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1.
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
2.
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
3.
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
4.
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
6.
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
7.
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
9.
Nat Commun ; 11(1): 4383, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32873799

RESUMO

Mongolia has the highest incidence of hepatocellular carcinoma (HCC) in the world, but its causative factors and underlying tumor biology remain unknown. Here, we describe molecular characteristics of HCC from 76 Mongolian patients by whole-exome and transcriptome sequencing. We present a comprehensive analysis of mutational signatures, driver genes, and molecular subtypes of Mongolian HCC compared to 373 HCC patients of different races and ethnicities and diverse etiologies. Mongolian HCC consists of prognostic molecular subtypes similar to those found in patients from other areas of Asia, Europe, and North America, as well as other unique subtypes, suggesting the presence of distinct etiologies linked to Mongolian patients. In addition to common driver mutations (TP53, CTNNB1) frequently found in pan-cancer analysis, Mongolian HCC exhibits unique drivers (most notably GTF2IRD2B, PNRC2, and SPTA1), the latter of which is associated with hepatitis D viral infection. These results suggest the existence of new molecular mechanisms at play in Mongolian hepatocarcinogenesis.


Assuntos
Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/genética , Regulação Neoplásica da Expressão Gênica , Hepatite D/genética , Neoplasias Hepáticas/genética , Idoso , Carcinogênese/genética , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/cirurgia , Carcinoma Hepatocelular/virologia , Análise Mutacional de DNA , Feminino , Perfilação da Expressão Gênica , Hepatectomia , Hepatite D/epidemiologia , Hepatite D/cirurgia , Hepatite D/virologia , Vírus Delta da Hepatite/isolamento & purificação , Humanos , Incidência , Fígado/patologia , Fígado/cirurgia , Fígado/virologia , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Mongólia/epidemiologia , Mutação , Prognóstico , Sequenciamento do Exoma
10.
Hepatol Int ; 14(5): 869-880, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32895876

RESUMO

PURPOSE: To evaluate the effect of hepatitis D virus (HDV) on hepatitis B virus-hepatocellular carcinoma (HBV-HCC) co-recurrence in patients undergoing living donor liver transplantation (LDLT) for HBV alone or HBV-HDV coinfection. METHODS: Between 2002 and 2019, 254 HBV-HCC patients underwent LDLT. The patients were divided into two groups after the application of the exclusion criteria: HBV-HCC (Group B; n = 163) and HBV-HDV-HCC (Group D; n = 31). First, the B and D groups were compared in terms of demographic and clinical parameters. Second, patients with (n = 16) and without (n = 178) post-transplant HBV-HCC co-recurrences were grouped and compared in terms of the same parameters. RESULTS: Although the risk of HBV-HCC co-recurrence in group D was 4.99-fold higher than in group B, the risk of HBV recurrence alone in group D was 12.5-fold lower than in group B. The AFP (OR = 4.4), Milan criteria (beyond; OR = 18.8), and HDV (OR = 8.1) were identified as the independent risk factors affecting post-transplant HBV-HCC co-recurrence. The Milan criteria (OR = 2.1) and HBV-HCC co-recurrence (OR = 10.9) were identified as the risk factors affecting post-transplant mortality. HBV-HCC co-recurrence developed in 26.5% of patients in Group B and 100% in Group D (OR = 40; p = 0.001). HCC recurrence alone developed in 10% of patients without HBV recurrence in group B and 0% of patients without HBV recurrence in group D (OR = 5.7). CONCLUSION: This study showed that the risk of HBV recurrence alone was reduced by 12.5-fold in the presence of HDV; however, the HCC recurrence occurred in all patients with HDV when HBV recurrence developed.


Assuntos
Carcinoma Hepatocelular , Vírus da Hepatite B , Hepatite B Crônica , Hepatite D , Neoplasias Hepáticas , Transplante de Fígado , Complicações Pós-Operatórias , Adulto , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/cirurgia , Carcinoma Hepatocelular/virologia , Coinfecção/epidemiologia , Coinfecção/virologia , Feminino , Vírus da Hepatite B/isolamento & purificação , Vírus da Hepatite B/patogenicidade , Hepatite B Crônica/complicações , Hepatite B Crônica/diagnóstico , Hepatite B Crônica/epidemiologia , Hepatite B Crônica/fisiopatologia , Hepatite D/complicações , Hepatite D/diagnóstico , Vírus Delta da Hepatite/isolamento & purificação , Humanos , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/virologia , Transplante de Fígado/efeitos adversos , Transplante de Fígado/métodos , Masculino , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/fisiopatologia , Complicações Pós-Operatórias/virologia , Recidiva , Medição de Risco , Fatores de Risco , Turquia/epidemiologia
11.
Public Health ; 185: 341-347, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32738575

RESUMO

OBJECTIVES: The burden of hepatitis B virus (HBV) and hepatitis D virus (HDV) infections is unknown in Georgia. This analysis describes the prevalence of hepatitis B and coinfection with HDV and the demographic characteristics and risk factors for persons with HBV infection in Georgia. STUDY DESIGN: This is a cross-sectional seroprevalence study. METHODS: A cross-sectional, nationwide survey to assess hepatitis B prevalence among the general adult Georgian population (age ≥18 years) was conducted in 2015. Demographic and risk behavior data were collected. Blood specimens were screened for anti-hepatitis B core total antibody (anti-HBc). Anti-HBc-positive specimens were tested for hepatitis B surface antigen (HBsAg). HBsAg-positive specimens were tested for HBV and HDV nucleic acid. Nationally weighted prevalence estimates and adjusted odds ratios (aORs) for potential risk factors were determined for anti-HBc and HBsAg positivity. RESULTS: The national prevalence of anti-HBc and HBsAg positivity among adults were 25.9% and 2.9%, respectively. Persons aged ≥70 years had the highest anti-HBc positivity (32.7%), but the lowest HBsAg positivity prevalence (1.3%). Anti-HBc positivity was associated with injection drug use (aOR = 2.34; 95% confidence interval [CI] = 1.46-3.74), receipt of a blood transfusion (aOR = 1.68; 95% CI = 1.32-2.15), and sex with a commercial sex worker (aOR = 1.46; 95% CI = 1.06-2.01). HBsAg positivity was associated with receipt of a blood transfusion (aOR = 2.72; 95% CI = 1.54-4.80) and past incarceration (aOR = 2.72; 95% CI = 1.25-5.93). Among HBsAg-positive persons, 0.9% (95% CI = 0.0-2.0) were HDV coinfected. CONCLUSIONS: Georgia has an intermediate to high burden of hepatitis B, and the prevalence of HDV coinfection among HBV-infected persons is low. Existing infrastructure for hepatitis C elimination could be leveraged to promote hepatitis B elimination.


Assuntos
Coinfecção/epidemiologia , Hepatite B/epidemiologia , Hepatite D/epidemiologia , Adolescente , Adulto , Idoso , Estudos Transversais , Feminino , Georgia/epidemiologia , Anticorpos Anti-Hepatite B/sangue , Antígenos de Superfície da Hepatite B/sangue , Vírus da Hepatite B/isolamento & purificação , Vírus Delta da Hepatite/isolamento & purificação , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Estudos Soroepidemiológicos , Profissionais do Sexo/estatística & dados numéricos , Inquéritos e Questionários , Adulto Jovem
12.
BMC Infect Dis ; 20(1): 565, 2020 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-32746807

RESUMO

BACKGROUND: Patients coinfected with HBV and hepatitis D virus (HDV) have a greater risk of HCC and cirrhosis. The current study was undertaken to assess HDV genotype distribution and determine clinical characteristics of hepatitis delta virus (HDV) among HBsAg positive individuals in Shanghai. METHOD: This retrospective study involved 225 serum samples from HBsAg positive hospitalized patients from October 2010 to April 2013. HDV-specific RT-nested PCR was used to amplify HDV RNA. HDV genotypes were characterized by Next-generation sequencing (NGS), followed by phylogenetic analyses. HDV/HBV co-infected patients and HBV mono-infected patients were compared clinically and virologically. RESULTS: Out of the 225 HBsAg-positive serum samples with elevated transaminases, HDV-RNA was identified in 11 (4.9%) patients. The HBV loads in the HDV positive group were significantly lower than the HDV negative HBV-infected patients. The aminotransferase enzymes were significantly higher in HDV/HBV co-infected compared to HDV negative patients (P < 0.05). Phylogenetic analyses indicated that HDV-2 genotype being the predominant genotype, other HDV genotypes were not observed. HDV/HBV patients were significantly associated with a rather unfavourable clinical outcome. CONCLUSION: In summary, the prevalence of HDV infection in patients with elevated transaminases is not low and the predominance of HDV genotype 2 infection in Shanghai. This finding helps us to better understand the correlation of HDV/HBV co-infection. Moreover, Next-generation sequencing (NGS) technologies provide a rapid, precise method for generating HDV genomes to define infecting genotypes.


Assuntos
Hepatite D/diagnóstico , Vírus Delta da Hepatite/genética , Adulto , Sequência de Aminoácidos , China/epidemiologia , Coinfecção , Feminino , Genótipo , Hepatite B/diagnóstico , Hepatite B/virologia , Antígenos de Superfície da Hepatite B/sangue , Hepatite D/epidemiologia , Hepatite D/virologia , Vírus Delta da Hepatite/classificação , Vírus Delta da Hepatite/isolamento & purificação , Humanos , Masculino , Pessoa de Meia-Idade , Filogenia , Prevalência , RNA Viral/química , RNA Viral/metabolismo , Estudos Retrospectivos , Fatores de Risco , Carga Viral , Adulto Jovem
13.
J Hepatol ; 73(5): 1046-1062, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32634548

RESUMO

BACKGROUND & AIMS: HDV infection causes severe chronic liver disease in individuals infected with HBV. However, the factors associated with poor prognosis are largely unknown. Thus, we aimed to identify prognostic factors in patients with HDV infection. METHODS: The French National Reference Centre for HDV performed a nationwide retrospective study on 1,112 HDV-infected patients, collecting epidemiological, clinical, virological and histological data from the initial referral to the last recorded follow-up. RESULTS: The median age of our cohort was 36.5 (29.9-43.2) years and 68.6% of our cohort were male. Most patients whose birthplace was known were immigrants from sub-Saharan Africa (52.5%), southern and eastern Europe (21.3%), northern Africa and the Middle East (6.2%), Asia (5.9%) and South America (0.3%). Only 150 patients (13.8%) were French native. HDV load was positive in 659 of 748 tested patients (88.1%). HDV-1 was predominant (75.9%), followed by sub-Saharan genotypes: HDV-5 (17.6%), HDV-7 (2.9%), HDV-6 (1.8%) and HDV-8 (1.6%). At referral, 312 patients (28.2%) had cirrhosis, half having experienced at least 1 episode of hepatic decompensation. Cirrhosis was significantly less frequent in African than in European patients regardless of HDV genotype. At the end of follow-up (median 3.0 [0.8-7.2] years), 48.8% of the patients had developed cirrhosis, 24.2% had ≥1 episode(s) of decompensation and 9.2% had hepatocellular carcinoma. European HDV-1 and African HDV-5 patients were more at risk of developing cirrhosis. Persistent replicative HDV infection was associated with decompensation, hepatocellular carcinoma and death. African patients displayed better response to interferon therapy than non-African patients (46.4% vs. 29.1%, p <0.001). HDV viral load at baseline was significantly lower in responders than in non-responders. CONCLUSION: Place of birth, HDV genotype and persistent viremia constitute the main determinants of liver involvement and response to treatment in chronic HDV-infected patients. LAY SUMMARY: Chronic liver infection by hepatitis delta virus (HDV) is the most severe form of chronic viral hepatitis. Despite the fact that at least 15-20 million people are chronically infected by HDV worldwide, factors determining the severity of liver involvement are largely unknown. By investigating a large cohort of 1,112 HDV-infected patients followed-up in France, but coming from different areas of the world, we were able to determine that HDV genotype, place of birth (reflecting both viral and host-related factors) and persistent viremia constitute the main determinants of liver involvement and response to treatment.


Assuntos
Carcinoma Hepatocelular , Hepatite D Crônica , Vírus Delta da Hepatite , Cirrose Hepática , Neoplasias Hepáticas , Viremia , Adulto , Carcinoma Hepatocelular/etnologia , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/virologia , Feminino , França/epidemiologia , Hepatite D Crônica/complicações , Hepatite D Crônica/diagnóstico , Hepatite D Crônica/epidemiologia , Hepatite D Crônica/terapia , Vírus Delta da Hepatite/genética , Vírus Delta da Hepatite/isolamento & purificação , Vírus Delta da Hepatite/patogenicidade , Humanos , Interferons/uso terapêutico , Cirrose Hepática/diagnóstico , Cirrose Hepática/etnologia , Cirrose Hepática/etiologia , Neoplasias Hepáticas/etnologia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/virologia , Masculino , Características de Residência/estatística & dados numéricos , Estudos Retrospectivos , Índice de Gravidade de Doença , Carga Viral/métodos , Carga Viral/estatística & dados numéricos , Viremia/diagnóstico , Viremia/etnologia
14.
Viruses ; 12(5)2020 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-32422927

RESUMO

Hepatitis D virus (HDV) causes the most severe form of viral hepatitis, which may rapidly progress to liver cirrhosis and hepatocellular carcinoma (HCC). It has been estimated that 15-20 million people worldwide are suffering from the chronic HDV infection. Currently, no effective therapies are available to treat acute or chronic HDV infection. The remarkable sequence variability of the HDV genome, particularly within the hypervariable region has resulted in the provisional classification of eight major genotypes and various subtypes. We have developed a specialized database, HDVdb (http://hdvdb.bio.wzw.tum.de/), which contains a collection of partial and complete HDV genomic sequences obtained from the GenBank and from our own patient cohort. HDVdb enables the researchers to investigate the genetic variability of all available HDV sequences, correlation of genotypes to epidemiology and pathogenesis. Additionally, it will contribute in understanding the drug resistant mutations and develop effective vaccines against HDV infection. The database can be accessed through a web interface that allows for static and dynamic queries and offers integrated generic and specialized sequence analysis tools, such as annotation, genotyping, primer prediction, and phylogenetic analyses.


Assuntos
Bases de Dados Genéticas , Vírus Delta da Hepatite/genética , Genoma Viral , Hepatite D/virologia , Vírus Delta da Hepatite/classificação , Vírus Delta da Hepatite/isolamento & purificação , Humanos , Internet , Filogenia
16.
BMC Gastroenterol ; 20(1): 24, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32000689

RESUMO

BACKGROUND: Chronic hepatitis delta virus (HDV) infection causes severe liver disease which often leads to cirrhosis and hepatocellular carcinoma (HCC). Aim of this study was to establish the disease severity and prognostic factors for disease outcome by analysing frequencies of clinical events and their correlation with baseline virological and biochemical parameters as well as interferon and nucleos(t)ide analogue treatment choice. METHODS: We studied a single-centre cohort of 49 anti-HDAg-positive patients with HBsAg persistence for at least 6 months. Virological and biochemical parameters, interferon and nucleos(t)ide analogue treatment choice as well as clinical events during follow-up were analysed by retrospective chart review (mean follow-up time 3 years, range 0.25-7.67 years). RESULTS: Severe clinical events occurred in 11/49 hepatitis D patients, including HCC (8/49), death (8/49) or liver transplantation (2/49). HCCs only occurred secondary to liver cirrhosis and their event rates in this cohort of hepatitis D patients did not differ from a matched HBV mono-infected cohort with comparable frequency of liver cirrhosis. A stepwise multivariate logistic regression revealed low platelet count (p = 0. 0290) and older age (p = 0.0337) correlating most strongly with overall clinical events, while serum HDV RNA positivity at baseline did not correlate with any clinical outcome. Interferon-free but not nucleos(t)ide analogue-free patient care correlated with the occurrence of HCC at logistic regression, although only 3/18 interferon-treated patients demonstrated repeatedly negative HDV PCR results post therapy. CONCLUSIONS: Our data indicate that progressive liver disease at baseline plays a major role as predictive factor for overall clinical outcome of hepatitis D patients. In particular, HCC risk may not be underestimated in hepatitis D virus RNA negative hepatitis D patients with advanced liver fibrosis.


Assuntos
Carcinoma Hepatocelular/epidemiologia , Coinfecção/epidemiologia , Hepatite B Crônica/epidemiologia , Hepatite D Crônica/epidemiologia , Cirrose Hepática/epidemiologia , Neoplasias Hepáticas/epidemiologia , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/virologia , Estudos de Coortes , Coinfecção/complicações , Coinfecção/tratamento farmacológico , Feminino , Alemanha/epidemiologia , Antígenos de Superfície da Hepatite B/sangue , Vírus da Hepatite B/genética , Vírus da Hepatite B/isolamento & purificação , Hepatite B Crônica/complicações , Hepatite B Crônica/tratamento farmacológico , Hepatite D Crônica/complicações , Hepatite D Crônica/tratamento farmacológico , Vírus Delta da Hepatite/genética , Vírus Delta da Hepatite/isolamento & purificação , Antígenos da Hepatite delta/sangue , Humanos , Interferons/uso terapêutico , Cirrose Hepática/virologia , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/virologia , Transplante de Fígado , Estudos Longitudinais , Masculino , Morbidade , Nucleosídeos/uso terapêutico , Estudos Retrospectivos
18.
Viruses ; 11(11)2019 10 29.
Artigo em Inglês | MEDLINE | ID: mdl-31671829

RESUMO

The hepatitis delta virus (HDV) is a globally distributed agent, and its genetic variability allows for it to be organized into eight genotypes with different geographic distributions. In South America, genotype 3 (HDV-3) is frequently isolated and responsible for the most severe form of infection. The objective of this study was to evaluate the evolutionary and epidemiological dynamics of HDV-3 over the years and to describe its distribution throughout this continent in an evolutionary perspective. While using Bayesian analysis, with strains being deposited in the Nucleotide database, the most recent common ancestor was dated back to 1964 and phylogenetic analysis indicated that the dispersion may have started in Brazil, spreading to Venezuela and then to Colombia, respectively. Exponential growth in the effective number of infections was observed between the 1950s and 1970s, years after the first report of the presence of HDV on the continent, during the Labrea Black Fever outbreak, which showed that the virus continued to spread, increasing the number of cases decades after the first reports. Subsequently, the analysis showed a decrease in the epidemiological levels of HDV, which was probably due to the implantation of the vaccine against its helper virus, hepatitis B virus, and serological screening methods implemented in the blood banks.


Assuntos
Hepatite D/virologia , Vírus Delta da Hepatite/classificação , Vírus Delta da Hepatite/genética , Teorema de Bayes , Evolução Molecular , Variação Genética , Genótipo , Hepatite D/epidemiologia , Hepatite D/transmissão , Vírus Delta da Hepatite/isolamento & purificação , Antígenos da Hepatite delta/genética , Humanos , Filogenia , Filogeografia , RNA Viral/genética , América do Sul/epidemiologia
19.
Viral Immunol ; 32(8): 335-340, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31553269

RESUMO

Hepatitis delta virus (HDV) is a highly pathogenic virus and causes rapid disease progression from fulminant hepatitis to development of hepatocellular carcinoma in patients infected with hepatitis B virus (HBV). HDV is endemic in Pakistan; however, there are no available data on HDV prevalence among the high-risk group of HBV-infected pregnant women. A total of 1,394 pregnant women, visiting different public-sector hospitals in Lahore, were enrolled in this study. Their demographic data and blood samples were collected from May 2016 to July 2017. Samples were screened for both HBsAg and anti-HDV. Anti-HDV positive samples were tested for HDV RNA, and samples positive for HDV RNA were further sequenced to determine the HDV genotype. Of the 1,394 samples, HBsAg was positive in 63 (4.5%). Of these 63 HBsAg-positive samples, 13 (20.63%) were positive for anti-HDV. Of the 13 HBsAg/anti-HDV positive samples, HDV RNA was detected in 4 (30.8%) samples and all 4 carried HDV genotype 1. The age of enrolled women varied from 20 to 40 years, with most of the women living in urban areas, having education more than secondary school level, belonging to middle class, and being housewives. Majority of the tested women were of age from 25 to 30 years (39.2%); however, the prevalence of HBV was higher in age group 31-35 years (10.7%, confidence interval [CI]: 4.73-16.67); however, anti-HDV prevalence was 1.9% (CI: -0.7 to 4.7). This study is the first report on HDV prevalence among pregnant women in Pakistan. Our study showed a high predominance of HDV (20.63%) in HBV-infected pregnant women and the prevalence of HDV genotype 1 infection. The findings contribute to a better understanding of the HDV/HBV coinfection among pregnant women and circulating HDV genotypes in the country.


Assuntos
Coinfecção/epidemiologia , Hepatite B/epidemiologia , Hepatite D/epidemiologia , Hepatite D/virologia , Vírus Delta da Hepatite/isolamento & purificação , Adulto , Anticorpos Antivirais/sangue , Coinfecção/virologia , Feminino , Genótipo , Hepatite B/virologia , Antígenos de Superfície da Hepatite B/sangue , Vírus da Hepatite B/imunologia , Vírus Delta da Hepatite/classificação , Vírus Delta da Hepatite/genética , Vírus Delta da Hepatite/imunologia , Humanos , Paquistão/epidemiologia , Filogenia , Gravidez , Prevalência , RNA Viral/sangue , RNA Viral/genética , Adulto Jovem
20.
Diagn Microbiol Infect Dis ; 95(4): 114873, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31473034

RESUMO

Hepatitis B/D virus infection leads to severe liver disease. HDV infection is not routinely investigated since the diagnosis is based on enzyme immunoassays (EIAs), which are not available in all laboratories. This study investigates the performance of new automated assay for anti HDV Ab detection: LIAISON® XL Murex anti-HDV. HBsAg-positive samples were evaluated for HDV serology using the ETI-AB-DELTAK-2 and the new LIAISON® XL Murex with a concordance of 97.5% and 2.42% discordant results. The discordant specimens reacted negatively with EIA and positively with the new test. Dilutions of HDV-purified antibodies and HDV-positive samples were tested with both assays, showing a lower detection limit for the new assay. In conclusion, LIAISON® XL Murex showed a good concordance with the reference method and allowed a more rapid HDV detection. This new diagnostic tool may be useful for a more efficient approach to the HDV diagnosis and evaluation of HDV epidemiology.


Assuntos
Anticorpos Anti-Hepatite/sangue , Hepatite D/diagnóstico , Vírus Delta da Hepatite/imunologia , Vírus Delta da Hepatite/isolamento & purificação , Técnicas Imunoenzimáticas/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Automação Laboratorial , Feminino , Antígenos de Superfície da Hepatite B/sangue , Humanos , Técnicas Imunoenzimáticas/normas , Medições Luminescentes , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Testes Sorológicos , Adulto Jovem
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