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1.
An Bras Dermatol ; 94(4): 446-448, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31644618

RESUMO

Necrolytic acral erythema is a distinct erythema that has been described as an extrahepatic manifestation of hepatitis C virus infection. Most reported cases have been in Africa, especially Egypt. We report the first case (to the best of our knowledge) of necrolytic acral erythema in a Chinese patient with HCV and HBV coinfection. We aim to increase awareness for recognizing this condition in the Chinese population.


Assuntos
Coinfecção/complicações , Eritema/patologia , Eritema/virologia , Hepatite B/complicações , Hepatite C/complicações , Adulto , China , Coinfecção/patologia , Extremidades/patologia , Hepatite B/patologia , Hepatite C/patologia , Humanos , Masculino , Necrose/virologia
2.
PLoS Pathog ; 15(9): e1008021, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31525236

RESUMO

Hepatitis C virus (HCV) is a positive-strand RNA virus replicating in a membranous replication organelle composed primarily of double-membrane vesicles (DMVs) having morphological resemblance to autophagosomes. To define the mechanism of DMV formation and the possible link to autophagy, we conducted a yeast two-hybrid screening revealing 32 cellular proteins potentially interacting with HCV proteins. Among these was the Receptor for Activated Protein C Kinase 1 (RACK1), a scaffolding protein involved in many cellular processes, including autophagy. Depletion of RACK1 strongly inhibits HCV RNA replication without affecting HCV internal ribosome entry site (IRES) activity. RACK1 is required for the rewiring of subcellular membranous structures and for the induction of autophagy. RACK1 binds to HCV nonstructural protein 5A (NS5A), which induces DMV formation. NS5A interacts with ATG14L in a RACK1 dependent manner, and with the ATG14L-Beclin1-Vps34-Vps15 complex that is required for autophagosome formation. Both RACK1 and ATG14L are required for HCV DMV formation and viral RNA replication. These results indicate that NS5A participates in the formation of the HCV replication organelle through interactions with RACK1 and ATG14L.


Assuntos
Hepatite C/metabolismo , Hepatite C/virologia , Proteínas de Neoplasias/metabolismo , Receptores de Quinase C Ativada/metabolismo , Proteínas Adaptadoras de Transporte Vesicular/metabolismo , Autofagossomos/metabolismo , Autofagossomos/virologia , Autofagia , Proteínas Relacionadas à Autofagia/metabolismo , Linhagem Celular , Hepacivirus/genética , Hepacivirus/patogenicidade , Hepacivirus/fisiologia , Hepatite C/patologia , Hepatócitos/metabolismo , Hepatócitos/patologia , Hepatócitos/virologia , Interações entre Hospedeiro e Microrganismos/fisiologia , Humanos , Redes e Vias Metabólicas , Ligação Proteica , Domínios e Motivos de Interação entre Proteínas , RNA Viral/biossíntese , Técnicas do Sistema de Duplo-Híbrido , Proteínas não Estruturais Virais/química , Proteínas não Estruturais Virais/metabolismo , Replicação Viral
3.
Int J Mol Sci ; 20(18)2019 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-31546975

RESUMO

With respect to their genome and their structure, the human hepatitis B virus (HBV) and hepatitis C virus (HCV) are complete different viruses. However, both viruses can cause an acute and chronic infection of the liver that is associated with liver inflammation (hepatitis). For both viruses chronic infection can lead to fibrosis, cirrhosis and hepatocellular carcinoma (HCC). Reactive oxygen species (ROS) play a central role in a variety of chronic inflammatory diseases. In light of this, this review summarizes the impact of both viruses on ROS-generating and ROS-inactivating mechanisms. The focus is on the effect of both viruses on the transcription factor Nrf2 (nuclear factor erythroid 2 (NF-E2)-related factor 2). By binding to its target sequence, the antioxidant response element (ARE), Nrf2 triggers the expression of a variety of cytoprotective genes including ROS-detoxifying enzymes. The review summarizes the literature about the pathways for the modulation of Nrf2 that are deregulated by HBV and HCV and describes the impact of Nrf2 deregulation on the viral life cycle of the respective viruses and the virus-associated pathogenesis.


