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1.
Viruses ; 16(8)2024 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-39205210

RESUMO

Hepatitis delta virus (HDV) is a satellite of hepatitis B virus (HBV), which requires the HBV surface antigen (HBsAg) for its assembly and propagation. Although countries affected by HBV infection in Africa are well identified, data on HDV infection are still scarce, like in Nigeria, where HBV infection is endemic. In this study, we aimed to determine the prevalence of HDV infection and identify the circulating genotypes/strains in the country. A nationwide study was performed on 1281 HBsAg-positive samples collected from patients across eleven sites drawn from the six geopolitical zones in Nigeria. Anti-HDV antibody (HDV-Ab) screening and HDV-RNA viral load quantification were performed using a commercial ELISA assay and real-time RT-PCR kit, respectively. HDV genotyping was performed by the Sanger sequencing of amplicons from the so-called R0 region of the viral genome, followed by phylogenetic analyses. Of the 1281 HBsAg-positive samples, 61 (4.8%) were HDV-Ab positive, among which, 12 (19.7%) were HDV-RNA positive. Genotypes were obtained for nine of them: seven "African" HDV-1, one "Asian/European" HDV-1 and one HDV-6. This study shows that Nigeria is a country of low HDV prevalence where mainly "African" genotype-1 strains are circulating.


Assuntos
Genótipo , Hepatite D , Vírus Delta da Hepatite , Epidemiologia Molecular , Filogenia , Vírus Delta da Hepatite/genética , Vírus Delta da Hepatite/classificação , Vírus Delta da Hepatite/isolamento & purificação , Nigéria/epidemiologia , Humanos , Hepatite D/epidemiologia , Hepatite D/virologia , Prevalência , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Adulto Jovem , Antígenos de Superfície da Hepatite B/genética , Antígenos de Superfície da Hepatite B/sangue , RNA Viral/genética , Adolescente , Anticorpos Anti-Hepatite/sangue , Idoso , Carga Viral , Hepatite B/epidemiologia , Hepatite B/virologia , Criança
3.
Niger J Clin Pract ; 27(8): 1004-1011, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-39212438

RESUMO

BACKGROUND: The near total absence of routine Hepatitis Delta Virus (HDV) screening in many countries in sub-Saharan Africa is a major challenge to understanding the burden of HDV in the region. AIM: To evaluate Hepatitis Delta Virus screening practices and associated factors among clinicians in Nigeria. METHODS: A cross-sectional study was conducted in June-July 2022, in which a self-administered questionnaire that inquired about HDV awareness, screening practices, and treatment options was shared electronically with consenting clinicians practicing in Nigeria. At the end of the survey, data was analyzed using descriptive and inferential statistics. The level of significance was set at 0.05. RESULTS: At the end of the survey, 210 of the 213 responses retrieved from respondents were analyzed. The respondent's mean age was 38.60 ± 7.27 years with a male-to-female ratio of 1:2.5. They comprised 13.8% gastroenterologists and 86.2% respondents in other areas of clinical medicine. The study showed that 89.5% of the respondents knew that HDV infection occurs only in hepatitis B virus (HBV)-infected individuals. Most (91.4%) respondents do not screen for HDV in chronic HBV patients, mainly due to the non-availability of screening tools and lack of awareness of any screening test for HDV. Research interest was reported as the reason for screening among clinicians who had ever screened for HDV. Pegylated interferon was the main regimen used for treatment by 87.5% of respondents. About 2% did not know treatment options for HDV. A significant association between knowledge of HDV infection and area of specialty, as well as the nature of medical practice was noted (P = 0.008 and 0.013, respectively). CONCLUSION: The study showed a high level of awareness of HDV dependency on HBV, for natural infection to occur. However, it documented very minimal HDV screening in clinical settings and factors affecting screening among clinicians.


Assuntos
Hepatite D , Vírus Delta da Hepatite , Programas de Rastreamento , Humanos , Estudos Transversais , Nigéria/epidemiologia , Feminino , Masculino , Adulto , Hepatite D/diagnóstico , Hepatite D/epidemiologia , Hepatite D/tratamento farmacológico , Vírus Delta da Hepatite/isolamento & purificação , Pessoa de Meia-Idade , Inquéritos e Questionários , Programas de Rastreamento/métodos , Programas de Rastreamento/estatística & dados numéricos , Padrões de Prática Médica/estatística & dados numéricos , Conhecimentos, Atitudes e Prática em Saúde , Hepatite B/epidemiologia , Hepatite B/diagnóstico
4.
Methods Mol Biol ; 2837: 171-184, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39044084

RESUMO

The hepatitis delta virus (HDV) is a small RNA virus (1700 base pairs), which uses the surface proteins of the hepatitis B virus (HBV) as an envelope. Accurate and reliable quantitative detection of HDV RNA is central for scientific and translational clinical research or diagnostic purposes. However, HDV poses challenges for nucleic acid amplification techniques: (1) the circular genome displays high intramolecular base pairing; (2) high content of cytosine and guanine; and (3) enormous genomic diversity among the eight known HDV genotypes (GTs). Here, we provide step-by-step instructions for (A) a manual workflow to perform a quantitative HDV reverse transcription (RT)-PCR from serum and liver tissue and (B) a quantitative HDV RT-PCR assay with whole process control to be used for serum or plasma samples run on a fully automated system. Both assays target the conserved ribozyme region and demonstrate inclusivity for all eight HDV GTs. The choice of assay depends on the experimental needs and equipment availability. While the former is ideal for scientific research laboratories, the latter provides a useful tool in the field of translational research or diagnostics.


