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1.
Braz. j. biol ; 83: e244977, 2023. tab, graf
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-1285621

RESUMO

Abstract Hepatitis C virus (HCV) is the serious global public health burden of liver disease. Approximately 170 million people in the world are infected with (HCV). In Pakistan, where the disease has high occurrence rate. The present study envisages an up-to-date prevalence of HCV and genotypic distribution in the general population of Mardan District, Khyber Pakhtunkhwa (KP), Pakistan. The blood samples from 6,538 individuals including 3,263 males and 3,275 females were analyzed for hepatitis C surface antigen by Immuno-chromatographic test (ICT), Enzyme-linked immunosorbent assay (ELISA), and reverse transcription-polymerase chain reaction (PCR). It was found that 396 (12.13%) out of 3263 individuals contained antibodies in their blood against HCV, while among the different age groups, the highest incidences of HCV antibodies were found in the 31-40 age group (11.01%). The ICT positive samples were further screened by nested PCR to determine the existence of active HCV-RNA. It was identified that 7.11% (3263) of the total population (6538) tested was positive, among which the 461 (14.07%) females possessed antibodies in their blood against HCV. Our data showed total HCV infection in the investigated population was 5.78%. Higher percentage of HCV prevalence was detected in males than females in the age group 31-40 and 41-50. To compare the prevalence of HCV genotypes age-wise in male and female genotype 3a was found most prevalent genotype followed by 1a, 2a and 3b, respectively.


Resumo O vírus da hepatite C (HCV) é o grave problema de saúde pública das doenças hepáticas. Aproximadamente 170 milhões de pessoas no mundo estão infectadas com HCV; no Paquistão, a doença tem alto índice de ocorrência. O presente estudo prevê uma prevalência atualizada do HCV e distribuição genotípica na população geral do distrito de Mardan, Khyber Pakhtunkhwa (KP), Paquistão. As amostras de sangue de 6.538 indivíduos, incluindo 3.263 homens e 3.275 mulheres, foram analisadas para o antígeno de superfície da hepatite C por teste imunocromatográfico (ICT), ensaio imunoenzimático (ELISA) e reação em cadeia da polimerase de transcrição reversa (PCR). Verificou-se que 396 (12,13%) de 3.263 indivíduos continham anticorpos no sangue contra o HCV, enquanto entre as diferentes faixas etárias as maiores incidências de anticorpos anti-HCV foram encontradas na faixa etária de 31 a 40 anos (11,01%). As amostras positivas para ICT foram posteriormente rastreadas por nested PCR para determinar a existência de HCV-RNA ativo. Identificou-se que 7,11% (3.263) do total da população (6.538) testada foram positivos, dentre os quais 461 (14,07%) mulheres possuíam anticorpos no sangue contra o HCV. Nossos dados mostraram que a infecção total pelo HCV na população investigada foi de 5,78%. Maior porcentagem de prevalência de HCV foi detectada em homens do que em mulheres nas faixas etárias de 31-40 e 41-50. Para comparar a prevalência de genótipos de HCV com relação à idade no genótipo masculino e feminino 3a foi encontrado o genótipo mais prevalente seguido por 1a, 2a e 3b, respectivamente.


Assuntos
Humanos , Masculino , Feminino , Hepatite C/epidemiologia , Hepacivirus/genética , Paquistão/epidemiologia , Prevalência , Genótipo
2.
Clin. transl. oncol. (Print) ; 24(10): 1998–2009, octubre 2022. graf
Artigo em Inglês | IBECS | ID: ibc-207955

RESUMO

The Wnt/β-catenin signaling pathway is frequently activated in hepatocellular carcinoma (HCC). A number of studies have focused on the aberrant hypermethylation of the DKK family proteins and its role in regulating the activation of specific signaling pathways. However, the exact way by which DKK regulates the signaling pathway caused by Core protein of HCV has not been reported. In the present study, we evaluated the expression level of DKK and its aberrant promoter methylation to investigate the involvement of epigenetic regulation in hepatoma cell lines. The transcription and protein expression of DKK1 was significantly increased, whereas the transcription and protein expression levels of DKK2, DKK3, and DKK4 were significantly decreased following overexpression of Core protein. Pyrosequencing indicated that hypermethylation of DKK3 was increased. This was associated with increased expression of Dnmt1. The investigation of the molecular mechanism indicated that HCV Core protein interacted with Dnmt1, which combined with the promoter of DKK3, leading to methylation of DKK3. Functional studies indicated that Core protein promoted the growth, migration and invasion of cancer cells. However, upregulation of the expression of DKK3 and/or the knockdown of the expression of Dnmt1 inhibited the growth, migration and invasion of cancer cells. Taken together, the data indicated that epigenetic silencing of DKK3 caused by Dnmt1 activated the Wnt/β-catenin pathway in HCV Core-mediated HCC. Therefore, DKK3 may be a potential diagnostic and therapeutic target for HCC. (AU)


