Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 7.397
Filtrar
1.
BMC Infect Dis ; 20(1): 664, 2020 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-32907538

RESUMO

BACKGROUND: Hepatitis C virus (HCV) infection and type 2 diabetes mellitus (T2DM) are two major public health problems associated with increasing complications and mortality rates worldwide. The objective of this study is to evaluate the prevalence of hepatitis C virus (HCV) infection in diabetic patients and to investigate the influence of several epidemiological and clinical factors on HCV infection. METHOD: A total number of one hundred and eighty diabetic patients were recruited for this study. Consented subjects made up of 71(39.4%) males and 109(60.56%) females were recruited for the study. While one-Hundred (100) Non-Diabetics (Controls) were also recruited for the study. Structured questionnaires were administered to the consented participants to obtain relevant data. Sera samples were assayed for antibodies to HCV using an enzyme linked immunosorbent assay [Inteco Diagnostic Limited]. ELISA technique. RESULT: Overall prevalence of HCV infection among diabetes patients assayed was 13.3% out of which 8(11.3%) was obtained from the male subjects compared to 16 (14.7%) seropositivity recorded among the females (P = 0.511; P > 0.05). Considering age distribution, Subjects aged 41-50 years recorded, 9 (22.5%) positivity (P = 0.238; P > 0.05).Considering educational status of subjects screened, 22 (14.9%) positivity was rescored among subjects who have attained tertiary status of education.(P = 0.574;P > 0.05).Risk factors considered showed that, 7 (18.9%) seropositive subject were alcoholic consumers(P value = 0.2621;P > 0.05) while 5 (8.9%) recorded history of sharing sharp objects P = 0.2427;P > 0.05). CONCLUSION: Our study shows a slightly higher prevalence of hepatitis C infection in type 2 diabetics. This call for urgent routine screening exercise among diabetic patients for HCV infection. This study also emphasizes the need for public enlightenment on the association between HCV infection and T2DM, to avert possible complications among diabetic patients.


Assuntos
Diabetes Mellitus Tipo 2/epidemiologia , Hepacivirus/imunologia , Hepatite C/epidemiologia , Centros de Atenção Terciária , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Comorbidade , Ensaio de Imunoadsorção Enzimática , Feminino , Hepatite C/virologia , Anticorpos Anti-Hepatite C/sangue , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Nigéria/epidemiologia , Prevalência , Fatores de Risco , Inquéritos e Questionários , Adulto Jovem
2.
PLoS Pathog ; 16(8): e1008346, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32764824

RESUMO

Viruses subvert macromolecular pathways in infected host cells to aid in viral gene amplification or to counteract innate immune responses. Roles for host-encoded, noncoding RNAs, including microRNAs, have been found to provide pro- and anti-viral functions. Recently, circular RNAs (circRNAs), that are generated by a nuclear back-splicing mechanism of pre-mRNAs, have been implicated to have roles in DNA virus-infected cells. This study examines the circular RNA landscape in uninfected and hepatitis C virus (HCV)-infected liver cells. Results showed that the abundances of distinct classes of circRNAs were up-regulated or down-regulated in infected cells. Identified circRNAs displayed pro-viral effects. One particular up-regulated circRNA, circPSD3, displayed a very pronounced effect on viral RNA abundances in both hepatitis C virus- and Dengue virus-infected cells. Though circPSD3 has been shown to bind factor eIF4A3 that modulates the cellular nonsense-mediated decay (NMD) pathway, circPSD3 regulates RNA amplification in a pro-viral manner at a post-translational step, while eIF4A3 exhibits the anti-viral property of the NMD pathway. Findings from the global analyses of the circular RNA landscape argue that pro-, and likely, anti-viral functions are executed by circRNAs that modulate viral gene expression as well as host pathways. Because of their long half-lives, circRNAs likely play hitherto unknown, important roles in viral pathogenesis.


Assuntos
Carcinoma Hepatocelular/virologia , Hepacivirus/genética , Hepatite C/complicações , Neoplasias Hepáticas/virologia , Provírus/genética , RNA Circular/genética , RNA Viral/genética , Replicação Viral , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , RNA Helicases DEAD-box/genética , RNA Helicases DEAD-box/metabolismo , Fator de Iniciação 4A em Eucariotos/genética , Fator de Iniciação 4A em Eucariotos/metabolismo , Perfilação da Expressão Gênica , Hepatite C/virologia , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Degradação do RNAm Mediada por Códon sem Sentido , Proteínas Virais/genética , Proteínas Virais/metabolismo
3.
PLoS One ; 15(8): e0237162, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32750098

