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1.
Artigo em Inglês | MEDLINE | ID: mdl-38324877

RESUMO

Hepatitis C virus (HCV) infection is a significant cause of morbidity and mortality among hematopoietic stem cell transplant (HCT) recipients. In Brazil, its occurrence in HCT recipients remains undetermined. We now report on HCV prevalence in HCT recipients and its clinical consequences. The medical records of all HCT recipients seen at Hospital das Clinicas, Sao Paulo University Medical School, from January 2010 to January 2020 were reviewed to determine HCV serostatus. A retrospective analysis of medical charts was undertaken on all seropositive cases to determine HCV genotype, presence of liver fibrosis, co-infections with other viruses, previous treatments, and clinical evolution of liver pathology after HCT. Of the 1,293 HCT recipients included in the study, seven (0.54%) were HCV antibody-positive and five (0.39%) were also viremic for HCV-RNA. Four of these individuals had moderate to severe liver fibrosis (METAVIR F2/F3) and one was cirrhotic. Two of the viremic patients developed acute liver dysfunction following transplantation. All patients had their acute episode of liver dysfunction resolved with no further complications. Four of the viremic patients were treated for HCV infection with direct acting agents (DAA). Information regarding HCV treatment was lacking for one of the viremic HCV patients due to loss of follow up. Sustained anti-virologic responses were observed in three cases after the use of DAA. The detection of HCV in hematological adults undergoing HCT and its successful treatment with DAA highlight the necessity of testing for HCV both prior to and following transplantation.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Hepatite C Crônica , Hepatite C , Humanos , Adulto , Hepacivirus/genética , Estudos Retrospectivos , Prevalência , Antivirais/uso terapêutico , Brasil/epidemiologia , Hepatite C/complicações , Hepatite C/epidemiologia , Cirrose Hepática/epidemiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Hepatite C Crônica/tratamento farmacológico
2.
Emergencias ; 36(1): 25-32, 2024 Jan.
Artigo em Espanhol, Inglês | MEDLINE | ID: mdl-38318739

RESUMO

OBJECTIVES: The prevalence of active hepatitis C virus (HCV) infection in Spain is estimated to be 0.2%, but a large number of persons are unaware of their infection status. Additional approaches to early diagnosis of HCV infection in vulnerable populations with scarce contact with the national health care system are therefore needed. Our aim was to evaluate the impact of an opportunistic screening program to detect HCV-infected patients attended in our university hospital emergency department (ED). MATERIAL AND METHODS: Opportunistic screening was implemented from August 2021 to April 2023 in ED patients aged 18 to 69 years. The test was ordered if HCV screening had not been done in the last year and blood extraction for testing was indicated for any reason as part of routine ED care. RESULTS: A total of 110 267 patients were seen; 22 712 of them (20.6%) were eligible for screening. Serology for HCV was done for 11 368 of the eligible patients (50.1%). Forty-three cases (in 0.4% of tested samples) of active HCV infection (viremia) were found. In 24 of these cases (56%) the patients had not been aware that they were infected. Their mean (SD) age was 57 (6) years, 34 (79.1%) were men, and 5 (11.6%) were citizens of countries other than Spain. No risk factors related to HCV infection could be found for 22 of the patients (51.2%), and 41 (95.3%) could have been diagnosed during previous contact with the health care system. Of the 18 patients evaluated by transient elastography (FibroScan), 7 (38.8%) had signs of cirrhosis at the time of diagnosis. Thirty-three of the patients with active infections (77%) were subsequently able to access care. CONCLUSION: The rate of active HCV infection in the screening program was higher than the prevalence estimated for the general population. Opportunistic screening for HCV during ED visits is useful for increasing the number of diagnoses and should be considered as a tool for eradicating this disease.


OBJETIVO: Se estima que la prevalencia de infección activa por el virus de la hepatitis C (VHC) en España es de un 0,2%, pero un gran número de personas desconocen su estado de infección. Por ello, se requiere aumentar las estrategias de diagnóstico precoz dirigidas a población vulnerable y con escaso vínculo con el sistema sanitario. El objetivo es evaluar el impacto de un programa de cribado oportunista del VHC en los pacientes atendidos en el servicio de urgencias (SU) de un hospital universitario. METODO: Se realizó un cribado oportunista entre agosto de 2021 y abril de 2023 a los pacientes de 18 a 69 años atendidos en el SU que no se habían realizado la prueba del VHC el año anterior, y que requerían un análisis de sangre dentro de la práctica clínica habitual por cualquier motivo. RESULTADOS: Durante el periodo de estudio se atendieron 110.267 pacientes en el SU, fueron candidatos a realizar el cribado 22.712 (20,6%), y finalmente se realizó una serología frente al VHC a 11.368 pacientes (50,1%). Se identificaron 43 casos (0,4% de los test efectuados) de infección activa por VHC (viremia), de los cuales, 24 (56%) desconocían previamente su estado. La media de edad del total de pacientes virémicos fue de 57 (DE: 6 años), 34 (79,1%) eran hombres y 5 (11,6%) tenían nacionalidades distintas a la española. No se identificaron factores de riesgo relacionados con la infección por VHC en 22 (51,2%) de los pacientes, y 41 (95,3%) habían tenido oportunidades de diagnóstico en visitas previas al sistema de salud. De los 18 pacientes analizados mediante elastografía transitoria, 7 (38,8%) presentaban cirrosis en el momento del diagnóstico. Se logró vincular a la atención médica posterior a 33 (77%) de los pacientes con infección activa. CONCLUSIONES: Las tasas de infección activa por VHC detectadas en el programa de cribado fueron más altas que la prevalencia estimada en la población general. El cribado oportunista de VHC en los SU puede ser de utilidad para aumentar el diagnóstico y debe ser considerado como una herramienta para la eliminación de la hepatitis C.


