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ABSTRACT Hepatitis C virus infection may be implicated in 12.7% of ocular adnexal marginal zone lymphomas. We present the first case of an orbital-systemic mucosa-associated lymphoid tissue lymphoma that responded to hepatitis C virus medical treatment. A 62-year-old male with a right-sided orbital mass was diagnosed with stage IIA orbital marginal zone lymphoma in addition to hepatitis C virus infection based on clinical, imaging, laboratory, and histological examinations. The systemic and orbital responses were achieved 1 year after undergoing hepatitis C virus treatment with glecaprevir/pibrentasvir. The association between the hepatitis C virus infection and orbital-systemic mucosa-associated lymphoid tissue lymphoma is relevant. Accordingly, patients with orbital mucosa-associated lymphoid tissue lymphoma should be assessed for hepatitis C virus seroreactivity for therapeutic and prognostic purposes.
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INTRODUCTION AND OBJECTIVES: We aimed to analyze the trends of total and sex-stratified mortality from hepatitis C virus (HCV) and to estimate the proportion of non-alcoholic liver disease deaths in Mexico attributable to HCV from 2001-2017. MATERIALS AND METHODS: Using the mortality multiple-cause dataset, we selected the codes for acute HCV and chronic HCV to analyze trends from 2001 to 2017. We then estimated the proportion of HCV-related deaths out of non-alcoholic chronic liver disease deaths, by including in the denominator: other acute and chronic viral hepatitis, malignant neoplasm of the liver, liver failure, chronic hepatitis, fibrosis, and cirrhosis of the liver, and other inflammatory diseases of the liver. Average percent change (APC) for trends, overall and by sex, were estimated using Joinpoint regression. RESULTS: The trend in crude mortality rate significantly increased from 2001-2005 (APC 18.4%; 95%CI=12.5, 24.5; p value<0.001), and then significantly decreased from 2013-2017 (APC -6.5%; 95%CI=-10.1, -2.9; p value<0.001). Stratified by sex women experienced a more rapid decline in the 2014-2017 period than men. CONCLUSIONS: HCV mortality seems to have started to decrease, but much remains to be done in terms of prevention, diagnosis, and timely access to treatment.
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Hepatite C Crônica , Hepatite C , Masculino , Humanos , Feminino , Hepacivirus , México/epidemiologia , Hepatite C/diagnóstico , Hepatite C/epidemiologia , Cirrose Hepática , Hepatite C Crônica/diagnóstico , Hepatite C Crônica/epidemiologiaRESUMO
The chronic hepatitis C (CHC) treatment is currently based on the use of direct-acting antivirals (DAAs), and patients infected with hepatitis C virus genotype 3 (GT3) have emerged as a more difficult-to-cure population. The NS5A inhibitor daclatasvir (DCV) and sofosbuvir (SOF), an NS5B viral polymerase inhibitor, are among the drugs that compose more effective and safer treatment regimens. The virus genetic variability is related to resistance-associated substitutions (RASs) that adversely impact DAAs effectiveness. The aims of this study were to analyze the association of NS5A and NS5B RASs and other clinical factors with DAAs regimens effectiveness in patients with GT3 CHC infection. This was a prospective cohort study performed in a Brazilian university hospital. Individuals older than 18 years with GT3 CHC treated with SOF + DCV ± ribavirin (RBV) or SOF + peginterferon (PEG) + RBV were included. Blood samples were collected at baseline and post-treatment. A total of 121 patients were included. Sustained virological response rates were 87.6% for the SOF + DCV ± RBV group and 80.0% for the SOF + PEG + RBV arm. Cirrhosis, prior treatment with interferon/PEG + RBV, and baseline NS5A RAS were associated with higher risk of treatment failure. The NS5A analysis suggested that A30K, Y93H, and RAS at site 62 were related to failure. Interestingly, a likely compensatory effect was shown between A30K and A62T. Emergence of Y93H was always associated with RAS at position 62. The RASs dynamics comprehension is an important tool to indicate more effective treatment for GT3 patients.
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Antivirais , Hepatite C Crônica , Humanos , Antivirais/uso terapêutico , Antivirais/farmacologia , Hepatite C Crônica/complicações , Hepacivirus/genética , Estudos Prospectivos , Sofosbuvir/uso terapêutico , Sofosbuvir/farmacologia , Ribavirina/uso terapêutico , Ribavirina/farmacologia , Resultado do Tratamento , Quimioterapia Combinada , Genótipo , Farmacorresistência Viral/genéticaRESUMO
Equine hepacivirus (EqHV) belongs to the Flaviviridae family, genus Hepacivirus and has the greatest genomic identity with the hepatitis C virus (HCV), one of the main causes of chronic liver disease in humans. Due to the limited applicability of studies of HCV in animal hosts, the interest in studies of characterization of viral homologues has been growing. For this reason, we performed a systematic review of the literature with meta-analysis of the prevalence of EqHV and genetic sequencing studies. Twenty-three studies from four different continents were analyzed. The OR meta-analysis (0.98; 95% CI = 0.69-1.39) showed no influence of sex (female or male) on the risk of infection. Variables associated with EqHV infection were indirectly related to animal management such as transport, reproductive practices, among others. The combined prevalence of positive animals was 7.88% (95% CI = 5.23-11.69%), with the highest proportions in Asia (16.13%; 95% CI = 7.79-30.43%), followed by South America (12.03%; 95% CI = 9.58-15.01%), Africa (8.69%; 95% CI = 6.71-11.20%), and Europe (3.63%; 95% CI = 2.10-6.22%). However, these results represent the regional stratification of the epidemiological studies for EqHV published to date and, therefore, cannot extrapolate to determine the continental prevalence of EqHV. It is therefore important to update the systematic review as further research becomes available.