RESUMO

Viral diversity is an important feature of hepatitis C virus (HCV) infection and an important predictor of disease progression and treatment response. HIV/HCV co-infection is associated with enhanced HCV replication, increased fibrosis, and the development of liver disease. HIV also increases quasispecies diversity of HCV structural genes, although limited data are available regarding the impact of HIV on non-structural genes of HCV, particularly in the absence of direct-acting therapies. The genetic diversity and presence of drug resistance mutations within the RNA-dependent RNA polymerase (NS5B) gene were examined in 3 groups of women with HCV genotype 1a infection, including those with HCV mono-infection, antiretroviral (ART)-naïve women with HIV/HCV co-infection and CD4 cell count <350 cells/mm3, and ART-naïve women with HIV/HCV co-infection and CD4 cell count ≥350 cells/mm3. None had ever been treated for HCV infection. There was evidence of significant diversity across the entire NS5B gene in all women. There were several nucleotides and amino acids with distinct distributions across the three study groups, although no obvious clustering of NS5B sequences was observed based on HIV co-infection or CD4 cell count. Polymorphisms at amino acid positions associated with resistance to dasabuvir and sofosbuvir were limited, although the Q309R variant associated with ribavirin resistance was present in 12 individuals with HCV mono-infection, 8 HIV/HCV co-infected individuals with CD4 <350 cells/mm3, and 12 HIV/HCV co-infected individuals with CD4 ≥350 cells/mm3. Previously reported fitness altering mutations were rare. CD8+ T cell responses against the human leukocyte antigen (HLA) B57-restricted epitopes NS5B2629-2637 and NS5B2936-2944 are critical for HCV control and were completely conserved in 44 (51.8%) and 70 (82.4%) study participants. These data demonstrate extensive variation across the NS5B gene. Genotypic variation may have a profound impact on HCV replication and pathogenesis and deserves careful evaluation.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/genética , Coinfecção/genética , Variação Genética , HIV , Hepacivirus/genética , Hepatite C/genética , Proteínas não Estruturais Virais/genética , Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Infecções Oportunistas Relacionadas com a AIDS/virologia , Adulto , Sequência de Aminoácidos , Antivirais/uso terapêutico , Contagem de Linfócito CD4 , Estudos de Coortes , Coinfecção/tratamento farmacológico , Coinfecção/virologia , Farmacorresistência Viral/genética , Feminino , Genótipo , Hepatite C/tratamento farmacológico , Hepatite C/virologia , Humanos , Filogenia , RNA Replicase/genética , RNA Viral/genética , RNA Viral/isolamento & purificação , Sofosbuvir/uso terapêutico , Sulfonamidas/uso terapêutico , Uracila/análogos & derivados , Uracila/uso terapêutico
4.
PLoS One ; 15(8): e0237236, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32764799

RESUMO

We previously reported that the non-immunosuppressive cyclophilin inhibitors (CypIs)-cyclosporin A analog CRV431 and sanglifehrin analog NV556-efficiently inhibit HCV replication in vitro. In this study, we asked whether they can also reduce HCV replication in vivo. We found that a single oral administration of CRV431 and NV556 to HCV-infected humanized-liver mice drastically reduced HCV blood levels. The antiviral effect was observed when CRV431 or NV556 were each individually administered with HCV, 3, 6 weeks or even 3 months post-infection when viral replication is robust. These results were confirmed in chimeric mice implanted with human hepatocytes isolated from three distinct donors. Remarkably, no viral rebound was observed 5 months after a single dose administration of 50 mg/kg of CRV431 or NV556 four weeks post-HCV infection, indicating the possibility of suppression of an established viral infection. Since we recently demonstrated that both CRV431 and NV556 also inhibit the development of liver fibrosis and hepatocellular carcinoma in nonviral-induced non-alcoholic steatohepatitis mouse models, our present data suggest that the two entirely structurally different CypIs-CRV431 and NV556-derived from unrelated natural products, represent attractive partners to current direct-acting agent (DAA) regimens for the treatment of hepatitis C and liver diseases.


Assuntos
Antivirais/uso terapêutico , Ciclosporinas/uso terapêutico , Hepacivirus/efeitos dos fármacos , Hepatite C/tratamento farmacológico , Animais , Antivirais/farmacologia , Ciclosporinas/farmacologia , Hepacivirus/fisiologia , Hepatite C/virologia , Humanos , Fígado/efeitos dos fármacos , Fígado/virologia , Camundongos , Camundongos SCID , Camundongos Transgênicos , Replicação Viral/efeitos dos fármacos
5.
Arch Virol ; 165(9): 2013-2020, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32601956

RESUMO

The hepatitis C virus (HCV) NS5B protein is an RNA-dependent RNA polymerase that is required for viral genome replication and constitutes the most important target region for drugs being developed as direct-acting antivirals (DAAs) against HCV genotype 1. However, the extreme genetic variability leading to drug resistance mutations and genetic barriers has dramatically compromised the effectiveness of DAA therapy. The purpose of this study was to analyze the genetic variability of NS5B polymerase in HCV patients from different provinces of China to identify the impact of these resistance sites on genetic barriers. We analyzed 3489 NS5B sequences of HCV strains circulating in different regions of China, obtained from the GenBank database, 153 of which were from three cities in Sichuan Province (Yibin, Zigong and Zhangzhou). Sequence alignment was conducted using MEGA 6.0, the genetic information was translated into amino acids, and the percentage of polymorphic amino acid sites was calculated. The Vijver method was used to evaluate the occurrence of genetic barriers in HCV NS5B sequences. Blood samples were collected from 153 HCV patients from Sichuan for NS5B sequence analysis using real-time PCR and the Sanger method. Of the 17 antiviral drug resistance sites summarized from the published literature, nine were found in Chinese NS5B sequences, and C316Y was identified as the dominant mutation. Analysis of genetic barriers revealed that the probability of mutation to a drug-resistance-associated amino acid, in response to selective pressure from antiviral drugs was 100% at site 96 and 99.7% at site 282. Our study is the first to analyze the drug resistance sites and to evaluate genetic barriers in NS5B sequences that could affect the responsiveness of Chinese HCV patients to DAA therapy. The results provide a valuable basis for drug development and introduction of foreign-origin antiviral drugs in China that targeting the HCV NS5B region.