Assuntos
Hepacivirus , Hepatite C , Masculino , Humanos , Feminino , Espanha/epidemiologia , Hepatite C/diagnóstico , Hepatite C/epidemiologia , Fatores de Risco , Serviço Hospitalar de Emergência
3.
J Med Virol ; 96(2): e29385, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38318918

RESUMO

The aim of this study was to investigate the interference of lipemia on measurement of HBsAg, anti-HBs, HBeAg, anti-HBe, anti-HBc, anti-HCV, HIV Ag/Ab, and anti-TP in serum by chemiluminescent microparticle immunoassay (CMIA) and compare lipemia removing performance between high-speed centrifugation and Lipoclear reagent. Mixed native serum samples (NSs) and hyperlipemia serum samples (HLS) were prepared for the investigated parameters. The levels of these parameters in NS and HLS were determined by CMIA on an Abbott ARCHITECT i2000SR immunoassay analyzer. HBsAg, anti-HBs, and anti-TP were affected with relative bias >12.5% (acceptable limit) when the level of triacylglycerol (TG) was higher than 27.12 mmol/L in HLS. Clinically unacceptable bias were observed for HBeAg and anti-HBe in HLS with TG higher than 40.52 mmol/L. However, anti-HCV and HIV Ag/Ab were not interfered in severe lipemia with TG < 52.03 mmol/L. In addition, the Lipoclear reagent did not reduce the interference of lipemia with relative bias from -62.50% to -18.02%. The high-speed centrifugation under the optimized condition of 12 000g for 10 min successfully removed the interference of lipemia with relative bias from -5.93% to 0% for HBsAg, anti-HBs, HBeAg, anti-HBe, anti-HBc, and anti-TP. To conclude, high-speed centrifugation can be used for removing the interference of lipemia to measure HBsAg, anti-HBs, HBeAg, anti-HBe, anti-HBc, and anti-TP. Accordingly, a standardized sample preanalytical preparation of the patients and other screening participants as well as a specimen examination procedure for removing lipemia interference on the serological tests was recommended.


Assuntos
Síndrome de Imunodeficiência Adquirida , Hepatite B , Hepatite C , Hiperlipidemias , Sífilis , Humanos , Antígenos de Superfície da Hepatite B , Antígenos E da Hepatite B , Indicadores e Reagentes , Sífilis/diagnóstico , Vírus da Hepatite B , Anticorpos Anti-Hepatite B , Imunoensaio , Hepatite C/diagnóstico , Testes Sorológicos , Triglicerídeos , Centrifugação
4.
Arkh Patol ; 86(1): 52-56, 2024.
Artigo em Russo | MEDLINE | ID: mdl-38319273

RESUMO

Cryoglobulinemic vasculitis is a disease characterized by damage of small vessels and in some cases can be a manifestation of mixed cryoglobulinemia. Mixed cryoglobulinemia is a condition in which immunoglobulins in the blood serum form precipitates at temperatures below 37 °C and dissolve again when it rises. Currently, hepatitis C (HCV) is considered the most common etiological factor of mixed cryoglobulinemia. In addition, mixed cryoglobulinemia may be associated with other infectious agents, as well as autoimmune and lymphoproliferative diseases. In the absence of such association, we can talk about essential mixed cryoglobulinemia. To understand how different nosologies in their clinical and morphological picture lead to the development of mixed cryoglobulinemia, it is necessary to carefully analyze the mechanisms of the development of some of them, namely, HCV-associated cryoglobulinemic vasculitis and Sjögren's syndrome. It is noteworthy that mixed cryoglobulinemia in relation to Sjögren's syndrome can be perceived both as its consequence and as a manifestation of the underlying disease. Such an ambiguous nature of mixed cryoglobulinemia makes it currently impossible to select clear diagnostic criteria. For this reason, it is necessary to carry out a comparison between different immunopathogenesis of mixed cryoglobulinemia in order to identify the features that form its classical manifestations.


Assuntos
Crioglobulinemia , Hepatite C , Síndrome de Sjogren , Vasculite , Humanos , Crioglobulinemia/complicações , Síndrome de Sjogren/complicações
5.
BMC Gastroenterol ; 24(1): 57, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38302914

RESUMO

BACKGROUND: Liver fibrosis is a major risk factor for hepatocellular carcinoma (HCC). We have previously reported that differentially methylated regions (DMRs) are correlated with the fibrosis stages of metabolic dysfunction-associated steatotic liver disease (MASLD). In this study, the methylation levels of those DMRs in liver fibrosis and subsequent HCC were examined. METHODS: The methylation levels of DMRs were investigated using alcoholic cirrhosis and HCC (GSE60753). The data of hepatitis C virus-infected cirrhosis and HCC (GSE60753), and two datasets (GSE56588 and GSE89852) were used for replication analyses. The transcriptional analyses were performed using GSE114564, GSE94660, and GSE142530. RESULTS: Hypomethylated DMR and increased transcriptional level of zinc finger and BTB domain containing 38 (ZBTB38) were observed in HCC. Hypermethylated DMRs, and increased transcriptional levels of forkhead box K1 (FOXK1) and zinc finger CCCH-type containing 3 (ZC3H3) were observed in HCC. The methylation levels of DMR of kazrin, periplakin interacting protein (KAZN) and its expression levels were gradually decreased as cirrhosis progressed to HCC. CONCLUSIONS: Changes in the methylation and transcriptional levels of ZBTB38, ZC3H3, FOXK1, and KAZN are important for the development of fibrosis and HCC; and are therefore potential therapeutic targets and diagnostic tools for cirrhosis and HCC.