Assuntos
Hepacivirus , Vírus da Hepatite B , Hepatite B/metabolismo , Hepatite C/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Transdução de Sinais , Replicação Viral/fisiologia , Animais , Hepacivirus/patogenicidade , Hepacivirus/fisiologia , Hepatite B/patologia , Vírus da Hepatite B/patogenicidade , Vírus da Hepatite B/fisiologia , Hepatite C/patologia , Humanos
5.
BMC Med Genet ; 20(1): 142, 2019 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-31419949

RESUMO

BACKGROUND & AIMS: Various studies have investigated the relationship between the polymorphism, rs2596542, in the promoter of the major histocompatibility complex class I-related gene A (MICA) gene with susceptibility to hepatitis B virus (HBV)/ hepatitis C virus (HCV)-induced hepatocellular carcinoma (HCC); however, the results are inconclusive. This meta-analysis was conducted to investigate the relationship between rs2596542 and HCV/HBV-induced HCC. METHODS: Three electronic scientific publication databases (MEDLINE, Web of Science, and Embase) were screened using specific search terms and relevant literature identified using literature traceability methods. Selected publications were evaluated according to the inclusion and exclusion criteria, and 11 articles were included in the study. Effect size information (odds ratio [OR] and corresponding 95% confidence interval [CI]) were obtained following quality assessment and data extraction from the included publications, and a meta-analysis conducted. RESULTS: A total of 11 publications were included in the study, including 4582 patients with HCC and 21,095 non-HCC patients. TT genotype at rs2596542 was a risk factor for the development of HCC in patients with HCV/HBV infection (OR = 1.248, 95% CI: 1.040-1.499, P = 0.017), particularly those with HCV infection (OR = 1.326, 95% CI: 1.101-1.599, P = 0.003) and Asians (OR = 1.273, 95% CI: 1.002-1.618, P = 0.048), or when the control group was patients with chronic hepatitis C (CHC) (OR = 1.506, 95% CI: 1.172-1.936, P = 0.001). CONCLUSION: The findings of this meta-analysis suggest that the rs2596542 variant in the MICA promoter region may affect MICA and soluble MICA (sMICA) protein expression, thereby influencing physiological vulnerability to HCC cells and the development of HCC. These data provide a theoretical basis for the diagnosis and treatment of patients with HCC and viral hepatitis infection.


Assuntos
Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/virologia , Hepatite B/genética , Hepatite C/genética , Antígenos de Histocompatibilidade Classe I/genética , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/virologia , Bases de Dados Factuais , Predisposição Genética para Doença , Variação Genética , Hepacivirus , Hepatite B/patologia , Vírus da Hepatite B , Hepatite C/patologia , Humanos , Razão de Chances , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas
6.
An. bras. dermatol ; 94(4): 446-448, July-Aug. 2019. graf
Artigo em Inglês | LILACS | ID: biblio-1038296

RESUMO

Abstract: Necrolytic acral erythema is a distinct erythema that has been described as an extrahepatic manifestation of hepatitis C virus infection. Most reported cases have been in Africa, especially Egypt. We report the first case (to the best of our knowledge) of necrolytic acral erythema in a Chinese patient with HCV and HBV coinfection. We aim to increase awareness for recognizing this condition in the Chinese population.


Assuntos
Humanos , Masculino , Adulto , Hepatite C/complicações , Eritema/patologia , Eritema/virologia , Coinfecção/complicações , Hepatite B/complicações , China , Hepatite C/patologia , Extremidades/patologia , Coinfecção/patologia , Hepatite B/patologia , Necrose/virologia
7.
Int J Mol Sci ; 20(14)2019 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-31340446

RESUMO

Alcoholic liver disease (ALD) is a highly prevalent spectrum of pathologies caused by alcohol overconsumption. Morbidity and mortality related to ALD are increasing worldwide, thereby demanding strategies for early diagnosis and detection of ALD predisposition. A potential candidate as a marker for ALD susceptibility is the transcription factor nuclear factor erythroid-related factor 2 (Nrf2), codified by the nuclear factor erythroid 2-related factor 2 gene (NFE2L2). Nrf2 regulates expression of proteins that protect against oxidative stress and inflammation caused by alcohol overconsumption. Here, we assessed genetic variants of NFE2L2 for association with ALD. Specimens from patients diagnosed with cirrhosis caused by ALD were genotyped for three NFE2L2 single nucleotide polymorphisms (SNP) (SNPs: rs35652124, rs4893819, and rs6721961). Hematoxylin & eosin and immunohistochemistry were performed to determine the inflammatory score and Nrf2 expression, respectively. SNPs rs4893819 and rs6721961 were not specifically associated with ALD, but analysis of SNP rs35652124 suggested that this polymorphism predisposes to ALD. Furthermore, SNP rs35652124 was associated with a lower level of Nrf2 expression. Moreover, liver samples from ALD patients with this polymorphism displayed more severe inflammatory activity. Together, these findings provide evidence that the SNP rs35652124 variation in the Nrf2-encoding gene NFE2L2 is a potential genetic marker for susceptibility to ALD.