Assuntos
Antivirais/farmacologia , Farmacorresistência Viral , Hepacivirus/genética , Hepatite C/virologia , Proteínas não Estruturais Virais/genética , Sequência de Aminoácidos , China , Hepacivirus/classificação , Hepacivirus/isolamento & purificação , Hepacivirus/metabolismo , Humanos , Mutação , Polimorfismo Genético , Proteínas não Estruturais Virais/metabolismo , Replicação Viral
6.
Arch Virol ; 165(9): 1947-1958, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32617764

RESUMO

Coinfections of hepatitis C virus (HCV) and/or hepatitis B virus (HBV) with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) are associated with high morbidity and mortality and poor prognosis. The main objective of this study was to evaluate the prevalence of HCV and/or HBV coinfections among people who inject drugs (PWID) and female sex workers (FSWs) who live with HIV/AIDS worldwide. Data sources were searched from January 2008 to October 2018 in different databases, including PubMed, Scopus, Web of Science, Embase, and Ovid. Data were analyzed in Stata 14 software using the Metaprop command. The results showed that the prevalence of HCV among PWID and FSWs with HIV/AIDS was 72% (95% CI: 59%-83%) and 40% (95% CI: 0%-94%), respectively. The prevalence of HBV among PWID and FSWs with HIV/AIDS was 8% (95% CI: 5%-13%) and 2% (95% CI: 0%-7%), respectively, and the prevalence of HCV/HBV in PWID with HIV/AIDS was 11% (95% CI: 7%-15%). The highest prevalence of HCV was observed in PWID in the Eastern Mediterranean and Europe regions, and the lowest was observed in the Africa region. The South-East Asia region had the highest prevalence of HBV among PWID, and the Africa region had the lowest prevalence. The high prevalence of HCV coinfection among PWID and FSWs with HIV/AIDS was an alarming health problem and requires appropriate interventions. Therefore, considering that these populations are key populations for HCV elimination, it is recommended to screen them regularly for HCV. In addition, harm reduction and HBV vaccination should be carefully considered.


Assuntos
Síndrome de Imunodeficiência Adquirida/virologia , Hepatite B/epidemiologia , Hepatite C/epidemiologia , Abuso de Substâncias por Via Intravenosa/virologia , Síndrome de Imunodeficiência Adquirida/epidemiologia , Adulto , Coinfecção/epidemiologia , Coinfecção/virologia , Feminino , HIV/isolamento & purificação , HIV/fisiologia , Hepacivirus/isolamento & purificação , Hepacivirus/fisiologia , Hepatite B/virologia , Vírus da Hepatite B/isolamento & purificação , Vírus da Hepatite B/fisiologia , Hepatite C/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Profissionais do Sexo/estatística & dados numéricos , Abuso de Substâncias por Via Intravenosa/epidemiologia , Adulto Jovem
7.
BMC Infect Dis ; 20(1): 529, 2020 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-32698841

RESUMO

BACKGROUND: The risk of viral hepatitis among healthcare students (HCSs) is greater than that among the general population. Therefore, this study was conducted to investigate the seroprevalence of the hepatitis A virus (HAV), hepatitis B virus (HBV) and hepatitis C virus (HCV) among first-year HCSs at a university in Turkey and as a secondary objective, to determine the factors associated with HAV and HBV seropositivity. METHODS: This cross-sectional study was performed in first-year HCSs in Izmir, western Turkey. Data were collected using a self-administered questionnaire including items on sociodemographic characteristics, medical history, and hygiene. A total of 650 HCSs were tested for the HAV, HBV and HCV markers. Categorical variables were compared using the chi-square test. The association between independent variables and anti-HAV seropositivity and anti-HBs seropositivity was assessed by multinomial logistic regression analysis. RESULTS: The overall frequency of total anti-HAV seropositivity was 34.9%. HBsAg, total anti-HBc and anti-HBs seropositivity were found in 0.3, 1.2 and 93.7% of samples, respectively. All of the HCSs were negative for anti-HCV. Total anti-HAV seropositivity was found to be 1.73 times higher in those ≥21 years old, and it was 1.61 times higher in those who perceived their economic status to be average and 2.75 times higher in those who perceived their economic status to be low. Total anti-HAV seropositivity was found to be 4.37 times higher in those who lived in provinces with intermediate human development index levels. Total anti-HBs seropositivity was found to be 2.48 times higher in those ≤20 years old, and it was 2.13 times higher in those who perceived their economic status to be average. CONCLUSIONS: Approximately two out of three HCSs were susceptible to HAV infection. Since HCSs are at high risk for HAV infection, they should be vaccinated before medical clerkships begin. Our results indicate that there is a high prevalence of anti-HBs seropositivity among HCSs. This result may be largely attributed to the implementation of a successful vaccination program in Turkey since 1998.