Assuntos
Carcinoma Hepatocelular , Hepatite C , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Metilação de DNA , Cirrose Hepática/complicações , Hepatite C/complicações , Fatores de Transcrição Forkhead
6.
Emergencias (Sant Vicenç dels Horts) ; 36(1): 25-32, feb. 2024. ilus, tab
Artigo em Espanhol | IBECS | ID: ibc-229846

RESUMO

Objetivo. Se estima que la prevalencia de infección activa por el virus de la hepatitis C (VHC) en España es de un 0,2%, pero un gran número de personas desconocen su estado de infección. Por ello, se requiere aumentar las estrategias de diagnóstico precoz dirigidas a población vulnerable y con escaso vínculo con el sistema sanitario. El objetivo es evaluar el impacto de un programa de cribado oportunista del VHC en los pacientes atendidos en el servicio de urgencias (SU) de un hospital universitario. Método. Se realizó un cribado oportunista entre agosto de 2021 y abril de 2023 a los pacientes de 18 a 69 años atendidos en el SU que no se habían realizado la prueba del VHC el año anterior, y que requerían un análisis de sangre dentro de la práctica clínica habitual por cualquier motivo. Resultados. Durante el periodo de estudio se atendieron 110.267 pacientes en el SU, fueron candidatos a realizar el cribado 22.712 (20,6%), y finalmente se realizó una serología frente al VHC a 11.368 pacientes (50,1%). Se identificaron 43 casos (0,4% de los test efectuados) de infección activa por VHC (viremia), de los cuales, 24 (56%) desconocían previamente su estado. La media de edad del total de pacientes virémicos fue de 57 (DE: 6 años), 34 (79,1%) eran hombres y 5 (11,6%) tenían nacionalidades distintas a la española. No se identificaron factores de riesgo relacionados con la infección por VHC en 22 (51,2%) de los pacientes, y 41 (95,3%) habían tenido oportunidades de diagnóstico en visitas previas al sistema de salud. De los 18 pacientes analizados mediante elastografía transitoria, 7 (38,8%) presentaban cirrosis en el momento del diagnóstico. Se logró vincular a la atención médica posterior a 33 (77%) de los pacientes con infección activa. Conclusiones. Las tasas de infección activa por VHC detectadas en el programa de cribado fueron más altas que la prevalencia estimada en la población general... (AU)


Background and objective. The prevalence of active hepatitis C virus (HCV) infection in Spain is estimated to be 0.2%, but a large number of persons are unaware of their infection status. Additional approaches to early diagnosis of HCV infection in vulnerable populations with scarce contact with the national health care system are therefore needed. Our aim was to evaluate the impact of an opportunistic screening program to detect HCV-infected patients attended in our university hospital emergency department (ED). Methods. Opportunistic screening was implemented from August 2021 to April 2023 in ED patients aged 18 to 69 years. The test was ordered if HCV screening had not been done in the last year and blood extraction for testing was indicated for any reason as part of routine ED care. Results. A total of 110 267 patients were seen; 22 712 of them (20.6%) were eligible for screening. Serology for HCV was done for 11 368 of the eligible patients (50.1%). Forty-three cases (in 0.4% of tested samples) of active HCV infection (viremia) were found. In 24 of these cases (56%) the patients had not been aware that they were infected. Their mean (SD) age was 57 (6) years, 34 (79.1%) were men, and 5 (11.6%) were citizens of countries other than Spain. No risk factors related to HCV infection could be found for 22 of the patients (51.2%), and 41 (95.3%) could have been diagnosed during previous contact with the health care system. Of the 18 patients evaluated by transient elastography (FibroScan), 7 (38.8%) had signs of cirrhosis at the time of diagnosis. Thirty-three of the patients with active infections (77%) were subsequently able to access care. Conclusions. The rate of active HCV infection in the screening program was higher than the prevalence estimated for the general population. Opportunistic screening for HCV during ED visits is useful for increasing the number of diagnoses and should be considered as a tool for eradicating this disease. (AU)


Assuntos
Humanos , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Programas de Rastreamento , Serviços Médicos de Emergência , Hepatite C/diagnóstico , Hepatite C/prevenção & controle , Hepacivirus , Espanha
7.
Emergencias (Sant Vicenç dels Horts) ; 36(1): 25-32, feb. 2024. ilus, tab
Artigo em Espanhol | IBECS | ID: ibc-EMG-464