Assuntos
Predisposição Genética para Doença , Cirrose Hepática Alcoólica/genética , Fator 2 Relacionado a NF-E2/genética , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas , Adulto , Estudos de Casos e Controles , Etanol/farmacologia , Feminino , Expressão Gênica , Hepacivirus/crescimento & desenvolvimento , Hepacivirus/patogenicidade , Hepatite C/patologia , Hepatite C/virologia , Humanos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Cirrose Hepática Alcoólica/metabolismo , Cirrose Hepática Alcoólica/patologia , Cirrose Hepática Alcoólica/cirurgia , Transplante de Fígado , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo
8.
EBioMedicine ; 46: 227-235, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31345785

RESUMO

BACKGROUND: Whether achieving sustained virological response (SVR) in patients with hepatitis C attains complete elimination of hepatitis C virus (HCV) is unknown, because occult HCV infection (OCI), defined as the detection of HCV-RNA in hepatocytes or peripheral blood mononuclear cells (PBMC) in absence of serum HCV-RNA, may occur. We thus investigated the prevalence and clinical relevance of OCI. METHODS: Subjects from three hospitals who had achieved serum HCV clearance, including 60 of Direct-acting antiviral agents (DAAs) induced SVR, 50 of pegylated interferon plus ribavirin (PR) induced SVR, and 30 of spontaneous resolution, were subjected to detect HCV-RNA in liver by robust RNAscope assay and PBMC by qPCR. Paired liver biopsies at baseline and at SVR24 were analyzed. RESULTS: OCI was detected in 16 of 140 subjects (11.4%), with 15.0% in DAA-based group, 10.0% in PR group and 6.7% in spontaneously resolved group. In DAA-based subgroups, the incidence of OCI was gradually increased in group of solely DAA(s) therapy, combining DAA and PR therapy and combining DAA and ribavirin therapy. OCI is more frequent in patients with genotype 3. No correlation between baseline viral load, interleukin-28B genotype, baseline transaminases, post-SVR transaminases and OCI were found. However, OCI was significantly linked with severity of fibrosis and active inflammation at post-SVR, even considering basal fibrosis status. In addition, both the magnitude and the frequency of fibrosis regression were lower in patients with OCI than in those without OCI. In the multivariate analysis, PR therapy was identified an independent negative prognostic factor for both hepatic inflammation (P = .022) and fibrosis regression (P = .015). Importantly, we found HCV relapse in one of the OCI patients at 48 weeks after the end of PR treatment. CONCLUSIONS: HCV-RNA can persist in hepatocytes and/or PBMC in a certain of patients who achieved spontaneous or treatment-induced HCV RNA clearance from serum and associated with persistent histological abnormality. Our findings provide new insights into cure of HCV and could influence the following-up scenario after SVR.


Assuntos
Hepacivirus/fisiologia , Hepatite C/patologia , Hepatite C/virologia , Fígado/patologia , Fígado/virologia , Carga Viral , Adulto , Idoso , Antivirais/farmacologia , Antivirais/uso terapêutico , Biópsia , Feminino , Hepatite C/tratamento farmacológico , Humanos , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , RNA Viral , Resposta Viral Sustentada , Resultado do Tratamento , Adulto Jovem
9.
Cancer Control ; 26(1): 1073274819862793, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31290350

RESUMO

Epidemiological characteristics of hepatocellular carcinoma (HCC) in Southern Vietnam has been well reported as in Globocan 2018 while data from the North has still not been fully presented. Therefore, we conducted this retrospective descriptive study on 198 advanced HCC patients treated at 3 major hospitals in Northern Vietnam to describe demographic features, HCC risk factors, and correlation among them in patients with advanced HCC. This information will lead to prevention efforts and provide information for allocating funds for treatment. The median age at diagnosis was 57 years (range: 19-86) and the male/female ratio was 8.9/1. The proportions of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection were 81.3% and 5.6%, respectively. Hepatitis C virus infection rate was significantly higher in patients <50 years old (12.5% vs 3.3%, P = .016). There was no significant difference in age or viral hepatitis infection status by gender. Only 7.6% of patients diagnosed with advanced HCC were asymptomatic. In conclusion, with the high rate of HBV infection among patients with advanced HCC, it is necessary for increasing prevention efforts in HBV screening. Furthermore, HCV infection should be noticed in patients with advanced HCC younger than 50 years old.