Assuntos
Hepatite D , Vírus Delta da Hepatite , Fígado , RNA Viral , Fluxo de Trabalho , Vírus Delta da Hepatite/genética , Vírus Delta da Hepatite/isolamento & purificação , Humanos , RNA Viral/genética , Hepatite D/diagnóstico , Hepatite D/virologia , Fígado/virologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Reação em Cadeia da Polimerase em Tempo Real/métodos , Genótipo
5.
Front Cell Infect Microbiol ; 14: 1422299, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38988808

RESUMO

Objectives: Precise HDV-RNA detection and quantification are pivotal for diagnosis and monitoring of response to newly approved treatment. We evaluate the performance of three HDV RNA detection and quantification assays. Methods: Hepatitis Delta RT-PCR system kit, EurobioPlex HDV assay, and RoboGene HDV RNA Quantification kit 2.0 were used for testing 151 HBsAg-positive samples, 90 HDV-RNA negative and 61 HDV-RNA positive. We also evaluated serial dilutions of the WHO international standard for HDV, PEI 7657/12. All HDV-RNA positive samples were genotyped using a next-generation sequencing strategy. Results: Qualitative results indicated a 100% concordance between tests. Quantitative results correlated well, r2 = 0.703 (Vircell-vs-Eurobio), r2 = 0.833 (Vircell-vs-RoboGene), r2 = 0.835 (Robogene-vs-Eurobio). Bias index was 2.083 (Vircell-vs-Eurobio), -1.283 (Vircell-vs-RoboGene), and -3.36 (Robogene-vs-Eurobio). Using the WHO IS, Vircell overestimated the viral load by 0.98 log IU/mL, Eurobio by 1.46 log IU/mL, and RoboGene underestimated it by 0.98 log IU/mL. Fifty-nine samples were successfully genotyped (Genotype 1, n=52; Genotype 5, n=7; Genotype 6, n=1), with similar results for correlation and bias. Conclusion: This study underscores the necessity of using reliable HDV-RNA detection and quantification assays, as evidenced by the high concordance rates in qualitative detection and the observed variability in quantitative results. These findings highlight the importance of consistent assay use in clinical practice to ensure accurate diagnosis and effective treatment monitoring of HDV infection.


Assuntos
Genótipo , Hepatite D , Vírus Delta da Hepatite , RNA Viral , Carga Viral , Vírus Delta da Hepatite/genética , Vírus Delta da Hepatite/isolamento & purificação , Humanos , RNA Viral/genética , Carga Viral/métodos , Hepatite D/diagnóstico , Hepatite D/virologia , Kit de Reagentes para Diagnóstico/normas , Sensibilidade e Especificidade , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Técnicas de Diagnóstico Molecular/métodos
6.
N Engl J Med ; 391(2): 133-143, 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38842520

RESUMO

BACKGROUND: In a phase 3 trial, bulevirtide monotherapy led to a virologic response in patients with chronic hepatitis D. Pegylated interferon (peginterferon) alfa-2a is recommended by guidelines as an off-label treatment for this disease. The role of combination therapy with bulevirtide and peginterferon alfa-2a, particularly with regard to finite treatment, is unclear. METHODS: In this phase 2b, open-label trial, we randomly assigned patients to receive peginterferon alfa-2a alone (180 µg per week) for 48 weeks; bulevirtide at a daily dose of 2 mg or 10 mg plus peginterferon alfa-2a (180 µg per week) for 48 weeks, followed by the same daily dose of bulevirtide for 48 weeks; or bulevirtide at a daily dose of 10 mg alone for 96 weeks. All the patients were followed for 48 weeks after the end of treatment. The primary end point was an undetectable level of hepatitis D virus (HDV) RNA at 24 weeks after the end of treatment. The primary comparison was between the 10-mg bulevirtide plus peginterferon alfa-2a group and the 10-mg bulevirtide monotherapy group. RESULTS: A total of 24 patients received peginterferon alfa-2a alone, 50 received 2 mg and 50 received 10 mg of bulevirtide plus peginterferon alfa-2a, and 50 received 10 mg of bulevirtide monotherapy. At 24 weeks after the end of treatment, HDV RNA was undetectable in 17% of the patients in the peginterferon alfa-2a group, in 32% of those in the 2-mg bulevirtide plus peginterferon alfa-2a group, in 46% of those in the 10-mg bulevirtide plus peginterferon alfa-2a group, and in 12% of those in the 10-mg bulevirtide group. For the primary comparison, the between-group difference was 34 percentage points (95% confidence interval, 15 to 50; P<0.001). At 48 weeks after the end of treatment, HDV RNA was undetectable in 25% of the patients in the peginterferon alfa-2a group, in 26% of those in the 2-mg bulevirtide plus peginterferon alfa-2a group, in 46% of those in the 10-mg bulevirtide plus peginterferon alfa-2a group, and in 12% of those in the 10-mg bulevirtide group. The most frequent adverse events were leukopenia, neutropenia, and thrombocytopenia. The majority of adverse events were of grade 1 or 2 in severity. CONCLUSIONS: The combination of 10-mg bulevirtide plus peginterferon alfa-2a was superior to bulevirtide monotherapy with regard to an undetectable HDV RNA level at 24 weeks after the end of treatment. (Funded by Gilead Sciences; MYR 204 ClinicalTrials.gov number, NCT03852433.).