Assuntos
Humanos , Proteínas Adaptadoras de Transdução de Sinal , Carcinoma Hepatocelular , Linhagem Celular Tumoral , Proliferação de Células , Epigênese Genética , Peptídeos e Proteínas de Sinalização Intercelular , Via de Sinalização Wnt , beta Catenina , Hepatite C , Neoplasias Hepáticas
4.
World J Gastroenterol ; 28(35): 5217-5229, 2022 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-36188718

RESUMO

BACKGROUND: Chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are known risk factors for liver disease, cirrhosis and hepatocellular carcinoma (HCC). There is substantial global variation in HBV and HCV prevalence resulting in variations in cirrhosis and HCC. We previously reported high prevalence of HBV and HCV infections in Somali immigrants seen at an academic medical center in Minnesota. AIM: To determine the prevalence of chronic viral hepatitis in Somali immigrants in Minnesota through a community-based screening program. METHODS: We conducted a prospective community-based participatory research study in the Somali community in Minnesota in partnership with community advisory boards, community clinics and local mosques between November 2010 and December 2015 (data was analyzed in 2020). Serum was tested for hepatitis B surface antigen, hepatitis B core antibody, hepatitis B surface antibody and anti-HCV antibody. RESULTS: Of 779 participants, 15.4% tested positive for chronic HBV infection, 50.2% for prior exposure to HBV and 7.6% for chronic HCV infection. Calculated age-adjusted frequencies in males and females for chronic HBV were 12.5% and 11.6%; for prior exposure to HBV were 44.8% and 41.3%; and for chronic HCV were 6.7% and 5.7%, respectively. Seven participants developed incident HCC during follow up. CONCLUSION: Chronic HBV and HCV are major risk factors for liver disease and HCC among Somali immigrants, with prevalence of both infections substantially higher than in the general United States population. Community-based screening is essential for identifying and providing health education and linkage to care for diagnosed patients.


Assuntos
Carcinoma Hepatocelular , Hepatite B Crônica , Hepatite B , Hepatite C Crônica , Hepatite C , Neoplasias Hepáticas , Carcinoma Hepatocelular/patologia , Feminino , Hepacivirus , Hepatite B/complicações , Anticorpos Anti-Hepatite B , Antígenos de Superfície da Hepatite B , Vírus da Hepatite B , Hepatite B Crônica/complicações , Hepatite B Crônica/epidemiologia , Hepatite C/complicações , Hepatite C Crônica/complicações , Hepatite C Crônica/diagnóstico , Hepatite C Crônica/epidemiologia , Humanos , Incidência , Cirrose Hepática/complicações , Neoplasias Hepáticas/patologia , Masculino , Minnesota/epidemiologia , Prevalência , Estudos Prospectivos , Somália
5.
Front Immunol ; 13: 984728, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36189208

RESUMO

Hepatocellular carcinoma(HCC) is the sixth most common cancer in the world and is usually caused by viral hepatitis (HBV and HCV), alcoholic, and non-alcoholic fatty liver disease(NAFLD). Viral hepatitis accounts for 80% of HCC cases worldwide. In addition, With the increasing incidence of metabolic diseases, NAFLD is now the most common liver disease and a major risk factor for HCC in most developed countries. This review mainly described the specificity and similarity between the pathogenesis of viral hepatitis(HBV and HCV)-induced HCC and NAFLD-induced HCC. In general, viral hepatitis promotes HCC development mainly through specific encoded viral proteins. HBV can also exert its tumor-promoting mechanism by integrating into the host chromosome, while HCV cannot. Viral hepatitis-related HCC and NASH-related HCC differ in terms of genetic factors, and epigenetic modifications (DNA methylation, histone modifications, and microRNA effects). In addition, both of them can lead to HCC progression through abnormal lipid metabolism, persistent inflammatory response, immune and intestinal microbiome dysregulation.