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Hepatite C , Doenças dos Cavalos , Animais , Feminino , Hepacivirus/genética , Hepatite C/epidemiologia , Hepatite C/veterinária , Doenças dos Cavalos/epidemiologia , Cavalos/genética , Masculino , Filogenia , Prevalência , RNARESUMO
Abstract Infection by the hepatitis C virus is more prevalent in patients on dialysis than in the general population in Brazil, and has been associated with worse outcomes. Current therapy for hepatitis C is highly effective, safe, and widely available in Brazil, with coverage provided to dialysis patients with chronic kidney disease, which makes the elimination of hepatitis C a viable target. The Brazilian Society of Nephrology, the Brazilian Society of Hepatology, and the Brazilian Liver Institute developed the "Brazilian Registry for the Elimination of Hepatitis C in Dialysis Units". This project aims to identify, treat, and monitor the response to treatment of patients on chronic dialysis infected with the hepatitis C virus in Brazil. This article presents the issue and invites Brazilian nephrologists to rally around the achievement of a significant goal.
Resumo A infecção pelo vírus da hepatite C é mais prevalente em pacientes em diálise do que na população geral no Brasil e implica um pior prognóstico. O tratamento atual para hepatite C é altamente eficaz, seguro e disponível no país, inclusive para a população de pacientes crônicos em diálise, o que torna a eliminação do vírus da hepatite C uma meta viável. A Sociedade Brasileira de Nefrologia, a Sociedade Brasileira de Hepatologia e o Instituto Brasileiro do Fígado desenvolveram o "Registro Brasileiro para Eliminação da Hepatite C nas Unidades de Diálise". O projeto visa identificar pacientes em diálise crônica com vírus da hepatite C no Brasil, além de tratar e monitorar a resposta virológica após o tratamento. Este breve artigo apresenta o problema e convida os nefrologistas brasileiros a unirem forças nesse objetivo comum.
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ABSTRACT The chronic hepatitis C (CHC) treatment is currently based on the use of direct-acting antivirals (DAAs), and patients infected with hepatitis C virus genotype 3 (GT3) have emerged as a more difficult-to-cure population. The NS5A inhibitor daclatasvir (DCV) and sofosbuvir (SOF), an NS5B viral polymerase inhibitor, are among the drugs that compose more effective and safer treatment regimens. The virus genetic variability is related to resistance-associated substitutions (RASs) that adversely impact DAAs effectiveness. The aims of this study were to analyze the association of NS5A and NS5B RASs and other clinical factors with DAAs regimens effectiveness in patients with GT3 CHC infection. This was a prospective cohort study performed in a Brazilian university hospital. Individuals older than 18 years with GT3 CHC treated with SOF + DCV ± ribavirin (RBV) or SOF + peginterferon (PEG) + RBV were included. Blood samples were collected at baseline and post-treatment. A total of 121 patients were included. Sustained virological response rates were 87.6% for the SOF + DCV ± RBV group and 80.0% for the SOF + PEG + RBV arm. Cirrhosis, prior treatment with interferon/PEG + RBV, and baseline NS5A RAS were associated with higher risk of treatment failure. The NS5A analysis suggested that A30K, Y93H, and RAS at site 62 were related to failure. Interestingly, a likely compensatory effect was shown between A30K and A62T. Emergence of Y93H was always associated with RAS at position 62. The RASs dynamics comprehension is an important tool to indicate more effective treatment for GT3 patients.
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Background Direct-acting antivirals (DAA) allowed a radical change in the treatment of hepatitis C virus (HCV), achieving the elimination of the virus or sustained viral response (SVR) in > 95% of patients, with good tolerance and few adverse effects. Aim To characterize the treated population and evaluate the efficacy of DAA treatment in the Chilean public health system. Material and Methods: Retrospective analysis of data sheets of pa- tients with chronic HCV infection collected by the Ministry of Health of Chile between 2016 and May 2019. Results Two hundred and fifty-five patients with a mean age of 59 years (51% males) were collected. Genotype 1b was predominant, 72% patients had a diagnosis of cirrhosis at the beginning of treatment. Sofosbuvir-Velpatasvir was predominantly used in 56%. SVR was achieved in 92% of cases, only 4% persisted with detectable load at 24 weeks. A significant decrease in alanine aminotransferase values (88 and 31 U/L respectively, p < 0.01) and a significant increase in plasma albumin (3.7 and 3.9 mg/dl respectively, p = 0.02) were observed. The comparative analysis of MELD-Na before and after treatment did not show a signifi- cant variation (10.8 and 10.4 respectively, p = 0.34). Conclusions These patients treated with DAAs presented SVR rates comparable with national and international data.
