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1.
J Viral Hepat ; 30(12): 959-969, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37697495

RESUMO

Hepatitis E is a disease associated with acute inflammation of the liver. It is related to several dysregulated metabolic pathways and alterations in the concentration of several metabolites. However, longitudinal analysis of the alterations in metabolites and lipids is generally lacking. This study investigated the changes in levels of metabolites and lipids over time in sera from men with acute hepatitis E compared to healthy controls similar in age and gender. Untargeted measurement of levels of various metabolites and lipids was done using mass spectrometry on 65 sera sequentially sampled from 14 patients with acute hepatitis E and 25 serum samples from five controls. Temporal changes in intensities of metabolites and lipids were determined over different times at 3-day periods for the hepatitis E virus (HEV) group. In carbohydrate metabolism, glucose levels, fructose 1-6-bisphosphate and ribulose-5-phosphate were increased in the HEV-infected persons compared to the healthy controls. HEV infection is significantly associated with decreased levels of inosine, guanosine, adenosine and urate in purine metabolism and thymine, uracil and ß-aminoisobutyrate in pyrimidine metabolism. Glutamate, alanine and valine levels were significantly lower in the HEV group than in healthy individuals. Homogentisate of tyrosine metabolism and cystathionine of serine metabolism were increased, whereas kynurenate of tryptophan metabolism decreased in the HEV group. Metabolites of the bile acid biosynthesis, urea cycle (arginine and citrulline) and ammonia recycling (urocanate) were significantly altered. Co-enzymes, pantothenate and pyridoxal, and co-factors, lipoamide and FAD, were elevated in the HEV group. The acylcarnitines, sphingomyelins, phosphatidylcholine (PC), phosphatidylethanolamine (PE), lysoPC and lysoPE tended to be lower in the HEV group. In conclusion, acute hepatitis E is associated with altered metabolite and lipid profiles, significantly increased catabolism of carbohydrates, purines/pyrimidines and amino acids, and decreased levels of several glycerophospholipids.


Assuntos
Vírus da Hepatite E , Hepatite E , Masculino , Humanos , Estudos Longitudinais , Lipídeos
2.
Colomb. med ; 54(3)sept. 2023.
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1534290

RESUMO

This statement revises our earlier "WAME Recommendations on ChatGPT and Chatbots in Relation to Scholarly Publications" (January 20, 2023). The revision reflects the proliferation of chatbots and their expanding use in scholarly publishing over the last few months, as well as emerging concerns regarding lack of authenticity of content when using chatbots. These recommendations are intended to inform editors and help them develop policies for the use of chatbots in papers published in their journals. They aim to help authors and reviewers understand how best to attribute the use of chatbots in their work and to address the need for all journal editors to have access to manuscript screening tools. In this rapidly evolving field, we will continue to modify these recommendations as the software and its applications develop.


Esta declaración revisa las anteriores "Recomendaciones de WAME sobre ChatGPT y Chatbots en Relation to Scholarly Publications" (20 de enero de 2023). La revisión refleja la proliferación de chatbots y su creciente uso en las publicaciones académicas en los últimos meses, así como la preocupación por la falta de autenticidad de los contenidos cuando se utilizan chatbots. Estas recomendaciones pretenden informar a los editores y ayudarles a desarrollar políticas para el uso de chatbots en los artículos sometidos en sus revistas. Su objetivo es ayudar a autores y revisores a entender cuál es la mejor manera de atribuir el uso de chatbots en su trabajo y a la necesidad de que todos los editores de revistas tengan acceso a herramientas de selección de manuscritos. En este campo en rápida evolución, seguiremos modificando estas recomendaciones a medida que se desarrollen el software y sus aplicaciones.