Assuntos
Carcinoma Hepatocelular , Hepatite C , Hepatite Viral Humana , Neoplasias Hepáticas , MicroRNAs , Hepatopatia Gordurosa não Alcoólica , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Hepatite C/complicações , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Hepatopatia Gordurosa não Alcoólica/patologia , Proteínas Virais
7.
Intern Med ; 61(18): 2721-2729, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36104175

RESUMO

Objective Owing to advances in direct-acting antiviral (DAA) therapy, a considerable number of patients with hepatitis C virus (HCV)-positive hepatocellular carcinoma (HCC) are now able to achieve a sustained viral response (SVR) after curative treatment of HCC. However, the beneficial effect of a DAA-SVR on the survival remains unclear. Methods A total of 205 patients with HCC who were HCV-positive with Child-Pugh A at the onset from 2008 to 2018 were categorized into 2 groups: 140 patients untreated for HCV throughout the entire course after HCC development (untreated group) and 65 patients treated for HCV with DAAs following HCC treatment who achieved an SVR (SVR group). After propensity score matching, 63 patients from each group were selected. Using these patients, the survival and maintenance of Child-Pugh A after HCC treatment were compared between the untreated group and SVR group. Results There was a significant difference in the overall survival (p<0.001) and the rate of maintaining Child-Pugh A (p<0.001) between the groups. The 5-year survival rates were 96% (SVR group) and 60% (untreated group), and the proportions of patients with Child-Pugh A at 5 years after HCC treatment were 96% (SVR group) and 38% (untreated group). Conclusion In patients with HCV-positive HCC, achieving a DAA-SVR after HCC treatment significantly improved the overall survival rate compared with HCV-untreated patients. The contribution of DAA-SVR during the course of HCC treatment to a longer survival is mainly due to the prevention of the progression of Child-Pugh A to B/C. Further research is needed to determine whether aggressive antiviral therapy is also effective for HCC patients with Child-Pugh B/C.


Assuntos
Carcinoma Hepatocelular , Hepatite C Crônica , Hepatite C , Neoplasias Hepáticas , Antivirais , Hepacivirus , Hepatite C/complicações , Hepatite C/tratamento farmacológico , Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Humanos , Neoplasias Hepáticas/terapia , Resposta Viral Sustentada
8.
Arq Gastroenterol ; 59(3): 394-401, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36102438

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC) is the most common type of liver cancer. Risk factors for HCC include hepatitis C (HCV) and B (HBV) virus infection, alcoholic cirrhosis and genetic alterations that can affect several cellular pathways. OBJECTIVE: This study purposed to analyze the gene and serum protein expression of vascular endothelial growth factor (VEGF), angiogenesis, alpha fetoprotein, cystatin B (CSTB), ß-catenin and glypican-3 (GPC3) in groups with HCC, cirrhosis or HCV and controls, and their relation with clinical staging in the HCC and cirrhosis groups, as well its sensitivity and specificity values. METHODS: A total of 230 individuals were distributed in Group 1 (G1) - 80 patients with HCC; Group 2 (G2) - 76 patients with cirrhosis due to any etiology; Group 3 (G3) - 33 patients with HCV; Group 4 (G4 - controls) - 41 individuals without clinical or biochemical signs of any liver disease. Gene expression was analyzed by qRT-PCR and serum proteins were performed using the ELISA method. RESULTS: Increased VEGF and angiogenesis, alpha fetoprotein expression could be observed in BCLC stage-D patients compared to stage-B patients, and stage-C patients showed higher expression of ß-catenin, compared to stage-B patients (P<0.05). For VEGF and GPC3, discriminatory power was observed between HCC patients and controls (AUC =0.71; 0.82, respectively). CSTB showed discriminatory power in the comparison between patients with HCV and controls (AUC =0.74). CONCLUSION: The present study confirms the sensitivity of serum CSTB in the diagnosis of hepatitis C, and gene expression of VEGF and serum GPC3, confer both sensitivity and specificity for the diagnosis of HCC.


Assuntos
Carcinoma Hepatocelular , Hepatite C , Neoplasias Hepáticas , Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/genética , Glipicanas/genética , Hepacivirus , Humanos , Cirrose Hepática/diagnóstico , Cirrose Hepática/etiologia , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/genética , Fator A de Crescimento do Endotélio Vascular , alfa-Fetoproteínas/análise , beta Catenina
9.
Microb Pathog ; 171: 105739, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36055570

