RESUMO
Hepatitis B (HBV) and delta (HDV) viruses are endemic in the Amazon region, but vaccine coverage against HBV is still limited. People who use illicit drugs (PWUDs) represent a high-risk group due to common risk behavior and socioeconomic factors that facilitate the acquisition and transmission of pathogens. The present study assessed the presence of HBV and HBV-HDV co-infection, identified viral sub-genotypes, and verified the occurrence of mutations in coding regions for HBsAg and part of the polymerase in HBV-infected PWUDs in municipalities of the Brazilian states of Amapá and Pará, in the Amazon region. In total, 1074 PWUDs provided blood samples and personal data in 30 municipalities of the Brazilian Amazon. HBV and HDV were detected by enzyme-linked immunosorbent assay and polymerase chain reaction. Viral genotypes were identified by nucleotide sequencing followed by phylogenetic analysis, whereas viral mutations were analyzed by specialized software. High rates of serological (32.2%) and molecular (7.2%) markers for HBV were detected, including cases of occult HBV infection (2.5%). Sub-genotypes A1, A2, D4, and F2a were most frequently found. Escape mutations due to vaccine and antiviral resistance were identified. Among PWUDs with HBV DNA, serological (19.5%) and molecular (11.7%) HDV markers were detected, such as HDV genotypes 1 and 3. These are worrying findings, presenting clear implications for urgent prevention and treatment needs for the carriers of these viruses.
Assuntos
Hepatite B/genética , Hepatite D/genética , Transtornos Relacionados ao Uso de Substâncias/virologia , Adulto , Brasil/epidemiologia , Coinfecção , Estudos Transversais , DNA Viral/genética , Usuários de Drogas , Ensaio de Imunoadsorção Enzimática/métodos , Feminino , Genótipo , Hepatite B/diagnóstico , Antígenos de Superfície da Hepatite B/análise , Antígenos de Superfície da Hepatite B/sangue , Vírus da Hepatite B/genética , Vírus da Hepatite B/patogenicidade , Hepatite D/diagnóstico , Vírus Delta da Hepatite/genética , Vírus Delta da Hepatite/patogenicidade , Humanos , Drogas Ilícitas , Masculino , Pessoa de Meia-Idade , Epidemiologia Molecular/métodos , Filogenia , RNA Viral/genética , Análise de Sequência de DNA/métodosRESUMO
This review aims to summarize the current evidence on the treatment of viral hepatitis, focusing on its clinical management. Also, future treatment options and areas of potential research interest are detailed. PubMed and Scopus databases were searched for primary studies published within the last ten years. Keywords included hepatitis A virus, hepatitis B virus (HBV), hepatitis C virus, hepatitis D virus (HDV), hepatitis E virus, and treatment. Outcomes reported in the studies were summarized, tabulated, and synthesized. Significant advances in viral hepatitis treatment were accomplished, such as the advent of curative therapies for hepatitis C and the development and improvement of hepatitis A, hepatitis B, and hepatitis E vaccination. Drugs that cure hepatitis B, going beyond viral suppression, are so far unavailable; however, targeted antiviral drugs against HBV (immunomodulatory therapies and gene silencing technologies) are promising approaches to eradicating the virus. Ultimately, high vaccination coverage and large-scale test-and-treat programmes with high screening rates may eliminate viral hepatitis and mitigate their burden on health systems. The development of curative hepatitis C treatment renewed the enthusiasm for curing hepatitis B, albeit further investigation is required. Novel therapeutic options targeting HDV life cycle are currently under clinical investigation.
Assuntos
Hepatite B , Hepatite C , Hepatite D , Antivirais/uso terapêutico , Hepatite B/diagnóstico , Hepatite B/tratamento farmacológico , Vírus da Hepatite B , Hepatite C/diagnóstico , Hepatite C/tratamento farmacológico , Hepatite D/diagnóstico , Hepatite D/tratamento farmacológico , Hepatite D/epidemiologia , Vírus Delta da Hepatite/genética , HumanosRESUMO
INTRODUCTION AND OBJECTIVES: Research has shown that hepatitis B (HBV) and Delta virus (HDV) are a worldwide public health problem. This study aims to estimate the prevalence rates of HBV and HDV infection in five municipalities of Maranhão, Northeastern Brazil. MATERIALS AND METHODS: A total sample between 3856 and 4000 individuals. Questionnaires were used to register sociodemographic characteristics and factors associated with transmission. Patients were tested for hepatitis B virus surface antigen (HBsAg), anti-hepatitis B core antigen (anti-HBc), and antibodies against hepatitis Delta virus (anti-HDV). Factors associated with HBV were detected by means of multivariate Poisson regression. RESULTS: Overall, 3983 subjects were included. Ninety-two of the participants were HBsAg-positive (2.30%, 95% CI 1.80-2.80), and anti-HBc was detected in 1535 (38.50%, 95% CI 37-40). The factors associated with the presence of anti-HBc were: (1) Municipality (P<0.001); Age (P<0.001); School education (P<0.001); Illicit drug use (P=0.001); non-HBV vaccine (P=0.041). Among the HBsAg carriers, eight were anti-HDV-positive (8.69%, 95% CI 2.90-14.40). The most frequent HBV genotype was D4. The only HDV genotype was HDV-8. CONCLUSION: HBV exhibited intermediate endemicity in the studied region. Traditional factors were associated with exposure to the virus. The presence of the HDV was confirmed. The most frequent HBV and HDV genotypes were unlike the ones currently described in Brazil.
Assuntos
Hepatite B/complicações , Hepatite B/epidemiologia , Hepatite D/complicações , Hepatite D/epidemiologia , Adolescente , Adulto , Brasil/epidemiologia , Criança , Pré-Escolar , Feminino , Hepatite B/diagnóstico , Hepatite D/diagnóstico , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores Socioeconômicos , Inquéritos e Questionários , Adulto JovemRESUMO
Hepatitis D virus (HDV) genotype III is endemic in the western Amazon basin and is considered to cause the most severe form of chronic viral hepatitis. Recently, noninvasive fibrosis scores to determine the stage of liver fibrosis have been evaluated in individuals positive for HDV genotype I, but their utility in HDV genotype III-positive patients is unknown. In this retrospective study conducted in an outpatient viral hepatitis referral clinic in the Brazilian Amazon region, the aspartate aminotransferase (AST) to Aspartate aminotransferase to Platelet Ratio Index (APRI) and Fibrosis Index for Liver Fibrosis (FIB-4) values were calculated and compared with histological fibrosis stages. Among the 50 patients analyzed, the median age at liver biopsy was 35.6 years, 66% were male, and all had compensated liver disease. Histological staging revealed fibrosis stages 0, 1, 2, 3, and 4 in four (8%), eight (16%), 11 (22), 11 (22%), and 16 (32%) patients, respectively. The area under the receiver operating curve (AUROC) of AST-to-alanine aminotransferase (ALT) ratio, APRI, and FIB-4 for detection of significant fibrosis (F ≥ 2) was 0.550 (P = 0.601), 0.853 (P < 0.001), and 0.853 (P < 0.0001), respectively. Lower AUROC values were obtained for cirrhosis: the AST-to-ALT ratio was 0.640 (P = 0.114), APRI was 0.671 (P = 0.053), and FIB-4 was 0.701 (P = 0.023). The optimal cutoff value for significant fibrosis for APRI was 0.708 (sensitivity 84% and specificity 92%) and for FIB-4 was 1.36 (sensitivity 76% and specificity 92%). Aspartate aminotransferase to Platelet Ratio Index and FIB-4 were less useful to predict cirrhosis. In contrast to recent reports from Europe and North America, both APRI and FIB-4 may identify significant fibrosis in HDV-III-infected patients from northwestern Brazil.
