Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 89
Filtrar
1.
Front Med (Lausanne) ; 8: 762291, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34869468

RESUMO

Background and Objective: An increase in the international normalized ratio (INR) is associated with increased mortality in patients with cirrhosis and other chronic liver diseases, while little is known about the quantitative relationship. This study aimed to investigate the quantitative relationship between the INR and short-term prognosis among patients hospitalized with cirrhosis or advanced fibrosis and to evaluate the role of the INR as a risk factor for short-term liver transplant (LT)-free mortality in these patients. Patients and Methods: This study prospectively analyzed multicenter cohorts established by the Chinese Acute-on-Chronic Liver Failure (CATCH-LIFE) study. Cox regression was used to describe the relationship between the INR and independent risk factors for short-term LT-free mortality. Forest plots were used in the subgroup analysis. Generalized additive models (GAMs) and splines were used to illustrate the quantitative curve relationship between the INR and the outcome and inflection point on the curve. Results: A total of 2,567 patients with cirrhosis and 924 patients with advanced fibrosis were included in the study. The 90-day LT-free mortality of patients with cirrhosis and advanced fibrosis was 16.7% (428/2,567) and 7.5% (69/924), respectively. In the multivariable Cox regression analysis, the increase in the INR was independently associated with the risk of 90-day LT-free mortality both in patients with cirrhosis (HR, 1.06; 95% CI, 1.04-1.07, p < 0.001) and in patients with advanced fibrosis (HR, 1.09; 95% CI, 1.06-1.12, p < 0.001). An INR of 1.6/1.7 was found to be the starting point of coagulation dysfunction with a rapid increase in mortality in patients with cirrhosis or in patients with advanced fibrosis, respectively. A 28-day LT-free mortality of 15% was associated with an INR value of 2.1 in both cirrhosis and advanced fibrosis patients. Conclusions: This study was the first to quantitatively describe the relationship between the INR and short-term LT-free mortality in patients with cirrhosis or advanced fibrosis. The starting points of INR indicating the rapid increase in mortality and the unified cutoff value of coagulation failure in cirrhosis and advanced fibrosis, will help clinicians accurately recognize early disease deterioration.

2.
J Vis Exp ; (176)2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34747404

RESUMO

CD4 T cells play important roles in the pathogenesis of chronic hepatitis B. As a versatile cell population, CD4 T cells have been classified as distinct functional subsets based on the cytokines they secreted: for example, IFN-γ for CD4 T helper 1 cells, IL-4 and IL-13 for CD4 T helper 2 cells, IL-21 for CD4 T follicular helper cells, and IL-17 for CD4 T helper 17 cells. Analysis of hepatitis B virus (HBV)-specific CD4 T cells based on cytokine secretion after HBV-derived peptides stimulation could provide information not only about the magnitude of HBV-specific CD4 T-cell response but also about the functional subsets of HBV-specific CD4 T cells. Novel approaches, such as transcriptomics and metabolomics analysis, could provide more detailed functional information about HBV-specific CD4 T cells. These approaches usually require isolation of viable HBV-specific CD4 T cells based on peptide-major histocompatibility complex-II multimers, while currently the information about HBV-specific CD4 T-cell epitopes is limited. Based on an HBV-derived peptide matrix, a method has been developed to evaluate HBV-specific CD4 T-cell responses and identify HBV-specific CD4 T-cell epitopes simultaneously using peripheral blood mononuclear cells samples from chronic HBV infection patients.

4.
EMBO Mol Med ; 13(11): e14563, 2021 11 08.
Artigo em Inglês | MEDLINE | ID: mdl-34585848

RESUMO

Semaphorin 7A (SEMA7A) is a membrane-bound protein that involves axon growth and other biological processes. SEMA7A mutations are associated with vertebral fracture and Kallmann syndrome. Here, we report a case with a mutation in SEMA7A that displays familial cholestasis. WGS reveals a SEMA7AR148W homozygous mutation in a female child with elevated levels of serum ALT, AST, and total bile acid (TBA) of unknown etiology. This patient also carried a SLC10A1S267F allele, but Slc10a1S267F homozygous mice exhibited normal liver function. Similar to the child, Sema7aR145W homozygous mice displayed elevated levels of serum ALT, AST, and TBA. Remarkably, liver histology and LC-MS/MS analyses exhibited hepatocyte hydropic degeneration and increased liver bile acid (BA) levels in Sema7aR145W homozygous mice. Further mechanistic studies demonstrated that Sema7aR145W mutation reduced the expression of canalicular membrane BA transporters, bile salt export pump (Bsep), and multidrug resistance-associated protein-2 (Mrp2), causing intrahepatic cholestasis in mice. Administration with ursodeoxycholic acid and a dietary supplement glutathione improved liver function in the child. Therefore, Sema7aR145W homozygous mutation causes intrahepatic cholestasis by reducing hepatic Bsep and Mrp2 expression.