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RESUMEN Fundamento: La infección por el virus de la Hepatitis C ha sido reconocida como problema de salud a nivel mundial. Objetivo: Determinar las características de los pacientes con Hepatitis C que reciben tratamiento en el servicio de hemodiálisis del Centro Especializado Ambulatorio de Cienfuegos, en el periodo de enero a agosto del 2019. Metodología Se realizó un estudio observacional, descriptivo, longitudinal retrospectivo con los 54 pacientes en hemodiálisis portadores de Hepatitis C. Las variables utilizadas fueron: edad, sexo, lugar de procedencia, tipo de acceso vascular y tiempo en tratamiento. Se utilizó como fuente de información la base de datos del Centro Provincial de Higiene, Epidemiología y Microbiología en Cienfuegos. Resultados: El mayor porcentaje de personas con Hepatitis C se concentró entre los 50 a 54 años; siendo la edad promedio 53 años, sobresalió el sexo masculino para un 84.93%, y predominó el municipio de Cienfuegos como lugar de residencia. En relación al tipo de acceso vascular, la fístula arterio -venosa aportó el 98.14%, mientras el tiempo de tratamiento que prevaleció fue de más de 3 años para un 77.8%. Conclusiones La Hepatitis C en el servicio de hemodiálisis mostró un comportamiento similar a lo descrito en la literatura.
ABSTRACT Background Infection by the hepatitis c virus has been recognized as a health problem worldwide. Objective: To determine the characteristics of patients with hepatitis C receiving treatment in the Hemodialysis Service of the Cienfuegos Specialized Outpatient Center from January 2019 to August 2019. Methodology An observational, descriptive, longitudinal retrospective study was carried out with the 54 Hemodialysis patients with Hepatitis C. The variables used were: age, sex, place of origin, type of vascular access and time in treatment. The database of the Provincial Center for Hygiene, Epidemiology and Microbiology in Cienfuegos was used as a source of information. Results The highest percentage of people with hepatitis C was concentrated between 50 to 54 years old; The average age being 53 years, the male sex stood out for the 84.93%, with the municipality of Cienfuegos predominating as the place of residence. Regarding the type of vascular access, the arterio-venous fistula contributed the 98.14%, while the treatment time that prevailed was more than 3 years for the 77.8%. Conclusions: Hepatitis C in the hemodialysis service showed a similar behavior as described in the literature.
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Abstract In addition to liver disease, the hepatitis C virus (HCV) has been associated with autoimmune phenomena, such as mixed cryoglobulin and glomerulonephritis (GN). Until recently, both chronic hepatitis and HCV extra-hepatic manifestations were treated with peg-interferon plus ribavirin, however these drugs presented low efficacy and induced severe side effects. Nowadays, the HCV chronic hepatitis has been treated with direct acting antivirals (DAA), but studies on the DAA therapy for HCV-associated glomerulonephritis are scarce. Here, we describe two cases of HCV-associated glomerulonephritis that were treated with DAAs. In these two cases, previously experienced to peg-interferon plus ribavirin, the sofosbuvir plus simeprevir therapy was effective, without significant side effects, and interrupted the evolution of at least 20 years of both hepatic and renal diseases. These cases join the seven previously described cases that were treated with this DAAs association.
Resumo Além da doença hepática, o vírus da hepatite C (HCV) tem sido associado a fenômenos autoimunes, como crioglobulinemia mista (CM) e glomerulonefrite (GN). Até recentemente, a hepatite crônica e as manifestações extra-hepáticas do HCV eram tratadas com peg-interferon com ribavirina; no entanto, essas drogas apresentavam baixa eficácia e induziam efeitos colaterais graves. Atualmente, a hepatite crônica por HCV tem sido tratada com antivirais de ação direta (AAD), mas estudos sobre a terapia com AAD para glomerulonefrite associada ao HCV são escassos. Aqui, descrevemos dois casos de glomerulonefrite associada ao HCV que foram tratados com AAD. Nestes dois casos, previamente tratados com peg-interferon e ribavirina, a terapia com sofosbuvir com simeprevir foi eficaz, sem efeitos colaterais significativos, e interrompeu a evolução de pelo menos 20 anos de doenças hepáticas e renais. Esses casos se juntam aos sete casos descritos anteriormente que foram tratados com essa associação de AAD.
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Humanos , Preparações Farmacêuticas , Hepatite C/tratamento farmacológico , Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Antivirais/uso terapêutico , HepacivirusRESUMO
Hepatitis C virus infection is a major global public health problem. Treatment with direct-acting antivirals is intended to eradicate the chronic form of this infection by 2030. Although uncommon, the acute form of presentation is increasingly recognized, especially in some high-risk populations, such as men who have sex with men without protection. Its virological and serological diagnosis is not standardized, so clinical suspicion is essential. Its early detection allows a timely treatment. We report seven cases of acute HCV hepatitis in a national reference center, its presentation, diagnosis and treatment. We discuss populations at risk and the change in therapeutics with the use of direct-acting antiviral drugs.
