RESUMO
BACKGROUND: The influence of sex on hepatitis C virus (HCV)-related outcomes is often neglected. The effects of sex on liver fibrosis progression and the effect of socioeconomic status on management are unclear. PATIENTS AND METHODS: Data were evaluated from patients followed at The Ottawa Hospital and Regional Viral Hepatitis Program. RESULTS: Of 1978 chronic HCV-infected patients, 630 (32%) were women. Women had lower liver enzyme levels, HCV RNA levels, and weight compared with men. Women were more likely to be non-genotype-1 infected, Black or Asian, and immigrants from Africa and Asia (all P<0.01). Under 50 years of age, women on average had lower fibrosis scores than men. Beyond the age of 50 years, the mean fibrosis scores were similar, suggesting a 'catch-up' phase. Women were less likely to have initiated interferon-based HCV antiviral therapy (35.3 vs. 43.3%, P=0.01). Crude sustained virological responses were higher in women (65.3 vs. 56.3%, P=0.03), but were similar to men as determined by multivariable analysis (odds ratio: 0.92, 95% confidence interval: 0.58-1.46). Women of low socioeconomic status were more likely to be HIV coinfected and had higher rates of fibrosis progression. Women living in low-income neighborhoods were less likely to achieve sustained virological response (odds ratio: 0.50, 95% confidence interval: 0.34-0.75, P=0.01) compared with women in higher income regions. CONCLUSION: Sex differences have been identified as a potential barrier to overcome when managing viral infections. Our analysis suggests that sex influences fibrosis progression, likelihood of initiating HCV antiviral therapy, and treatment outcomes.
Assuntos
Antivirais/uso terapêutico , Disparidades nos Níveis de Saúde , Disparidades em Assistência à Saúde , Hepatite C Crônica/tratamento farmacológico , Vírus de Hepatite/efeitos dos fármacos , Cirrose Hepática/tratamento farmacológico , Adulto , Antivirais/efeitos adversos , Biomarcadores/sangue , Distribuição de Qui-Quadrado , Progressão da Doença , Feminino , Genótipo , Hepatite C Crônica/sangue , Hepatite C Crônica/diagnóstico , Hepatite C Crônica/etnologia , Vírus de Hepatite/genética , Vírus de Hepatite/patogenicidade , Humanos , Cirrose Hepática/diagnóstico , Cirrose Hepática/etnologia , Cirrose Hepática/virologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Ontário/epidemiologia , RNA Viral/sangue , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais , Fatores de Tempo , Resultado do Tratamento , Carga ViralRESUMO
A novel hepatotropic virus, named NV-F virus, was recently identified. The clinical information for this virus is still scarce. Using PCR assay, NV-F viral DNA (NV-F-DNA) was detected in 12 of 50 (24%) hepatitis C virus (HCV)-infected patients (HCV-coinfected [HCVCI] group), 34 of 250 (13.6%) hepatitis B virus (HBV)-infected patients (HBV-coinfected [HBVCI] group), and 28 of 100 (28%) non-A-to-E (NAE) hepatitis patients. Basic clinical parameters were not significantly different among the three groups. By use of a PCR-based quantitative assay, the NV-F-DNA concentration was found to be above the detection limit (1.2 x 10(5) copies/ml) in 12/12 (100%) HCVCI patients, 14/34 (41.2%) HBVCI patients, and 4/28 (14.3%) NAE patients. The median serum NV-F-DNA concentration was 9.3 x 10(5) copies/ml in HCVCI patients, but it was below the detection limit in HBVCI and NAE patients (P values were 0.0045 and 0.0001, respectively). Stepwise multiple regression analysis identified the presence of anti-HCV as an independent factor for NV-F-DNA concentrations (beta = 6.2 x 10(9); P = 0.0245). In HBVCI patients, the NV-F-DNA concentration was inversely correlated with the HBV DNA concentration. The median NV-F-DNA concentration was below the detection limit in patients with HBV DNA concentrations above 1.4 x 10(5) copies/ml, but it was 1.58 x 10(6) copies/ml in patients with HBV DNA concentrations below 1.4 x 10(5) copies/ml (P = 0.030). In conclusion, NV-F-DNA concentrations were higher in HCVCI patients. A reciprocal relationship was found between NV-F-DNA and HBV DNA concentrations in HBVCI patients, indicating the presence of viral interference between these two DNA viruses.