RESUMO

Gut microbial dysbiosis during the development of Hepatitis C virus and liver-related diseases is not well studied. Nowadays, HCV and liver cirrhosis are the major concerns that cause gut bacterial alteration, which leads to dysbiosis. For this purpose, the present study was aimed at correlating the gut bacterial community of the control group in comparison to HCV and liver cirrhotic patients. A total of 23 stool samples were collected, including control (9), liver cirrhotic (8), and HCV (6). The collected samples were subjected to 16 S rRNA Illumina gene sequencing. In comparison with control, a significant gut bacterial alteration was observed in the progression of HCV and liver cirrhosis. Overall, Firmicutes were significantly abundant in the whole study. No significant difference was observed in the alpha diversity of the control and patient studies. Additionally, the beta diversity based on non-metric multidimensional scaling (NMDS) has a significant difference (p = 0.005) (ANOSIM R2 = 0.14) in all groups. The discriminative results based on the LEfSe tool revealed that the HCV-infected patients had higher Enterobacteriaceae and Enterobacterial, as well as Lactobacillus and Bacilli in comparison than the liver-cirrhotic patients. These taxa were significantly different from the control group (p < 0.05). Regarding prospects, a detailed analysis of the function through metagenomics and transcriptomics is needed.


Assuntos
Microbioma Gastrointestinal , Hepatite C , Hepatopatias , Bactérias/genética , Disbiose/microbiologia , Enterobacteriaceae/genética , Hepacivirus/genética , Hepatite C/complicações , Humanos , Cirrose Hepática , Projetos Piloto , RNA Ribossômico 16S/genética
10.
Annu Int Conf IEEE Eng Med Biol Soc ; 2022: 3572-3576, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36085978

RESUMO

AIMS: The hepatitis C virus (HCV) has developed a strategy to coexist with its host resulting in varying degrees of tissue and cell damage, which generate different pathological phenotypes, such as varying degrees of fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). However, there is no integrated information that can predict the evolutionary course of the infection. We propose to combine Near-infrared spectroscopy (NIRS) and machine learning techniques to provide a predictive model. In this work, we propose to discriminate HCV positivity in biobank patient serum samples. METHODS: 126 serum samples from 38 HCV patients in different stages of the disease were obtained from the Biobank of Hospital Universitario Fundación Alcorcon. NIRS spectrum was captured by a FT-NIRS Spectrum 100 (Perkin Elmer) device in reflectance mode. For each patient, the HCV positivity was identified (PCR) and labeled as detectable =1 and undetectable =0. We propose an L1-penalized logistic regression model to classify each spectrum as positive (1) or negative (0) for HCV presence (x). The regularization parameter is selected using 5- fold cross-validation. The penalized model will induce sparsity in the solution so that only a few relevant wavelengths will be different from zero. RESULTS: L1-penalized logistic regression model provided 167 wavelengths different from zero. The accuracy on an independent test set was 0.78. CONCLUSIONS: We present a straightforward promising approach to detect HCV positivity from patient serum samples combining NIRS and machine learning techniques. This result is encouraging to predict HCV progression, among other applications. Clinical relevance- We presented a simple while promising approach to use machine learning and NIRS to analyze viral presence on sample serums.


Assuntos
Carcinoma Hepatocelular , Hepatite C , Neoplasias Hepáticas , Hepacivirus/genética , Hepatite C/complicações , Hepatite C/diagnóstico , Humanos , Espectroscopia de Luz Próxima ao Infravermelho
11.
Front Public Health ; 10: 956712, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36091549

RESUMO

Objective: This study aims to reveal epidemiological features and trends of liver cancer (LC) in China. Methods: We retrieved data from the Global Burden of Disease database 2019. Joinpoint regression was used to examine the temporal trend of LC. Future trends of LC were estimated using the Nordpred. Results: The incidence, mortality, and disability-standardized life year (DALY) rate of LC declined in China from 1990 to 2019. Among >210,000 LC cases in 2019, the LC incidences were nearly 3.15 times higher in males than in females. LC cases and LC-associated deaths were mostly found among patients aged 65 to 69 years. The proportion of LC attributable to hepatitis B decreased over time, whereas the proportions of LC attributable to hepatitis C, alcohol use, and non-alcoholic steatohepatitis increased modestly from 1990 to 2019. The majority of LC-associated deaths could be traced to four risk factors: smoking (20%), drug use (13.6%), alcohol use (11.7%), and high body mass index (10.1%). Based on the Nordpred prediction, there will be a steady decline in the incidence (39.0%) and mortality (38.3%) of liver cancer over a 25-year period from 2020 to 2044. Conclusion: The disease burden of liver cancer in China has declined over the past 30 years. However, it remains important to control liver cancer among high-risk populations, especially elderly males with obesity, alcohol use, tobacco use, and/or drug abuse.