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Humanos , Masculino , Hepatite C , Hepatite C Crônica , Minorias Sexuais e de Gênero , Antivirais/uso terapêutico , Hepatite C/diagnóstico , Hepatite C/tratamento farmacológico , Homossexualidade Masculina , Hepatite C Crônica/tratamento farmacológicoRESUMO
ABSTRACT Backgrounds: Hepcidin is related to the pathogenesis of chronic renal failure anemia, which is considered a chronic inflammatory state as well as HCV infection. IL-6 stimulates the release of hepcidin from the liver, suppresses intestinal iron uptake, and releases iron from internal stores. Method: To detect the association between IL-6 gene polymorphism and anemia markers, 80 hemodialysis (HD) patients [40 negative HCV HD patients and 40 positive HCV HD patients] were studied by routine chemistry and complete blood count, in addition to the assessment of serum hepcidin, iron parameters [serum iron and serum ferritin], and hepatitis C markers. IL-6 polymorphism -174G/C was determined by MS-PCR, while IL-6 polymorphisms -597G/A and -572 G/C were detected by PCR-SSP. Results: Hepcidin was non-significantly elevated in HCV-positive compared with HCV-negative hemodialysis patients. A statistically significant difference was detected between the negative and positive HCV HD patients in frequencies of IL-6 -174 G/C and -597 G/A (P≤ 0.01 and P≤ 0.001, respectively). On the other hand, a non-significant difference was reported between negative and positive HCV HD patients in the frequencies of IL-6 -572 G/C. Conclusions: Our study indicated that IL-6 -174 G/C and -597 G/A polymorphisms may play a role in HCV susceptibility in HD patients. Additional prospective studies on a larger population are needed to confirm our findings.
RESUMO Introdução: A hepcidina está associada à patogênese da anemia por insuficiência renal crônica, considerada um estado inflamatório crônico e também infecção por HCV. A IL-6 estimula a liberação de hepcidina a partir do fígado, suprime a captação intestinal de ferro e libera ferro das reservas internas. Método: Para detectar a associação entre o polimorfismo do gene IL-6 e os marcadores de anemia, 80 pacientes em hemodiálise (HD) [40 pacientes em HD, negativos para HCV; e 40 em HD, positivos para HCV] foram avaliados por exames químicos de rotina e hemograma completo, além da avaliação da hepcidina sérica, parâmetros do ferro [ferro sérico e ferritina sérica] e marcadores de hepatite C. O polimorfismo da IL-6 -174G/C foi determinado por MS-PCR, enquanto os polimorfismos de IL-6 -597G/A e -572 G/C foram detectados por PCR-SSP. Resultados: A hepcidina não esteve significativamente elevada em pacientes com HCV em comparação com pacientes em hemodiálise negativos para HCV. Uma diferença estatisticamente significativa foi detectada entre os pacientes em HD HCV negativos comparados aos positivos nas frequências de IL-6 -174 G/C e -597 G/A (P≤ 0,01 e P≤ 0,001, respectivamente). Por outro lado, foi relatada uma diferença não significativa entre pacientes em HD HCV negativos e positivos nas frequências de IL-6 -572 G/C. Conclusões: Nosso estudo indicou que os polimorfismos de IL-6 -174 G/C e -597 G/A podem desempenhar um papel na suscetibilidade ao HCV em pacientes em HD. Ainda necessitamos de estudos prospectivos adicionais em uma população maior para confirmar nossos achados.
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Humanos , Interleucina-6/genética , Hepatite C , Polimorfismo Genético , Estudos Prospectivos , Diálise Renal , FerroRESUMO
ABSTRACT BACKGROUND: Hepatitis C virus (HCV) infection is the most common hepatotropic viral infection affecting the patients on maintenance hemodialysis. Treatment of chronic HCV infection in stage 4 and 5 CKD includes a combination of elbasvir/grazoprevir and glecaprevir/pibrentasvir, which are not available in many countries. OBJECTIVE: Hence, we have conducted this study to look for the safety and efficacy of sofosbuvir combination therapy in this difficult to treat population. METHODS: We conducted a single-center, prospective, open-label study in which Stage 5 CKD patients on maintenance hemodialysis with HCV infection. Total of 18 patients was included. sofosbuvir with daclatasvir or ledipasvir was used according to genotype for 12 weeks. HCV RNA, genotype, transient elastography (TE) was considered for every patient. HCV RNA was quantified at 4th week, 12th week and 12 weeks post-treatment to look for sustained virologic response (SVR 12). RESULTS: Infection due to genotype 1 was seen in 12 (66.7%) patients followed by genotype 3 in 4 (22.3%) with each patient of genotype 2 and 5. The median value of HCV RNA was 2,35,000 IU/mL. On TE, all had liver stiffness of <9.4 KPa. All patients had HCV RNA of <15 IU/mL at 4th and 12th week of treatment and 12 weeks post-treatment. No significant change in hemoglobin, eGFR and liver stiffness was observed. CONCLUSION: Full dose sofosbuvir i.e. 400 mg, in combination with NS5A inhibitors daclatasvir or ledipasvir is found to be safe and effective in patients with end stage renal disease, who are on maintenance hemodialysis.