Assuntos
DNA Viral/sangue , Hepatite B/complicações , Hepatite C/complicações , Vírus de Hepatite/isolamento & purificação , Hepatite Viral Humana/complicações , Hepatite Viral Humana/virologia , Adulto , Feminino , Hepacivirus/genética , Hepacivirus/isolamento & purificação , Hepatite B/fisiopatologia , Hepatite B/virologia , Vírus da Hepatite B/genética , Vírus da Hepatite B/isolamento & purificação , Hepatite C/fisiopatologia , Hepatite C/virologia , Vírus de Hepatite/genética , Hepatite Viral Humana/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase/métodos , RNA Viral/sangueRESUMO
Recent events illustrate the imperative to rapidly and accurately detect and identify pathogens during disease outbreaks, whether they are natural or engineered. Particularly for our primary goal of detecting bioterrorist releases, detection techniques must be both species-wide (capable of detecting all known strains of a given species) and species specific. Due to classification restrictions on the publication of data for species that may pose a bioterror threat, we illustrate the challenges of finding such assays using five nonthreat organisms that are nevertheless of public health concern: human immunodeficiency virus (HIV) and four species of hepatitis viruses. Fluorogenic probe-based PCR assays (TaqMan; Perkin-Elmer Corp., Applied Biosystems, Foster City, Calif.) may be sensitive, fast methods for the identification of species in which the genome is conserved among strains, such as hepatitis A virus. For species such as HIV, however, the strains are highly divergent. We use computational methods to show that nine TaqMan primer and probe sequences, or signatures, are needed to ensure that all strains will be detected, but this is an unfeasible number, considering the cost of TaqMan probes. Strains of hepatitis B, C, and E viruses show intermediate divergence, so that two to three TaqMan signatures are required to detect all strains of each virus. We conclude that for species such as hepatitis A virus with high levels of sequence conservation among strains, signatures can be found computationally for detection by the TaqMan assay, which is a sensitive, rapid, and cost-effective method. However, for species such as HIV with substantial genetic divergence among strains, the TaqMan assay becomes unfeasible and alternative detection methods may be required. We compare the TaqMan assay with some of the alternative nucleic acid-based detection techniques of microarray, chip, and bead technologies in terms of sensitivity, speed, and cost.
Assuntos
Infecções por HIV/virologia , HIV-1/classificação , Vírus de Hepatite/classificação , Hepatite Viral Humana/virologia , Reação em Cadeia da Polimerase/métodos , Taq Polimerase/metabolismo , Biologia Computacional , Primers do DNA , HIV-1/genética , HIV-1/isolamento & purificação , Vírus de Hepatite/genética , Vírus de Hepatite/isolamento & purificação , Humanos , Filogenia , Reação em Cadeia da Polimerase/economia , Especificidade da EspécieAssuntos
Doadores de Sangue , Sangue/virologia , DNA Viral/sangue , Controle de Infecções/métodos , Programas de Rastreamento/métodos , RNA Viral/sangue , Doadores de Sangue/legislação & jurisprudência , Transfusão de Sangue/legislação & jurisprudência , Transfusão de Sangue/normas , Transmissão de Doença Infecciosa/prevenção & controle , Infecções por HIV/sangue , Infecções por HIV/prevenção & controle , Infecções por HIV/transmissão , HIV-1/genética , HIV-1/isolamento & purificação , Antígenos de Superfície da Hepatite B/sangue , Vírus de Hepatite/genética , Vírus de Hepatite/isolamento & purificação , Hepatite Viral Humana/sangue , Hepatite Viral Humana/prevenção & controle , Hepatite Viral Humana/transmissão , Humanos , Controle de Infecções/legislação & jurisprudência , Licenciamento , Programas de Rastreamento/legislação & jurisprudência , Programas de Rastreamento/normas , Análise de Sequência com Séries de Oligonucleotídeos , Infecções por Parvoviridae/sangue , Infecções por Parvoviridae/prevenção & controle , Infecções por Parvoviridae/transmissão , Parvovirus B19 Humano/isolamento & purificação , Plasma , Guias de Prática Clínica como Assunto , Política Pública , Sensibilidade e Especificidade , Reação Transfusional , Inativação de VírusRESUMO
Despite the much lower actual yield than that estimated for hepatitis C virus (HCV) and human immunodeficiency virus (HIV) nucleic acid testing (NAT)-only positives in the USA and Germany, look-back procedures have revealed that no HCV transmission has occurred in Germany since the introduction of NAT. This indicates sufficient sensitivity of the pool-PCR approach. The slow ramp-up of hepatitis B virus (HBV) however, may require a different approach. It has been shown in Germany that the pooling of samples followed by virus enrichment results in a significant yield. Single donation testing for HBV would not increase the yield, because virus enrichment from mini-pool results in a similar sensitivity to that of single donation testing. Both strategies may be useful for extending future NAT to HBV screening. New candidate viruses for NAT are Parvo B19 and hepatitis A virus (HAV) because of their extreme resistance to inactivation procedures. Their low pathogenicity and epidemiologic characteristics, however, make them candidate viruses only for pooled source plasma. The main future issues of NAT will be related to the automation of pooling, extraction and amplification as a single homogeneous process. Depending on the throughput, automated single donation NAT as demonstrated by the 'Tigris' system may be an option, as far as all transfusion-relevant viruses will be included. In the near future high throughput systems will rely on pooled donor samples, most probably in conjunction with efficient enrichment procedures. For these systems, automation of the extraction and amplification process will be one of the first steps. These procedures will also limitthe costs of NAT and keep it available for use with future candidate viruses.