Assuntos
Colestase Intra-Hepática , Colestase , Semaforinas , Transportadores de Cassetes de Ligação de ATP/genética , Animais , Antígenos CD , Colestase/genética , Colestase Intra-Hepática/genética , Cromatografia Líquida , Feminino , Humanos , Camundongos , Mutação , Transportadores de Ânions Orgânicos Dependentes de Sódio/genética , Semaforinas/genética , Simportadores/genética , Espectrometria de Massas em Tandem
5.
Front Med (Lausanne) ; 8: 729030, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34568387

RESUMO

Background: HBV-related acute-on-chronic liver failure (HBV-ACLF) has a high short-term mortality and urgently needs an early warning system with simplicity and high accuracy. Previous studies show that sex hormones play potential roles in the progression of HBV-related liver diseases. Aims: To explore the effect of testosterone and estradiol on the occurrence and prognosis of HBV-ACLF. Methods: A prospective cohort of 300 chronic hepatitis B (CHB) patients was enrolled among which 108 were diagnosed with HBV-ACLF at admission and 20 developed to HBV-ACLF during hospitalization. We compared the level of serum testosterone and estradiol of patients with varied ACLF background, disease severity and cirrhosis conditions and analyzed the predictive ability of short-term prognosis. A novel prognostic model involving testosterone was developed and further validated in the HBV-ACLF group. Results: The baseline estradiol level of HBV-ACLF group was significantly higher while testosterone was lower than that of non-ACLF group. The estradiol level increased while the testosterone level decreased as the number of organ failures increased. Testosterone had high accuracy in predicting the short-term mortality in HBV-ACLF (AUROC = 0.726) and estradiol did better in predicting the occurrence of ACLF during hospitalization (AUROC = 0.695). The novel prognostic model involving testosterone (TATIM model) was proved to have considerable prediction efficiency in HBV-ACLF cohort with or without cirrhosis. Conclusion: Testosterone could be utilized as short-term prognostic indicator for HBV-related ACLF and estradiol can help to predict its occurrence. TATIM model is a novel prognostic model for HBV-related ACLF with simplicity and good performance irrespectively of liver cirrhosis. Clinical Trial Registration Number: This study was based on a sub-cohort from the prospective multicenter cohort (NCT02457637).

6.
Front Med (Lausanne) ; 8: 726950, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34532334

RESUMO

Background: Patients with cirrhosis have an increased risk of short-term mortality, however, few studies quantify the association between neutrophil-to-lymphocyte ratio (NLR) and 90-day transplant-free mortality in cirrhotic patients. Methods: We prospectively analyzed 3,970 patients with chronic liver diseases from two multicenter cohorts in China (January 2015 to December 2016 and July 2018 to January 2019). Restricted cubic splines (RCS) were used to analyze the relation of NLR and all-causes 90-day transplant-free mortality in cirrhosis. Results: A total of 2,583 cirrhotic patients were enrolled in our study. Restricted cubic splines showed that the odds ratio (OR) of all causes 90-day transplant-free mortality started to increase rapidly until around NLR 6.5, and then was relatively flat (p for non-linearity <0.001). The risk of 90-day transplant-free mortality in cirrhotic patients with NLR < 6.5 increased with an increment of 23% for every unit increase in NLR (p < 0.001). The patients with NLR < 4.5 had the highest risk (OR: 2.34, 95% CI 1.66-3.28). In multivariable-adjusted stratified analyses, the increase in the incidence of 90-day transplant-free mortality with NLR increasing was consistent (OR >1.0) across all major prespecified subgroups, including infection group (OR: 1.04, 95% CI 1.00-1.09) and non-infection (OR: 1.06, 95% CI 1.02-1.11) group. The trends for NLR and numbers of patients with organ failure varied synchronously and were significantly increased with time from day 7 to day 28. Conclusions: We found a non-linear association between baseline NLR and the adjusted probability of 90-day transplant-free mortality. A certain range of NLR is closely associated with poor short-term prognosis in patients with cirrhosis.