Assuntos
Vírus da Hepatite B/patogenicidade , Hepatite B/diagnóstico , Hepatite D/diagnóstico , Vírus Delta da Hepatite/patogenicidade , Cirrose Hepática/diagnóstico , Adulto , Alanina Transaminase/metabolismo , Área Sob a Curva , Aspartato Aminotransferases/metabolismo , Biomarcadores/análise , Plaquetas/patologia , Plaquetas/virologia , Brasil , Doença Crônica , Coinfecção , Feminino , Hepatite B/enzimologia , Hepatite B/patologia , Hepatite B/virologia , Hepatite D/enzimologia , Hepatite D/patologia , Hepatite D/virologia , Humanos , Cirrose Hepática/enzimologia , Cirrose Hepática/patologia , Cirrose Hepática/virologia , Masculino , Pessoa de Meia-Idade , Pacientes Ambulatoriais , Contagem de Plaquetas , Curva ROC , Estudos Retrospectivos , Sensibilidade e Especificidade , Índice de Gravidade de DoençaRESUMO
BACKGROUND: Hepatitis delta virus (HDV) infections in hepatitis B virus (HBV) carriers are the most severe form of viral hepatitis. HDV prevalence is high in the Brazilian Amazon, but studies in other regions of the country are still scarce and often underestimated its prevalence by including a small numbers of individuals. OBJECTIVE: This study aimed to determine the serological prevalence of hepatitis D, the genotypes circulating and to evaluate the associated risk factors for acquisition of HDV in Minas Gerais state, Brazil. METHODS: We screened plasma samples (n = 498) from HBV chronic carriers for anti-HD antibodies using a commercial enzyme-linked immunosorbent assay (ELISA) kit. For those samples that were positive for anti-HD antibodies, we performed a reverse transcriptase (RT) nested-polymerase chain reaction (nested-PCR) in order to detect the viral genome and identify the viral genotypes circulating in the state. FINDINGS: The prevalence was 6.22% (31/498). Blood transfusion was the only risk factor associated with HDV infection [risk ratio: 3.73; 95% confidence interval (CI): 1.44 to 9.65]. For 26 anti-HD positive patients, HDAg gene sequences were determined and in all patients HDV genotype 1 was found. CONCLUSIONS: This study confirmed the circulation of HDV in Minas Gerais, an area previously considered non-endemic for hepatitis D in Brazil. The prevalence found in this study is much higher when compared to other studies performed in Brazil, probably because the population in our study was selected with minimal bias. Furthermore, in 26 anti-HD positive plasma samples, we were also able to detect the viral genome, indicating that these patients were experienced an active infection at the time of sample collection. These findings emphasise the importance of anti-HD testing in HBV infected individuals, which may contribute to this disease control in Brazil.
Assuntos
Anticorpos Anti-Hepatite/sangue , Hepatite B Crônica/epidemiologia , Hepatite D/epidemiologia , Vírus Delta da Hepatite , RNA Viral/genética , Adolescente , Adulto , Brasil/epidemiologia , Criança , Pré-Escolar , Estudos Transversais , Ensaio de Imunoadsorção Enzimática , Feminino , Genótipo , Hepatite B Crônica/complicações , Hepatite D/complicações , Hepatite D/diagnóstico , Vírus Delta da Hepatite/genética , Vírus Delta da Hepatite/imunologia , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Epidemiologia Molecular , Filogenia , Prevalência , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Risco , Adulto JovemAssuntos
Coinfecção , Vírus da Hepatite B , Hepatite B/diagnóstico , Hepatite D/diagnóstico , Vírus Delta da Hepatite , Biomarcadores/sangue , DNA Viral/sangue , DNA Viral/genética , Ensaio de Imunoadsorção Enzimática , Hepatite B/sangue , Hepatite B/etnologia , Hepatite B/virologia , Anticorpos Anti-Hepatite B/sangue , Anticorpos Anti-Hepatite B/imunologia , Vírus da Hepatite B/genética , Vírus da Hepatite B/imunologia , Hepatite D/sangue , Hepatite D/etnologia , Hepatite D/virologia , Vírus Delta da Hepatite/genética , Vírus Delta da Hepatite/imunologia , Antígenos da Hepatite delta/genética , Antígenos da Hepatite delta/imunologia , Humanos , Indígenas Sul-Americanos , Mutação , Valor Preditivo dos Testes , Kit de Reagentes para Diagnóstico , Reprodutibilidade dos TestesRESUMO
INTRODUCTION: Hepatitis B virus infection is an important cause of liver disease in hemodialysis patients and renal transplant recipients. Hepatitis Delta virus is a defective virus transmitted by the same route of hepatitis B virus, which requires the helper function of hepatitis B virus. Data about hepatitis B virus/hepatitis delta virus coinfection are scarce and there are no studies regarding the coinfection among hemodialysis patients and renal transplant in our country. OBJECTIVE: This study aimed to investigate the prevalence of hepatitis delta virus infection among hemodialysis patients and renal transplant recipients. METHODS: Cross-sectional study analyzing virological markers of hepatitis B virus and hepatitis delta virus infection and biochemical and clinical features of liver disease of patients infected with hepatitis B virus in hemodialysis and renal transplant. RESULTS: A total of 117 HBsAg-positive patients (46 hemodialysis and 71 renal transplant) were included. The mean age was 48.5 ± 11.8 years and 67% were males. Antiviral therapy was given to 74% of patients. Liver function tests were within the normal range. HBeAg-positive was found in 35% of patients and median hepatitis B virus DNA was 2.98 log (IU/mL). Cirrhosis was detected in 26.5% of patients. The prevalence of anti-hepatitis delta virus total antibody (+) was 1.7% (2/117). None of the 2 patients had active hepatitis delta virus infection, since all samples tested negative for hepatitis delta virus-RNA. CONCLUSION: The results suggest a low prevalence rate of coinfection B and D in hemodialysis and renal transplant recipients in this population.