RESUMO CONTEXTO: A infecção pelo vírus da hepatite C (HCV) é a infecção viral hepática mais comum que afeta pacientes em hemodiálise de manutenção. O tratamento da infecção crônica por HCV no estágio 4 e 5 da doença renal crônica inclui uma combinação de elbasvir/grazoprevir e glecaprevir/pibrentasvir, que não estão disponíveis em muitos países. OBJETIVO: Portanto, realizamos este estudo para procurar a segurança e eficácia da terapia combinada de sofosbuvir nesta população de difícil tratamento. MÉTODOS: Realizamos um estudo de centro único, prospectivo e aberto, no qual pacientes com doença renal crônica em estágio 5 em hemodiálise de manutenção com infecção por HCV. Um total de 18 pacientes foi incluído. Sofosbuvir com daclatasvir ou ledipasvir foi usado de acordo com o genótipo por 12 semanas. O HCV RNA, genótipo, elastografia transitória foi considerado para cada paciente. O HCV RNA foi quantificado na 4ª semana, 12ª semana e 12 semanas após o tratamento para procurar uma resposta virológica sustentada. RESULTADOS: A infecção por genótipo 1 foi observada em 12 (66,7%) pacientes, seguido pelo genótipo 3 em 4 (22,3%), em um paciente do genótipo 2 e em outro, 5. O valor mediano do HCV RNA foi de 2.35.000 IU/mL. Na elastografia transitória, todos tinham rigidez hepática de <9.4 KPa. Todos os pacientes tinham RNA HCV <15 IU/mL na 4ª e 12ª semana de tratamento e 12 semanas após o tratamento. Não foi observada nenhuma alteração significativa na hemoglobina, eGFR e rigidez hepática. CONCLUSÃO: A dose completa sofosbuvir ou seja, 400 mg, em combinação com inibidores NS5A daclatasvir ou ledipasvir foi considerada segura e eficaz em pacientes com doença renal em estágio final, que estão em manutenção hemodiálise.
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Humanos , Masculino , Feminino , Adulto , Antivirais/administração & dosagem , Hepatite C Crônica/tratamento farmacológico , 2-Piridinilmetilsulfinilbenzimidazóis/administração & dosagem , Fluorenos/administração & dosagem , Sofosbuvir/administração & dosagem , Imidazóis/administração & dosagem , Índice de Gravidade de Doença , RNA Viral , Estudos Prospectivos , Diálise Renal , Resultado do Tratamento , Hepacivirus/genética , Quimioterapia Combinada , Resposta Viral Sustentada , Genótipo , Pessoa de Meia-IdadeRESUMO
Infections produced by hepaciviruses have been associated with liver disease in horses. Currently, at least three viruses belonging to the Flaviviridae family are capable of producing a chronic infection in equines: non-primate hepacivirus (NPHV), Theiler's disease-associated virus (TDAV), and equine pegivirus (EPgV). The RNA-dependent RNA polymerases of viruses (RdRp) (NS5 protein), from the flavivirus family, use de novo RNA synthesis to initiate synthesis. The two antiviral drugs currently used to treat hepatitis C (HCV), sofosbuvir and dasabuvir, act on the viral NS5B polymerase as nucleoside and non-nucleoside inhibitors, respectively. Both drugs have shown significant clinical inhibition of viral response. In this work, we aimed to model the NS5B polymerase of the equine hepacivirus (EHCV) subtypes 1 and 2, TDAV and EPgV, to assess whether current direct-acting antiviral drugs against HCV interact with these proteins. Crystal structures of HCV-NS5B were used as templates for modeling target sequences in both conformations (open and closed). Also, molecular docking of sofosbuvir and dasabuvir were performed to predict their possible binding modes at the modeled NS5B polymerase binding sites. We observed that the NS5B models of the EHCV and EPgV shared well-conserved 3D structures to HCV-NS5B and other RdRps, suggesting functional conservation. Interactions of EHCV subtypes 1, 2 and TDAV polymerases with sofosbuvir showed a similar molecular interaction pattern compared to HCV-NS5B, while interactions with dasabuvir were less conserved. In silico studies of molecular interactions between these modeled structures and sofosbuvir suggest that this compound could be efficient in combating equine pathogens, thus contributing to animal welfare.
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Antivirais/farmacologia , Inibidores Enzimáticos/farmacologia , Hepacivirus/química , Pegivirus/química , Proteínas não Estruturais Virais/química , Animais , Antivirais/química , Inibidores Enzimáticos/química , Hepacivirus/efeitos dos fármacos , Cavalos/virologia , Simulação de Acoplamento Molecular , Pegivirus/efeitos dos fármacos , Alinhamento de SequênciaRESUMO
ABSTRACT BACKGROUND: Hepatitis B and C virus (HBV and HCV) are the two most common infections among human immunodeficiency virus (HIV)-infected patients. OBJECTIVE: To identify the frequency of HIV subtypes and HCV genotypes in HIV-coinfected patients. METHODS: A cross-sectional and retrospective study was carried out into two reference centers in Southern Brazil between January 1, 2002 and June 30, 2016. The Abbott Real Time HCV Genotype II system was used for routine diagnostics to determine the HCV genotype based on dual-target real-time PCR. Proviral HIV-1 RNA was extracted from serum samples and fragments of the pol gene were generated by PCR. The HIV-1 PT and RT gene sequences were submitted to Maximum Likelihood Phylogenetic analysis by collecting reference sequences from the HIV-1 group M subtype of the Los Alamos database. RESULTS: During the study period, 3340 patients with HIV were diagnosed at both referral centers, of which 4.97% (166/3340) had HBV and/or HCV coinfection. Seroprevalence of HIV-HBV, HIV-HCV and HIV-HBV-HCV was 37.4%, 58.4%, and 4.2%, respectively. HIV-HCV-coinfected patients had a lower median nadir CD4+ T-cell count when compared to HIV-HBV-coinfected patients (P=0.01). Among those coinfected with HCV, HCV-1 (HCV-1) and HCV-3 (HCV-3) genotypes were the most prevalent, being detected in 73.8% and 21.4%, respectively. Among the HCV-1 coinfected patients, 79.3% and 20.1% had subtypes 1a and 1b, respectively. HIV subtype B was the most prevalent in HIV-coinfected patients. There was no significant difference regarding nadir CD4+ T-cell count and HIV viral load when compared to coinfected with HCV-1 with HCV-3, as well as those co-infected with HCV-1a with HCV-1b. CONCLUSION: In the present study, a higher frequency of subtype B of HIV and HCV-1 were found in HIV-coinfected patients. Further larger-scale and long-term studies are needed to better understand the effect of HCV genotypes in HIV-infected patients.