7.
Microbiol Spectr ; 9(1): e0026121, 2021 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-34346744

RESUMO

The dynamics of quasispecies afford RNA viruses a great fitness on cell tropism and host range. To study the quasispecies features and the intra-host evolution of SARS-CoV-2, we collected nine confirmed patients and sequenced the haplotypes of spike gene using a single-molecule real-time platform. Fourteen samples were extracted from sputum, nasopharyngeal swabs, or stool, which in total produced 283,655 high-quality circular consensus sequences. We observed a stable quasispecies structure that one master mutant (mean abundance ∼0.70), followed by numerous minor mutants (mean abundance ∼1.21 × 10-3). Under high selective pressure, minor mutants may obtain a fitness advantage and become the master ones. The later predominant substitution D614G existed in the minor mutants of more than one early patient. An epidemic variant had a possibility to be independently originated from multiple hosts. The mutant spectrums covered ∼85% amino acid variations of public genomes (GISAID; frequency ≥ 0.1) and likely provided an advantage mutation pool for the current/future epidemic variants. Notably, 32 of 35 collected antibody escape substitutions were preexistent in the early quasispecies. Virus populations in different tissues/organs revealed potentially independent replications. The quasispecies complexity of sputum samples was significantly lower than that of nasopharyngeal swabs (P = 0.02). Evolution analysis revealed that three continuous S2 domains (HR1, CH, and CD) had undergone a positive selection. Cell fusion-related domains may play a crucial role in adapting to the intrahost immune system. Our findings suggested that future epidemiologic investigations and clinical interventions should consider the quasispecies information that has missed by routine single consensus genome. IMPORTANCE RNA virus population in a host does not consist of a consensus single haplotype but rather an ensemble of related sequences termed quasispecies. The dynamics of quasispecies afford SARS-CoV-2 a great ability on genetic fitness during intrahost evolution. The process is likely achieved by changing the genetic characteristics of key functional genes, such as the spike glycoprotein. Previous studies have applied the next-generation sequencing (NGS) technology to evaluate the quasispecies of SARS-CoV-2, and results indicated a low genetic diversity of the spike gene. However, the NGS platform cannot directly obtain the full haplotypes without assembling, and it is also difficult to predict the extremely low-frequency variations. Therefore, we introduced a single-molecule real-time technology to directly obtain the haplotypes of the RNA population and further study the quasispecies features and intrahost evolution of the spike gene.


Assuntos
Epidemias , Mutação , Quase-Espécies , SARS-CoV-2/classificação , SARS-CoV-2/genética , Adulto , Idoso , Sequência de Bases , COVID-19/virologia , Criança , Feminino , Genoma Viral , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Pessoa de Meia-Idade , Glicoproteína da Espícula de Coronavírus/genética
8.
Ann Palliat Med ; 10(9): 9342-9353, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34412498

RESUMO

BACKGROUND: Chronic liver diseases (CLD), including cirrhosis and non-cirrhotic liver diseases, are globally widespread and create a serious disease burden. Platelet count is a clinically accessible and affordable prognostic indicator of liver disease. We investigated the relationship between platelet count and 90-day prognosis in patients with acute-on-chronic liver diseases (AoCLD). METHODS: A total of 3,970 patients with AoCLD from the Chinese Acute-on-Chronic Liver Failure (CATCH-LIFE) study, which included two prospective multi-center cohorts, were included in the study. We grouped the patients according to the platelet count and analyzed the 90-day adverse outcome (death or liver transplantation). RESULTS: In the final analysis, 3,939 patients with AoCLD were included, of whom 2,802 had definite liver cirrhosis. The cumulative incidence of 90-day adverse outcomes in patients increased with the change of platelet group (log-rank P<0.001). From univariate and multivariate analyses, platelet count was inversely associated with the incidence of 90-day adverse outcomes in patients (P for trend <0.001). The group with platelet count <20×109/L had the highest risk (odds ratio, 3.15; 95% confidence interval, 1.59-6.25), with 21 (36.8%) of these patients having adverse outcomes within 90 days. The risk of a 90-day adverse outcome in patients increased by 5% for every 10×109/L decrease in platelet count below 210×109/L. CONCLUSIONS: Lower platelet count was associated with a higher incidence of 90-day adverse outcomes in patients with AoCLD. Even within the normal platelet count range, the risk of a 90-day adverse outcome in patients increased with decreases in platelet count. TRIAL REGISTRATION: NCT02457637, NCT03641872.