Assuntos
Antivirais , Hepatite D Crônica , Interferon-alfa , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Antivirais/efeitos adversos , Antivirais/uso terapêutico , Antivirais/administração & dosagem , Quimioterapia Combinada , Hepatite D Crônica/tratamento farmacológico , Vírus Delta da Hepatite/genética , Vírus Delta da Hepatite/isolamento & purificação , Vírus Delta da Hepatite/efeitos dos fármacos , Interferon-alfa/uso terapêutico , Interferon-alfa/administração & dosagem , Interferon-alfa/efeitos adversos , Proteínas Recombinantes/uso terapêutico , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/efeitos adversos , RNA Viral/sangue , Carga Viral
7.
J Clin Virol ; 173: 105689, 2024 08.
Artigo em Inglês | MEDLINE | ID: mdl-38781633

RESUMO

BACKGROUND: HDV antibody testing is recommended for universal screening and as the first line in an HDV double reflex testing strategy for effectively identifying patients with active infection for therapeutic treatments. OBJECTIVE: The aim of this study is to evaluate the performance of a newly developed ARCHITECT HDV Total Ig (ARCHITECT HDV Ig) prototype assay. STUDY DESIGN: Performance characteristics were determined for the ARCHITECT HDV Ig and a reference test, LIAISON XL Anti-HDV using a well-characterized specimen panel, comprising HDV RNA positive (n = 62) and negative (n = 70) samples, and healthy US blood donors. RESULTS: Healthy US blood donors (n=200) showed 99.5% (199/200, 95%CI=97.65-99.98) specificity with ARCHITECT HDV Ig and 98.5 % (197/200, 95 %CI = 96.10-99.64) with LIAISON Anti-HDV. Among known HDV RNA positive samples, ARCHITECT HDV Ig detected 59/62 demonstrating 95.2 % sensitivity while LIAISON Anti-HDV sensitivity was 90.3 % (56/62). Among 101 HBV positive samples, 70 were reactive in the ARCHITECT test, 59 of which tested positive for HDV RNA for a positive predictive value (PPV) for the presence of HDV RNA was 84.3 %. For LIAISON Anti-HDV, 79 specimens were reactive and 56 contained HDV RNA: PPV for HDV RNA was 70.9 %. Among 70 HDV RNA negative samples, 39 were HBV positive. ARCHITECT HDV Ig negative predictive value (NPV) was 71.8 % and LIAISON Anti-HDV NPV was 41 % for the HBV positive group, respectively. CONCLUSION: When compared to the LIASON Anti-HDV test, the ARCHITECT HDV Ig assay demonstrated enhanced sensitivity and specificity and better NPV and PPV values for HDV RNA status. The ARCHITECT HDV Ig assay represents a promising tool for universal screening of all HBsAg-positive persons.


Assuntos
Anticorpos Anti-Hepatite , Hepatite D , Vírus Delta da Hepatite , Ensaios de Triagem em Larga Escala , Sensibilidade e Especificidade , Humanos , Hepatite D/diagnóstico , Hepatite D/imunologia , Vírus Delta da Hepatite/imunologia , Vírus Delta da Hepatite/genética , Vírus Delta da Hepatite/isolamento & purificação , Anticorpos Anti-Hepatite/sangue , Ensaios de Triagem em Larga Escala/métodos , Testes Sorológicos/métodos , Automação Laboratorial/métodos , Doadores de Sangue
8.
Eur J Gastroenterol Hepatol ; 36(6): 735-741, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38683191

RESUMO

BACKGROUND: Data on the management of Hepatitis B-Delta (HB-D) by hepatogastroenterologists (HGs) practicing in nonacademic hospitals or private practices are unknown in France. OBJECTIVE: We aimed to evaluate the knowledge and practices of HGs practicing in nonacademic settings regarding HB-D. METHODS: A Google form document was sent to those HGs from May to September 2021. RESULTS: A total of 130 HGs (mean age, 45 years) have participated in this survey. Among HBsAg-positive patients, Delta infection was sought in only 89% of cases. Liver fibrosis was assessed using FibroScan in 77% of the cases and by liver biopsy in 81% of the cases. A treatment was proposed for patients with >F2 liver fibrosis in 49% of the cases regardless of transaminase levels and for all the patients by 39% of HGs. Responding HGs proposed a treatment using pegylated interferon in 50% of cases, bulevirtide in 45% of cases and a combination of pegylated interferon and bulevirtide in 40.5% of cases. Among the criteria to evaluate the treatment efficacy, a decrease or a normalization of transaminases was retained by 89% of responding HGs, a reduction of liver fibrosis score for 70% of them, an undetectable delta RNA and HBsAg for 55% of them and a 2 log 10 decline in delta viremia for 62% of the cases. CONCLUSION: Hepatitis Delta screening was not systematically performed in HBsAg-positive patients despite the probable awareness and knowledge of the few responders who were able to prescribe treatments of hepatitis delta.


