RESUMO
Some individuals infected with hepatitis C virus (HCV) experience multiple episodes of acute hepatitis. It is unclear whether these episodes are due to reinfection with HCV or to reactivation of the original virus infection. Markers of viral replication and host immunity were studied in five chimpanzees sequentially inoculated over a period of 3 years with different HCV strains of proven infectivity. Each rechallenge of a convalescent chimpanzee with the same or a different HCV strain resulted in the reappearance of viremia, which was due to infection with the subsequent challenge virus. The evidence indicates that HCV infection does not elicit protective immunity against reinfection with homologous or heterologous strains, which raises concerns for the development of effective vaccines against HCV.
Assuntos
Hepatite C/imunologia , Doença Aguda , Idoso , Alanina Transaminase/biossíntese , Animais , Sequência de Bases , Hepacivirus/fisiologia , Anticorpos Anti-Hepatite/biossíntese , Anticorpos Anti-Hepatite C , Humanos , Imunidade Ativa , Estudos Longitudinais , Dados de Sequência Molecular , Pan troglodytes , Reação em Cadeia da Polimerase , Homologia de Sequência , Transcrição Gênica , Viremia , Replicação ViralRESUMO
The mechanisms by which hepatitis C virus (HCV) induces chronic infection in the vast majority of infected individuals are unknown. Sequences within the HCV E1 and E2 envelope genes were analyzed during the acute phase of hepatitis C in 12 patients with different clinical outcomes. Acute resolving hepatitis was associated with relative evolutionary stasis of the heterogeneous viral population (quasispecies), whereas progressing hepatitis correlated with genetic evolution of HCV. Consistent with the hypothesis of selective pressure by the host immune system, the sequence changes occurred almost exclusively within the hypervariable region 1 of the E2 gene and were temporally correlated with antibody seroconversion. These data indicate that the evolutionary dynamics of the HCV quasispecies during the acute phase of hepatitis C predict whether the infection will resolve or become chronic.
Assuntos
Evolução Molecular , Hepacivirus/genética , Hepatite C Crônica/virologia , Hepatite C/virologia , Proteínas do Envelope Viral/genética , Doença Aguda , Adulto , Idoso , Anticorpos Antivirais , Progressão da Doença , Feminino , Genes Virais , Variação Genética , Hepacivirus/imunologia , Hepacivirus/fisiologia , Hepatite C/imunologia , Anticorpos Anti-Hepatite C/biossíntese , Hepatite C Crônica/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Filogenia , Estudos Prospectivos , Seleção Genética , Fatores de Tempo , Proteínas do Envelope Viral/imunologia , Replicação ViralRESUMO
Natural products are a successful source in drug discovery, playing a significant role in maintaining human health. We investigated the in vitro cytotoxicity and antiviral activity of extracts from 18 traditionally used Mediterranean plants. Noteworthy antiviral activity was found in the extract obtained from the branches of Daphne gnidium L. against human immunodeficiency virus type-1 (EC50 = 0.08 µg/mL) and coxsackievirus B5 (EC50 = 0.10 µg/mL). Other relevant activities were found against BVDV, YFV, Sb-1, RSV and HSV-1. Interestingly, extracts from Artemisia arborescens L. and Rubus ulmifolius Schott, as well as those from D. gnidium L., showed activities against two different viruses. This extensive antiviral screening allowed us to identify attractive activities, offering opportunities to develop lead compounds with a great pharmaceutical potential.
