) and its satellite hepatitis D virus (HDV). Species barriers to HBV/HDV infection are mainly determined at entry level by variations in the sequences of particular NTCP orthologs. In this study, we sought to determine whether the NTCP ortholog in woodchuck (Marmota monax), woodchuck NTCP (wNTCP) supports viral infection. We found that wNTCP is capable of supporting HBV/HDV infection in HepG2 cells, but to much lower extent than human NTCP (hNTCP), which is about 90% reduction of hNTCP. Comprehensive site-directed mutagenesis mapping of hNTCP and wNTCP revealed that the residue at position 263 is a novel site crucial for viral entry. The important role of site 263 in infection is conserved among NTCP orthologs and may therefore be a potential target for blocking the viral entry. [Mh] Termos MeSH primário: Vírus da Hepatite B/metabolismo Vírus Delta da Hepatite/metabolismo Especificidade de Hospedeiro/genética Transportadores de Ânions Orgânicos Dependentes de Sódio/genética Receptores Virais/genética Simportadores/genética Internalização do Vírus [Mh] Termos MeSH secundário: Sequência de Aminoácidos/genética Animais Sítios de Ligação/genética Linhagem Celular Tumoral Clonagem Molecular Células Hep G2 Hepatócitos/virologia Seres Humanos Fígado/metabolismo Fígado/virologia Masculino Marmota/virologia Transportadores de Ânions Orgânicos Dependentes de Sódio/metabolismo Ligação Proteica/genética Receptores Virais/metabolismo Simportadores/metabolismo [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Organic Anion Transporters, Sodium-Dependent); 0 (Receptors, Virus); 0 (Symporters); 145420-23-1 (sodium-bile acid cotransporter) [Em] Mês de entrada: 1705 [Cu] Atualização por classe: 170526 [Lr] Data última revisão: 170526 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170219 [St] Status: MEDLINE

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MEDLINE

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[PMID]: 28202798 [Au] Autor: Makiala-Mandanda S; Le Gal F; Ngwaka-Matsung N; Ahuka-Mundeke S; Onanga R; Bivigou-Mboumba B; Pukuta-Simbu E; Gerber A; Abbate JL; Mwamba D; Berthet N; Leroy EM; Muyembe-Tamfum JJ; Becquart P [Ad] Endereço: Centre International de Recherches Médicales de Franceville (CIRMF), Franceville, Gabon shemakiala@yahoo.fr pierre.becquart@ird.fr. [Ti] Título: High Prevalence and Diversity of Hepatitis Viruses in Suspected Cases of Yellow Fever in the Democratic Republic of Congo. [So] Source: J Clin Microbiol;55(5):1299-1312, 2017 May. [Is] ISSN: 1098-660X [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: The majority of patients with acute febrile jaundice (>95%) identified through a yellow fever surveillance program in the Democratic Republic of Congo (DRC) test negative for antibodies against yellow fever virus. However, no etiological investigation has ever been carried out on these patients. Here, we tested for hepatitis A (HAV), hepatitis B (HBV), hepatitis C (HCV), hepatitis D (HDV), and hepatitis E (HEV) viruses, all of which can cause acute febrile jaundice, in patients included in the yellow fever surveillance program in the DRC. On a total of 498 serum samples collected from suspected cases of yellow fever from January 2003 to January 2012, enzyme-linked immunosorbent assay (ELISA) techniques were used to screen for antibodies against HAV (IgM) and HEV (IgM) and for antigens and antibodies against HBV (HBsAg and anti-hepatitis B core protein [HBc] IgM, respectively), HCV, and HDV. Viral loads and genotypes were determined for HBV and HVD. Viral hepatitis serological markers were diagnosed in 218 (43.7%) patients. The seroprevalences were 16.7% for HAV, 24.6% for HBV, 2.3% for HCV, and 10.4% for HEV, and 26.1% of HBV-positive patients were also infected with HDV. Median viral loads were 4.19 × 10 IU/ml for HBV (range, 769 to 9.82 × 10 IU/ml) and 1.4 × 10 IU/ml for HDV (range, 3.1 × 10 to 2.9 × 10 IU/ml). Genotypes A, E, and D of HBV and genotype 1 of HDV were detected. These high hepatitis prevalence rates highlight the necessity to include screening for hepatitis viruses in the yellow fever surveillance program in the DRC. [Mh] Termos MeSH primário: Anticorpos Antivirais/imunologia Hepacivirus/isolamento & purificação Vírus da Hepatite A/isolamento & purificação Vírus da Hepatite B/isolamento & purificação Vírus Delta da Hepatite/isolamento & purificação Vírus da Hepatite E/isolamento & purificação Febre Amarela/virologia Vírus da Febre Amarela/isolamento & purificação [Mh] Termos MeSH secundário: República Democrática do Congo Ensaio de Imunoadsorção Enzimática Hepacivirus/imunologia Vírus da Hepatite A/imunologia Antígenos do Núcleo do Vírus da Hepatite B/imunologia Antígenos de Superfície da Hepatite B/imunologia Vírus da Hepatite B/imunologia Vírus Delta da Hepatite/imunologia Vírus da Hepatite E/imunologia Seres Humanos Icterícia/diagnóstico Icterícia/virologia Estudos Soroepidemiológicos Carga Viral Febre Amarela/complicações Vírus da Febre Amarela/imunologia [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Antibodies, Viral); 0 (Hepatitis B Core Antigens); 0 (Hepatitis B Surface Antigens) [Em] Mês de entrada: 1710 [Cu] Atualização por classe: 171031 [Lr] Data última revisão: 171031 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170217 [St] Status: MEDLINE [do] DOI: 10.1128/JCM.01847-16

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