Assuntos
Hepatite C , Neoplasias Hepáticas , Idoso , China/epidemiologia , Efeitos Psicossociais da Doença , Feminino , Humanos , Incidência , Neoplasias Hepáticas/epidemiologia , Masculino
12.
Int J Mol Sci ; 23(17)2022 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-36077436

RESUMO

The most commonly used antiviral treatment against hepatitis C virus is a combination of direct-acting antivirals (DAAs) and ribavirin (RBV), which leads to a shortened duration of therapy and a sustained virologic response until 98%. Nonetheless, several dose-related side effects of RBV could limit its applications. This study aims to measure the urinary concentration of RBV and its main metabolites in order to evaluate the drug metabolism ability of HCV patients and to evaluate the adverse effects, such as anemia, with respect to RBV metabolite levels. RBV and its proactive and inactive metabolites were identified and quantified in the urine of 17 HCV males with severe liver fibrosis using proton nuclear magnetic resonance (1H-NMR) at the fourth week (TW4) and at the twelfth week of treatment (EOT). Four prodrug urinary metabolites, including RBV, were identified and three of them were quantified. At both the TW4 and EOT stages, six HCV patients were found to maintain high concentrations of RBV, while another six patients maintained a high level of RBV proactive metabolites, likely due to nucleosidase activity. Furthermore, a negative correlation between the reduction in hemoglobin (Hb) and proactive forms was observed, according to RBV-triphosphate accumulation causing the hemolysis. These findings represent a proof of concept regarding tailoring the drug dose in relation to the specific metabolic ability of the individual, as expected by the precision medicine approach.


Assuntos
Hepatite C Crônica , Hepatite C , Antivirais/efeitos adversos , Quimioterapia Combinada , Hepacivirus , Hepatite C/tratamento farmacológico , Hepatite C Crônica/tratamento farmacológico , Humanos , Masculino , Medicina de Precisão , Proteínas Recombinantes/farmacologia , Ribavirina/efeitos adversos , Resultado do Tratamento
13.
Sci Rep ; 12(1): 14904, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-36050335

RESUMO

A considerable number of patients with high clinical suspicion for cryoglobulinaemic vasculitis either show negative results for the detection of cryoglobulins or show only trace amounts which cannot be characterized for composition. We aimed at establishing whether the failure to detect or the detection of trace amounts of cryoglobulin with conventional methods either identifies a peculiar subset of low level cryoglobulinaemia (from now on hypocryoglobulinaemia) or represents a separate entity. Using a modified precipitation technique in hypo-ionic medium, we prospectively identified between 2008 and 2021 237 patients (median age 60.8 years [22-97], 137 females) having < 0.5% cryocrit and clinical suspicion of autoimmune disorder. Of these 237 patients, only 54 (22.7%) had a history of HCV infection. One hundred and sixty-nine out of 237 patients (71%) had an established underlying disease, while 68 patients (28.6%) (median age 62.9 years [29-93], 35 females) did not show either laboratory markers or clinical symptoms consonant with an underlying aetiology. These 68 cases with only trace amounts of cryoglobulins were defined as having a putatively idiopathic hypocryoglobulinaemia. Nineteen of these 68 patients (27.9%) had a history of HCV infection. Twenty-four patients out of 68 (35.3%) were positive for rheumatoid factor (RF), while 25 (36.7%) patients had signs of complement consumption (i.e., C4 < 15 mg/dl and/or C3 < 80 mg/dl ), and 36 (52.9%) had increased inflammatory indexes. Seven patients only had arthralgia and constitutional symptoms while 61 out of 68 (89.7%) presented with at least one of the three cardinal signs of cryoglobulinaemic vasculitis including skin lesions, peripheral nerve involvement, and glomerulonephritis. Seventy-five percent of the subjects had type III hypocryoglobulins. In patients with hypocryoglobulinaemia the histologic features of glomerulonephritis (also examined by electron microscopy) resembled those of mixed cryoglobulinaemia-associated glomerulonephritis. In conclusion, hypocryoglobulins are often polyclonal and are mainly unrelated to HCV infection. Patients who present high clinical suspicion for vasculitis, especially glomerulonephritis and yet test negative for cryoglobulinaemia detected by standard techniques, could require deeper investigation even in the absence of HCV infection, RF activity or signs of complement consumption.