RESUMO CONTEXTO: Os vírus das hepatites B e C (VHB e VHC) são os causadores das duas infecções mais comuns entre os pacientes infectados pelo vírus da imunodeficiência humana (HIV). OBJETIVO: Identificar a frequência dos subtipos do HIV e genótipos de VHC em pacientes coinfectados com HIV. MÉTODOS: Estudo transversal e retrospectivo realizado em dois centros de referência do Sul do Brasil, entre 1º de janeiro de 2002 e 30 de junho de 2016. O sistema Abbott Real Time HCV Genótipo II foi utilizado para diagnósticos de rotina para determinar o genótipo do HCV com base na PCR em tempo real de duplo alvo. O RNA viral do HIV-1 foi extraído de amostras de soro e fragmentos do gene pol foram obtidos por PCR. As sequências do gene PT e RT do HIV-1 foram submetidas à análise filogenética por máxima verossimilhança através da coleta de sequências de referência do subtipo M do grupo HIV-1 da base de dados Los Alamos. RESULTADOS: Durante o período do estudo, 3340 pacientes foram diagnosticados com HIV em ambos os centros de referência, dos quais 4,97% (166/3340) possuíam coinfecção com HBV e/ou HCV. A soroprevalência de HIV-HBV, HIV-HCV e HIV-HBV-HCV foi de 37,4%, 58,4% e 4,2%, respectivamente. Pacientes HIV-VHC possuíam menor nadir de células T CD4+ quando comparados aos pacientes HIV-VHB (P=0,01). Entre os pacientes HIV-VHC, os genótipos VHC-1 e VHC-3 foram os mais prevalentes, sendo encontrados em 73,8% e 21,4%, respectivamente. Entre os coinfectados com VHC-1, 79,3% e 20,1% tinham subtipos 1a e 1b, respectivamente. O subtipo B do HIV foi o mais prevalente em pacientes coinfectados. Não houve diferença significativa em relação nadir de células T CD4+ e carga viral do HIV quando comparadas os coinfectados com o VHC-1 com o VHC-3, assim como, os coinfectados com HCV-1a quando comparados com o HCV-1b. CONCLUSÃO: No presente estudo, uma maior frequência do subtipo B do HIV e do VHC-1 foram encontrados em pacientes coinfectados com HIV. Outros estudos em larga escala e a longo prazo são necessários para entender melhor o efeito dos genótipos do HCV em pacientes infectados pelo HIV.
Assuntos
Humanos , Masculino , Feminino , Adulto , Infecções por HIV/complicações , Hepatite C/virologia , Hepacivirus/genética , Brasil , Estudos Transversais , Estudos Retrospectivos , Hepatite C/complicações , Carga Viral , Coinfecção , Genótipo , Pessoa de Meia-IdadeRESUMO
Horses are often used as blood donors for commercial horse serum (HS) production and to manufacture biologicals. HS is an alternative for fetal bovine serum (FBS) used as a supplement for cell culture and vaccine production. Furthermore, HS is also frequently obtained in order to produce antisera toxins and pathogens. The advent of high-throughput sequencing (HTS) has promoted changes in virus detection, since previous knowledge of targets is not required. Thus, the present study aimed to describe the virome of five different batches of commercial HS from New Zealand (three batches) and Brazil and the United States (one batch each) using HTS. Each HS pool were processed and sequenced using an Illumina MiSeq platform. Sequences-related to viruses belonging to the Flaviviridae, Herpesviridae, and Parvoviridae families were detected. Particularly, equine hepacivirus (EqHV), equine pegivirus (EPgV), and Theiler's disease-associated virus (TDAV) were more frequent found in the batches analyzed. The presence of viral genomes in cell culture sera illustrates that these commercial sera can contain a mixture of different viruses and, therefore, can be regarded as potentially infectious for susceptible hosts. Moreover, the innocuity of commercial HS is important for the efficiency and security of diagnostics and the production of biological products.