Assuntos
Gastroenterologistas , Hepatite D , Vírus Delta da Hepatite , Padrões de Prática Médica , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Antivirais/uso terapêutico , Biópsia , França , Gastroenterologia , Conhecimentos, Atitudes e Prática em Saúde , Antígenos de Superfície da Hepatite B/sangue , Vírus Delta da Hepatite/isolamento & purificação , Vírus Delta da Hepatite/genética , Cirrose Hepática/virologia , Padrões de Prática Médica/estatística & dados numéricos , Hepatite D/sangue , Hepatite D/diagnóstico , Hepatite D/tratamento farmacológico , Hepatite D/epidemiologia
9.
Emerg Microbes Infect ; 13(1): 2350167, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38687692

RESUMO

Hepatitis B virus (HBV) infection remains a major public health problem and, in associated co-infection with hepatitis delta virus (HDV), causes the most severe viral hepatitis and accelerated liver disease progression. As a defective satellite RNA virus, HDV can only propagate in the presence of HBV infection, which makes HBV DNA and HDV RNA the standard biomarkers for monitoring the virological response upon antiviral therapy, in co-infected patients. Although assays have been described to quantify these viral nucleic acids in circulation independently, a method for monitoring both viruses simultaneously is not available, thus hampering characterization of their complex dynamic interactions. Here, we describe the development of a dual fluorescence channel detection system for pan-genotypic, simultaneous quantification of HBV DNA and HDV RNA through a one-step quantitative PCR. The sensitivity for both HBV and HDV is about 10 copies per microliter without significant interference between these two detection targets. This assay provides reliable detection for HBV and HDV basic research in vitro and in human liver chimeric mice. Preclinical validation of this system on serum samples from patients on or off antiviral therapy also illustrates a promising application that is rapid and cost-effective in monitoring HBV and HDV viral loads simultaneously.


Assuntos
Vírus da Hepatite B , Hepatite B , Hepatite D , Vírus Delta da Hepatite , Carga Viral , Vírus Delta da Hepatite/genética , Vírus Delta da Hepatite/isolamento & purificação , Humanos , Vírus da Hepatite B/genética , Vírus da Hepatite B/isolamento & purificação , Animais , Hepatite D/virologia , Hepatite D/diagnóstico , Hepatite B/virologia , Hepatite B/diagnóstico , Camundongos , RNA Viral/genética , RNA Viral/sangue , Coinfecção/virologia , Coinfecção/diagnóstico , DNA Viral/genética , DNA Viral/sangue , Genótipo , Sensibilidade e Especificidade
10.
J Hepatol ; 81(2): 248-257, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38479612

RESUMO

BACKGROUND & AIMS: Non-invasive tests (NITs) for clinically significant portal hypertension (CSPH) require validation in patients with hepatitis D virus (HDV)-related compensated advanced chronic liver disease (cACLD). Therefore, we aimed to validate existing NIT algorithms for CSPH in this context. METHODS: Patients with HDV-cACLD (LSM ≥10 kPa or histological METAVIR F3/F4 fibrosis) who underwent paired HVPG and NIT assessment at Medical University of Vienna or Hannover Medical School between 2013 and 2023 were retrospectively included. Liver stiffness measurement (LSM), von Willebrand factor to platelet count ratio (VITRO), and spleen stiffness measurement (SSM) were assessed. Individual CSPH risk was calculated according to previously published models (ANTICIPATE, 3P/5P). The diagnostic performance of Baveno VII criteria and refined algorithms (Baveno VII-VITRO, Baveno VII-SSM) was evaluated. The prognostic utility of NITs was investigated in the main cohort and an independent, multicenter, validation cohort. RESULTS: Fifty-one patients (HVPG ≥10 mmHg/CSPH prevalence: 62.7%, varices: 42.2%) were included. Patients with CSPH had significantly higher LSM (25.8 [17.2-31.0] vs. 14.0 [10.5-19.8] kPa; p <0.001), VITRO (n = 31, 3.5 [2.7-4.5] vs. 1.3 [0.6-2.0] %/[G/L]; p <0.001), and SSM (n = 20, 53.8 [41.7-75.5] vs. 24.0 [17.0-33.9] kPa; p <0.001). Composite CSPH risk models yielded excellent AUROCs (ANTICIPATE: 0.885, 3P: 0.903, 5P: 0.912). Baveno VII criteria ruled out CSPH with 100% sensitivity and ruled in CSPH with 84.2% specificity. The Baveno VII 'grey zone' (41.1%) was significantly reduced by Baveno VII-VITRO or Baveno VII-SSM algorithms, which maintained diagnostic accuracy. Hepatic decompensation within 2 years only occurred in patients who had CSPH or met Baveno VII rule-in criteria. The prognostic value of NITs was confirmed in the validation cohort comprising 92 patients. CONCLUSIONS: Standalone and composite NIT/diagnostic algorithms are useful for CSPH diagnosis in patients with HDV-cACLD. Thus, NITs may be applied to identify and prioritize patients with CSPH for novel antiviral treatments against chronic hepatitis D. IMPACT AND IMPLICATIONS: Non-invasive tests (NITs) for clinically significant portal hypertension (CSPH) have been developed to identify patients with compensated advanced chronic liver disease (cACLD) at risk of decompensation, but conflicting data has been published regarding the accuracy of liver stiffness measurement (LSM) for the staging of fibrosis in patients infected with hepatitis D virus (HDV). In our study, including 51 patients with HDV-cACLD, LSM- and lab-based NITs yielded high AUROCs for CSPH. Moreover, only patients with CSPH or high non-invasively assessed CSPH risk were at risk of decompensation within 2 years, with the prognostic value of NITs confirmed in a validation cohort. Thus, NITs should be applied and updated in yearly intervals in clinical routine to identify patients with HDV-cACLD at short-term risk of clinical events; NITs may also guide prioritization for novel antiviral treatment options.