Assuntos
Hepatopatias , Transplante de Fígado , Humanos , Hepatopatias/etiologia , Contagem de Plaquetas , Prognóstico , Estudos Prospectivos
9.
Front Med (Lausanne) ; 8: 709884, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34409052

RESUMO

Importance: Hepatic encephalopathy is a severe complication, and its contribution to clinical adverse outcomes in patients with acute-on-chronic liver diseases from the East is unclear. Objective: We aimed to investigate the impact of hepatic encephalopathy on clinical characteristics and adverse outcomes in prospective and multicenter cohorts of patients with acute-on-chronic liver diseases. Design: We conducted a cohort study of two multicenter prospective cohorts. Setting: China. Participants: Acute-on-chronic liver disease patients with various etiologies. Exposure: The diagnosis and severity of hepatic encephalopathy were assessed using the West Haven scale. Main Outcome Measure: The correlation between clinical adverse outcomes and varying hepatic encephalopathy grades was analyzed in the target patients. Results: A total of 3,949 patients were included, and 340 of them had hepatic encephalopathy. The incidence of hepatic encephalopathy was higher in patients with alcohol consumption (9.90%) than in those with hepatitis B virus infection (6.17%). The incidence of 28- and 90-day adverse outcomes increased progressively from hepatic encephalopathy grades 1-4. Logistic regression analysis revealed that hepatic encephalopathy grades 3 and 4 were independent risk factors for the 28- and 90-day adverse outcome in the fully adjusted model IV. Stratified analyses showed similar results in the different subgroups. Compared to grades 1-2 and patients without hepatic encephalopathy, those with grade 3 hepatic encephalopathy had a significant increase in clinical adverse outcomes, independent of other organ failures. Conclusions and Relevance: Hepatic encephalopathy grades 3-4 were independent risk factors for 28- and 90-day adverse outcomes. Hepatic encephalopathy grade 3 could be used as an indicator of brain failure in patients with acute-on-chronic liver disease.

10.
Front Med (Lausanne) ; 8: 704452, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34249983

RESUMO

Introduction: Total bilirubin (TB) is a major prognosis predictor representing liver failure in patients with acute on chronic liver failure (ACLF). However, the cutoff value of TB for liver failure and whether the same cutoff could be applied in both cirrhotic and non-cirrhotic patients remain controversial. There is a need to obtain the quantitative correlation between TB and short-term mortality via evidence-based methods, which is critical in establishing solid ACLF diagnostic criteria. Methods: Patients hospitalized with cirrhosis or advanced fibrosis (FIB-4 > 1.45) were studied. TB and other variables were measured at baseline. The primary outcome was 90-day transplantation-free mortality. Multi-variable Cox proportional hazard model was used to present the independent risk of mortality due to TB. Generalized additive model and second derivate (acceleration) were used to plot the "TB-mortality correlation curves." The mathematical (maximum acceleration) and clinical (adjusted 28-day transplantation-free mortality rate reaching 15%) TB cutoffs for liver failure were both calculated. Results: Among the 3,532 included patients, the number of patients with cirrhosis and advanced fibrosis were 2,592 and 940, respectively, of which cumulative 90-day mortality were 16.6% (430/2592) and 7.4% (70/940), respectively. Any increase of TB was found the independent risk factor of mortality in cirrhotic patients, while only TB >12 mg/dL independently increased the risk of mortality in patients with advanced fibrosis. In cirrhotic patients, the mathematical TB cutoff for liver failure is 14.2 mg/dL, with 23.3% (605/2592) patients exceeding it, corresponding to 13.3 and 25.0% adjusted 28- and 90-day mortality rate, respectively. The clinical TB cutoff for is 18.1 mg/dL, with 18.2% (471/2592) patients exceeding it. In patients with advanced fibrosis, the mathematical TB cutoff is 12.1 mg/dL, 33.1% (311/940) patients exceeding it, corresponding to 2.9 and 8.0% adjusted 28- and 90-day mortality rate, respectively; the clinical TB cutoff was 36.0 mg/dL, 1.3% (12/940) patients above it. Conclusion: This study clearly demonstrated the significantly different impact of TB on 90-day mortality in patients with cirrhosis and advanced fibrosis, proving that liver failure can be determined by TB alone in cirrhosis but not in advanced fibrosis. The proposed TB cutoffs for liver failure provides solid support for the establishment of ACLF diagnostic criteria.