Assuntos
Crioglobulinemia , Glomerulonefrite , Hepatite C , Vasculite , Crioglobulinemia/diagnóstico , Crioglobulinas , Feminino , Glomerulonefrite/complicações , Hepatite C/complicações , Humanos , Pessoa de Meia-Idade , Fator Reumatoide , Vasculite/complicações
14.
ACS Sens ; 7(9): 2680-2690, 2022 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-36073895

RESUMO

The path toward field-effect transistor (FET) application from laboratory to clinic has delivered a compelling push in the biomedical domain, yet ultrasensitive and timely pathogen identification without PCR remains a long-lasting challenge. Herein, we create a generic check station termed "CRISPR-FET", first incorporating the CRISPR/Cas13a system within the FET modality, for accelerated and unamplified detection of viral RNA. Unlike conventional FETs bearing target-specific receptors, this sensor holds three unique advancements: (i) an ingenious sensing mechanism is used, which converts the signal of a large-sized analyte into an on-chip cleavage response of an immobilized CRISPR reporter, enabling signal generation events to occur all within the Debye length; (ii) the multipurpose inspection of the CoV ORF1ab, CoV N gene, and HCV RNA unveils the potential for "one-for-all" scalable FET-based molecular diagnostics; and (iii) it is shown that Cas13a-crRNAs targeting different sites of the viral genome can be deployed in tandem to amplify the FET response, empowering the detection limit down to 1.56 aM, which is a world-record level of sensitivity in the FET for direct viral gene sensing. Notably, a brilliant clinical applicability was made in distinguishing HCV-infected patients from normal controls. Overall, this study sheds new insights into FET-based nucleic acid sensing technology and invokes a vision for its possible future roles in diagnosis of various viral diseases.


Assuntos
Técnicas Biossensoriais , Hepatite C , Sistemas CRISPR-Cas/genética , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas/genética , Hepatite C/genética , Humanos , RNA Viral/genética
15.
Front Immunol ; 13: 980079, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36119023

RESUMO

Treatment of systemic lupus erythematosus (SLE) currently employs agents with relatively unselective immunosuppressive properties. However, two target-specific biological drugs have been approved: belimumab (anti-B-cell-activating factor/BAFF) and anifrolumab (anti-interferon alpha receptor-1/IFNAR1). Here, we performed a comparative risk-benefit assessment for both drugs based on the role of BAFF and IFNAR1 in host defense and the pathogenesis of SLE and by considering the available data on safety and efficacy. Due to differences in target expression sites, anti-IFNAR1, but not anti-BAFF, might elicit organ-specific effects, consistent with clinical efficacy data. The IFNAR1 is specifically involved in innate and adaptive antiviral immunity in most cells of the body. Consistent with this observation, the available safety data obtained from patients negatively selected for LN and neuropsychiatric SLE, primary immunodeficiencies, splenectomy and chronic HIV, HBV, HCV infections suggest an increased risk for some viral infections such as varicella zoster and perhaps influenza. In contrast, BAFF is mainly involved in adaptive immune responses in lymphoid tissues, thus anti-BAFF therapy modulates SLE activity and prevents SLE flares without interfering with local innate host defense mechanisms and should only marginally affect immune memory to previous pathogen exposures consistent with the available safety data from SLE patients without chronic HIV, HBV or HCV infections. When using belimumab and anifrolumab, careful patient stratification and specific precautions may minimize risks and maximize beneficial treatment effects for patients with SLE.


Assuntos
Produtos Biológicos , Infecções por HIV , Hepatite C , Lúpus Eritematoso Sistêmico , Anticorpos Monoclonais Humanizados , Antivirais/uso terapêutico , Produtos Biológicos/uso terapêutico , Infecções por HIV/tratamento farmacológico , Hepatite C/tratamento farmacológico , Humanos , Medição de Risco
16.
Virus Res ; 321: 198928, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36100006

RESUMO

BACKGROUND: The combination of epigenetic and genetic abnormalities contributes together to the development of liver cancer. The methylation status of the repetitive elements (REs) in DNA has been investigated in a variety of human illnesses. However, the methylation patterns of Sat-α and Alu REs in chronic liver disease (CLD) and hepatocellular carcinoma (HCC) caused by hepatitis C virus (HCV) have never been studied before. METHODOLOGY: In this study, 3 groups of participants including 50 patients having HCV-induced CLD, 50 patients having HCV-induced HCC, and 46 healthy subjects were subjected to measurement of Sat-α and Alu methylation using the quantitative MethyLight assay. RESULTS: Sat-α and Alu methylation percentages decreased significantly in both CLD and HCC, compared to control. Also, a significant Sat-α hypomethylation was detected in HCC, compared to CLD. In addition, Sat-α and Alu methylation showed a significant decline as lesion size grew. However, only Sat-α hypomethylation was significantly increased in association with portal vein thrombosis and the MELD score. Sat-α methylation percentage had the highest sensitivity and specificity for diagnosing HCC (100% and 84.4%) followed by α-fetoprotein (80% and 84.4%) and Alu methylation (66% and 61.5%). Furthermore, there was a strong positive correlation between Sat-α and Alu methylation. CONCLUSIONS: Measuring Sat-α and Alu methylation provides us with a new tool for early detecting HCV-induced CLD and hepatocarcinogenesis. Sat-α has the potential to be utilized as an independent predictive parameter for HCC development and progression because of its ability to distinguish between CLD and HCC with their different MELD scores.