RESUMO

Objetivo. Se estima que la prevalencia de infección activa por el virus de la hepatitis C (VHC) en España es de un 0,2%, pero un gran número de personas desconocen su estado de infección. Por ello, se requiere aumentar las estrategias de diagnóstico precoz dirigidas a población vulnerable y con escaso vínculo con el sistema sanitario. El objetivo es evaluar el impacto de un programa de cribado oportunista del VHC en los pacientes atendidos en el servicio de urgencias (SU) de un hospital universitario. Método. Se realizó un cribado oportunista entre agosto de 2021 y abril de 2023 a los pacientes de 18 a 69 años atendidos en el SU que no se habían realizado la prueba del VHC el año anterior, y que requerían un análisis de sangre dentro de la práctica clínica habitual por cualquier motivo. Resultados. Durante el periodo de estudio se atendieron 110.267 pacientes en el SU, fueron candidatos a realizar el cribado 22.712 (20,6%), y finalmente se realizó una serología frente al VHC a 11.368 pacientes (50,1%). Se identificaron 43 casos (0,4% de los test efectuados) de infección activa por VHC (viremia), de los cuales, 24 (56%) desconocían previamente su estado. La media de edad del total de pacientes virémicos fue de 57 (DE: 6 años), 34 (79,1%) eran hombres y 5 (11,6%) tenían nacionalidades distintas a la española. No se identificaron factores de riesgo relacionados con la infección por VHC en 22 (51,2%) de los pacientes, y 41 (95,3%) habían tenido oportunidades de diagnóstico en visitas previas al sistema de salud. De los 18 pacientes analizados mediante elastografía transitoria, 7 (38,8%) presentaban cirrosis en el momento del diagnóstico. Se logró vincular a la atención médica posterior a 33 (77%) de los pacientes con infección activa. Conclusiones. Las tasas de infección activa por VHC detectadas en el programa de cribado fueron más altas que la prevalencia estimada en la población general... (AU)


Background and objective. The prevalence of active hepatitis C virus (HCV) infection in Spain is estimated to be 0.2%, but a large number of persons are unaware of their infection status. Additional approaches to early diagnosis of HCV infection in vulnerable populations with scarce contact with the national health care system are therefore needed. Our aim was to evaluate the impact of an opportunistic screening program to detect HCV-infected patients attended in our university hospital emergency department (ED). Methods. Opportunistic screening was implemented from August 2021 to April 2023 in ED patients aged 18 to 69 years. The test was ordered if HCV screening had not been done in the last year and blood extraction for testing was indicated for any reason as part of routine ED care. Results. A total of 110 267 patients were seen; 22 712 of them (20.6%) were eligible for screening. Serology for HCV was done for 11 368 of the eligible patients (50.1%). Forty-three cases (in 0.4% of tested samples) of active HCV infection (viremia) were found. In 24 of these cases (56%) the patients had not been aware that they were infected. Their mean (SD) age was 57 (6) years, 34 (79.1%) were men, and 5 (11.6%) were citizens of countries other than Spain. No risk factors related to HCV infection could be found for 22 of the patients (51.2%), and 41 (95.3%) could have been diagnosed during previous contact with the health care system. Of the 18 patients evaluated by transient elastography (FibroScan), 7 (38.8%) had signs of cirrhosis at the time of diagnosis. Thirty-three of the patients with active infections (77%) were subsequently able to access care. Conclusions. The rate of active HCV infection in the screening program was higher than the prevalence estimated for the general population. Opportunistic screening for HCV during ED visits is useful for increasing the number of diagnoses and should be considered as a tool for eradicating this disease. (AU)


Assuntos
Humanos , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Programas de Rastreamento , Serviços Médicos de Emergência , Hepatite C/diagnóstico , Hepatite C/prevenção & controle , Hepacivirus , Espanha
8.
BMC Public Health ; 24(1): 363, 2024 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-38310221

RESUMO

BACKGROUND: This study aimed to assess the global, regional, and national burden of liver cirrhosis and other chronic liver diseases between 1990 and 2019, considering five etiologies (hepatitis B, hepatitis C, alcohol use, NAFLD and other causes), age, gender, and sociodemographic index (SDI). METHODS: Data on liver cirrhosis and other chronic liver diseases mortality, incidence, and disability-adjusted life years (DALYs) were collected from the Global Burden of Diseases, Injuries, and Risk Factors (GBD) Study 2019. RESULTS: In 2019, liver cirrhosis and other chronic liver diseases accounted for 1,472,011 (95% UI 1,374,608-1,578,731) deaths worldwide, compared to 1,012,975 (948,941-1,073,877) deaths in 1990. Despite an increase in absolute deaths, the age-standardized death rate declined from 24.43 (22.93-25.73) per 100,000 population in 1990 to 18.00 (19.31-16.80) per 100,000 population in 2019. Eastern sub-Saharan Africa exhibited the highest age-standardized death rate (44.15 [38.47-51.91] per 100,000 population), while Australasia had the lowest rate (5.48 [5.05-5.93] deaths per 100,000 population in 2019). The age-standardized incidence rate of liver cirrhosis and other chronic liver diseases attributed to hepatitis B virus has declined since 1990, but incidence rates for other etiologies have increased. Age-standardized death and DALYs rates progressively decreased with higher SDI across different GBD regions and countries. Mortality due to liver cirrhosis and other chronic liver diseases increased with age in 2019, and the death rate among males was estimated 1.51 times higher than that among females globally. CONCLUSION: Liver cirrhosis and other chronic liver diseases continues to pose a significant global public health challenge. Effective disease control, prevention, and treatment strategies should account for variations in risk factors, age, gender, and regional disparities.