Assuntos
Carcinoma Hepatocelular/epidemiologia , Hepatite B/epidemiologia , Hepatite C/epidemiologia , Neoplasias Hepáticas/epidemiologia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/virologia , Feminino , Hepatite B/patologia , Hepatite B/virologia , Hepatite C/patologia , Hepatite C/virologia , Humanos , Incidência , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais , Vietnã/epidemiologia , Adulto Jovem
10.
PLoS Genet ; 15(6): e1008181, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31216276

RESUMO

The increasing worldwide prevalence of Hepatocellular carcinoma (HCC), characterized by resistance to conventional chemotherapy, poor prognosis and eventually mortality, place it as a prime target for new modes of prevention and treatment. Hepatitis C Virus (HCV) is the predominant risk factor for HCC in the US and Europe. Multiple epidemiological studies showed that sustained virological responses (SVR) following treatment with the powerful direct acting antivirals (DAAs), which have replaced interferon-based regimes, do not eliminate tumor development. We aimed to identify an HCV-specific pathogenic mechanism that persists post SVR following DAAs treatment. We demonstrate that HCV infection induces genome-wide epigenetic changes by performing chromatin immunoprecipitation followed by next-generation sequencing (ChIP-seq) for histone post-translational modifications that are epigenetic markers for active and repressed chromatin. The changes in histone modifications correlate with reprogramed host gene expression and alter signaling pathways known to be associated with HCV life cycle and HCC. These epigenetic alterations require the presence of HCV RNA or/and expression of the viral proteins in the cells. Importantly, the epigenetic changes induced following infection persist as an "epigenetic signature" after virus eradication by DAAs treatment, as detected using in vitro HCV infection models. These observations led to the identification of an 8 gene signature that is associated with HCC development and demonstrate persistent epigenetic alterations in HCV infected and post SVR liver biopsy samples. The epigenetic signature was reverted in vitro by drugs that inhibit epigenetic modifying enzyme and by the EGFR inhibitor, Erlotinib. This epigenetic "scarring" of the genome, persisting following HCV eradication, suggest a novel mechanism for the persistent pathogenesis of HCV after its eradication by DAAs. Our study offers new avenues for prevention of the persistent oncogenic effects of chronic hepatitis infections using specific drugs to revert the epigenetic changes to the genome.


Assuntos
Carcinoma Hepatocelular/genética , Epigênese Genética/genética , Hepacivirus/genética , Hepatite C/genética , Neoplasias Hepáticas/genética , Idoso , Antivirais/administração & dosagem , Biópsia , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/virologia , Cromatina/genética , Epigênese Genética/efeitos dos fármacos , Receptores ErbB/antagonistas & inibidores , Cloridrato de Erlotinib , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Hepacivirus/patogenicidade , Hepatite C/tratamento farmacológico , Hepatite C/patologia , Hepatite C/virologia , Código das Histonas/genética , Histonas/genética , Interações Hospedeiro-Patógeno/genética , Humanos , Interferons/administração & dosagem , Fígado/efeitos dos fármacos , Fígado/patologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Transdução de Sinais/efeitos dos fármacos , Resposta Viral Sustentada
11.
Cells ; 8(6)2019 06 17.
Artigo em Inglês | MEDLINE | ID: mdl-31213010

RESUMO

Hepatitis C virus (HCV) infection is commonly attributed as a major cause of chronic hepatotropic diseases, such as, steatosis, cirrhosis and hepatocellular carcinoma. As HCV infects only humans and primates, its narrow host tropism hampers in vivo studies of HCV-mammalian host interactions and the development of effective therapeutics and vaccines. In this context, we will focus our discussion on humanized mice in HCV research. Here, these humanized mice are defined as animal models that encompass either only human hepatocytes or both human liver and immune cells. Aspects related to immunopathogenesis, anti-viral interventions, drug testing and perspectives of these models for future HCV research will be discussed.