Assuntos
Carcinoma Hepatocelular , Hepatite C , Neoplasias Hepáticas , Carcinoma Hepatocelular/genética , DNA , Metilação de DNA , Hepacivirus/genética , Hepatite C/genética , Humanos , Neoplasias Hepáticas/genética , alfa-Fetoproteínas/genética
17.
Harm Reduct J ; 19(1): 107, 2022 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-36175872

RESUMO

BACKGROUND: Access to sterile needles, syringes and methadone maintenance therapy (MMT) is critical to reduce the prevalence of bloodborne virus infections among people who inject drugs (PWID). We aimed to explore the experiences of PWID with respect to accessing needles/syringes services and MMT in Yangon, Myanmar. METHODS: Burnet Institute implemented a community-based hepatitis C testing and treatment (CT2) program for PWID with on-site needles and syringes distribution. Separate from CT2, MMT was available at two government-run sites in Yangon. We conducted in-depth interviews with 15 PWID who received hepatitis C care in this program. Interviews were transcribed verbatim and translated into English. Thematic data analysis was performed using NVivo12 software. RESULTS: Self-reported changes to needles/syringes sharing behaviour after hepatitis C education in the CT2 program and commencement of treatment were observed. One third of participants reported they became aware of the risks of sharing and reusing needles/syringes, and consequently refrained from sharing after the CT2 program. Inadequate availability of NSPs, cost of needles/syringes, and issues maintaining privacy when accessing needles/syringes emerged as key barriers to accessibility of needles/syringes. Participants described difficulties in accessing free needles/syringes. They were not aware of other free needles/syringes services at the time of the interview. Purchasing needles/syringes from pharmacies had privacy and confidentiality concerns. Structural barriers to accessibility of MMT were identified for both MMT sites in Yangon. Of the two MMT sites in Yangon, participants reported that the Ywarthargyi center had strict eligibility criteria for take-home methadone and transportation issues as it was located in the outskirt of the town. The Thingyangyun center was in a more convenient location, but only offered daily observed doses and had a long waiting time which was burdensome for some employed participants. CONCLUSION: Expansion of free needles/syringes services and adaptations of MMT to consider the needs and individual preferences of PWID will improve their access to these services and would likely reduce injecting related harms.


Assuntos
Usuários de Drogas , Infecções por HIV , Hepatite C , Abuso de Substâncias por Via Intravenosa , Infecções por HIV/epidemiologia , Hepatite C/complicações , Hepatite C/epidemiologia , Humanos , Metadona/uso terapêutico , Mianmar , Compostos Organometálicos , Abuso de Substâncias por Via Intravenosa/epidemiologia , Seringas
18.
Hepatol Int ; 16(5): 1020-1031, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36085539

RESUMO

BACKGROUND: Hepatitis C (HCV)-induced decompensated cirrhosis warrants liver transplantation (LT) as the only ultimate solution. These patients experience liver deterioration, while on the transplant waitlist. However, debate remains over the optimal timing for treating HCV relative to before or after LT. METHODS: We performed a literature search between 1/2011 and 1/2022 on PubMed and OVID Medline. Data were extracted from direct antiviral agent (DAA) studies in English. The outcomes of interest included sustained virological response (SVR) rates from various cohorts as well as long- and short-term outcomes in the LT settings. RESULTS: After screening, 54 studies were eligible and included into the review. In aligning with the EASL and AASLD guidelines and suggestions, many studies supported DAA therapy before LT in patients with Model for End-stage Liver Disease (MELD) scores < 18 and DAA therapy post-LT in MELD scores > 20 through SVR rates, long-term survival factors, liver deterioration, and incidences of severe adverse events. However, uncertainty still lies in the guideline recommendations and unsettled issues remain for various patient cohorts that may benefit from opposing the guideline cutoffs. Based on the recent studies on predictors of treatment outcomes in decompensated patients and the impact of DAA on the waiting list for LT, we proposed an algorithm to manage patients with MELD scores between 18 and 20. CONCLUSION: DAA therapy for decompensated patients must be personalized with consideration of different factors, particularly among those with MELD scores between the two cutoff-values proposed by the current associational guidelines.