Assuntos
Antivirais/farmacologia , Artemisia/química , Daphne/química , Extratos Vegetais/farmacologia , Rubus/química , Antivirais/isolamento & purificação , Enterovirus Humano B/efeitos dos fármacos , HIV-1/efeitos dos fármacos , Região do Mediterrâneo , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologiaRESUMO
OBJECTIVES: To investigate the correlation between the serum levels of the CC-chemokines RANTES, macrophage inflammatory protein (MIP)-1alpha and MIP-1beta, and the progression of HIV-1 disease. DESIGN: Retrospective analysis of serial serum samples from HIV-1 seroconverters selected according to clinical outcome. METHODS: Twenty-one patients, derived from a cohort recruited between 1985 and 1996 for a prospective study of the natural history of HIV infection, were analysed. All patients had at least one HIV-1-seronegative sample within 1 year prior to the first seropositive test and were followed longitudinally throughout the course of HIV-1 infection (mean follow-up, 73.5 months). Nine were rapid progressors (RP; patients who developed AIDS within 60 months of antibody seroconversion), seven were slow progressors (SP; patients who developed AIDS after 60 months), and five were long-term asymptomatic (LTA; patients with circulating CD4+ cells higher than 400 x 10(6)/l, no signs of HIV disease, no antiretroviral therapy for more than 96 months). A total of 339 serum samples was studied (mean, 16.1 per patient). The levels of RANTES, MIP-1alpha and MIP-1beta were measured by enzyme-linked immunosorbent assay and correlated with different immunological and clinical parameters. RESULTS: Over the entire follow-up period, the geometric mean of serum RANTES was significantly higher in RP [68.6 ng/ml; 95% confidence interval (CI), 56.9-82.7] than in SP (23.7 ng/ml; 95% CI, 20.0-28.2; P < 0.001) and LTA (19.5 ng/ml; 95% CI, 15.5-24.5; P < 0.001). This difference was already significant during the early clinical stages, when patients had peripheral blood CD4+ cell counts still greater than 400 x 10(6)/l (P < 0.001). By contrast, the mean serum levels of MIP-1alpha and MIP-1beta did not differ significantly between the three study groups. Multivariate analysis using the Cox proportional hazard model demonstrated that the mean serum concentration of RANTES before the development of AIDS was independently associated with the time to AIDS (relative risk, 4.5; 95% CI, 1.1-18.2; P = 0.035). In patients with low versus high mean serum RANTES before the fall of CD4+ cells below 400 x 10(6)/l, the median AIDS-free time was 117.5 and 42.7 months, respectively (P = 0.037). CONCLUSION: These data suggest that an elevation of serum RANTES predicts a rapid progression of the disease since the early stages of HIV-1 infection.
Assuntos
Quimiocina CCL5/sangue , Infecções por HIV/sangue , HIV-1 , Proteínas Inflamatórias de Macrófagos/sangue , Adulto , Quimiocina CCL3 , Quimiocina CCL4 , Feminino , Humanos , Estudos Longitudinais , Masculino , Estudos RetrospectivosRESUMO
Although recent evidence indicates that the quasispecies nature of HCV constitutes a critical strategy for the virus to survive in the host, the mechanisms of viral persistence remain unknown. Similarly, the correlates of immune protection in a limited proportion of individuals who succeed in clearing HCV are still largely undefined. Understanding the mechanisms of sterilizing immunity is essential for devising preventive measures against HCV and unraveling how the virus eludes such immunity. As in other viral infections, the complex interactions between the virus and the host early in the course of HCV infection probably determine the outcome of the disease (i.e., resolution or persistence). The evidence now accumulated on HCV and other models of viral infection is compatible with the hypothesis that both cellular and humoral components are needed for definitive viral clearance. Nevertheless, detailed studies of the specific cellular and humoral immune responses during the incubation period and the acute phase of hepatitis C, in relation to the viral quasispecies evolution and the clinical outcome, are still lacking both in humans and in the chimpanzee model. Until such studies are performed, most ideas of viral clearance mechanisms remain hypothetical, and the immunologic basis of HCV clearance will continue to be inferred from associations rather than from causal relationships.