11.
Ann Transl Med ; 9(12): 992, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34277792

RESUMO

Background: This study aimed to investigate the clinicopathological significance of sine oculis homeobox homolog 1 (SIX1) and eyes absent 1 (EYA1) in patients with chronic hepatitis B (CHB) and other liver diseases. Methods: SIX1 and EYA1 levels were detected in human serum and liver tissues by enzyme linked immunosorbent assay (ELISA) and immunofluorescent staining method, respectively. Results: The serum SIX1 and EYA1 levels in 313 CHB patients were 7.24±0.11 and 25.21±0.51 ng/mL, respectively, and these values were significantly higher than those in 33 healthy controls (2.84±0.15 and 13.11±1.01 ng/mL, respectively; P<0.05). Serum SIX1 and EYA1 levels were also markedly increased in patients with numerous other liver diseases, including liver fibrosis, hepatocellular carcinoma, fatty liver disease, alcoholic liver disease, fulminant hepatic failure, autoimmune liver disease, and hepatitis C, compared to the healthy controls (P<0.05). Dynamic observation of these proteins over time in 35 selected CHB patients revealed that SIX1 and EYA1 serum levels increased over an interval. Immunofluorescent staining revealed that both SIX1 and EYA1 were only expressed in hepatic stellate cells (HSCs), and their increased expression was evident in CHB liver tissue. Conclusions: SIX1 and EYA1 are novel biomarkers of liver damage in patients of CHB and other liver diseases, with potential clinical utility.

12.
Front Immunol ; 12: 640335, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34113340

RESUMO

Background: Studies have shown that autoimmune response contributes to chronic hepatitis B (CHB) development. Aim: This study aimed to identify autoantibodies in the sera of patients with CHB and to investigate the association of autoimmune response with disease severity in CHB. Methods: Proteins from human liver carcinoma cell line HepG2 were separated by two-dimensional electrophoresis. The candidate autoantigens were recognized by serum autoantibodies from Chinese CHB patients. Immunohistochemical staining was performed to determine the hepatic expression of the autoantigen in CHB patients with different inflammatory grades. Enzyme-linked immunosorbent assay (ELISA) was conducted to measure the prevalence and the levels of serum autoantibody in CHB patients with different disease severity. Flow cytometry analysis was carried out to assess the autoreactive T cell response in the peripheral circulation of CHB patients. Results: ErbB-3-binding protein-1 (EBP-1) was identified as an autoantigen of serum autoantibodies in CBP patients. EBP-1 protein expression was upregulated in the liver of CHB patients with high-grade hepatic inflammation. The prevalence and levels of serum anti-EBP1 IgG were significantly increased in CHB patients with severe diseases compared with those with mild or moderate diseases, but none was detectable in the healthy controls. EBP-1 peptides induced proinflammatory cytokine expression in CD4+ T cells from CHB patients. Conclusion: Our results demonstrate the presence of an autoantibody against EBP-1 in the sera as well as EBP-1-reactive T cells in the peripheral blood of CHB patient. EBP-1-induced autoimmune response is positively associated with the disease severity, suggesting that EBP-1-induced autoimmune response possibly contributes to progressive liver failure.


Assuntos
Autoanticorpos/imunologia , Autoantígenos/imunologia , Hepatite B Crônica/imunologia , Adolescente , Adulto , Idoso , Autoanticorpos/sangue , Feminino , Hepatite B Crônica/sangue , Humanos , Queratina-20/imunologia , Masculino , Pessoa de Meia-Idade , Linfócitos T/imunologia , Adulto Jovem
13.
Clin Cancer Res ; 27(13): 3772-3783, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-33947693

RESUMO

PURPOSE: Intratumoral hepatitis B virus (HBV) integrations and mutations are related to hepatocellular carcinoma (HCC) progression. Circulating cell-free DNA (cfDNA) has shown itself as a powerful noninvasive biomarker for cancer. However, the HBV integration and mutation landscape on cfDNA remains unclear. EXPERIMENTAL DESIGN: A cSMART (Circulating Single-Molecule Amplification and Resequencing Technology)-based method (SIM) was developed to simultaneously investigate HBV integration and mutation landscapes on cfDNA with HBV-specific primers covering the whole HBV genome. Patients with HCC (n = 481) and liver cirrhosis (LC; n = 517) were recruited in the study. RESULTS: A total of 6,861 integration breakpoints including TERT and KMT2B were discovered in HCC cfDNA, more than in LC. The concentration of circulating tumor DNA (ctDNA) was positively correlated with the detection rate of these integration hotspots and total HBV integration events in cfDNA. To track the origin of HBV integrations in cfDNA, whole-genome sequencing (WGS) was performed on their paired tumor tissues. The paired comparison of WGS data from tumor tissues and SIM data from cfDNA confirmed most recurrent integration events in cfDNA originated from tumor tissue. The mutational landscape across the whole HBV genome was first generated for both HBV genotype C and B. A region from nt1100 to nt1500 containing multiple HCC risk mutation sites (OR > 1) was identified as a potential HCC-related mutational hot zone. CONCLUSIONS: Our study provides an in-depth delineation of HBV integration/mutation landscapes at cfDNA level and did a comparative analysis with their paired tissues. These findings shed light on the possibilities of noninvasive detection of virus insertion/mutation.

14.
Cell ; 184(7): 1895-1913.e19, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33657410

RESUMO

A dysfunctional immune response in coronavirus disease 2019 (COVID-19) patients is a recurrent theme impacting symptoms and mortality, yet a detailed understanding of pertinent immune cells is not complete. We applied single-cell RNA sequencing to 284 samples from 196 COVID-19 patients and controls and created a comprehensive immune landscape with 1.46 million cells. The large dataset enabled us to identify that different peripheral immune subtype changes are associated with distinct clinical features, including age, sex, severity, and disease stages of COVID-19. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA was found in diverse epithelial and immune cell types, accompanied by dramatic transcriptomic changes within virus-positive cells. Systemic upregulation of S100A8/A9, mainly by megakaryocytes and monocytes in the peripheral blood, may contribute to the cytokine storms frequently observed in severe patients. Our data provide a rich resource for understanding the pathogenesis of and developing effective therapeutic strategies for COVID-19.


Assuntos
COVID-19/imunologia , Megacariócitos/imunologia , Monócitos/imunologia , RNA Viral , SARS-CoV-2/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , China , Estudos de Coortes , Citocinas/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , RNA Viral/sangue , RNA Viral/isolamento & purificação , Análise de Célula Única , Transcriptoma/imunologia , Adulto Jovem
15.
BMJ Open ; 11(1): e037793, 2021 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-33419900

RESUMO

PURPOSE: Acute-on-chronic liver failure (ACLF) is a clinical syndrome with high short-term mortality, unclear mechanism and controversial diagnosis criteria. The Chinese Acute-on-Chronic Liver Failure (CATCH-LIFE) study has been conducted in China to fill the gaps. In the first phase (the CATCH-LIFE investigation cohort), 2600 patients were continuously recruited from 14 national nationwide liver centres from 12 different provinces of China in 2015-2016, and a series of important results were obtained. To validate the preliminary results, we designed and conducted this multicentre prospective observational cohort (the CATCH-LIFE validation cohort). PARTICIPANTS: Patients diagnosed with chronic liver disease and hospitalised for acute decompensation (AD) or acute liver injure were enrolled, received standard medical therapy. We collected the participants' demographics, medical history, laboratory data, and blood and urine samples during their hospitalisation. FINDINGS TO DATE: From September 2018 to March 2019, 1370 patients (73.4% men) aged from 15 to 79 years old were enrolled from 13 nationwide liver centres across China. Of these patients, 952 (69.5%) had chronic hepatitis B, 973 (71.1%) had cirrhosis and 1083 (79.1%) complicated with AD at admission. The numbers and proportions of enrolled patients from each participating centre and the patients' baseline characteristics are presented. FUTURE PLANS: A total of 12 months is required for each participant to complete follow-up. Outcome information (survival, death or receiving liver transplantation) collection and data cleansing will be done before June 2020. The data in the CATCH-LIFE validation cohort will be used for comparison between the new ACLF diagnostic criteria derivated from the CATCH-LIFE investigation cohort with existing ones. Moreover, future proteomic and metabolic omics analyses will provide valuable insights into the mechanics of ACLF, which will promote the development of specific therapy that leads to decrease patients' mortality. REGISTRATION: NCT03641872.


Assuntos
Insuficiência Hepática Crônica Agudizada , Adolescente , Adulto , Idoso , China/epidemiologia , Feminino , Humanos , Cirrose Hepática , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Proteômica , Adulto Jovem
16.
Virology ; 553: 131-134, 2021 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-33276282

RESUMO

In patients coinfected with SARS-CoV-2 and HBV, liver injury was common. However, the interactions between SARS-CoV-2 and HBV coinfection remained unknown. Sixty-seven COVID-19 patients from the previous cohort were enrolled and classified into 2 groups (7 with HBsAg+ and 60 with HBsAg-). The association of HBV- and SARS-CoV-2-related markers were analyzed. During the acute course of SARS-CoV-2 infection, markers of HBV replication did not extensively fluctuate during SARS-CoV-2 infection. Coinfection with HBV did not extend the viral shedding cycle or incubation periods of SARS-CoV-2. Effects of SARS-CoV-2 on the dynamics of chronic HBV infection seemed not apparent. SARS-CoV-2 infection would not be the source of HBV reactivation in these individuals.


Assuntos
COVID-19/virologia , Coinfecção/virologia , Hepatite B Crônica/virologia , SARS-CoV-2 , Adulto , Idoso , COVID-19/tratamento farmacológico , Coinfecção/tratamento farmacológico , Feminino , Hepatite B Crônica/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Ativação Viral , Eliminação de Partículas Virais
17.
Clin Microbiol Infect ; 27(2): 289.e1-289.e4, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33031947

RESUMO

OBJECTIVES: Rapid, reliable and easy-to-implement diagnostics that can be adapted in early severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) diagnosis are critical to combat the epidemic. SARS-CoV-2 nucleocapsid protein (NP) is an ideal target for viral antigen-based detection. A rapid and convenient method was developed based on fluorescence immunochromatographic (FIC) assay to detect the SARS-CoV-2 NP antigen. However, the accuracy of this diagnostic method needs to be examined. METHODS: This prospective study was carried out between 10 and 15 February 2020 in seven hospitals in Wuhan and one hospital in Chongqing, China. Participants with clinically suspected SARS-CoV-2 infection were enrolled. NP antigen testing by FIC assay and nucleic acid (NA) testing by real-time reverse transcriptase PCR (RT-PCR) were performed simultaneously in a blinded manner with the same nasopharyngeal swab sample. The diagnostic accuracy of NP antigen testing was calculated by taking NA testing of RT-PCR as the reference standard, in which samples with a cycle threshold (Ct) value of ≤40 were interpreted as positive for SARS-CoV-2. RESULTS: A total of 253 participants were enrolled; two participants were excluded from the analyses because of invalid NP testing results. Of 251 participants (99.2%) included in the diagnostic accuracy analysis, 201 (80.1%) had a Ct value of ≤40. With Ct value 40 as the cutoff of NA testing, the sensitivity, specificity and percentage agreement of the FIC assay was 75.6% (95% confidence interval, 69.0-81.3), 100% (95% confidence interval, 91.1-100) and 80.5% (95% confidence interval, 75.1-84.9) respectively. CONCLUSIONS: With RT-PCR assay as the reference standard, NP antigen testing by FIC assay shows high specificity and relatively high sensitivity in SARS-CoV-2 diagnosis in the early phase of infection.


Assuntos
Antígenos Virais/análise , Teste para COVID-19/métodos , COVID-19/diagnóstico , Proteínas do Nucleocapsídeo de Coronavírus/análise , SARS-CoV-2/isolamento & purificação , Adolescente , Adulto , Idoso , Teste para COVID-19/normas , Feminino , Humanos , Imunoensaio , Masculino , Pessoa de Meia-Idade , Nasofaringe/virologia , Fosfoproteínas/análise , Estudos Prospectivos , RNA Viral/genética , SARS-CoV-2/genética , SARS-CoV-2/imunologia , Sensibilidade e Especificidade , Adulto Jovem
18.
BMC Med Genomics ; 13(1): 180, 2020 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-33261607

RESUMO

BACKGROUND: Host genetic factors such as single nucleotide variations may play a crucial role in the onset and progression of HBV-related acute-on-chronic liver failure (ACLF). However, the underlying genomic copy number variations (CNVs) involved in the pathology are currently unclear. METHODS: We genotyped two cohorts with 389 HBV-related ACLF patients and 391 asymptomatic HBV carriers (AsCs), and then carried out CNV-based global burden analysis and a genome-wide association study (GWAS). RESULTS: For 1874 rare CNVs, HBV-related ACLF patients exhibited a high burden of deletion segments with a size of 100-200 kb (P value = 0.04), and the related genes were significantly enriched in leukocyte transendothelial migration pathway (P value = 4.68 × 10-3). For 352 common CNVs, GWAS predicted 17 significant association signals, and the peak one was a duplication segment located on 1p36.13 (~ 38 Kb, P value = 1.99 × 10-4, OR = 2.66). The associated CNVs resulted in more copy number of pro-inflammatory genes (MST1L, DEFB, and HCG4B) in HBV-related ACLF patients than in AsC controls. CONCLUSIONS: Our results suggested that the impact of host CNV on HBV-related ACLF may be through decreasing natural immunity and enhancing host inflammatory response during HBV infection. The findings highlighted the potential importance of gene dosage on excessive hepatic inflammation of this disease.


Assuntos
Insuficiência Hepática Crônica Agudizada/genética , Variações do Número de Cópias de DNA , Hepatite B/genética , Inflamação/genética , Insuficiência Hepática Crônica Agudizada/etiologia , Infecções Assintomáticas , Dosagem de Genes , Duplicação Gênica , Ontologia Genética , Estudo de Associação Genômica Ampla , Hepatite B/complicações , Humanos , MicroRNAs/genética , Polimorfismo de Nucleotídeo Único , Deleção de Sequência , Transcriptoma
19.
Virulence ; 11(1): 1443-1452, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33108255

RESUMO

The diagnosed COVID-19 cases revealed that the incubation periods (IP) varied a lot among patients. However, few studies had emphasized on the different clinical features and prognosis of patients with different IP. A total of 330 patients with laboratory-confirmed COVID-19 were enrolled and classified into immediate onset group(IP<3 days, I group, 57 cases) and late onset group(IP>10 days, L group, 75 cases) based on IP. The difference of clinical characteristics and prognosis of the two groups were compared. There were more patients with fever in I group than in L group(P = 0.003), and counts of all the total lymphocytes, total T lymphocytes, CD4 + and CD8 + T lymphocytes were significantly different between the two groups(all P < 0.01). Besides, patients in L group had more GGOs in CT scan than I group and there were more patients in I group receiving antibiotic treatment than in L group(P < 0.001). For disease aggravation, the median CT scores were comparable between the two groups, but individually, there were more patients with increased CT score during hospitalization in I group than in L group. The aggravation incidence of CT presentation was 21.1% in I group, significantly higher than L group(8.0%, P = 0.042). Multivariable COX models suggested that IP was the only independent factors for CT aggravation. Conclusively, patients with different IP were different in clinical symptoms, laboratory tests, and CT presentations. Shorter IP was associated with the aggravation of lung involvement in CT scan.


Assuntos
Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/patologia , Período de Incubação de Doenças Infecciosas , Pneumonia Viral/epidemiologia , Pneumonia Viral/patologia , Adulto , Betacoronavirus/patogenicidade , COVID-19 , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/diagnóstico por imagem , Progressão da Doença , Feminino , Febre/epidemiologia , Febre/patologia , Hospitalização , Humanos , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/diagnóstico por imagem , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , SARS-CoV-2 , Tomografia Computadorizada por Raios X
20.
Drug Dev Res ; 2020 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-32657473

RESUMO

Faced with the current large-scale public health emergency, collecting, sorting, and analyzing biomedical information related to the "SARS-CoV-2" should be done as quickly as possible to gain a global perspective, which is a basic requirement for strengthening epidemic control capacity. However, for human researchers studying viruses and hosts, the vast amount of information available cannot be processed effectively and in a timely manner, particularly if our scientific understanding is also limited, which further lowers the information processing efficiency. We present TWIRLS (Topic-wise inference engine of massive biomedical literatures), a method that can deal with various scientific problems, such as liver cancer, acute myeloid leukemia, and so forth, which can automatically acquire, organize, and classify information. Additionally, this information can be combined with independent functional data sources to build an inference system via a machine-based approach, which can provide relevant knowledge to help human researchers quickly establish subject cognition and to make more effective decisions. Using TWIRLS, we automatically analyzed more than three million words in more than 14,000 literature articles in only 4 hr. We found that an important regulatory factor angiotensin-converting enzyme 2 (ACE2) may be involved in host pathological changes on binding to the coronavirus after infection. On triggering functional changes in ACE2/AT2R, the cytokine homeostasis regulation axis becomes imbalanced via the Renin-Angiotensin System and IP-10, leading to a cytokine storm. Through a preliminary analysis of blood indices of COVID-19 patients with a history of hypertension, we found that non-ARB (Angiotensin II receptor blockers) users had more symptoms of severe illness than ARB users. This suggests ARBs could potentially be used to treat acute lung injury caused by coronavirus infection.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...