3.
Indian J Pediatr ; 90(3): 240-248, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36112267

RESUMO

OBJECTIVE: To report genotype data of the patients with Wilson disease (WD) hailing from across several parts of India to add to the available spectrum of causative variants in ATP7B gene (ATPase copper transporting beta polypeptide gene) and associated phenotypes in the Indian population. METHODS: The entire ATP7B gene was sequenced in 58 patients with WD and additional testing was also done by MLPA to look for intragenic deletions duplications and exome sequencing to rule out genetic variations with similar phenotypic overlap. RESULTS: Of all patients, 37 patients had a total of 33 distinct pathogenic variations, including 29 in the exonic regions and 4 at intronic splice sites. Of the variations identified, six were novel. The underlying genomic variations could be identified in nearly two-thirds of the patients by sequencing the entire gene. CONCLUSIONS: This study reports the genotype-phenotype data to add to the available spectrum of causative variants in ATP7B gene. The inability to detect a pathogenic variation in some patients and the existence of phenotypic variations in individuals with the same variation suggest that additional factors or genes may play a role in causation of the disease. Further, a marked genetic heterogeneity was found in the study patients, indicating ethnic diversity of the Indian population.


Assuntos
Degeneração Hepatolenticular , Humanos , Degeneração Hepatolenticular/diagnóstico , Degeneração Hepatolenticular/genética , ATPases Transportadoras de Cobre/genética , Mutação , Genótipo , Genômica
4.
Vaccines (Basel) ; 12(1)2023 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-38276663

RESUMO

As of November 2023, 140 World Health Organization (WHO) member states had introduced human papillomavirus (HPV) vaccination in their routine immunization schedules. Despite a continuously increasing demand from countries across all income groups, supply constraints, COVID-19 pandemic disruptions, and other factors have slowed the pace of introduction, particularly in low-resource settings. Using a population-based forecasting methodology and leveraging the WHO's yearly vaccine supply data collection, we updated global demand and supply projections for the HPV vaccine for the period of 2022-2031. The analysis aimed at clarifying the magnitude of the challenges to bringing in equitable access to HPV vaccines, which can hinder the achievement of the Global Strategy for the Elimination of Cervical Cancer. The results of this analysis show that the risk of HPV shortages has significantly decreased, and global supply is now, under normal circumstances, sufficient to meet global demand. In the long term, HPV supply will be more than sufficient to meet the Global Strategy's goal of 90% of girls fully vaccinated with the HPV vaccine by the age of 15 years. Nonetheless, paying attention to the formulation of policies and carefully managing demand and supply will be required to ensure the long-term sustainability of the HPV vaccine program.

5.
Mol Microbiol ; 118(5): 570-587, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36203260

RESUMO

Hepatitis C virus (HCV) infection is one of the most common causes of liver cancer. HCV infection causes chronic disease followed by cirrhosis, which often leads to hepatocellular carcinoma (HCC). In this study, we investigated the roles of exosome-associated miRNAs in HCV-induced disease pathology. Small RNA sequencing was performed to identify miRNAs that are differentially regulated in exosomes isolated from patient sera at two different stages of HCV infection: cirrhosis and hepatocellular carcinoma. Among the differentially expressed miRNAs, miR-375 was found to be significantly upregulated in exosomes isolated from patients with cirrhosis and HCC. A similar upregulation was observed in intracellular and extracellular/exosomal levels of miR-375 in HCV-JFH1 infected Huh7.5 cells. The depletion of miR-375 in infected cells inhibited HCV-induced cell migration and proliferation, suggesting a supportive role for miR-375 in HCV pathogenesis. miR-375, secreted through exosomes derived from HCV-infected cells, could also be transferred to naïve Huh7.5 cells, resulting in an increase in cell proliferation and migration in the recipient cells. Furthermore, we identified Insulin growth factor binding protein 4 (IGFBP4), a gene involved in cell growth and malignancy, as a novel target of miR-375. Our results demonstrate the critical involvement of exosome-associated miR-375 in HCV-induced disease progression.