Assuntos
Flaviviridae/genética , Genoma Viral , Herpesviridae/genética , Cavalos/virologia , Parvoviridae/genética , Soro/virologia , Animais , Meios de Cultura , Flaviviridae/classificação , Herpesviridae/classificação , Cavalos/sangue , Parvoviridae/classificaçãoRESUMO
Recent advances in the study of equine pegivirus (EPgV), Theiler's disease-associated virus (TDAV) and equine hepacivirus (EqHV) highlight their importance to veterinary and human health. To gain some insight into virus distribution, possible risk factors, presence of liver damage and genetic variability of these viruses in Brazil, we performed a cross-sectional study of EPgV and TDAV infections using a simultaneous detection assay, and assessed EqHV coinfection in different horse cohorts. Of the 500 serum samples screened, TDAV, EPgV and EPgV-EqHV were present in 1.6%, 14.2% and 18.3%, respectively. EPgV-positive horses were present in four Brazilian states: Espírito Santo, Mato Grosso do Sul, Minas Gerais and Rio de Janeiro. Serum biochemical alterations were present in 40.4% of EPgV-infected horses, two of them presenting current liver injury. Chance of infection was 2.7 times higher in horses ≤5 years old (p = 0.0008) and 4.9 times higher in horses raised under intensive production systems (p = 0.0009). EPgV-EqHV coinfection was 75% less likely in horses older than 5 years comparatively to those with ≤5 years old (p = 0.047). TDAV-positive animals were detected in different horse categories without biochemical alteration. Nucleotide sequences were highly conserved among isolates from this study and previous field and commercial product isolates (≥88% identity). Tree topology revealed the formation of two clades (pp = 1) for both EPgV and TDAV NS3 partial sequences. In conclusion, the widespread presence of EPgV-RNA suggests an enzootic infection with subclinical viremia in Brazil. Horse management can influence virus spread. This first report of TDAV-infected horses outside the USA reveals the existence of subclinical viremic horses in distant geographical regions. EPgV and TDAV have similar circulating isolates worldwide. These findings contribute to global efforts to understand the epidemiology and pathogenesis of these equine viruses.
Assuntos
Coinfecção/veterinária , Infecções por Flaviviridae/veterinária , Flaviviridae/fisiologia , Doenças dos Cavalos , Animais , Sequência de Bases , Brasil/epidemiologia , Coinfecção/epidemiologia , Coinfecção/patologia , Coinfecção/virologia , Estudos Transversais , DNA Viral , Feminino , Infecções por Flaviviridae/epidemiologia , Infecções por Flaviviridae/patologia , Infecções por Flaviviridae/virologia , Hepacivirus/isolamento & purificação , Hepatite C/epidemiologia , Hepatite C/patologia , Hepatite C/veterinária , Hepatite C/virologia , Doenças dos Cavalos/epidemiologia , Doenças dos Cavalos/patologia , Doenças dos Cavalos/virologia , Cavalos , Fígado/patologia , Masculino , Filogenia , Prevalência , Fatores de Risco , Alinhamento de Sequência/veterináriaRESUMO
The Hepacivirus genus comprises single-stranded positive-sense RNA viruses within the family Flaviviridae. Several hepaciviruses have been identified in different mammals, including multiple rodent species in Africa, Asia, Europe, and North America. To date, no rodent hepacivirus has been identified in the South American continent. Here, we describe an unknown hepacivirus discovered during a metagenomic screen in Akodon montensis, Calomys tener, Oligoryzomys nigripes, Necromys lasiurus, and Mus musculus from São Paulo State, Brazil. Molecular detection of this novel hepacivirus by RT-PCR showed a frequency of 11.11% (2/18) in Oligoryzomys nigripes. This is the first identification of hepavivirus in sigmondonine rodents and in rodents from South America. In sum, our results expand the host range, viral diversity, and geographical distribution of the Hepacivirus genus.
Assuntos
Reservatórios de Doenças/virologia , Genoma Viral , Hepacivirus/classificação , Hepacivirus/isolamento & purificação , Sigmodontinae/virologia , Animais , Especificidade de Hospedeiro , Filogenia , RNA Viral/genética , América do SulRESUMO
ABSTRACT BACKGROUND: The infection for the hepatitis C virus (HCV) is a leading cause of liver-related morbidity and mortality through its evolution to liver cirrhosis, end-stage liver complications and hepatocellular carcinoma. Currently, the new drugs for the HCV infection, based on direct antiviral agents, have changed the outcomes in this setting. OBJECTIVE: To assess death incidence, during the wait for the treatment with the new drugs, and to analyze which independent variable (age, sex, ascite, HDA, albumin, α-fetoprotein, platelets and Meld score) had relation with death. METHODS: Prospective study with cirrhotic patients by HCV. Inclusion: cirrhotic patients by hepatic biopsy (METAVIR), clinic or image, detectable RNA (HCV). Exclusion: Other stages of hepatic fibrosis and hepatocellular carcinoma. Descriptive statistic in continue variables. Fisher Exact and Kaplan Meier and Cox Regression Analysis to assess the association of variables studied with death. P<0.05. RESULTS: A total of 129 patients were included. Of this, 73% were men. Mean age was 57.8±12.1, albumin of 3.5±0.6 mg/dL, platelets of 123.4±59.6 and Meld score of 10.59±3.56. The time of observation was 11.2±3.26 months, and the number of death 9/129 (6,9%). The Kaplan-Meier showed association between death with albumin lower than 2.9 (0.0006), MELD score higher than 15 (0.007) and α-fetoprotein higher than 40 ng/mL (<0.0001). Adjusted Cox Regression Analysis showed that α-fetoprotein higher than 40 ng/ml could be considered an independent risk for death. CONCLUSION: We conclude that, patients with advanced cirrhosis should be prioritized for treatment with direct antiviral agents.