Assuntos
Hepatite C , Hepatopatia Gordurosa não Alcoólica , Morte Perinatal , Masculino , Feminino , Humanos , Anos de Vida Ajustados por Qualidade de Vida , Cirrose Hepática/epidemiologia , Fatores de Risco , Hepatite C/complicações , Carga Global da Doença , Saúde Global , Incidência
9.
PLoS Pathog ; 20(2): e1011976, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38315728

RESUMO

Viral infections trigger the expression of interferons (IFNs) and interferon stimulated genes (ISGs), which are crucial to modulate an antiviral response. The human guanylate binding protein 1 (GBP1) is an ISG and exhibits antiviral activity against several viruses. In a previous study, GBP1 was described to impair replication of the hepatitis C virus (HCV). However, the impact of GBP1 on the HCV life cycle is still enigmatic. To monitor the expression and subcellular distribution of GBP1 and HCV we performed qPCR, Western blot, CLSM and STED microscopy, virus titration and reporter gene assays. In contrast to previous reports, we observed that HCV induces the expression of GBP1. Further, to induce GBP1 expression, the cells were stimulated with IFNγ. GBP1 modulation was achieved either by overexpression of GBP1-Wt or by siRNA-mediated knockdown. Silencing of GBP1 impaired the release of viral particles and resulted in intracellular HCV core accumulation, while overexpression of GBP1 favored viral replication and release. CLSM and STED analyses revealed a vesicular distribution of GBP1 in the perinuclear region. Here, it colocalizes with HCV core around lipid droplets, where it acts as assembly platform and thereby favors HCV morphogenesis and release. Collectively, our results identify an unprecedented function of GBP1 as a pro-viral factor. As such, it is essential for viral assembly and release acting through tethering factors involved in HCV morphogenesis onto the surface of lipid droplets.


Assuntos
Hepacivirus , Hepatite C , Humanos , Animais , Hepacivirus/fisiologia , Hepatite C/genética , Replicação Viral , Interferons , Antivirais/farmacologia , Estágios do Ciclo de Vida
10.
Proc Natl Acad Sci U S A ; 121(7): e2313002121, 2024 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-38319965

RESUMO

It is known that pre-mRNAs in eukaryotic cells can be processed to circular RNAs by a backsplicing mechanism. Circular RNAs have great stability and can sequester proteins or small RNAs to exert functions on cellular pathways. Because viruses often exploit host pathways, we explored whether the RNA genome of the cytoplasmic hepatitis C virus is processed to yield virus-derived circRNAs (vcircRNAs). Computational analyses of RNA-seq experiments predicted that the viral RNA genome is fragmented to generate hundreds of vcircRNAs. More than a dozen of them were experimentally verified by rolling-circle amplification. VcircRNAs that contained the viral internal ribosome entry site were found to be translated into proteins that displayed proviral functions. Furthermore, two highly abundant, nontranslated vcircRNAs were shown to enhance viral RNA abundance. These findings argue that novel vcircRNA molecules modulate viral amplification in cells infected by a cytoplasmic RNA virus.


Assuntos
Hepatite C , RNA Circular , Humanos , Hepacivirus/genética , RNA Viral/genética , Provírus/genética
11.
Front Cell Infect Microbiol ; 14: 1338606, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38357447

RESUMO

The tetraspanin CD81 is one of the main entry receptors for Hepatitis C virus, which is a major causative agent to develop liver cirrhosis and hepatocellular carcinoma (HCC). Here, we identify CD81 as one of few surface proteins that are downregulated in HCV expressing hepatoma cells, discovering a functional role of CD81 beyond mediating HCV entry. CD81 was downregulated at the mRNA level in hepatoma cells that replicate HCV. Kinetics of HCV expression were increased in CD81-knockout cells and accompanied by enhanced cellular growth. Furthermore, loss of CD81 compensated for inhibition of pro-survival TBK1-signaling in HCV expressing cells. Analysis of functional phenotypes that could be associated with pro-survival signaling revealed that CD81 is a negative regulator of NF-κB. Interaction of the NF-κB subunits p50 and p65 was increased in cells lacking CD81. Similarly, we witnessed an overall increase in the total levels of phosphorylated and cellular p65 upon CD81-knockout in hepatoma cells. Finally, translocation of p65 in CD81-negative hepatoma cells was markedly induced upon stimulation with TNFα or PMA. Altogether, CD81 emerges as a regulator of pro-survival NF-κB signaling. Considering the important and established role of NF-κB for HCV replication and tumorigenesis, the downregulation of CD81 by HCV and the associated increase in NF-κB signaling might be relevant for viral persistence and chronic infection.