Assuntos
Carcinoma Hepatocelular , Exossomos , Hepatite C , Neoplasias Hepáticas , MicroRNAs , Humanos , Hepacivirus/genética , Hepacivirus/metabolismo , Exossomos/metabolismo , Exossomos/patologia , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Insulina/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Hepatite C/genética , Hepatite C/patologia , MicroRNAs/genética , MicroRNAs/metabolismo , Proliferação de Células/genética , Cirrose Hepática/metabolismo , Cirrose Hepática/patologia
6.
J Gastroenterol Hepatol ; 37(6): 964-972, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35263807

RESUMO

BACKGROUND: This systematic review was aimed to estimate hepatitis C virus (HCV) seroprevalence and burden in disease in WHO South East Asia Region (SEAR). METHODS: Electronic databases (PubMed, Scopus, Embase, and Google Scholar) and websites of non-indexed national medical journals, government and international health agencies were searched to identify English language literature published between 1991 and June 2020. We selected the studies reporting HCV seroprevalence in asymptomatic general (low-risk) and high-risk adult populations, that is, persons living with HIV (PLHIV), persons who inject drugs (PWID), sex workers, persons on maintenance hemodialysis (MHD), people in prison, and men sex with men (MSM). Seroprevalence data were combined to estimate weighted pooled prevalence (95% confidence interval) in each group and in each country, using the random-effects model. Estimated pooled seroprevalences were multiplied with estimated populations at risk to estimate the overall HCV burden. RESULTS: The analysis included 538 studies (35 Bangladesh, 6 Bhutan, 2 DPR Korea, 323 India, 43 Indonesia, 2 Maldives, 18 Myanmar, 29 Nepal, 11 Sri Lanka, 67 Thailand, and 2 Timor-Leste). In SEAR, the weighted pooled anti-HCV seroprevalence was estimated as 0.84% (0.56-1.12) in low-risk population and 13.67% (10.95-16.40) in PLHIV, 51.44% (43.67-59.20) in PWID, 25.80% (20.34-32.09) in MHD, 8.39% (5.84-11.51) in prison inmates, 2.69% (1.43-4.13) in people with high-risk sex behavior, and 11.43% (8.61-14.74) in MSM. The total HCV burden in low-risk and high-risk populations in SEAR countries was estimated as 12.45 million and 1.65 million, respectively. CONCLUSION: Our estimates of HCV seroprevalence and burden should help the respective countries in planning their HCV elimination strategies.


Assuntos
Usuários de Drogas , Infecções por HIV , Hepatite C , Minorias Sexuais e de Gênero , Abuso de Substâncias por Via Intravenosa , Ásia Oriental , Infecções por HIV/epidemiologia , Hepacivirus , Hepatite C/epidemiologia , Homossexualidade Masculina , Humanos , Masculino , Prevalência , Fatores de Risco , Estudos Soroepidemiológicos , Abuso de Substâncias por Via Intravenosa/epidemiologia , Organização Mundial da Saúde
7.
J Gen Virol ; 103(12)2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36748628

RESUMO

Chronic hepatitis C virus (HCV) infection is a leading cause of end-stage liver diseases, such as fibrosis, cirrhosis and hepatocellular carcinoma (HCC). Several cellular entities, including paraspeckles and their related components, are involved in viral pathogenesis and cancer progression. NEAT1 lncRNA is a major component of paraspeckles that has been linked to several malignancies. In this study, analysis of the Cancer Genome Atlas (TCGA) database and validation in HCV-induced HCC tissue and serum samples showed significantly high expression of NEAT1 in patients with liver cancer. Moreover, we found that NEAT1 levels increased upon HCV infection. To further understand the mechanism of NEAT1-induced HCC progression, we selected one of its targets, miR-9-5 p, which regulates BGH3 mRNA levels. Interestingly, miR-9-5 p levels were downregulated upon HCV infection, whereas BGH3 levels were upregulated. Additionally, partial NEAT1 knockdown increased miR-9-5 p levels and decreased BGH3 levels, corroborating our initial results. BGH3 levels were also upregulated in HCV-induced HCC and TCGA tissue samples, which could be directly correlated with NEAT1 levels. As a known oncogene, BGH3 is directly linked to HCC progression mediated by NEAT1. We also found that NEAT1 levels remained upregulated in serum samples from patients treated with direct-acting antivirals (DAA), indicating that NEAT1 might be a molecular trigger that promotes HCC development. Collectively, these findings provide molecular insights into HCV-induced HCC progression via the NEAT1-miR-9-BGH3 axis.