Assuntos
Hepacivirus/imunologia , Vírus da Hepatite A/imunologia , Hepatite A/epidemiologia , Vírus da Hepatite B/imunologia , Hepatite B/epidemiologia , Hepatite C/epidemiologia , Estudantes de Medicina , Adolescente , Adulto , Estudos Transversais , Feminino , Hepatite A/sangue , Hepatite A/virologia , Hepatite B/sangue , Hepatite B/virologia , Anticorpos Anti-Hepatite B/sangue , Antígenos de Superfície da Hepatite B/sangue , Hepatite C/sangue , Hepatite C/virologia , Humanos , Programas de Imunização , Masculino , Prevalência , Autorrelato , Estudos Soroepidemiológicos , Turquia/epidemiologia , Adulto Jovem
9.
PLoS One ; 15(7): e0235237, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32667919

RESUMO

The epidemic of hepatitis C virus (HCV) infection among HIV-infected men who have sex with men (MSM) is in its second decade, but the routes of transmission remain poorly understood. We hypothesized that by pairing single genome sequencing (SGS), to enumerate infecting HCV genomes (viruses), with detailed sexual and drug histories, we could gain insight into the routes of transmission among MSM. We used SGS to analyze blood specimens from eight HIV-infected MSM who had 10 episodes of acute (seronegative) or early HCV infections. Seven of eight men reported condomless receptive anal intercourse (CRAI), six with rectal exposure to semen, and all eight denied rectal trauma or bleeding. Of the 10 HCV infections, eight resulted from transmission of a single virus; one infection resulted from transmission of either one or a few (three or four) closely-related viruses; and one infection resulted from transmission of >10 distinct viruses. The participant infected by >10 viruses reported sharing injection equipment for methamphetamine during sex. Two other participants also injected methamphetamine during sex but they did not share injection equipment and were infected by a single virus. Conclusions: Most HCV infections of HIV-infected MSM without a history of either rectal trauma or bleeding or shared injection equipment were caused by a single virus. Intra-rectal exposure to semen during CRAI is therefore likely sufficient for HCV transmission among MSM. Conversely, rectal trauma or bleeding or shared injection equipment are not necessary for HCV transmission among MSM. These results help clarify routes of HCV transmission among MSM and can therefore help guide the design of much-needed behavioral and other interventions to prevent HCV transmission among MSM.


Assuntos
Coinfecção/epidemiologia , Infecções por HIV/epidemiologia , Hepacivirus/genética , Hepatite C/transmissão , Adulto , Coinfecção/virologia , Genoma Viral/genética , Infecções por HIV/virologia , Hepacivirus/isolamento & purificação , Hepatite C/epidemiologia , Hepatite C/virologia , Humanos , Masculino , Metanfetamina/administração & dosagem , Pessoa de Meia-Idade , Uso Comum de Agulhas e Seringas/efeitos adversos , Uso Comum de Agulhas e Seringas/estatística & dados numéricos , Cidade de Nova Iorque/epidemiologia , Filogenia , RNA Viral/genética , RNA Viral/isolamento & purificação , Fatores de Risco , Análise de Sequência de RNA , Minorias Sexuais e de Gênero/estatística & dados numéricos , Abuso de Substâncias por Via Intravenosa/epidemiologia , Sexo sem Proteção/estatística & dados numéricos
10.
PLoS One ; 15(7): e0235715, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32722701

RESUMO

BACKGROUND: New hepatitis C virus (HCV) treatments spurred the World Health Organization (WHO) in 2016 to adopt a strategy to eliminate HCV as a public health threat by 2030. To achieve this, key policies must be implemented. In the absence of monitoring mechanisms, this study aims to assess the extent of policy implementation from the perspective of liver patient groups. METHODS: Thirty liver patient organisations, each representing a country, were surveyed in October 2018 to assess implementation of HCV policies in practice. Respondents received two sets of questions based on: 1) WHO recommendations; and 2) validated data sources verifying an existing policy in their country. Academic experts selected key variables from each set for inclusion into policy scores. The similarity scores were calculated for each set with a multiple joint correspondence analysis. Proxy reference countries were included as the baseline to contextualize results. We extracted scores for each country and standardized them from 0 to 10 (best). RESULTS: Twenty-five countries responded. For the score based on WHO recommendations, Bulgaria had the lowest score whereas five countries (Cyprus, Netherlands, Portugal, Slovenia, and Sweden) had the highest scores. For the verified policy score, a two-dimensional solution was identified; first dimension scores pertained to whether verified policies were in place and second dimension scores pertained to the proportion of verified policies in-place that were implemented. Spain, UK, and Sweden had high scores for both dimensions. CONCLUSIONS: Patient groups reported that the European region is not on track to meet WHO 2030 HCV goals. More action should be taken to implement and monitor HCV policies.


Assuntos
Registros Eletrônicos de Saúde/normas , Implementação de Plano de Saúde/legislação & jurisprudência , Política de Saúde , Hepacivirus/isolamento & purificação , Hepatite C/prevenção & controle , Saúde Pública , Coleta de Dados , Hepatite C/virologia , Humanos , Inquéritos e Questionários , Organização Mundial da Saúde
11.
BMC Infect Dis ; 20(1): 480, 2020 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-32631335