Assuntos
Carcinoma Hepatocelular , Hepatite C , Neoplasias Hepáticas , Humanos , Hepacivirus/genética , NF-kappa B , Neoplasias Hepáticas/patologia , Tetraspanina 28/metabolismo
12.
Sci Rep ; 14(1): 3707, 2024 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-38355630

RESUMO

Transcatheter arterial chemoembolization (TACE) is a standard treatment for intermediate-stage hepatocellular carcinoma (HCC). However, TACE can cause deterioration of liver functions. We aimed to identify the factors that influence deterioration of liver function after TACE. We retrospectively analyzed 262 patients who underwent TACE as initial treatment for HCC with Child-Pugh grade A. We divided them into three groups stratified by the etiology of underlying liver disease. Patients were classified into hepatitis B virus (HBV) group, hepatitis C virus (HCV) group, and non-HBV / non-HCV (NBNC) group. Liver functions at one month after TACE and time to Child-Pugh grade B or C were compared between the three groups. The HBV, HCV and NBNC groups contained 23, 123 and 116 patients, respectively. The decline in albumin level after TACE was significantly higher in NBNC group than other groups (p = 0.02). NBNC group showed a shorter time to Child-Pugh grade deterioration compared with HBV group and HCV group (p < 0.001). Multivariate Cox regression analysis showed that NBNC group was a significant factor for Child-Pugh grade deterioration (Hazard ratio 3.74, 95% confidence interval 1.89-7.40, p < 0.001). These results revealed that liver functions worsened most remarkably in NBNC group after TACE.


Assuntos
Carcinoma Hepatocelular , Quimioembolização Terapêutica , Hepatite C , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Estudos Retrospectivos , Quimioembolização Terapêutica/efeitos adversos , Quimioembolização Terapêutica/métodos , Hepatite C/complicações , Hepatite C/terapia
13.
Clin Transplant ; 38(2): e15260, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38369851

RESUMO

BACKGROUND: National data demonstrate that hepatitis C virus (HCV)-infected organ donors are increasingly being used in the US, including for lung transplantation. We aimed to assess whether there were any differences in the acute or chronic rejection rates at 1 year following lung transplantation from HCV-viremic versus uninfected donors. METHODS: We retrospectively reviewed all lung transplant recipients at our institution from April 1, 2017 to October 1, 2020 and then assessed various outcomes between those who received a transplant from HCV-viremic donors versus HCV-negative donors. Primary outcome was to determine if there was a higher incidence of acute and/or chronic allograft rejection when using HCV NAT+ lung donation. We carried out univariate and multivariate analyses. RESULTS: We transplanted 135 patients during the study period, including 18 from HCV-viremic donors. Standard induction therapy with basiliximab and maintenance triple drug immunosuppression was utilized per UC San Diego protocol. All 17 patients receiving HCV-viremic organs developed acute HCV infection and were treated in the postoperative period with 12 weeks of direct acting antivirals (DAA). HCV genotypes included 1, 2, and 3. DAA used included glecaprevir/pibrentasvir (12), sofosbuvir/velpatasvir (1), and ledipasvir/sofosbuvir (2) with drug choice determined by patient's medical insurance coverage. Sustained virological response at 12 weeks after end of DAA therapy (SVR12), indicative of a cure, was achieved in all (100%) recipients. No recipient had a serious adverse event related to HCV infection. The lung transplant recipient (LTR) HCV-viremic donors had lower rates of clinically significant rejection (5.9% vs. 11% LTR HCV-nonviremic donors), and no chronic lung allograft dysfunction at 1 year (vs. 5.9% LTR HCV-nonviremic donors). One-year survival was 100% in the LTR HCV-viremic donors compared to 95.8% in the LTR HCV-nonviremic donors. CONCLUSIONS: We demonstrate the feasibility and success of using HCV NAT + donors with excellent results and without a higher incidence of rejection. Longer term follow-up and a larger sample size are needed to allow this to be a more widely accepted practice for lung transplant programs and payors.


Assuntos
Hepatite C Crônica , Hepatite C , Transplante de Pulmão , Humanos , Sofosbuvir/uso terapêutico , Hepacivirus , Antivirais/uso terapêutico , Estudos Retrospectivos , Hepatite C/tratamento farmacológico , Doadores de Tecidos
14.
Front Immunol ; 15: 1305157, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38370419

RESUMO

The interplay between autophagy and host innate immunity has been of great interest. Hepatitis C virus (HCV) impedes signaling pathways initiated by pattern-recognition receptors (PRRs) that recognize pathogens-associated molecular patterns (PAMPs). Autophagy, a cellular catabolic process, delivers damaged organelles and protein aggregates to lysosomes for degradation and recycling. Autophagy is also an innate immune response of cells to trap pathogens in membrane vesicles for removal. However, HCV controls the autophagic pathway and uses autophagic membranes to enhance its replication. Mitophagy, a selective autophagy targeting mitochondria, alters the dynamics and metabolism of mitochondria, which play important roles in host antiviral responses. HCV also alters mitochondrial dynamics and promotes mitophagy to prevent premature cell death and attenuate the interferon (IFN) response. In addition, the dysregulation of the inflammasomal response by HCV leads to IFN resistance and immune tolerance. These immune evasion properties of HCV allow HCV to successfully replicate and persist in its host cells. In this article, we discuss HCV-induced autophagy/mitophagy and its associated immunological responses and provide a review of our current understanding of how these processes are regulated in HCV-infected cells.