Assuntos
Hepacivirus/genética , Hepacivirus/patogenicidade , Doença Aguda , Animais , Antivirais/uso terapêutico , Evolução Biológica , Farmacorresistência Viral , Variação Genética , Hepacivirus/efeitos dos fármacos , Hepacivirus/imunologia , Hepatite C/tratamento farmacológico , Hepatite C/etiologia , Hepatite C/virologia , Hepatite C Crônica/etiologia , HumanosRESUMO
The cause of acute viral hepatitis in 141 patients admitted to both Infectious Diseases Hospitals in Harare (Zimbabwe) was hepatitis A in 44, hepatitis B in 86 and hepatitis Non-A Non-B in 11. The wide distribution of hepatitis A and B viruses and early exposure to both in Zimbabwe are shown by the high positivity rate for anti-HAV antibody in patients under 10 years old (87.5%) and for anti-HBs antibody in patients over 20 (60%). Among the 86 hepatitis B cases, e and delta systems were also investigated: 66 patients (76.5%) were HBeAg positive, six (7%) anti-HBe positive and 14 (16.5%) negative for both; only one was anti-delta positive. Two cases of fulminant liver failure (both occurring in HBsAg and anti-HBc IgM positive, but delta-markers negative patients) and five cases of hepatoma (only one of whom was negative for all HBV markers) are described.
Assuntos
Hepatite Viral Humana/epidemiologia , Doença Aguda , Adolescente , Adulto , Idoso , Carcinoma Hepatocelular/epidemiologia , Criança , Pré-Escolar , Feminino , Hepatite A/epidemiologia , Hepatite B/epidemiologia , Hepatite C/epidemiologia , Hepatite Viral Humana/imunologia , Humanos , Neoplasias Hepáticas/epidemiologia , Masculino , Pessoa de Meia-Idade , Grupos Raciais , ZimbábueRESUMO
Hepatitis C virus (HCV), the major causative agent of post-transfusion and community-acquired non-A, non-B (NANB), is a single-stranded RNA virus characterized by a high degree of genetic heterogeneity. HCV is endemic worldwide and is a major cause of chronic liver disease and hepatocellular carcinoma. The development of a broadly reactive vaccine is a high priority for the control of HCV infection. In recent years, however, serious concerns have been raised regarding the degree of protective immunity elicited by HCV in the host. Several observations, both in patients and in the chimpanzee model, have suggested a lack of protective immunity against HCV. Chronic HCV infection develops in more than 80% of patients, suggesting that in most cases the immune response of the host fails to mediate resolution of the infection. Cross-challenge studies demonstrated that convalescent chimpanzees are not protected against re-infection with homologous or heterologous HCV strains. Similar evidence has been obtained in polytransfused beta-thalassemic children, in whom re-infection with HCV was associated with multiple episodes of acute hepatitis. Although most of the evidence thus far accumulated suggests that HCV does not elicit a protective immune response, recent studies have provided experimental evidence, both in vitro and in vivo, that HCV infection induces a neutralizing antibody response in humans. However, such antibodies are isolate-restricted and ineffective against variant HCV strains emerging in vivo. Recently, using recombinant envelope proteins of HCV, a successful vaccination of chimpanzees against challenge with a homologous viral strain was reported. Whether this vaccine can provide protection against challenge with a higher infectious dose of the homologous virus or against challenge with heterologous strains of HCV remains to be established. Overall, the data hitherto accumulated indicate that the genetic heterogeneity of HCV will be a major impediment for the development of a broadly reactive vaccine for the control of HCV infection.
Assuntos
Hepacivirus/imunologia , Formação de Anticorpos , Heterogeneidade Genética , Hepacivirus/genética , Hepacivirus/patogenicidade , Hepatite C/genética , Hepatite C/imunologia , Humanos , Imunidade Celular , Imunidade Inata , Linfócitos T Citotóxicos/imunologiaRESUMO
The presence of HBV DNA was assessed in the serum samples from 878 HBsAg negative Sardinian blood donors. They were composed of 481 (55%) donors selected because of abnormal serum alanine aminotransferase (ALT) levels during routine testing of their blood donation, and of 397 donors (45%) selected on the basis of normal serum ALT activities. HBV DNA sequences were detected in 37 (7.7%) out of 481 subjects with abnormal ALT and in 2 (0.5%) out of 397 subjects with normal ALT. Anti-HBc was detected in 199 (41%) of the 481 subjects with abnormal ALT and in 81 (20%) out of 397 subjects with normal ALT. Among the 39 subjects positive for serum HBV DNA, 12 (31%) were positive for anti-HBc, while 27 (69%) were negative for all serological HBV markers. These data show in Sardinia, where HBV infection is endemic, there is a high frequency of HBsAg negative HBV DNA positive individuals in whom multiplication of HBV may occur without conventional serological HBV markers, suggesting the possible existence of HBV-like viruses which may be responsible for some of the presumed non-A non-B hepatitis.
Assuntos
Doadores de Sangue , DNA Viral/sangue , Antígenos de Superfície da Hepatite B/sangue , Vírus da Hepatite B/genética , Adulto , Autorradiografia , Sequência de Bases , Feminino , Anticorpos Anti-Hepatite B/sangue , Antígenos do Núcleo do Vírus da Hepatite B/imunologia , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Hibridização de Ácido Nucleico , Transaminases/sangueRESUMO
In order to determine whether the immunological abnormalities described in intravenous drug addicts (IDA), are due to HIV infection, other viral infections or to the abuse of narcotic drugs, we studied the T lymphocyte subsets and serological markers of infection with hepatitis B and delta virus, cytomegalovirus and Epstein Barr virus, in 49 IDA. The immunological and serological features of IDA were compared with the control group, made up of 20 healthy subjects. In intravenous drug abusers we found a significant increase in the number of total lymphocytes (P less than 0.01), T-lymphocytes (P less than 0.05), T-suppressor cells (P less than 0.05), and serum IgG levels (P less than 0.0001) as compared with the control group. The prevalence of serological markers of infection with hepatitis B virus, hepatitis delta virus, cytomegalovirus and Epstein Barr virus was significantly higher in IDA as compared with the controls. In conclusion our study demonstrates that T-lymphocyte subsets in IDA seronegative for HIV infection are characterized by an enhancement of peripheral lymphocyte cells with a normal OKT4/OKT8 ratio.
Assuntos
Soropositividade para HIV , Dependência de Heroína/imunologia , Imunoglobulinas/análise , Linfócitos/imunologia , Viroses/imunologia , Adulto , Infecções por Citomegalovirus/imunologia , Ensaio de Imunoadsorção Enzimática , Feminino , Hepatite B/imunologia , Hepatite D/imunologia , Infecções por Herpesviridae/imunologia , Herpesvirus Humano 4 , Humanos , Contagem de Leucócitos , Masculino , Linfócitos T/imunologia , Linfócitos T Reguladores/imunologiaRESUMO
Hepatitis B virus (HBV) DNA sequences were assessed in 26 patients with acute type B hepatitis, using dot-blot hybridization technique from peripheral blood mononuclear cells (PBMC), during different phases of the illness. At clinical presentation, 15% of patients showed HBV-DNA sequences in PBMC, while serum HBV-DNA was detected in 58% of patients. During clinical improvement 50% of patients had HBV-DNA in PBMC but only 11.5% were positive for serum HBV-DNA. Twenty-three (88.5%) patients recovered and cleared HBV-DNA from serum and from PBMC; three (11.5%) patients with acute hepatitis progressing to chronicity showed persistently HBV-DNA sequences in serum and in PBMC. In conclusion, our study shows that HBV-DNA sequences may be found in PBMC, transiently in patients with acute hepatitis followed by recovery, persistently in patients with acute hepatitis progressing to chronicity.
Assuntos
Vírus da Hepatite B/genética , Hepatite B/genética , Linfócitos/microbiologia , Doença Aguda , Adolescente , Adulto , Sequência de Bases , Biomarcadores/sangue , DNA Viral/sangue , DNA Viral/genética , Feminino , Hepatite B/sangue , Hepatite B/microbiologia , Anticorpos Anti-Hepatite B/análise , Antígenos da Hepatite B/análise , Hepatite Crônica/sangue , Hepatite Crônica/genética , Hepatite Crônica/microbiologia , Humanos , Masculino , Pessoa de Meia-Idade , Hibridização de Ácido NucleicoAssuntos
Complexo Relacionado com a AIDS/epidemiologia , Síndrome da Imunodeficiência Adquirida/epidemiologia , Soropositividade para HIV/epidemiologia , Complexo Relacionado com a AIDS/imunologia , Adolescente , Adulto , Doadores de Sangue , Ensaio de Imunoadsorção Enzimática , Feminino , Soropositividade para HIV/imunologia , Humanos , Itália , Falência Renal Crônica/complicações , Masculino , Transtornos Relacionados ao Uso de Substâncias/complicações , Linfócitos T/imunologia , Talassemia/complicaçõesRESUMO
Molecular assays are instrumental in the clinical management of viral hepatitis. During the past years, a wide variety of molecular assays have been developed and implemented. This considerably improved the understanding of the natural history and pathogenesis of Hepatitis B virus (HBV), Hepatitis C virus (HCV) or Hepatitis delta virus (HDV) hepatitis, but also caused uncertainties in the selection of the most appropriate assays for clinical requirements. Indeed, a rational choice and application of these assays requires adequate knowledge of the performance of the single test. Moreover, the choice of the most accurate assay for patients' needs and physicians' objectives, needs to be oriented to specific contexts, such as diagnosis, management or treatment. In the past, a hurdle in the routine use of assays for hepatitis viruses nucleic acid quantification was represented by the availability of only "home brew" methods which lacked standardization. Major improvement in addressing the use of molecular assays for viral hepatitis has been derived from recent standardization procedures that allowed a comparison between different tests after results were given as International Units. In addition, it should be reminded that, before getting into the market, molecular assays should be approved by European regulation authorities and validated using internationally recognized standards. A subsequent clinical validation should address the diagnostic accuracy of the assay. These proceedings have the aim of identifying which molecular tests, among those currently available, meet clinical requirements for each specific application.
Assuntos
DNA Viral/análise , Hepatite Viral Humana/diagnóstico , RNA Viral/análise , Bioensaio , DNA Viral/genética , Genótipo , Hepatite B/diagnóstico , Hepatite C/diagnóstico , Humanos , Imunoensaio , RNA Viral/genética , Reprodutibilidade dos TestesRESUMO
Despite recent advances in the treatment of chronic viral hepatitis, therapy of chronic hepatitis D is not yet satisfactory. The only option currently available is interferon-alpha (IFN), whose efficacy is related to the dose and duration of treatment. However, the rate of sustained hepatitis D virus (HDV) clearance after a 1-year course with high doses of standard IFN is low. Better results have recently been reported with pegylated IFN both in IFN-naïve and in previous nonresponders to standard IFN, suggesting the use of pegylated IFN as a first-line therapy in chronic hepatitis D. Nucleoside analogues that inhibit hepatitis B virus (HBV) are ineffective against HDV and combination therapy with lamivudine or ribavirin has not shown significant advantages over monotherapy with either standard or pegylated IFN. Because the ultimate goal of treatment is eradication of both HDV and HBV, in responders IFN therapy should be continued as long as possible until the loss of hepatitis B surface antigen, adjusting the dose to patient tolerance. However, because side-effects are common, continuous monitoring is mandatory. Although the first results obtained with pegylated IFN have been encouraging, the rate of sustained virological response is still low and the rate of relapse high, emphasizing the need for developing novel classes of antivirals specifically interfering with the life cycle of this unique virus.
Assuntos
Hepatite D Crônica/tratamento farmacológico , Hepatite D Crônica/virologia , HumanosRESUMO
OBJECTIVE: In a trial of patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B, 24 week post-treatment biochemical and virological response rates with peginterferon alpha-2a with or without lamivudine were significantly higher than with lamivudine alone. The effect of pre-treatment factors on post-treatment responses was investigated. METHODS: Multivariate analyses were performed using available data from 518 patients treated with peginterferon alpha-2a with or without lamivudine, or with lamivudine alone. A post-treatment response was defined as alanine aminotransferase (ALT) normalisation and hepatitis B virus (HBV) DNA level of <20,000 copies/ml. RESULTS: In logistic regression analyses across all treatment arms, peginterferon alpha-2a (with or without lamivudine) therapy, younger age, female gender, high baseline ALT, low baseline HBV DNA and HBV genotype were identified as significant predictors of combined response at 24 weeks post-treatment. In the peginterferon alpha-2a and lamivudine monotherapy arms, patients with genotypes B or C had a higher chance of response than genotype D infected patients (p<0.001), the latter responding better to the combination than to peginterferon alpha-2a monotherapy (p = 0.015). At 1 year post-treatment, response rates by intention-to-treat analysis were 19.2% for the peginterferon alpha-2a, 19.0% for the combination, and 10.0% for the lamivudine groups, with genotypes B or C associated with a sustained combined response to peginterferon alpha-2a with or without lamivudine therapy. CONCLUSIONS: Baseline ALT and HBV DNA levels, patient age, gender, and infecting HBV genotype significantly influenced combined response at 24 weeks post-treatment, in patients treated with peginterferon alpha-2a and/or lamivudine. At 1 year post-treatment HBV genotype was significantly predictive of efficacy for patients treated with peginterferon alpha-2a with or without lamivudine.
Assuntos
Antivirais/uso terapêutico , Hepatite B Crônica/tratamento farmacológico , Interferon-alfa/uso terapêutico , Lamivudina/uso terapêutico , Polietilenoglicóis/uso terapêutico , Adulto , Fatores Etários , Alanina Transaminase/sangue , Biomarcadores/sangue , DNA Viral/sangue , Quimioterapia Combinada , Feminino , Genótipo , Antígenos E da Hepatite B/sangue , Vírus da Hepatite B/classificação , Vírus da Hepatite B/genética , Vírus da Hepatite B/isolamento & purificação , Hepatite B Crônica/virologia , Humanos , Interferon alfa-2 , Masculino , Pessoa de Meia-Idade , Prognóstico , Proteínas Recombinantes , Fatores Sexuais , Resultado do TratamentoRESUMO
Peginterferon alpha-2a (40 kDa) plus ribavirin is effective at achieving sustained viral response compared with no treatment in patients with chronic hepatitis C (CHC) and persistently normal aminotransferase levels (PNALT). The cost-effectiveness of treating CHC in the setting of PNALT has not been assessed. Disease progression in patients with PNALT was simulated in a Markov model. The rate of fibrosis progression, quality of life and costs for each health state were based on literature estimates. The perspective of the Italian National Health Service was adopted and costs (euro 2003) and benefits were discounted at 3%. Sensitivity analyses were performed on important parameters. The primary analysis compared combination therapy with peginterferon alpha-2a (40 kDa) plus ribavirin to no treatment in a cohort of patients with mean age 45 years, and was based on findings from a multinational, randomized trial in patients with PNALT. In genotype 1 patients, the risk of cirrhosis at 30 years is forecast to fall from 32% with no treatment to 19% with combination therapy, increasing quality-adjusted life years (QALYs) by 0.74 years at an incremental cost per QALY gained of euro 16,831. The 30-year risk of cirrhosis in genotype 2 or 3 is projected to fall to 9% with combination therapy, an increase in QALYs of 1.34 years, at an incremental cost per QALY gained of euro 3,000. Thus treatment of PNALT with peginterferon alpha-2a (40 kDa) plus ribavirin is projected to reduce the incidence of cirrhosis, increase life expectancy and have an acceptable cost-effectiveness ratio from a societal perspective.