Assuntos
Vírus da Hepatite B , Hepatite B , Hepatite D , Vírus Delta da Hepatite/isolamento & purificação , Transplante de Rim/efeitos adversos , Diálise Renal/efeitos adversos , Adulto , Brasil/epidemiologia , Coinfecção/epidemiologia , Estudos Transversais , Feminino , Hepatite B/diagnóstico , Hepatite B/epidemiologia , Antígenos de Superfície da Hepatite B/análise , Vírus da Hepatite B/imunologia , Vírus da Hepatite B/isolamento & purificação , Hepatite D/diagnóstico , Hepatite D/epidemiologia , Humanos , Transplante de Rim/métodos , Masculino , Pessoa de Meia-Idade , Prevalência , Diálise Renal/métodosRESUMO
There are an estimated 400 million chronic carriers of HBV worldwide; between 15 and 20 million have serological evidence of exposure to HDV. Traditionally, regions with high rates of endemicity are central and northern Africa, the Amazon Basin, eastern Europe and the Mediterranean, the Middle East and parts of Asia. There are two types of HDV/HBV infection which are differentiated by the previous status infection by HBV for the individual. Individuals with acute HBV infection contaminated by HDV is an HDV/HBV co-infection, while individuals with chronic HBV infection contaminated by HDV represent an HDV/HBV super-infection. The appropriate treatment for chronic hepatitis delta is still widely discussed since it does not have an effective drug. Alpha interferon is currently the only licensed therapy for the treatment of chronic hepatitis D. The most widely used drug is pegylated interferon but only approximately 25% of patients maintain a sustained viral response after 1 year of treatment. The best marker of therapeutic success would be the clearance of HBsAg, but this data is rare in clinical practice. Therefore, the best way to predict a sustained virologic response is the maintenance of undetectable HDV RNA levels.
Assuntos
Hepatite D/diagnóstico , Hepatite D/virologia , Vírus Delta da Hepatite/fisiologia , Animais , Antivirais/farmacologia , Antivirais/uso terapêutico , Biomarcadores , Carcinoma Hepatocelular/etiologia , Coinfecção , Genoma Viral , Genótipo , Hepatite B , Hepatite D/epidemiologia , Hepatite D/terapia , Vírus Delta da Hepatite/classificação , Vírus Delta da Hepatite/ultraestrutura , Humanos , Cirrose Hepática/etiologia , Neoplasias Hepáticas/etiologia , Prognóstico , RNA Viral , Superinfecção , Resultado do Tratamento , Replicação ViralRESUMO
There are an estimated 400 million chronic carriers of HBV worldwide; between 15 and 20 million have serological evidence of exposure to HDV. Traditionally, regions with high rates of endemicity are central and northern Africa, the Amazon Basin, eastern Europe and the Mediterranean, the Middle East and parts of Asia. There are two types of HDV/HBV infection which are differentiated by the previous status infection by HBV for the individual. Individuals with acute HBV infection contaminated by HDV is an HDV/HBV co-infection, while individuals with chronic HBV infection contaminated by HDV represent an HDV/HBV super-infection. The appropriate treatment for chronic hepatitis delta is still widely discussed since it does not have an effective drug. Alpha interferon is currently the only licensed therapy for the treatment of chronic hepatitis D. The most widely used drug is pegylated interferon but only approximately 25% of patients maintain a sustained viral response after 1 year of treatment. The best marker of therapeutic success would be the clearance of HBsAg, but this data is rare in clinical practice. Therefore, the best way to predict a sustained virologic response is the maintenance of undetectable HDV RNA levels
Assuntos
Humanos , Hepatite D/diagnóstico , Hepatite D/tratamento farmacológico , Hepatite D/virologiaRESUMO
HDV infection may occur within a primary HBV infection (co-infection) or by sub sequent acquisition ofthe virus in patients with chronic hepatitis B (superinfection). Acute HDV infection is rarely diagnosed. Since cero conversion usually takes place about six weeks after viral infection, early diagnosis requires the use of direct diagnostic techniques, such as antigen HD V (HDAg) detection, or genomic amplification by means of molecular biology methods (RT-PCR). Here were port the case of a patient with chronic HBV infection that develops a severe acute hepatitis due to VHD superinfec- tion only detected by molecular biology.