Assuntos
Hepacivirus , Hepatite C , Humanos , Imunidade Inata , Autofagia , Interferons/metabolismo
16.
BMC Gastroenterol ; 24(1): 73, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38355447

RESUMO

BACKGROUND: Sofosbuvir/Velpatasvir (Epclusa, ECS) is the first pan-genotype direct-acting antiviral agent (DAA) for hepatitis C virus (HCV) infection, and Danoprevir (DNV) is the first DAA developed by a Chinese local enterprise, which is suitable for combined use with other drugs to treat genotype 1b chronic hepatitis C. However, previous reports have never compared the real-world data of ECS and DNV. PATIENTS AND METHODS: 178 chronic hepatitis C patients were retrospectively recruited, and 94cases were accepted with Sofosbuvir/Velpatasvir ± Ribavirin (ECS group), and others (n = 84 treated with DNV combination therapy (DNV group). The HCV genotype, virological response, adverse effects and some laboratory biochemical indexes were contrasted between above two groups in the real world study. RESULTS: DNV group had significantly lower level of alpha-fetoprotein (AFP), lower rates of decompensated cirrhosis ( P < 0.05). ECS group possessed more 6a (31.91% vs.13.10%) while DNV group was provided with more 1b (48.81% vs. 22.34%) patients. Significantly poor liver function was detected in ECS group at 4-week treatment (ALT and AST) and 12-week follow-up (AST) (all P < 0.05). The SVR12 undetectable rates of both groups were 100%, and no serious event was observed during the treatment and follow-up in both groups. CONCLUSION: In this retrospective real-world study, the efficacy of DNV combined therapy is similar to Sofosbuvir/Velpatasvir ± Ribavirin for chronic HCV infection, and the safety is comparable. DNV based therapy is a promising regimen for chronic hepatitis C.


Assuntos
Benzimidazóis , Benzopiranos , Carbamatos , Ciclopropanos , Combinação de Medicamentos , Hepatite C Crônica , Hepatite C , Isoindóis , Lactamas Macrocíclicas , Prolina , Sulfonamidas , Humanos , Antivirais/efeitos adversos , China , Genótipo , Hepacivirus/genética , Hepatite C/tratamento farmacológico , Hepatite C Crônica/genética , Compostos Heterocíclicos de 4 ou mais Anéis/efeitos adversos , Cirrose Hepática/tratamento farmacológico , Prolina/análogos & derivados , Estudos Retrospectivos , Ribavirina/efeitos adversos , Sofosbuvir/efeitos adversos , Resultado do Tratamento
17.
Medicine (Baltimore) ; 103(7): e37212, 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38363923

RESUMO

In recent years, direct-acting antivirals (DAAs) have dramatically improved the sustained virological response (SVR) rates in chronic hepatitis C (CHC) patients with their favorable safety and efficacy. However, there is a lack of data on the long-term prognosis of DAA therapy for CHC patients after achieving SVR in the real world. The aim of this study was to evaluate the long-term clinical prognosis of patients with chronic hepatitis C treated by DAA after achieving SVR. This study was a single-center, retrospective, observational study that included 243 CHC patients who reached SVR after DAA treatment in the Third Affiliated Hospital of Sun Yat-sen University from January 2017 to December 2021, with a median follow-up period (FUP) of 24 months, to assess the long-term prognosis and clinical outcomes of CHC patients who reached SVR by DAA treatment. A total of 243 patients were enrolled in this study, 151 patients were male, the mean age of this study was 46.7 ±â€…12.3 years old, and 23.0% (n = 56) patients were cirrhosis in the baseline. At the end of follow-up, 9 patients (3.7%) progressed to hepatocellular carcinoma (HCC), and patients with cirrhosis at baseline (n = 5) had a significantly higher risk of HCC compared with noncirrhotic patients (n = 4; OR = 4.485, 95% CI: 1.162-17.318, P = .029); 2.9% patients (n = 7) relapsed at the median FUP of 12 months, and patients with genotype 3b had a significantly higher risk of relapsing than those without genotype 3b (OR = 18.48, P = .002, 95% CI: 2.866-119.169). ALT, AST, and ALB all showed improvement at the end of treatment compared with the baseline, remaining at normal levels during FUP meanwhile. The DAA-induced SVR was durable, with conspicuous improvement in clinical outcomes. Nevertheless, patients, especially patients with cirrhosis, still exist the risk of appearance of HCC after reaching SVR. Therefore, regular surveillance and monitoring is necessary even after patients reached SVR.


Assuntos
Carcinoma Hepatocelular , Hepatite C Crônica , Hepatite C , Neoplasias Hepáticas , Humanos , Masculino , Adulto , Pessoa de Meia-Idade , Feminino , Antivirais/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Estudos Retrospectivos , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/patologia , Neoplasias Hepáticas/tratamento farmacológico , Seguimentos , Recidiva Local de Neoplasia/tratamento farmacológico , Hepatite C/tratamento farmacológico , Cirrose Hepática/tratamento farmacológico , Resposta Viral Sustentada
18.
PLoS One ; 19(2): e0284169, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38330063