Assuntos
Algoritmos , Técnicas de Imagem por Elasticidade , Hipertensão Portal , Humanos , Hipertensão Portal/diagnóstico , Hipertensão Portal/etiologia , Hipertensão Portal/fisiopatologia , Feminino , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Técnicas de Imagem por Elasticidade/métodos , Adulto , Fígado/diagnóstico por imagem , Fígado/patologia , Hepatite D/diagnóstico , Hepatite D/complicações , Vírus Delta da Hepatite/isolamento & purificação , Contagem de Plaquetas , Prognóstico , Cirrose Hepática/diagnóstico , Cirrose Hepática/complicações , Cirrose Hepática/virologia , Fator de von Willebrand/análise , Fator de von Willebrand/metabolismo
11.
J Infect Dis ; 230(3): e679-e683, 2024 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-38457349

RESUMO

BACKGROUND: This study assessed the epidemiology of hepatitis delta virus (HDV) within the University of Utah UHealth health care system (2000-2021). METHODS: Analysis of HDV/HBV testing, diagnostic codes, liver enzymes, and comorbidities was performed. RESULTS: Among the 1962 HBV patients, only 22.2% underwent HDV testing, revealing an 8.3% positivity rate for HDV coinfections. This study observed a consistent increase in HBV and HDV cases, with higher HDV detection rates linked to increased testing. Limited HDV testing and potential screening biases were evident. DISCUSSION: Improved HDV testing and surveillance are crucial for early detection and implementation of targeted therapies.


Assuntos
Hepatite B , Hepatite D , Vírus Delta da Hepatite , Programas de Rastreamento , Humanos , Utah/epidemiologia , Vírus Delta da Hepatite/genética , Vírus Delta da Hepatite/isolamento & purificação , Hepatite D/epidemiologia , Hepatite D/diagnóstico , Feminino , Masculino , Hepatite B/epidemiologia , Hepatite B/diagnóstico , Programas de Rastreamento/métodos , Adulto , Pessoa de Meia-Idade , Coinfecção/epidemiologia , Coinfecção/virologia , Idoso , Adulto Jovem
12.
United European Gastroenterol J ; 12(4): 516-525, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38520063

RESUMO

BACKGROUND AND OBJECTIVE: The prevalence of Hepatitis Delta Virus (HDV) is underestimated and the assessment of fibrosis is recommended for this infection. We tested the diagnostic impact of an annual screening for HDV serology in Hepatitis B Surface Antigen (HBs Ag) chronic carriers and followed the progression of fibrosis in these patients. METHODS: Between January 2014 and October 2021, we annually tested all chronic HBs Ag-positive patients for HDV antibody (HDV Ab). Each HDV Ab positive patient underwent annually repeated elastometry. Patients with detectable HDV RNA levels (group 1) were compared to those with undetectable HDV RNA (group 2). RESULTS: We identified 610 chronic HBs Ag-positive patients, and repeated screening for HDV Ab was performed in 534 patients. Sixty (11%) patients were HDV Ab positive at baseline and were considered as "coinfected". Seven cases of HDV superinfection were diagnosed through repeated screening. In co-infected patients, cirrhosis was initially diagnosed in 12/60 patients and developed in six patients during follow-up. HDV RNA PCR was performed in 57/67 patients and 27 had detectable levels (group 1). Cumulative incidence of cirrhosis at 7 years was 13.8% (95% CI 0-30) in group 1 and 0 (95% CI 0-0) in group 2 (p = 0.026). CONCLUSION: A systematic screening for HDV in chronic HB Ag carriers revealed a high prevalence of HDV Ab. Repeated serological screening enables the diagnosis of superinfections in asymptomatic patients. Regular assessment of fibrosis using elastometry leads to the identification of incidental cirrhosis in patients with detectable HDV RNA.


Assuntos
Portador Sadio , Antígenos de Superfície da Hepatite B , Hepatite B Crônica , Hepatite D , Vírus Delta da Hepatite , Cirrose Hepática , Programas de Rastreamento , Humanos , Cirrose Hepática/virologia , Cirrose Hepática/diagnóstico , Masculino , Feminino , Vírus Delta da Hepatite/genética , Vírus Delta da Hepatite/imunologia , Vírus Delta da Hepatite/isolamento & purificação , Hepatite B Crônica/complicações , Hepatite B Crônica/diagnóstico , Hepatite B Crônica/virologia , Pessoa de Meia-Idade , Hepatite D/diagnóstico , Hepatite D/complicações , Hepatite D/epidemiologia , Antígenos de Superfície da Hepatite B/sangue , Programas de Rastreamento/métodos , Portador Sadio/diagnóstico , Adulto , RNA Viral/sangue , Coinfecção/diagnóstico , Progressão da Doença , Anticorpos Anti-Hepatite/sangue , Prevalência , Técnicas de Imagem por Elasticidade , Idoso , Incidência
13.
Viruses ; 14(2)2022 01 22.
Artigo em Inglês | MEDLINE | ID: mdl-35215809

RESUMO

The hepatitis delta virus (HDV) genome has an autocatalytic region called the ribozyme, which is essential for viral replication. The aim of this study was to use next-generation sequencing (NGS) to analyze the ribozyme quasispecies (QS) in order to study its evolution and identify highly conserved regions potentially suitable for a gene-silencing strategy. HDV RNA was extracted from 2 longitudinal samples of chronic HDV patients and the ribozyme (nucleotide, nt 688-771) was analyzed using NGS. QS conservation, variability and genetic distance were analyzed. Mutations were identified by aligning sequences with their specific genotype consensus. The main relevant mutations were tested in vitro. The ribozyme was conserved overall, with a hyper-conserved region between nt 715-745. No difference in QS was observed over time. The most variable region was between nt 739-769. Thirteen mutations were observed, with three showing a higher frequency: T23C, T69C and C64 deletion. This last strongly reduced HDV replication by more than 1 log in vitro. HDV Ribozyme QS was generally highly conserved and was maintained during follow-up. The most conserved portion may be a valuable target for a gene-silencing strategy. The presence of the C64 deletion may strongly impair viral replication, as it is a potential mechanism of viral persistence.


Assuntos
Vírus Delta da Hepatite/genética , RNA Catalítico/genética , Sequência Conservada , Genótipo , Hepatite D Crônica/virologia , Vírus Delta da Hepatite/isolamento & purificação , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Mutação , Quase-Espécies , RNA Viral/genética , Análise de Sequência de RNA , Replicação Viral/genética
14.
Viruses ; 13(12)2021 11 26.
Artigo em Inglês | MEDLINE | ID: mdl-34960640

RESUMO

Hepatitis Delta virus (HDV) is a satellite of the Hepatitis B virus (HBV) and causes severe liver disease. The estimated prevalence of 15-20 million infected people worldwide may be underestimated as international diagnostic guidelines are not routinely followed. Possible reasons for this include the limited awareness among healthcare providers, the requirement for costly equipment and specialized training, and a lack of access to reliable tests in regions with poor medical infrastructure. In this study, we developed an HDV rapid test for the detection of antibodies against the hepatitis delta antigen (anti-HDV) in serum and plasma. The test is based on a novel recombinant large hepatitis delta antigen that can detect anti-HDV in a concentration-dependent manner with pan-genotypic activity across all known HDV genotypes. We evaluated the performance of this test on a cohort of 474 patient samples and found that it has a sensitivity of 94.6% (314/332) and a specificity of 100% (142/142) when compared to a diagnostic gold-standard ELISA. It also works robustly for a broad range of anti-HDV titers. We anticipate this novel HDV rapid test to be an important tool for epidemiological studies and clinical diagnostics, especially in regions that currently lack access to reliable HDV testing.


Assuntos
Anticorpos Antivirais/sangue , Hepatite D Crônica/diagnóstico , Hepatite D/diagnóstico , Vírus Delta da Hepatite/imunologia , Antígenos da Hepatite delta/imunologia , Testes Imediatos , Estudos de Coortes , Ensaio de Imunoadsorção Enzimática , Genótipo , Hepatite D/virologia , Hepatite D Crônica/virologia , Vírus Delta da Hepatite/genética , Vírus Delta da Hepatite/isolamento & purificação , Humanos , Prevalência , Proteínas Recombinantes , Sensibilidade e Especificidade , Testes Sorológicos , Fatores de Tempo
15.
J Microbiol Immunol Infect ; 54(5): 901-908, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34162528

RESUMO

PURPOSE: To clarify and investigate the prevalence and clinical impact of hepatitis D virus (HDV) infection in Taiwan's communities. METHODS: HDV infection in patients with chronic hepatitis B viral (HBV) infection was examined using an anti-HDV antibody in Yonghe Cardinal Tien Hospital (YCTH), a district hospital in Taiwan. Clinical characteristics of anti-HDV-positive and anti-HDV-negative patients were collected and compared. These characteristics were also compared with the data collected from a medical center. Continuous variables and confounding factor adjustments were compared using the analysis of covariance method, whereas categorical variables were compared using the logistic regression method. RESULTS: A total of 346 patients with chronic HBV infection were assessed from 2018 to 2019. Among them, 4 (1.15%) were positive for anti-HDV. The clinical, virological, and biochemical characteristics were similar between anti-HDV-positive and anti-HDV-negative groups. None of the four patients was positive for serum HDV RNA. Another 18 anti-HDV-positive patients were identified from National Taiwan University Hospital (NTUH). The clinical, virological, and biochemical characteristics of anti-HDV-positive patients from YCTH and NTUH were also similar. CONCLUSION: The prevalence of HDV and the serum HDV RNA-positive rate were low in district hospitals in Taiwan. Coexisting HDV infection did not influence the clinical manifestation of patients with chronic HBV infection in Taiwan. However, because the number of HDV RNA cases was very small, our findings may not be conclusive. Besides, since the sensitivity of current anti-HDV kit is not 100%, more sensitive methods are needed to achieve reliable prevalence data.


Assuntos
Hepatite D/diagnóstico , Hepatite D/epidemiologia , Adulto , Coinfecção/diagnóstico , Coinfecção/epidemiologia , Coinfecção/virologia , Feminino , Anticorpos Anti-Hepatite/sangue , Hepatite B Crônica/diagnóstico , Hepatite B Crônica/epidemiologia , Hepatite B Crônica/virologia , Hepatite D/virologia , Vírus Delta da Hepatite/imunologia , Vírus Delta da Hepatite/isolamento & purificação , Hospitais , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Taiwan/epidemiologia
17.
Sci Rep ; 11(1): 8554, 2021 04 20.
Artigo em Inglês | MEDLINE | ID: mdl-33879825

RESUMO

The spreading of viral hepatitis among injecting drug users (IDU) is an emerging public health concern. This study explored the prevalence and the risks of hepatitis B virus (HBV), hepatitis C virus (HCV) and hepatitis D virus (HDV) among IDU-dominant prisoners in Taiwan. HBV surface antigen (HBsAg), antibodies to HCV (anti-HCV) and HDV (anti-HDV), viral load and HCV genotypes were measured in 1137(67.0%) of 1697 prisoners. 89.2% of participants were IDUs and none had HIV infection. The prevalence of HBsAg, anti-HCV, dual HBsAg/anti-HCV, HBsAg/anti-HDV, and triple HBsAg/anti-HCV/anti-HDV was 13.6%, 34.8%, 4.9%, 3.4%, and 2.8%, respectively. HBV viremia rate was significantly lower in HBV/HCV-coinfected than HBV mono-infected subjects (66.1% versus 89.9%, adjusted odds ratio/95% confidence intervals [aOR/CI] = 0.27/0.10-0.73). 47.5% anti-HCV-seropositive subjects (n = 396) were non-viremic, including 23.2% subjects were antivirals-induced. The predominant HCV genotypes were genotype 6(40.9%), 1a(24.0%) and 3(11.1%). HBsAg seropositivity was negatively correlated with HCV viremia among the treatment naïve HCV subjects (44.7% versus 72.4%, aOR/CI = 0.27/0.13-0.58). Anti-HCV seropositivity significantly increased the risk of anti-HDV-seropositivity among HBsAg carriers (57.1% versus 7.1%, aOR/CI = 15.73/6.04-40.96). In conclusion, IUDs remain as reservoirs for multiple hepatitis viruses infection among HIV-uninfected prisoners in Taiwan. HCV infection increased the risk of HDV infection but suppressed HBV replication in HBsAg carriers. An effective strategy is mandatory to control the epidemic in this high-risk group.


Assuntos
Hepacivirus/isolamento & purificação , Vírus da Hepatite B/isolamento & purificação , Hepatite B/epidemiologia , Hepatite C/epidemiologia , Hepatite D/epidemiologia , Vírus Delta da Hepatite/isolamento & purificação , Abuso de Substâncias por Via Intravenosa/complicações , Coinfecção/sangue , Coinfecção/diagnóstico , Coinfecção/epidemiologia , Feminino , Genótipo , Hepacivirus/genética , Hepacivirus/imunologia , Hepatite B/sangue , Hepatite B/diagnóstico , Vírus da Hepatite B/genética , Vírus da Hepatite B/imunologia , Hepatite C/sangue , Hepatite C/diagnóstico , Hepatite D/sangue , Hepatite D/diagnóstico , Vírus Delta da Hepatite/genética , Vírus Delta da Hepatite/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Prisioneiros/estatística & dados numéricos , Estudos Soroepidemiológicos , Taiwan/epidemiologia , Carga Viral/métodos
18.
Viruses ; 13(2)2021 02 22.
Artigo em Inglês | MEDLINE | ID: mdl-33671832

RESUMO

Hepatitis delta virus (HDV) coinfection will additionally aggravate the hepatitis B virus (HBV) burden in the coming decades, with an increase in HBV-related liver diseases. Between 2018 and 2019, a total of 205 HBV patients clinically characterized as chronic hepatitis B (CHB; n = 115), liver cirrhosis (LC; n = 21), and hepatocellular carcinoma (HCC; n = 69) were recruited. HBV surface antigen (HBsAg), antibodies against surface antigens (anti-HBs), and core antigens (anti-HBc) were determined by ELISA. The presence of hepatitis B viral DNA and hepatitis delta RNA was determined. Distinct HBV and HDV genotypes were phylogenetically reconstructed and vaccine escape mutations in the "a" determinant region of HBV were elucidated. All HBV patients were HbsAg positive, with 99% (n = 204) and 7% (n = 15) of them being positive for anti-HBc and anti-HBs, respectively. Anti-HBs positivity was higher among HCC (15%; n = 9) compared to CHB patients. The HBV-B genotype was predominant (65%; n = 134), followed by HBV-C (31%; n = 64), HBV-D, and HBV-G (3%; n = 7). HCC was observed frequently among young individuals with HBV-C genotypes. A low frequency (2%; n = 4) of vaccine escape mutations was observed. HBV-HDV coinfection was observed in 16% (n = 33) of patients with the predominant occurrence of the HDV-1 genotype. A significant association of genotypes with alanine aminotransferase (ALT) and aspartate aminotransferase (AST) enzyme levels was observed in HBV monoinfections. The prevalence of the HDV-1 genotype is high in Vietnam. No correlation was observed between HDV-HBV coinfections and disease progression when compared to HBV monoinfections.


Assuntos
Vírus da Hepatite B/genética , Hepatite B Crônica/virologia , Hepatite D/virologia , Vírus Delta da Hepatite/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Coinfecção/virologia , Feminino , Genótipo , Vírus da Hepatite B/classificação , Vírus da Hepatite B/isolamento & purificação , Vírus Delta da Hepatite/classificação , Vírus Delta da Hepatite/isolamento & purificação , Humanos , Masculino , Pessoa de Meia-Idade , Filogenia , Prevalência , Vietnã , Adulto Jovem
19.
PLoS One ; 16(1): e0244507, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33411715

RESUMO

BACKGROUND: Within HIV/HBV infected patients, an increase in HDV infection has been observed; there is inadequate information on HDV prevalence as well as virologic profile in Ghana. This study sought to determine the presence of HDV in HIV/HBV co-infected patients in Ghana. METHODS: This was a longitudinal purposive study which enrolled 113 HIV/HBV co-infected patients attending clinic at Korle-Bu Teaching Hospital (KBTH) in Accra, Ghana. After consenting, 5 mL whole blood was collected at two-time points (baseline and 4-6 months afterwards). The sera obtained were tested to confirm the presence of HIV, HBV antibodies and/or antigens, and HBV DNA. Antibodies and viral RNA were also determined for HDV. Amplified HBV DNA and HDV RNA were sequenced and phylogenetic analysis carried out with reference sequences from the GenBank to establish the genotypes. RESULTS: Of the 113 samples tested 63 (55.7%) were females and 50 (44.25%) were males with a median age of 45 years. A total of 100 (88.5%) samples had detectable HBV surface antigen (HBsAg), and 32 out of the 113 had detectable HBV DNA. Nucleotide sequences were obtained for 15 and 2 samples of HBV and HDV, respectively. Phylogenetic analysis was predominantly genotype E for the HBVs and genotype 1 for the HDVs. Of the 13 samples that were HBsAg unreactive, 4 (30.8%) had detectable HBV DNA suggesting the incidence of occult HBV infections. The percentage occurrence of HDV in this study was observed to be 3.54. CONCLUSION: Our data suggest the presence and circulation of HDV and incidence of occult HBV infection in HIV/HBV co-infected patients in Ghana. This informs health staff and makes it imperative to look out for the presence of HDV and occult HBV in HIV/HBV co-infected patients presenting with potential risk of liver cancers and HBV transmission through haemodialysis and blood transfusions.


Assuntos
Coinfecção/virologia , Infecções por HIV/virologia , Vírus da Hepatite B/isolamento & purificação , Vírus da Hepatite B/fisiologia , Hepatite B/virologia , Vírus Delta da Hepatite/isolamento & purificação , Adulto , Alanina Transaminase/metabolismo , Aspartato Aminotransferases/metabolismo , Coinfecção/enzimologia , Feminino , Técnicas de Genotipagem , Gana , Infecções por HIV/enzimologia , Hepatite B/enzimologia , Vírus da Hepatite B/genética , Vírus Delta da Hepatite/fisiologia , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Adulto Jovem
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