RESUMO

BACKGROUND: Influenza A virus (IAV) infection is a serious public health problem not only in South East Asia but also in European and African countries. Scientists are using network biology to dig deep into the essential host factors responsible for regulation of virus infections. Researchers can explore the virus invasion into the host cells by studying the virus-host relationship based on their protein-protein interaction network. METHODS: In this study, we present a comprehensive IAV-host protein-protein interaction network that is obtained based on the literature-curated protein interaction datasets and some important interaction databases. The network is constructed in Cytoscape and analyzed with its plugins including CytoHubba, CytoCluster, MCODE, ClusterViz and ClusterOne. In addition, Gene Ontology and KEGG enrichment analyses are performed on the highly IAV-associated human proteins. We also compare the current results with those from our previous study on Hepatitis C Virus (HCV)-host protein-protein interaction network in order to find out valuable information. RESULTS: We found out 1027 interactions among 829 proteins of which 14 are viral proteins and 815 belong to human proteins. The viral protein NS1 has the highest number of associations with human proteins followed by NP, PB2 and so on. Among human proteins, LNX2, MEOX2, TFCP2, PRKRA and DVL2 have the most interactions with viral proteins. Based on KEGG pathway enrichment analysis of the highly IAV-associated human proteins, we found out that they are enriched in the KEGG pathway of basal cell carcinoma. Similarly, the result of KEGG analysis of the common host factors involved in IAV and HCV infections shows that these factors are enriched in the infection pathways of Hepatitis B Virus (HBV), Viral Carcinoma, measles and certain other viruses. CONCLUSION: It is concluded that the list of proteins we identified might be used as potential drug targets for the drug design against the infectious diseases caused by Influenza A Virus and other viruses.


Assuntos
Interações Hospedeiro-Patógeno/genética , Vírus da Influenza A/metabolismo , Influenza Humana/metabolismo , Mapas de Interação de Proteínas/genética , Biologia de Sistemas/métodos , Proteínas de Transporte/genética , Proteínas de Ligação a DNA/genética , Hepacivirus/metabolismo , Hepatite C/metabolismo , Hepatite C/virologia , Humanos , Influenza Humana/virologia , Fatores de Transcrição/genética , Proteínas do Core Viral/genética , Proteínas não Estruturais Virais/genética , Replicação Viral
12.
Anticancer Res ; 40(7): 3983-3990, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32620641

RESUMO

BACKGROUND/AIM: Few studies have studied micro hepatic vein invasion in hepatocellular carcinoma (HCC). We explored the correlation between hepatic vein invasion and hepatitis B/C virus infection. PATIENTS AND METHODS: Between April 2000 and February 2018, 869 patients underwent liver resection for HCC at a single center. The patients were divided into two groups: those with micro hepatic vein invasion (VV+) and those without (VV-). The clinical data, overall survival (OS) and correlations with the presence of hepatitis B and C viruses were investigated. RESULTS: There were 817 VV- patients and 43 VV+ patients. OS was 66.2 months for VV- patients and 9.9 months for VV+ patients (p=0.0010). VV+ patients had significantly higher levels of serum HBV DNA (p=0.016). CONCLUSION: HCC patients with micro hepatic vein invasion showed significantly shorter OS. A higher level of HBV DNA appears to be a risk factor for micro hepatic vein invasion.


Assuntos
Carcinoma Hepatocelular/patologia , Veias Hepáticas/patologia , Neoplasias Hepáticas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos Virais/sangue , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/virologia , DNA Viral/sangue , Feminino , Hepacivirus/genética , Hepacivirus/imunologia , Hepatite B/patologia , Hepatite B/virologia , Vírus da Hepatite B/genética , Vírus da Hepatite B/imunologia , Hepatite C/patologia , Hepatite C/virologia , Humanos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Adulto Jovem
13.
Lancet Gastroenterol Hepatol ; 5(10): 948-953, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32730784

RESUMO

In 2019, a Lancet Gastroenterology & Hepatology Commission on accelerating the elimination of viral hepatitis reported on the status of 11 viral hepatitis policy indicators in 66 countries and territories with the heaviest burden by global region. Policies were reported as being either in place, in development, or not in place. This study uses the Commission findings to estimate hepatitis B virus (HBV) and hepatitis C virus (HCV) policy scores and rankings for these 66 countries and territories. We applied a multiple correspondence analysis technique to reduce data on policy indicators into a weighted summary for the HBV and HCV policies. We calculated HBV and HCV policy scores for each country. Countries and territories that received higher scores had more policies in place and in development than did countries with lower scores. The highest scoring country for HBV was Australia, whereas Somalia had the lowest score. For the HCV policy score, Australia and New Zealand had perfect scores, whereas Somalia, Sudan, and Yemen had the lowest scores, all having no policy indicators in place.


Assuntos
Erradicação de Doenças/economia , Hepatite B/prevenção & controle , Hepatite C/prevenção & controle , Austrália/epidemiologia , Estudos Transversais , Erradicação de Doenças/legislação & jurisprudência , Carga Global da Doença/economia , Política de Saúde/economia , Política de Saúde/tendências , Hepacivirus/isolamento & purificação , Hepatite B/epidemiologia , Hepatite B/virologia , Vírus da Hepatite B/isolamento & purificação , Hepatite C/epidemiologia , Hepatite C/virologia , Humanos , Nova Zelândia/epidemiologia , Somália/epidemiologia , Sudão/epidemiologia , Iêmen/epidemiologia
14.
PLoS One ; 15(6): e0234811, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32544182