RESUMO

Dialysis is a replacement therapy for patients with End-Stage Renal Disease (ESRD). Patients on dialysis are at high risk of acquiring hepatitis C virus (HCV), which has become a leading cause of morbidity and mortality in this population. There is a wide range of prevalence of HCV in dialysis populations around the world. It is still unknown how prevalent HCV infection is among worldwide dialysis patients (including those undergoing hemodialysis and peritoneal dialysis). A review was conducted to estimate the global epidemiology of hepatitis C in dialysis patients. We searched PubMed, Excerpta Medica Database (Embase), Global Index Medicus and Web of Science until October 2022. A manual search of references from relevant articles was also conducted. Heterogeneity was evaluated by the χ2 test on Cochrane's Q statistic, and the sources of heterogeneity were investigated using subgroup analysis. In order to assess publication bias, funnel plots and Egger tests were conducted, and pooled HCV prevalence estimates were generated using a DerSimonian and Laird meta-analysis model. The study is registered with PROSPERO under CRD42022237789. We included 634 papers involving 392160 participants. The overall HCV case fatality rate was 38.7% (95% CI = 28.9-49). The global prevalence of HCV infection in dialysis population group were 24.3% [95% CI = 22.6-25.9]. As indicated by UNSD region, country, dialysis type, and HCV diagnostic targeted; Eastern Europe had the highest prevalence of 48.6% [95% CI = 35.2-62], Indonesia had 63.6% [95% CI = 42.9-82], hemodialysis patients had 25.5% [95% CI = 23.8-27.3], and anti-HCV were detected in 24.5% [95% CI = 22.8-26.2]. Dialysis patients, particularly those on hemodialysis, have a high prevalence and case fatality rate of HCV infection. Hemodialysis units need to implement strict infection control measures.


Assuntos
Hepatite C , Falência Renal Crônica , Diálise Peritoneal , Humanos , Hepacivirus , Diálise Renal/efeitos adversos , Falência Renal Crônica/epidemiologia , Falência Renal Crônica/terapia , Falência Renal Crônica/etiologia , Diálise Peritoneal/efeitos adversos , Prevalência
19.
Zhonghua Gan Zang Bing Za Zhi ; 32(1): 87-90, 2024 Jan 20.
Artigo em Chinês | MEDLINE | ID: mdl-38320798

RESUMO

Chronic hepatitis C is a kind of viral hepatitis caused by hepatitis C virus infection, which can further progress to cirrhosis, liver failure, hepatocellular carcinoma, and even death. Presently, there is no preventive vaccine yet. Therefore, preventing infection and safe and effective drug treatment are currently the most effective strategies for dealing with hepatitis C virus infection. Since 2014, the clinical application of direct-acting antiviral drugs has brought revolutionary changes to the treatment of chronic hepatitis C. Direct-acting antiviral drugs have an excellent hepatitis C virus clearance effect, are well tolerated, have a good safety profile, and can significantly improve liver function, metabolic disorders, immune dysfunction, etc. However, some studies have pointed out that even if the hepatitis C virus is cleared during the treatment of chronic hepatitis C-related cirrhosis with direct-acting antiviral drugs, a considerable proportion of patients still have severe liver failure, hepatocellular carcinoma, and even liver disease-related death, so there are still some problems in the treatment of chronic hepatitis C- related cirrhosis with direct-acting antiviral drugs that need to be further explored. This article reviews the research progress of direct-acting antiviral drugs so as to provide meaningful references for the treatment of patients with chronic hepatitis C-related cirrhosis.


Assuntos
Carcinoma Hepatocelular , Hepatite C Crônica , Hepatite C , Neoplasias Hepáticas , Humanos , Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Antivirais/uso terapêutico , Antivirais/farmacologia , Neoplasias Hepáticas/patologia , Cirrose Hepática , Hepatite C/tratamento farmacológico , Hepacivirus
20.
J Infect Dev Ctries ; 18(1): 131-135, 2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-38377100

RESUMO

INTRODUCTION: The measurement of hepatitis C virus (HCV) RNA is a test that requires high cost, advanced technique, and qualified personnel. Diagnosis and treatment of patients may be delayed due to the high rate of false-positive results. This study aims to predict true antibody positivity and viremia by determining the most appropriate anti-HCV signal-to-cutoff (S/Co) value reflecting HCV infection. METHODOLOGY: The presence of anti-HCV antibodies and HCV RNA levels were examined in 72341 people who applied to the Mengücek Gazi Training and Research Hospital between January 2018 and December 2020. The anti-HCV levels were determined by using the Abbot Architect i2000 SR device (Abbot Diagnostics, Chicago, IL, USA). The levels of HCV RNA were determined in the COBAS AmpliPrep/COBAS, TaqMan 48 (Roche, Diagnostics, Pleasanton, USA) devices using serum samples from patients. Our study is a retrospective and methodological study. RESULTS: Of the 150 patients with anti-HCV antibodies, 50 (33.3%) were HCV RNA positive, and 100 (66.7%) were HCV RNA negative. Anti-HCV levels of HCV RNA-positive patients were statistically higher than HCV RNA-negative patients. The most appropriate anti-HCV S/Co value for diagnosing hepatitis C patients was 15.4. The sensitivity of this value was 72%, specificity 88%, positive predictive value (PPV) 73.5%, and negative predictive value (NPV) 86.1%. Receiver operating characteristic (ROC) curve was significantly higher than 0.5 (95% confidence interval 0.938-0.827). CONCLUSIONS: Correct approaches can be applied in the diagnosis of HCV infection using the anti-HCV S/Co value found in our study.


Assuntos
Hepacivirus , Hepatite C , Humanos , Hepacivirus/genética , Anticorpos Anti-Hepatite C , Estudos Retrospectivos , Turquia , RNA Viral , Hepatite C/diagnóstico , Hospitais , Sensibilidade e Especificidade
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