Assuntos
Hepatite C/patologia , Hepatite C/virologia , Interações Hospedeiro-Patógeno , Animais , Modelos Animais de Doenças , Progressão da Doença , Hepacivirus/fisiologia , Hepatite C/imunologia , Humanos , Camundongos , Vacinas contra Hepatite Viral/imunologia
12.
Ann Transplant ; 24: 312-318, 2019 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-31147531

RESUMO

BACKGROUND Hepatitis B and C viruses have been recognized as undoubtedly carcinogenic to humans. In the Polish population, where most people are protected by HBV vaccinations, hepatocellular carcinoma (HCC) and its main cause, persistent HCV infection, significantly affect the demand for liver transplantations. MATERIAL AND METHODS The purpose of this study was to categorize the number of primary liver transplantations in Poland in the years 2001-2017 by cause and to analyze changes in LTx indications during this period. Data were sourced from POLTRANSPLANT, the Organization and Coordination Center for Transplantation in Poland. Additionally, we compared the numbers of HCC cases and hepatitis B and C cases during this period. RESULTS In the analyzed period, in Poland, 3332 primary liver transplantations were performed. Overall, 44% (1456) of LTx cases were combined with HBV and/or HCV and/or HCC. In this group, transplants in patients with only 1 specific factor - HCV - formed the largest cohort, accounting for about 40% (581) of cases. Transplants in patients who only had HBV and in those who only had HCC accounted for 12% (185) and 5% (69), respectively. CONCLUSIONS The analyzed data suggest that HCV infections are a significant public health problem in Poland, as is also reflected by the growing number of LTx performed due to HCC. To limit the numbers of HCV and HCC cases, immediate implementation of a Polish National Program against HCV should be considered.


Assuntos
Carcinoma Hepatocelular/cirurgia , Hepatite B/cirurgia , Hepatite C/cirurgia , Neoplasias Hepáticas/cirurgia , Transplante de Fígado , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/patologia , Feminino , Hepatite B/complicações , Hepatite B/patologia , Hepatite C/complicações , Hepatite C/patologia , Humanos , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Polônia , Fatores de Risco , Adulto Jovem
13.
Drug Discov Ther ; 13(2): 108-113, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31080201

RESUMO

Portal hypertension and its complications are the leading causes of morbidity and mortality in patients with liver cirrhosis. Noninvasive assessment of liver stiffness had been an effective tool for assessment of fibrosis progression in chronic liver disease. It was intended to assess liver stiffness measurement (LSM), portal vein diameter (PVD), splenic bipolar diameter (SD), and the platelet count/spleen diameter (PC/SD) ratio in patients who test positive for the hepatitis C virus (HCV) and to study the impact of non-selective beta blockers (NSBB) on the grade of esophageal varices (EVs) and liver elasticity. Subjects were 80 patients with Child-Pugh grade A or B compensated cirrhosis who tested positive for HCV. All of the patients underwent a laboratory workup including AFP, HCV antibodies, HCV RNA, HBsAg, LSM according to real-time elastography, upper gastrointestinal endoscopy (UGIE) to detect and grade EVs, calculation of the PC/SD ratio, and measurement of the PVD and SD according to real-time abdominal ultrasonography. All patients were given the maximum tolerated dose of NSBB for three months, and UGIE, LSM, PC/SD, PVD, and SD were subsequently reassessed and reported. LSM and the PC/SD ratio were exceptional noninvasive tools for prediction of significant EVs (grade ≥ II, p < 0.001) with a sensitivity 82.4% and a specificity 82.6% at a cutoff point 18 kPa for LSM, and a sensitivity 94.1% and specificity 69.6% at a cutoff point 880 for the PC/SD ratio. LSM is highly correlated with PVD, the PC/SD ratio, SD, and the Child-Pugh score. NSBB significantly decreased PVD. The percent change in PVD significantly correlated with LSM, the grade of EVs, and SD. Findings indicated that LSM is a noninvasive, rapid, and reproducible tool with which to detect portal hypertension and EVs. NSBB therapy can effectively decrease PVD and may consequently improve the EV grade with no significant impact on LSM in patients with liver cirrhosis.


Assuntos
Antagonistas Adrenérgicos beta/administração & dosagem , Varizes Esofágicas e Gástricas/diagnóstico , Hepatite C/complicações , Hipertensão Portal/tratamento farmacológico , Cirrose Hepática/complicações , Propranolol/administração & dosagem , Antagonistas Adrenérgicos beta/efeitos adversos , Estudos de Casos e Controles , Progressão da Doença , Técnicas de Imagem por Elasticidade , Varizes Esofágicas e Gástricas/induzido quimicamente , Feminino , Hepatite C/patologia , Humanos , Cirrose Hepática/etiologia , Cirrose Hepática/patologia , Masculino , Propranolol/efeitos adversos , Estudos Prospectivos , Curva ROC
14.
BMC Infect Dis ; 19(1): 381, 2019 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-31053097

RESUMO

BACKGROUND: The epidemiology of hepatitis B virus (HBV) infection in the general population in Rwanda is not well known. This study examined the prevalence of HBV surface antigen (HBsAg) positivity and associated risk factors among people aged 25 years and over in an organized national screening campaign. METHODS: This is a cross-sectional study using data from a nationwide HBV screening campaign organized by the Rwanda Biomedical Centre from March to October 2018. This campaign targeted individuals aged > 25 years old from 24 of 30 districts of Rwanda. Sensitization was done through multimedia announcements, community health workers and local church leaders. During the campaign, a structured interview was administered by trained healthcare workers to collect information on socio-demographic, clinical and behavioral characteristics of participants; HBV screening was performed with HBsAg using enzyme-linked immunosorbent assays (ELISA) testing. Bivariate and multivariate logistic regressions were used to assess factors associated with HBsAg positivity in the screened participants. RESULTS: A total of 327,360 individuals were screened during the campaign. Overall 12,865(3.9%) were HBsAg positive. The highest prevalence (4.2%) was found in the 35-44-year-old group, but the difference from other groups was not significant (Odds Ratio [OR = 1.057, 95% Confidence Interval(CI) (0.904-1.235)]. Being male [OR = 1.348, 95% CI (1.30,1.40)]; being single [OR = 1.092, 95% CI (1.10-1.16)] compared to married; a previous positive TB screening test [OR = 2.352, 95% CI (1.63-3.39)]; history of surgical operation [OR = 1.082, 95% CI (1.00,1.17)]; exposure to traditional operational practices and scarification [OR = 1.187, 95% CI (1.13, 1.24)]; and having a person in the family with viral hepatitis [OR = 1.367, 95% CI (1.21, 1.53)] were significantly associated with HBV infection. CONCLUSIONS: These data provide the first national estimate of the prevalence of HBsAg seropositivity and its associated factors in Rwanda. The study identified people with the highest risk of HBV infection who should be the priority of future prevention efforts in Rwanda and in similar settings.


Assuntos
Antígenos de Superfície da Hepatite B/sangue , Hepatite B/epidemiologia , Adulto , Idoso , Estudos Transversais , Feminino , Infecções por HIV/patologia , Hepatite B/diagnóstico , Hepatite B/virologia , Hepatite C/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Prevalência , Fatores de Risco , Ruanda/epidemiologia , Tuberculose/patologia
15.
Wiad Lek ; 72(4): 595-599, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31055539

RESUMO

OBJECTIVE: Introduction: In this publication we analyzed the specific aspects of clinical course in case of combination of chronic pancreatitis and concomitant viral hepatitis C. The aim: Discover the clinical course of chronic pancreatitis with concomitant viral hepatitis C . PATIENTS AND METHODS: Materials and methods: 57 patients with chronic pancreatitis and concomitant viral hepatitis c were examined. Diagnosis of chronic pancreatitis and viral hepatitis c was verified based on disease history, clinical symptoms and the results of clinical-instrumental tests. Clinical and biochemical investigations in people with chronic pancreatitis were done in exacerbation and unstable remission phases and for people with viral hepatitis C - in stable remission phase. RESULTS: Results: In patients, who have chronic pancreatitis with concomitant hepatitis C, pain, dyspeptic syndromes and defecation disturbances take the major place in clinical course of the disease. These symptoms were more severe than in the control group (possible difference in numbers in the group of patents with isolate viral hepatitis C (p<0,05). CONCLUSION: Conclusions: According to the studies data-the negative influence of concomitant viral hepatitis C in clinical course of chronic pancreatitis was identified.


Assuntos
Hepatite C/complicações , Pancreatite Crônica/complicações , Doença Aguda , Hepatite C/patologia , Humanos , Pancreatite Crônica/patologia
16.
Biomed Res Int ; 2019: 3102414, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30984779

RESUMO

Etifoxine, an 18 kDa translocator protein (TSPO) agonist for the treatment of anxiety disorders in clinic, may be able to cause acute liver injury or cytolytic hepatitis. TSPO has been demonstrated to participate in inflammatory responses in infective diseases as well as to modulate glucose and lipid homeostasis. Hepatitis C virus (HCV) infection disrupts glucose and lipid homoeostasis, leading to insulin resistance (IR). Whether TSPO affects the HCV-induced IR remains unclear. Here, we found that the administration of etifoxine increased the TSPO protein expression and recovered the HCV-mediated lower mitochondrial membrane potential (MMP) without affecting HCV infection. Moreover, etifoxine reversed the HCV-induced lipid accumulation by modulating the expressions of sterol regulatory element-binding protein-1 and apolipoprotein J. On the other hand, in infected cells pretreated with etifoxine, the insulin-mediated insulin receptor substrate-1/Akt signals, forkhead box protein O1 translocation, and glucose uptake were blocked. Taken together, our results pointed out that etifoxine relieved the HCV-retarded MMP and reduced the lipid accumulation but deteriorated the HCV-induced IR by interfering with insulin signal molecules.


Assuntos
Hepatite C/tratamento farmacológico , Inflamação/tratamento farmacológico , Resistência à Insulina/genética , Oxazinas/administração & dosagem , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Proteína Forkhead Box O1/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Glucose/metabolismo , Hepatite C/genética , Hepatite C/patologia , Hepatite C/virologia , Humanos , Inflamação/genética , Inflamação/patologia , Inflamação/virologia , Proteínas Substratos do Receptor de Insulina/genética , Metabolismo dos Lipídeos/efeitos dos fármacos , Lipídeos/genética , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/genética , Receptores de GABA/genética
17.
Arch Virol ; 164(6): 1587-1595, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30949812

RESUMO

Epigallocatechin gallate (EGCG) is the most abundant component in green tea extract, that has powerful antioxidant and antiviral effects. It has been previously reported to inhibit HCV entry via several mechanisms. Hence, this study aimed at further investigating the potential impact of EGCG on HCV entry through regulation of the expression of tetraspanin receptor CD81 by the novel predicted miR-548m. Liver biopsies were obtained from 29 HCV patients and 10 healthy controls for expression profiling. Huh7 cells were stimulated with EGCG and subsequently miR-548m expression was assessed. Naïve, HCV- ED43/JFH-1 and HCV-JFH-1 infected Huh7 cells were transfected by miR-548m mimics and inhibitors. Consequently, CD81 protein and mRNA levels were assessed using flow cytometry and qRT-PCR, respectively. Additionally, these cells were used to investigate HCV permissiveness into Huh7 cells using qRT-PCR for viral quantification. Direct binding confirmation of miR-548m to CD81 was done using luciferase reporter assay. In-silico analysis revealed miR-548m to have two potential binding sites in the 3'UTR of CD81 mRNA. EGCG boosted miR-548m expression in Huh7 cells. Additionally, miR-548m caused a downregulation of CD81 protein and mRNA levels as well as reduction in HCV infectivity of Huh7 cells. Luciferase binding assay confirmed the binding of miR-548m to CD81 mRNA at the two predicted binding sites. Intriguingly, miR-548m expression was not detected in healthy liver biopsies but was found in liver biopsies of HCV patients. This study shows that EGCG might act as an anti-HCV agent that reduces cellular infectivity via enhancing miR-548m expression and repressing CD81 receptor.


Assuntos
Catequina/análogos & derivados , Hepacivirus/fisiologia , Hepatite C/patologia , MicroRNAs/genética , Tetraspanina 28/genética , Regiões 3' não Traduzidas , Estudos de Casos e Controles , Catequina/farmacologia , Linhagem Celular , Simulação por Computador , Perfilação da Expressão Gênica , Regulação da Expressão Gênica/efeitos dos fármacos , Hepacivirus/efeitos dos fármacos , Hepatite C/genética , Hepatite C/metabolismo , Hepatite C/virologia , Humanos , Tetraspanina 28/metabolismo , Internalização do Vírus/efeitos dos fármacos
18.
Lipids Health Dis ; 18(1): 87, 2019 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-30954078

RESUMO

BACKGROUND: The homeostasis of lipid droplets (LDs) plays a crucial role in maintaining the physical metabolic processes in cells, and is regulated by many LD-associated proteins, including perilipin 5 (Plin5) in liver. As the putative sites of hepatitis C virus (HCV) virion assembly, LDs are vital to viral infection. In addition, the hepatic LD metabolism can be disturbed by non-structural HCV proteins, such as NS5A, but the details are still inexplicit. METHODS: HCV NS5A was overexpressed in the livers and hepatocytes of wild-type and Plin5-null mice. BODIPY 493/503 and oil red O staining were used to detect the lipid content in mouse livers and hepatocytes. The levels of lipids, lipid peroxidation and inflammation biomarkers were further determined. Immunofluorescence assay and co-immunoprecipitation assay were performed to investigate the relationship of Plin5 and NS5A. RESULTS: One week after adenovirus injection, livers expressing NS5A showed more inflammatory cell aggregation and more severe hepatic injuries in Plin5-null mice than in control mice, which was consistent with the increased serum levels of IL-2 and TNF-α (P < 0.05) observed in Plin5-null mice. Moreover, Plin5 deficiency in the liver and hepatocytes aggravated the elevation of MDA and 4-HNE levels induced by NS5A expression (P < 0.01). The triglyceride (TG) content was increased approximately 25% by NS5A expression in the wild-type liver and hepatocytes but was unchanged in the Plin5-null liver and hepatocytes. More importantly, Plin5 deficiency in the liver and hepatocytes exacerbated the elevation of non-esterified fatty acids (NEFAs) stimulated by NS5A expression (P < 0.05 and 0.01 respectively). Using triacsin C to block acyl-CoA biosynthesis, we found that Plin5 deficiency aggravated the NS5A-induced lipolysis of TG. In contrast, Plin5 overexpression in HepG2 cells ameliorated the NS5A-induced lipolysis and lipotoxic injuries. Immunofluorescent staining demonstrated that NS5A expression stimulated the targeting of Plin5 to the surface of the LDs in hepatocytes without altering the protein levels of Plin5. By co-IP, we found that the N-terminal domain (aa 32-128) of Plin5 was pivotal for its binding with NS5A. CONCLUSIONS: Our data highlight a protective role of Plin5 against hepatic lipotoxic injuries induced by HCV NS5A, which is helpful for understanding the steatosis and injuries in liver during HCV infection.


Assuntos
Fígado Gorduroso/genética , Hepatite C/genética , Fígado/metabolismo , Perilipina-5/genética , Proteínas não Estruturais Virais/genética , Acil Coenzima A/antagonistas & inibidores , Acil Coenzima A/biossíntese , Adenoviridae/genética , Animais , Modelos Animais de Doenças , Fígado Gorduroso/metabolismo , Fígado Gorduroso/terapia , Regulação Viral da Expressão Gênica/genética , Hepacivirus/genética , Hepacivirus/patogenicidade , Hepatite C/metabolismo , Hepatite C/patologia , Hepatite C/virologia , Hepatócitos/metabolismo , Hepatócitos/patologia , Hepatócitos/virologia , Humanos , Gotículas Lipídicas/metabolismo , Gotículas Lipídicas/patologia , Metabolismo dos Lipídeos/genética , Lipólise/genética , Fígado/lesões , Fígado/patologia , Fígado/virologia , Camundongos , Triazenos/administração & dosagem , Triglicerídeos/genética , Triglicerídeos/metabolismo , Fator de Necrose Tumoral alfa/genética
19.
Transbound Emerg Dis ; 66(4): 1737-1751, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31017727

RESUMO

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/veterinária
20.
Cell Host Microbe ; 25(4): 588-601.e7, 2019 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-30974086

RESUMO

Patients infected with hepatitis C virus (HCV) have an increased risk of developing type 2 diabetes. HCV infection is linked to various liver abnormalities, potentially contributing to this association. We show that HCV infection increases the levels of hepatic selenoprotein P (SeP) mRNA (SEPP1 mRNA) and serum SeP, a hepatokine linked to insulin resistance. SEPP1 mRNA inhibits type I interferon responses by limiting the function of retinoic-acid-inducible gene I (RIG-I), a sensor of viral RNA. SEPP1 mRNA binds directly to RIG-I and inhibits its activity. SEPP1 mRNA knockdown in hepatocytes causes a robust induction of interferon-stimulated genes and decreases HCV replication. Clinically, high SeP serum levels are significantly associated with treatment failure of direct-acting antivirals in HCV-infected patients. Thus, SeP regulates insulin resistance and innate immunity, possibly inducing immune tolerance in the liver, and its upregulation may explain the increased risk of type 2 diabetes in HCV-infected patients.


Assuntos
Proteína DEAD-box 58/antagonistas & inibidores , Hepatite C/patologia , Interações Hospedeiro-Patógeno , Evasão da Resposta Imune , RNA Mensageiro/metabolismo , Selenoproteína P/biossíntese , Humanos
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