Assuntos
Carcinoma Hepatocelular , Hepatite C Crônica , Neoplasias Hepáticas , MicroRNAs , RNA Longo não Codificante , Humanos , Antivirais , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/virologia , Hepacivirus/genética , Hepatite C Crônica/complicações , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/virologia , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Longo não Codificante/genética
8.
Sci Rep ; 11(1): 21382, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34725356

RESUMO

The cost of testing can be a substantial contributor to hepatitis C virus (HCV) elimination program costs in many low- and middle-income countries such as Georgia, resulting in the need for innovative and cost-effective strategies for testing. Our objective was to investigate the most cost-effective testing pathways for scaling-up HCV testing in Georgia. We developed a Markov-based model with a lifetime horizon that simulates the natural history of HCV, and the cost of detection and treatment of HCV. We then created an interactive online tool that uses results from the Markov-based model to evaluate the cost-effectiveness of different HCV testing pathways. We compared the current standard-of-care (SoC) testing pathway and four innovative testing pathways for Georgia. The SoC testing was cost-saving compared to no testing, but all four new HCV testing pathways further increased QALYs and decreased costs. The pathway with the highest patient follow-up, due to on-site testing, resulted in the highest discounted QALYs (123 QALY more than the SoC) and lowest costs ($127,052 less than the SoC) per 10,000 persons screened. The current testing algorithm in Georgia can be replaced with a new pathway that is more effective while being cost-saving.


Assuntos
Hepatite C/diagnóstico , Adulto , Antivirais/uso terapêutico , Análise Custo-Benefício , Feminino , República da Geórgia/epidemiologia , Hepacivirus/isolamento & purificação , Hepatite C/tratamento farmacológico , Hepatite C/economia , Hepatite C/epidemiologia , Humanos , Masculino , Cadeias de Markov , Programas de Rastreamento/economia , Técnicas Microbiológicas/economia , Anos de Vida Ajustados por Qualidade de Vida
9.
Indian J Gastroenterol ; 39(2): 161-164, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32372189

RESUMO

INTRODUCTION: Transmission of hepatitis E virus (HEV) through transfusion has been reported from countries where genotype 3 virus is predominant. Data from countries with predominantly genotype 1 HEV, such as India, are limited. We studied the risk of HEV transmission following transfusion of blood or blood components in India. METHODS: Adult patients undergoing cardiac surgery who received transfusion of blood or blood products in the peri-operative period and who lacked history of any transfusion or surgery in the preceding 1 year were studied. A pre-transfusion blood specimen was collected for IgG anti-HEV antibody test. For the participants who were seronegative for anti-HEV, follow up specimens were collected at every 2-3-month intervals for up to 6 months after surgery and were tested for IgM and IgG anti-HEV antibodies. RESULTS: Of the 335 participants originally enrolled, 191 (57%) could be followed up. Of them, 103 (53.9%) were seropositive for HEV IgG at baseline and were excluded. Of the remaining 88 participants (age 42 ± 14.1 years; 55 [63%] male), none reported hepatitis-like illness during the follow up period of 81 ± 23 days. Also, none of these 88 participants was found to have seroconversion to anti-HEV IgM or IgG positivity in the follow up specimens. CONCLUSION: Transfusion-mediated transmission of HEV was not observed in our cohort and may be infrequent in the Indian population, where genotype 1 is the predominant HEV type.