Assuntos
Alanina Transaminase/metabolismo , Antivirais/economia , Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/economia , Polietilenoglicóis/economia , Ribavirina/economia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antivirais/uso terapêutico , Análise Custo-Benefício , Quimioterapia Combinada , Feminino , Hepatite C Crônica/enzimologia , Hepatite C Crônica/mortalidade , Hepatite C Crônica/fisiopatologia , Humanos , Interferon alfa-2 , Interferon-alfa/uso terapêutico , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/mortalidade , Cirrose Hepática/fisiopatologia , Masculino , Cadeias de Markov , Pessoa de Meia-Idade , Polietilenoglicóis/uso terapêutico , Anos de Vida Ajustados por Qualidade de Vida , Proteínas Recombinantes , Ribavirina/uso terapêuticoRESUMO
Hepatitis C virus (HCV) is a major cause of morbidity and mortality worldwide. The infection becomes chronic in about 85% of infected individuals, in the face of a strong humoral and cellular immune response. One of the most important features of HCV is its high degree of genetic variability, which is due to the inherent low fidelity of the viral replication machinery. As a consequence, HCV circulates in vivo as a population of divergent, albeit closely related, genomes exhibiting a distribution that follows the model referred to as a quasispecies. The genetic variability of HCV is complex and has been classified into four hierarchical strata: genotypes, subgenotypes, isolates, and quasispecies. Over the past few years, an extraordinary interest has been focused on the biologic and clinical implications of the genetic variability of HCV. Although there is consensus that the genotypes may influence the out come of antiviral therapy, their clinical significance in the natural history of the disease, as well as in transmission, infectivity, and pathogenesis of HCV infection, remains elusive. Conversely, evidence has accumulated that the quasispecies nature of HCV provides a large reservoir of biologically different viral variants that may have important clinical implications for viral persistence by immune escape mechanisms, for the generation of antiviral drug resistance, and for the development of an effective vaccine. This article reviews the state of the art on the biologic and clinical implications of the genetic variability of HCV.
Assuntos
Replicação do DNA/genética , Variação Genética , Hepacivirus/genética , Hepatite C/genética , Genótipo , Hepacivirus/classificação , Hepatite C/diagnóstico , Humanos , Especificidade da EspécieRESUMO
This study demonstrates the presence of serological markers of delta infection in HBsAg positive patients throughout the years 1976-1982. As in other Northern European countries, delta infection in Britain is predominantly found in drug addicts and haemophiliacs. delta Ag was detected transiently in serum in a minority of patients presenting with acute hepatitis. In the others and those presenting with chronic liver disease, anti-delta was the only serological evidence of delta infection. Our findings also confirm that delta infection is associated with a more severe and rapidly progressive liver disease.
Assuntos
Hepatite Viral Humana/epidemiologia , Doença Aguda , Adolescente , Adulto , Criança , Doença Crônica , Vírus Defeituosos , Feminino , Antígenos da Hepatite B/análise , Vírus de Hepatite , Antígenos da Hepatite delta , Hepatite Viral Humana/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Reino UnidoRESUMO
Infections with the hepatotropic viruses non-A, non-B (NANB), hepatitis B (HBV) and delta agent (HDV) are described in two patients with haemophilia. The first patient illustrates the phenomenon of interference following a simultaneous exposure to NANB and HBV. The second patient, a carrier of hepatitis B surface antigen (HBsAg), acquired superinfection with HDV which resulted in acute hepatitis progressing to chronic hepatitis. Liver disease seen in multitransfused haemophiliacs may be significantly different to that seen in other patients. As a consequence of the infusion of blood clotting factor concentrates, these patients become the site of complex viral interactions.