RESUMO

BACKGROUND: L31 and Y93 in the NS5A region of the hepatitis C virus (HCV) are the most important substitution positions associated with resistance to direct-acting antiviral (DAA) treatment. METHODS: We analyzed the frequency of NS5A L31M/V and Y93/H in NS5A inhibitor-naive HCV genotype 1 patients who received asunaprevir plus daclatasvir combination treatment using a conventional sequencing method and a deep sequencing method that can distinguish a single substitution at either position and a double substitution at both positions with a 0.1% detection threshold. RESULTS: The frequency of substitutions at both sites using the conventional method was very low, with 1 in 14 non-responders and 0 in 42 randomly selected responder patients. On the other hand, for the deep sequencing method, cases with double substitutions in the tandem sequence were detected in 8/14 non-responders and 1/42 responders (p<0.0001). For the conventional method, substitutions were detected at any position in 6/14 non-responders and 2/42 responders (p = 0.0019), with a clear difference between the two groups. The difference was also clear with the deep sequencing method, with 11/14 non-responders and 8/42 responders. Interestingly, for the deep sequencing method, the single substitution of L31 was found in 6/14 non-responders and 7/42 responders, whereas single substitutions of Y93 or double substitutions were found in 7/14 vs. 1/42 and 8/14 vs. 1/42 patients, respectively. CONCLUSIONS: NS5A L31 and Y93 substitutions were detected in tandem by the deep sequencing methods in several genotype 1 patients, who may be more resistant to DAA treatment containing an NS5A inhibitor.


Assuntos
Antivirais/uso terapêutico , Hepacivirus/genética , Hepatite C/tratamento farmacológico , Imidazóis/uso terapêutico , Isoquinolinas/uso terapêutico , Sulfonamidas/uso terapêutico , Proteínas não Estruturais Virais/genética , Idoso , Estudos de Casos e Controles , Farmacorresistência Viral/genética , Quimioterapia Combinada , Feminino , Genótipo , Hepacivirus/isolamento & purificação , Hepatite C/virologia , Humanos , Masculino , Mutação , Resposta Viral Sustentada , Falha de Tratamento
15.
Gene ; 754: 144887, 2020 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-32534059

RESUMO

BACKGROUND: Liver transplantation (LTX)is a lifesaving- effective protocol for patients suffering end stage liver disease (ESLD) and its complications post HCV infection. Recurrence of disease is a frequent clinical complication that is observed in patients undergoing LTX. Cytokines play a central role in the immunological events occurring after the surgery. METHODS: Using Allelic Discrimination PCR, the allelic variation G174C of IL-6 gene was investigated. The abundance of IL6- mRNA and plasma IL6 cytokine levels were evaluated by using qRT-PCR in peripheral blood mononuclear cells (PBMCs) and enzyme-linked immunosorbent assay (ELISA) respectively in 76 liver transplant recipients recruited from Al Sahel teaching hospital, Ministry of Health and Population Cairo Egypt within the period between June 2015 and October 2017. RESULTS: The frequencies of IL-6 GG genotype and the G allele were significantly detected more in LTX recipients who experienced HCV recurrence versus those who did not suffer recurrence when compared to healthy controls (P = 0.001) and (P = 0.006), respectively. On the contrary, levels of IL-6 related transcripts in PBMC's of recurrent patients were indifferent from non-recurrent patients and healthy controls (P ≥ 0.124). Interestingly, the circulating IL-6 protein in plasma was significantly elevated in recurrent as compared to the non-recurrent recipients (P = 0.002). CONCLUSION: HCV recurrence post liver transplantation occur more frequently in patients with -174 G/G IL-6 genotype and elevated plasma IL-6 levels.


Assuntos
Hepacivirus/fisiologia , Hepatite C/sangue , Interleucina-6/sangue , Interleucina-6/genética , Leucócitos Mononucleares/metabolismo , Transplante de Fígado/efeitos adversos , Polimorfismo de Nucleotídeo Único , Feminino , Hepatite C/cirurgia , Hepatite C/virologia , Humanos , Leucócitos Mononucleares/virologia , Masculino , Pessoa de Meia-Idade , Recidiva , Transplantados
16.
PLoS One ; 15(5): e0232931, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32407423

RESUMO

BACKGROUND: Hepatitis C virus (HCV) infection is one of the most common bloodborne viral infections reported in Pakistan. Frequent dialysis treatment of hemodialysis patients exposes them to a high risk of HCV infection. The main purpose of this paper is to quantify the prevalence of HCV in hemodialysis patients through a systematic review and meta-analysis. METHODS: We systematically searched PubMed, Medline, EMBASE, Pakistani Journals Online and Web of Science to identify studies published between 1 January 1995 and 30 October 2019, reporting on the prevalence of HCV infection in hemodialysis patients. Meta-analysis was performed using a random-effects model to obtain pooled estimates. A funnel plot was used in conjunction with Egger's regression test for asymmetry and to assess publication bias. Meta-regression and subgroup analyses were used to identify potential sources of heterogeneity among the included studies. This review was registered on PROSPERO (registration number CRD42019159345). RESULTS: Out of 248 potential studies, 19 studies involving 3446 hemodialysis patients were included in the meta-analysis. The pooled prevalence of HCV in hemodialysis patients in Pakistan was 32.33% (95% CI: 25.73-39.30; I2 = 94.3%, p < 0.01). The subgroup analysis showed that the prevalence of HCV among hemodialysis patients in Punjab was significantly higher (37.52%; 95% CI: 26.66-49.03; I2 = 94.5, p < 0.01) than 34.42% (95% CI: 14.95-57.05; I2 = 91.3%, p < 0.01) in Baluchistan, 27.11% (95% CI: 15.81-40.12; I2 = 94.5, p < 0.01) in Sindh and 22.61% (95% CI: 17.45-28.2; I2 = 78.6, p < 0.0117) in Khyber Pukhtoonkhuwa. CONCLUSIONS: In this study, we found a high prevalence (32.33%) of HCV infection in hemodialysis patients in Pakistan. Clinically, hemodialysis patients require more attention and resources than the general population. Preventive interventions are urgently needed to decrease the high risk of HCV infection in hemodialysis patients in Pakistan.