Assuntos
Doença Hepática Terminal , Hepatite C Crônica , Hepatite C , Transplante de Fígado , Antivirais/uso terapêutico , Doença Hepática Terminal/complicações , Hepacivirus , Hepatite C/complicações , Hepatite C/tratamento farmacológico , Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Humanos , Cirrose Hepática/tratamento farmacológico , Transplante de Fígado/efeitos adversos , Índice de Gravidade de Doença
19.
BMC Gastroenterol ; 22(1): 425, 2022 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-36115934

RESUMO

BACKGROUND: New direct-acting antiviral therapies have revolutionized hepatitis C virus (HCV) infection therapy. Nonetheless, once liver cirrhosis is established, the risk of hepatocellular carcinoma (HCC) still exists despite virus eradication. Late HCV diagnosis hinders timely access to HCV treatment. Thus, we determined trends and risk factors associated with late HCV among patients with a diagnosis of HCC in Taiwan. METHODS: We conducted a population-based unmatched case-control study. 2008-2018 Claims data were derived from the Taiwan National Health Insurance Research Database. Individuals with an initial occurrence of liver cancer between 2012 and 2018 were included. The late HCV group were referred as individuals who were diagnosed with HCC within 3 years after HCV diagnosis. The control group were referred as individuals who were diagnosed more than 3 years after the index date. We used multivariable logistic models to explore individual- and provider-level risk factors associated with a late HCV diagnosis. RESULTS: A decreasing trend was observed in the prevalence of late HCV-related HCC diagnosis between 2012 and 2018 in Taiwan. On an individual level, male, elderly patients, patients with diabetes mellitus (DM), and patients with alcohol-related disease had significantly higher risks of late HCV-related HCC diagnosis. On a provider level, patients who were mainly cared for by male physicians, internists and family medicine physicians had a significantly lower risk of late diagnosis. CONCLUSIONS: Elderly and patients who have DM and alcohol related disease should receive early HCV screening. In addition to comorbidities, physician factors also matter. HCV screening strategies shall take these higher risk patients and physician factors into consideration to avoid missing opportunities for early intervention.


Assuntos
Carcinoma Hepatocelular , Diabetes Mellitus , Hepatite C Crônica , Hepatite C , Neoplasias Hepáticas , Idoso , Antivirais , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/patologia , Estudos de Casos e Controles , Diagnóstico Tardio/efeitos adversos , Hepacivirus , Hepatite C/complicações , Hepatite C/diagnóstico , Hepatite C/epidemiologia , Hepatite C Crônica/complicações , Hepatite C Crônica/diagnóstico , Hepatite C Crônica/tratamento farmacológico , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/etiologia , Masculino
20.
Sci Rep ; 12(1): 15648, 2022 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-36123370

RESUMO

Many PTMs dysregulation is known to be the major cause of many cancers including HCV induced HCC. PTMs of hepatitis C virus (HCV) regions NS3/4A, NS5A and NS5B are crucial for proper protein functions and replication that directly affect the generation of infectious virus particles and completion of its life cycle. In this study, we have performed comprehensive analysis of PTMs within HCV non-structural proteins (NS3/4A, NS5A and NS5B) through bioinformatics analysis to examine post-translational crosstalk between phosphorylation, palmitoylation, methylation, acetylation and ubiquitination sites in selected viral proteins. Our analysis has revealed many highly putative PTMs sites that are also conserved among major genotypes conferring the importance of these sites. We have also analysed viral 3D structures in their modified and unmodified forms to address extent and signatures of structural changes upon PTM. This study provides evidence that PTMs induce significant conformational changes and make viral proteins more stable. To find the potential role of PTMs in HCV induced HCC, docking analysis between selected viral proteins and p38-MAPK has been performed which also confirms their strong association with HCV induced HCC. The major findings proposed that PTMs at specific sites of HCV viral proteins could dysregulate specific pathways that cause the development of HCC.


Assuntos
Carcinoma Hepatocelular , Hepatite C , Neoplasias Hepáticas , Hepacivirus/genética , Hepatite C/complicações , Humanos , Processamento de Proteína Pós-Traducional , Proteínas Virais/genética
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