Assuntos
Transfusão de Sangue , Hepatite E/etiologia , Hepatite E/transmissão , Resultados Negativos , Reação Transfusional/virologia , Adulto , Anticorpos Antivirais/sangue , Biomarcadores/sangue , Procedimentos Cirúrgicos Cardíacos , Estudos de Coortes , Feminino , Seguimentos , Hepatite E/diagnóstico , Hepatite E/epidemiologia , Vírus da Hepatite E/imunologia , Humanos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Índia/epidemiologia , Masculino , Pessoa de Meia-Idade , Período Perioperatório , Risco
10.
J Clin Exp Hepatol ; 10(1): 43-80, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32025166

RESUMO

Hepatocellular carcinoma (HCC) is one of the major causes of morbidity, mortality, and healthcare expenditure in patients with chronic liver disease in India. The Indian National Association for Study of the Liver (INASL) had published its first guidelines on diagnosis and management of HCC (The Puri Recommendations) in 2014, and these guidelines were very well received by the healthcare community involved in diagnosis and management of HCC in India and neighboring countries. However, since 2014, many new developments have taken place in the field of HCC diagnosis and management, hence INASL endeavored to update its 2014 consensus guidelines. A new Task Force on HCC was constituted that reviewed the previous guidelines as well as the recent developments in various aspects of HCC that needed to be incorporated in the new guidelines. A 2-day round table discussion was held on 5th and 6th May 2018 at Puri, Odisha, to discuss, debate, and finalize the revised consensus statements. Each statement of the guideline was graded according to the Grading of Recommendations Assessment Development and Evaluation system with minor modifications. We present here the 2019 Update of INASL Consensus on Prevention, Diagnosis, and Management of Hepatocellular Carcinoma in India: The Puri-2 Recommendations.

11.
Lancet Gastroenterol Hepatol ; 5(2): 167-228, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31852635

RESUMO

The Asia-Pacific region is home to more than half of the global population and accounted for 62·6% of global deaths due to liver diseases in 2015. 54·3% of global deaths due to cirrhosis, 72·7% of global deaths due to hepatocellular carcinoma, and more than two-thirds of the global burden of acute viral hepatitis occurred in this region in 2015. Chronic hepatitis B virus (HBV) infection caused more than half of the deaths due to cirrhosis in the region, followed by alcohol consumption (20·8%), non-alcoholic fatty liver disease (NAFLD; 12·1%), and chronic infection with hepatitis C virus (HCV; 15·7%). In 2015, HBV accounted for about half the cases of hepatocellular carcinoma in the region. Preventive strategies for viral hepatitis-related liver disease include increasing access to clean drinking water and sanitation. HBV vaccination programmes for neonates have been implemented by all countries, although birth-dose coverage is extremely suboptimal in some. Availability of screening tests for blood and tissue, donor recall policies, and harm reduction strategies are in their initial stages in most countries. Many governments have put HBV and HCV drugs on their essential medicines lists and the availability of generic versions of these drugs has reduced costs. Efforts to eliminate viral hepatitis as a public health threat, together with the rapid increase in per-capita alcohol consumption in countries and the epidemic of obesity, are expected to change the spectrum of liver diseases in the Asia-Pacific region in the near future. The increasing burden of alcohol-related liver diseases can be contained through government policies to limit consumption and promote less harmful patterns of alcohol use, which are in place in some countries but need to be enforced more strictly. Steps are needed to control obesity and NAFLD, including policies to promote healthy lifestyles and regulate the food industry. Inadequate infrastructure and insufficient health-care personnel trained in liver diseases are issues that also need to be addressed in the Asia-Pacific region. The policy response of most governments to liver diseases has thus far been inadequate and poorly funded. There must be a renewed focus on prevention, early detection, timely referral, and research into the best means to introduce and improve health interventions to reduce the burden of liver diseases in the Asia-Pacific region.


Assuntos
Gastroenterologia , Hepatopatias/epidemiologia , Publicações Periódicas como Assunto , Ásia/epidemiologia , Humanos , Morbidade/tendências , Ilhas do Pacífico/epidemiologia , Prognóstico , Taxa de Sobrevida/tendências
12.
J Virol ; 94(3)2020 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-31723027

RESUMO

To gain insight into the impact of mutations on the viability of the hepatitis C virus (HCV) genome, we created a set of full-genome mutant libraries, differing from the parent sequence as well as each other, by using a random mutagenesis approach; the proportion of mutations increased across these libraries with declining template amount or dATP concentration. The replication efficiencies of full-genome mutant libraries ranged between 71 and 329 focus-forming units (FFU) per 105 Huh7.5 cells. Mutant libraries with low proportions of mutations demonstrated low replication capabilities, whereas those with high proportions of mutations had their replication capabilities restored. Hepatoma cells transfected with selected mutant libraries, with low (4 mutations per 10,000 bp copied), moderate (33 mutations), and high (66 mutations) proportions of mutations, and their progeny were subjected to serial passage. Predominant virus variants (mutants) from these mutant libraries (Mutantl, Mutantm, and Mutanth, respectively) were evaluated for changes in growth kinetics and particle-to-FFU unit ratio, virus protein expression, and modulation of host cell protein synthesis. Mutantm and Mutantl variants produced >3.0-log-higher extracellular progeny per ml than the parent, and Mutanth produced progeny at a rate 1.0-log lower. More than 80% of the mutations were in a nonstructural part of the mutant genomes, the majority were nonsynonymous, and a moderate to large proportion were in the conserved regions. Our results suggest that the HCV genome has the ability to overcome lethal/deleterious mutations because of the high reproduction rate but highly selects for random, beneficial mutations.IMPORTANCE Hepatitis C virus (HCV) in vivo displays high genetic heterogeneity, which is partly due to the high reproduction and random substitutions during error-prone genome replication. It is difficult to introduce random substitutions in vitro because of limitations in inducing mutagenesis from the 5' end to the 3' end of the genome. Our study has overcome this limitation. We synthesized full-length genomes with few to several random mutations in the background of an HCV clone that can recapitulate all steps of the life cycle. Our study provides evidence of the capability of the HCV genome to overcome deleterious mutations and remain viable. Mutants that emerged from the libraries had diverse phenotype profiles compared to the parent, and putative adaptive mutations mapped to segments of the conserved nonstructural genome. We demonstrate the potential utility of our system for the study of sequence variation that ensures the survival and adaptation of HCV.


Assuntos
Genoma Viral , Hepacivirus/genética , Mutagênese , Mutação , Linhagem Celular , Humanos , Modelos Moleculares , Fenótipo , Inoculações Seriadas , Proteínas não Estruturais Virais/química , Proteínas não Estruturais Virais/genética , Proteínas Virais/química , Proteínas Virais/genética , Replicação Viral
13.
Indian J Gastroenterol ; 37(6): 492-503, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30560540

RESUMO

Hepatitis C virus (HCV) is a parenterally-transmitted hepatotropic virus that often causes chronic infection, which can progress to cirrhosis and hepatocellular carcinoma. Development of highly effective direct-acting anti-viral agents (DAAs) has led to a paradigm change in the treatment of HCV infection over the last 4-5 years. Patients with chronic kidney disease (CKD) are at a higher risk of acquiring HCV infection. In these patients, diagnosis of HCV infection, assessment of the consequent liver disease and management of HCV infection pose some specific problems. This article reviews the available recent information on HCV infection and CKD, including the association between these conditions and their effect on each other, and prevention, evaluation, and management of HCV infection in persons with CKD. This review looks at this issue particularly from the perspective of readers in Asia, especially India, since the epidemiology of HCV-CKD association and the repertoire of anti-HCV drugs available in this region differ from those elsewhere.


Assuntos
Hepatite C , Insuficiência Renal Crônica , Antivirais/uso terapêutico , Ásia/epidemiologia , Hepatite C/tratamento farmacológico , Hepatite C/epidemiologia , Hepatite C/prevenção & controle , Hepatite C/transmissão , Humanos , Prevalência , Diálise Renal , Risco
14.
J Clin Exp Hepatol ; 8(4): 403-431, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30568345

RESUMO

Hepatitis B Virus (HBV) reactivation in patients receiving chemotherapy, biologicals, immunosupressants, or corticosteroids is emerging to be an important cause of morbidity and mortality in patients with current or prior exposure to HBV infection. These patients suffer a dual onslaught of illness: one from the primary disease for which they are receiving the culprit drug that led to HBV reactivation, and the other from HBV reactivation itself. The HBV reactivation not only leads to a compromised liver function, which may culminate into hepatic failure; it also adversely impacts the treatment outcome of the primary illness. Hence, identification of patients at risk of reactivation before starting these drugs, and starting treatment aimed at prevention of HBV reactivation is the best strategy of managing these patients. There are no Indian guidelines on management of HBV infection in patients receiving chemotherapy, biologicals, immunosupressants, or corticosteroids for the treatment of rheumatologic conditions, malignancies, inflammatory bowel disease, dermatologic conditions, or solid-organ or bone marrow transplantation. The Indian National Association for Study of the Liver (INASL) had set up a taskforce on HBV in 2016, with a mandate to develop consensus guidelines for management of various aspects of HBV infection, relevant to India. In 2017 the taskforce had published the first INASL guidelines on management of HBV infection in India. In the present guidelines, which are in continuation with the previous guidelines, the issues on management of HBV infection in patients receiving chemotherapy, biologicals, immunosupressants, or corticosteroids are addressed.

15.
Virus Res ; 258: 1-8, 2018 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-30253192

RESUMO

Cellular miRNAs influence Hepatitis C virus (HCV) infection in multiple ways. In this study, we demonstrate that miR-125b-5p is upregulated in HCV infected patient serum samples as well as in HCV infected liver carcinoma cells and is involved in translational regulation of one of its predicted targets, Human antigen R (HuR). We used miRNA mimics and antagomiRs to confirm that HuR is a bonafide miR-125b target. Previously, we have shown that HuR is a positive regulator of HCV replication, whereas we noticed that miR-125b is a negative regulator of HCV infection. As a connecting link between these two observations, we showed that knockdown of miR-125b-5p increased HuR protein levels and rescued HCV replication when the availability of HuR in the cytoplasm was compromised using siRNAs against HuR or an inhibitor of HuR export to the cytoplasm. Overall, the study sheds light on the ability of host cell to use a miRNA as a tool to control virus propagation.


Assuntos
Proteína Semelhante a ELAV 1/genética , Hepacivirus/fisiologia , Interações Hospedeiro-Patógeno/genética , MicroRNAs/genética , RNA Mensageiro/genética , Replicação Viral , Adulto , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/virologia , Linhagem Celular Tumoral , Proteína Semelhante a ELAV 1/metabolismo , Exossomos/genética , Feminino , Perfilação da Expressão Gênica , Técnicas de Silenciamento de Genes , Hepacivirus/genética , Hepatite C/sangue , Hepatite C/virologia , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/virologia , Masculino , MicroRNAs/metabolismo , Pessoa de Meia-Idade , RNA Mensageiro/metabolismo , RNA Interferente Pequeno , Regulação para Cima
17.
Endosc Int Open ; 6(7): E821-E825, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29978000

RESUMO

BACKGROUND AND STUDY AIMS: Pseudoaneurysm most commonly involves the splenic artery and is conventionally treated with angioembolization or surgery. Herein we describe six patients with splenic artery pseudoaneurysm who were treated using a new technique of endoscopic ultrasound (EUS)-guided glue and coil injection. PATIENTS AND METHODS: Six patients (median age 36.7, range: 19 - 60, M: F = 5:1) with splenic artery pseudoaneurysm who had failed angiographic embolization underwent EUS-guided transgastric injection of coil and glue injection between July 2016 and September 2017. RESULTS: The diameter of the splenic artery pseudoaneurysms varied from 2.5 cm to 6.5 cm . The size (8, 14 and 16 mm) and number (1 to 5) of coils and amount of glue (1 - 2 mL) injected all were greater in larger aneurysm. All six patients had complete occlusion of the pseudoaneurysm as determined by using computed tomography at 4 weeks and EUS at 12 weeks. No complication was encountered. CONCLUSION: EUS-guided coil and glue injection for obliteration of splenic artery pseudoaneurysm is a feasible, highly effective and safe technique.