Assuntos
Hepacivirus/isolamento & purificação , Hepatite C/epidemiologia , Diálise Renal/estatística & dados numéricos , Hepatite C/virologia , Humanos , Paquistão/epidemiologia , Prevalência , Diálise Renal/efeitos adversos , Fatores de Risco
17.
Arch Microbiol ; 202(7): 1889-1898, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32448963

RESUMO

Alcohol consumption exacerbates the pathogenesis of hepatitis C virus (HCV) infection and aggravates disease consequences in alcohol-abusing patients. Although the exact reasons by which alcohol consumption affects several cellular pathways in liver cells are not clear, they might be partially attributed to the ability of alcohol to further suppress the innate immunity, modulation of autophagy and also its relationship with reactive oxygen species (ROS) generation. To evaluate these issues, Huh7 cells harboring HCV replicon and Cytochrome p450 (CYP2E1) plasmid were exposed to ethanol and mRNA expression of Beclin-1, interferon-stimulated gene15 (ISG15) genes and HCV NS5B for two different times were relatively quantitated. ROS was determined by flow cytometry. The results showed that alcohol treatment in a short time caused an increase in HCV NS5B and Beclin-1 mRNA and decreased ISG 15 mRNA. Long-lasting alcohol treatment increased ROS production in Huh-7 cells and HCV replication was reduced. In conclusion, acute alcohol treatment might contribute to increase HCV replication by interference in innate immunity and induction of autophagy. Chronic alcohol treatment caused oxidative stress, which disrupts autophagy and thereby increased the rate of Huh7 cell injury.


Assuntos
Etanol/toxicidade , Hepacivirus/fisiologia , Hepatite C/virologia , Estresse Oxidativo/efeitos dos fármacos , Replicação Viral/efeitos dos fármacos , Autofagia , Linhagem Celular Tumoral , Etanol/metabolismo , Hepatite C/imunologia , Humanos , Imunidade Inata
18.
J Vasc Interv Radiol ; 31(6): 953-960, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32376182

RESUMO

PURPOSE: To investigate the impact of direct-acting antivirals (DAAs) and 12-week sustained virologic response (SVR12) in patients with hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) treated by interventional oncology (IO) therapies. MATERIALS AND METHODS: Retrospective analysis of patients diagnosed from 2005 to 2016 with HCC and receiving IO therapies. A total of 478 patients met inclusion criteria. Patients were age 29-90 years (mean 63.6 ± 9.4 years) and 78.9% (n =3 77) male. Two hundred and eighty-five (57%) patients had chronic HCV, 93 (33%) received DAAs, and 63 (68%) achieved SVR12. Liver function, tumor characteristics, and IO therapy including ablation, image-guided transcatheter tumor therapies (ITTT) (eg, chemoembolization and radioembolization), and combination locoregional therapy were assessed in analysis. RESULTS: Median overall survival (OS) of the cohort was 26.7 months (95% confidence interval [CI] 21.9-29.9). OS for ablation, combination locoregional therapy and ITTT, was 37.3 (CI 30.7-49.9), 29.3 (CI 24.2-38.0), and 19.7 months (CI 16.5-22.8), respectively (P < .0001). OS in patients with HCV was 30.7 months (CI 24.2-35.2) versus 22.2 months in non-HCV patients (CI 17.8-27.8, P = .03). Patients with HCV who received DAA had higher survival, 49.2 months (CI 36.5-not reached) versus those not receiving DAA, 18.5 months (CI 14.1-25.3, P < .0001). OS was 71.8 months (CI 42.3-not reached) for patients who achieved SVR12 after DAA versus 26.7 months in the non-SVR12 group (CI 15.9-31.1, P < .0001). Multivariable analysis revealed independent factors for OS including IO treatment type, DAA use and achieving SVR12 (P < .05). CONCLUSIONS: DAA use and SVR12 is associated with higher OS in patients with HCV-related HCC treated by IO therapies.