RESUMO CONTEXTO: A infecção pelo vírus da hepatite C (VHC) é uma das principais causas de morbidade e mortalidade relacionada ao fígado, através de sua evolução para cirrose hepática, complicações hepáticas em estágio terminal e carcinoma hepatocelular. Atualmente, os novos fármacos para a infecção pelo VHC, baseados nos novos antivirais de ação direta (AADs), modificaram os resultados nesse cenário. OBJETIVO: Avaliar a incidência de morte, durante a espera pelo tratamento com as novas drogas, e analisar quais variáveis independentes (idade, sexo, ascite, HDA, albumina, α-fetoproteína, plaquetas e escore de MELD) tiveram relação com o óbito. MÉTODOS: Estudo prospectivo com pacientes cirróticos pelo VHC. Inclusão: pacientes cirróticos por biópsia hepática (METAVIR), clínica ou imagem, RNA detectável (VHC). Exclusão: Outras fases de fibrose hepática e carcinoma hepatocelular. Estatística descritiva em variáveis contínuas. Exato de Fisher e Kaplan Meier e Análise de Regressão de Cox para avaliar a associação das variáveis estudadas com o óbito. P<0,05. RESULTADOS: Um total de 129 pacientes foram incluídos. Destes, 73% eram homens. A idade média foi de 57,8±12,1, a albumina de 3,5±0,6 mg/dL, as plaquetas de 123,4±59,6 e o escore de MELD de 10,59±3,56. O tempo de observação foi de 11,2±3,26 meses e o número de mortes 9/129 (6,9%). O Kaplan-Meier mostrou associação entre o óbito com albumina menor que 2,9 (0,0006), escore MELD maior que 15 (0,007) e α-fetoproteína maior que 40 ng/mL (<0,0001). A análise de regressão de Cox ajustada mostrou que α-fetoproteína maior que 40 ng/mL poderia ser considerada um risco independente para morte. CONCLUSÃO: Concluímos que pacientes com cirrose avançada devem ser priorizados para tratamento com AADs.
Assuntos
Humanos , Masculino , Feminino , Antivirais/uso terapêutico , Listas de Espera , Cirrose Hepática/mortalidade , Cirrose Hepática/tratamento farmacológico , Incidência , Estudos Prospectivos , Fatores de Risco , Hepacivirus , Hepatite C Crônica/complicações , Cirrose Hepática/etiologia , Cirrose Hepática/virologia , Neoplasias Hepáticas/mortalidade , Pessoa de Meia-IdadeRESUMO
Anthropogenic environmental change can impact community and population traits such as species diversity and population densities, which have been shown to influence the prevalence of viruses in wildlife reservoirs. In particular, host species resilient to changes in their natural habitat may increase in numbers, which in turn can affect the prevalence of directly transmitted viruses. We have carried out a survey of small mammal communities in three tropical landscapes differing in their degree of environmental change in Central Panama and investigated the effects of community changes on Hepacivirus prevalence. The modification of continuous habitat into partly connected or isolated habitat patches during the past century was linked to changes in species diversity and species assemblages, which was further associated with shifts in the abundance of generalist marsupial (Didelphis marsupialis, Philander opossum) and rodent (Proechimys semispinosus) species. The latter has become dominant in isolated habitat patches and was the only identified Hepacivirus host in our study system. Our analyses suggest that, in addition to the effects of host age and sex, host population density in interaction with sex ratio is a crucial predictor of infection probability. Although we found no significant relationships between species diversity per se and infection probability, the lowest prevalence detected in the landscape with the highest species diversity indicates that shifts in species assemblages (e.g. changes in the presence and abundance of marsupial predators) impact the host's intraspecific contact rates, the probability of virus transmission and, thus, the virus prevalence. Our study additionally provides important data on the influence of human-induced landscape changes on infection probability and, therefore, on virus prevalence in wildlife and emphasizes the importance of a landscape-scale approach with concomitant consideration of the complex interactions between ecological factors.
Assuntos
Hepacivirus , Roedores , Animais , Ecologia , Ecossistema , Humanos , PanamáRESUMO
Hepaciviruses (HVs) have been detected in several domestic and wild animals and present high genetic diversity. The actual classification divides the genus Hepacivirus into 14 species (A-N), according to their phylogenetic relationships, including the bovine hepacivirus [Hepacivirus N (HNV)]. In this study, we confirmed HNV circulation in Brazil and sequenced the whole genome of two strains. Based on the current classification of HCV, which is divided into genotypes and subtypes, we analysed all available bovine hepacivirus sequences in the GenBank database and proposed an HNV classification. All of the sequences were grouped into a single genotype, putatively named 'genotype 1'. This genotype can be clearly divided into four subtypes: A and D containing sequences from Germany and Brazil, respectively, and B and C containing Ghanaian sequences. In addition, the NS3-coding region was used to estimate the time to the most recent common ancestor (TMRCA) of each subtype, using a Bayesian approach and a relaxed molecular clock model. The analyses indicated a common origin of the virus circulating in Germany and Brazil. Ghanaian sequences seemed to have an older TMRCA, indicating a long time of circulation of these viruses in the African continent.