18.
Perspect Clin Res ; 9(2): 99-102, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29862204

RESUMO

Diagnostic tests are used to identify subjects with and without disease. In a previous article in this series, we examined some attributes of diagnostic tests - sensitivity, specificity, and predictive values. In this second article, we look at likelihood ratios, which are useful for the interpretation of diagnostic test results in everyday clinical practice.

19.
J Clin Exp Hepatol ; 8(1): 58-80, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29743798

RESUMO

Hepatitis B Virus (HBV) infection is one of the major causes of morbidity, mortality and healthcare expenditure in India. There are no Indian consensus guidelines on prevention, diagnosis and management of HBV infection. The Indian National Association for Study of the Liver (INASL) set up a taskforce on HBV in 2016, with a mandate to develop consensus guidelines for diagnosis and management of HBV infection, relevant to disease patterns and clinical practices in India. The taskforce first identified contentious issues on various aspects of HBV management, which were allotted to individual members of the taskforce who reviewed them in detail. A 2-day round table discussion was held on 11th and 12th February 2017 at Port Blair, Andaman & Nicobar Islands, to discuss, debate, and finalize the consensus statements. The members of the taskforce reviewed and discussed the existing literature threadbare at this meeting and formulated the 'INASL position statements' on each of the issues. The evidence and recommendations in these guidelines have been graded according to the Grading of Recommendations Assessment Development and Evaluation (GRADE) system with minor modifications. The strength of recommendations (strong: 1, weak: 2) thus reflects the quality (grade) of underlying evidence (A, B, C, D). We present here the INASL position statements on prevention, diagnosis and management of HBV in India.

20.
Endosc Int Open ; 6(1): E67-E72, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29344562

RESUMO

BACKGROUND AND STUDY AIMS: Endoscopic ultrasound-guided choledochoduodenostomy (EUS-CDS) is an alternative to percutaneous transhepatic biliary drainage (PTBD) for patients with malignant distal biliary obstruction in whom ERCP has failed. We studied technical success, clinical success, stent patency rate and occurrence of adverse events in patients undergoing EUS-CDS with partially-covered self-expanding metal stent (PCSEMS). PATIENTS AND METHODS: Medical records of consecutive patients with unresectable malignant distal biliary obstruction requiring biliary drainage who underwent EUS-CDS because of failure of attempt at ERCP were reviewed. EUS-CDS was done using 6-cm, PCSEMS (Wallflex, Boston Scientific). Technical success, clinical success (more than 50 % reduction in total bilirubin at 2 weeks post-procedure), stent patency rate and adverse events (AEs) were assessed. Patients were followed up for 3 months post-procedure. RESULTS: Between January 2015 and December 2016, 30 patients underwent EUS-CDS, including 20 (67 %) with failed biliary cannulation and 10 (33 %) with duodenal stenosis. Technical success was achieved in 28 patients, all of whom also had clinical success. Median total serum bilirubin decreased from 20 mg/dL to 5 mg/dL at 2 weeks post-procedure. Three patients (10 %) had adverse events (bile leak, hemobilia, stent block in one patient each; no stent migration); none of these adverse events was major and all were managed successfully. There were no procedure-related deaths. Five patients died of disease progression in the 3-month period post-procedure, and the 3-month dysfunction-free stent patency rate was 83 %. CONCLUSION: EUS-CDS with a PCSEMS has a high technical and clinical success. Adverse events were infrequent, minor and could be managed easily.

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