Assuntos
Antivirais/uso terapêutico , Carcinoma Hepatocelular/terapia , Hepacivirus/efeitos dos fármacos , Hepatite C/tratamento farmacológico , Neoplasias Hepáticas/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antivirais/efeitos adversos , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/virologia , Feminino , Hepacivirus/patogenicidade , Hepatite C/diagnóstico , Hepatite C/mortalidade , Hepatite C/virologia , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Resposta Viral Sustentada , Fatores de Tempo , Resultado do Tratamento
19.
J Med Microbiol ; 69(5): 759-766, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32242792

RESUMO

Introduction. During chronic hepatitis C virus (HCV) infections, HCV antigens establish cross-tolerance of endotoxins, but additional lipopolysaccharide (LPS) stimulation effects in this condition are poorly understood.Aim. This study aims to investigate the effects of the upregulated LPS on MMP and TIMP expression during chronic hepatitis C infection.Methodology. In the present study, we analysed the effect of HCV antigens and LPS stimulation on peripheral blood mononuclear cells (PBMCs) both in vivo and in vitro. Macrophages from HCV patients were isolated and their association with endotoxin tolerance was examined. MMP/TIMP1 expression and the related signalling pathways in macrophages were analysed. The macrophage and Huh7.5 cell co-culture model was used to analyse the effects of the cross-tolerance on collagen I deposition.Results. LPS levels were found to be significantly higher in HCV patients, particularly in those with HCV-induced liver fibrosis. In addition, although LPS serum level was occasionally upregulated in the patients, it did not induce intense immune response in PBMCs due to endotoxin cross-tolerance, and this was measured according to the changes in IL-6 and TNF-α levels. However, TIMP1 expression increased significantly during stimulation, exhibiting a tolerance/resistance phenotype, which was associated with TGF-ß/Erk activation in macrophages. However, MMP levels did not increase due to endotoxin tolerance, which ultimately led to MMP/TIMP imbalance and influenced the deposition of collagen I.Conclusion. Increased LPS stimulation of macrophage during HCV antigen-induced endotoxin cross-tolerance contributes to MMP/TIMP1 imbalance and collagen I deposition.


Assuntos
Hepacivirus/fisiologia , Hepatite C/imunologia , Hepatite C/metabolismo , Macrófagos/imunologia , Macrófagos/metabolismo , Metaloproteinases da Matriz/metabolismo , Inibidor Tecidual de Metaloproteinase-1/metabolismo , Antígenos Virais/imunologia , Linhagem Celular , Colágeno/metabolismo , Endotoxinas/imunologia , Ensaio de Imunoadsorção Enzimática , Hepatite C/complicações , Hepatite C/virologia , Humanos , Tolerância Imunológica , Lipopolissacarídeos/imunologia , Sistema de Sinalização das MAP Quinases , Macrófagos/virologia , Fator de Crescimento Transformador beta/metabolismo , Proteínas não Estruturais Virais/metabolismo
20.
BMC Infect Dis ; 20(1): 264, 2020 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-32245397

RESUMO

BACKGROUND: Hepatitis C virus (HCV) infection is a leading cause of chronic liver disease and hepatocellular carcinoma. Treatment with first generation protease inhibitors (PI) + peg-interferon (pegIFN) and ribavirin (RBV) achieved sustained virologic response (SVR) rates of 65-75% but was associated with multiple side effects. The aim of this study was to evaluate safety and efficacy of Ombitasvir/Paritaprevir/Ritonavir and Dasabuvir (3D) ± RBV in HCV genotype 1 patients that failed previous treatment with first generation PIs. METHODS: An investigator-initiated, open-label, multi-centre clinical trial. HCV Genotype 1 patients who were previously null/partial responders or relapsers to telaprevir, boceprevir or simepravir+pegIFN/RBV and met eligibility criteria were included. 3D ± RBV were administrated for 12 or 24 weeks according to label. The primary outcome was antiviral response (SVR12); Secondary outcomes were patient reported outcomes, adverse events and resistance associated variants. RESULTS: Thirty-nine patients initiated treatment according to study protocol (59% men, age 54.0 ± 8.7 years, BMI 28.7 ± 4.5 kg/m2). Thirty-seven (94.9%) completed the study. Thirty-five patients had genotype 1b (9 cirrhotics) and 4 had genotype 1a (2 cirrhotics). Intention-to-treat SVR12 was 92.3% and per-protocol SVR12 was 97.3%. The rate of advanced fibrosis (FibroScan® score F3-4) declined from 46.2 to 25.7% (P = 0.045). Abnormal ALT levels declined from 84.6 to 8.6% (P < 0.001). Seven patients (17.9%) experienced serious adverse events (3 Psychiatric admissions, 1 pneumonia, 1 ankle fracture, 2 palpitations), and 12 patients (30.8%) experienced self-reported adverse events, mostly weakness. CONCLUSION: 3D ± RBV is safe and effective in achieving SVR among patients with HCV genotype 1 who failed previous first-generation PI treatment. TRIAL REGISTRATION: NCT02646111 (submitted to ClinicalTrials.gov, December 28, 2015).


Assuntos
Anilidas/uso terapêutico , Antivirais/uso terapêutico , Carbamatos/uso terapêutico , Hepatite C/tratamento farmacológico , Compostos Macrocíclicos/uso terapêutico , Inibidores de Proteases/uso terapêutico , Ribavirina/uso terapêutico , Ritonavir/uso terapêutico , Sulfonamidas/uso terapêutico , Uracila/análogos & derivados , Anilidas/efeitos adversos , Antivirais/efeitos adversos , Carbamatos/efeitos adversos , Quimioterapia Combinada , Feminino , Genótipo , Hepatite C/virologia , Humanos , Compostos Macrocíclicos/efeitos adversos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Inibidores de Proteases/efeitos adversos , Ribavirina/efeitos adversos , Ritonavir/efeitos adversos , Sulfonamidas/efeitos adversos , Resultado do Tratamento , Uracila/efeitos adversos , Uracila/uso terapêutico
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA