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1.
Medicine (Baltimore) ; 99(1): e18462, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31895778

RESUMO

Proinflammatory interleukin-26 (IL-26) is involved in chronic inflammation; however, the role of IL-26 in chronic hepatitis B (CHB) remains unknown.In this study, serum IL-26 was quantified in a cohort of CHB patients at baseline and during telbivudine (LdT) treatment.Our results showed that the serum IL-26 level was significantly elevated in CHB patients compared with that in healthy controls and was time-dependently decreased during LdT treatment, accompanying hepatitis B e antigen (HBeAg) seroconversion and reduced serum levels of hepatitis B virus (HBV) DNA, aspartate transaminase, and alanine transaminase across baseline and treatment. In addition, the serum level of IL-26 exhibited a similar declining trend to that of T helper 17 (Th17) cell-secreted IL-17 during LdT treatment in CHB patients. The percentage of IL-26-expressing CD4 cells was significantly higher than that of IL-26-expressing CD4 cells isolated from the peripheral blood mononuclear cells of CHB patients, suggesting that serum IL-26 might be mainly released from CD4 T cells. Furthermore, the baseline mRNA levels of IL-26 and orphan nuclear receptor RORγt-an important transcription factor expressed by Th17 cells-were positively correlated and displayed the same declining trend across the baseline and LdT treatment in CHB patients, suggesting that Th17 cells could be a possible cellular source of the increased serum IL-26 in CHB patients.Taken together, our results suggest that serum IL-26, possibly produced by Th17 CD4 cells, is a novel and potential biomarker for CHB prognosis and treatment.


Assuntos
Vírus da Hepatite B/imunologia , Hepatite B Crônica/sangue , Hepatite B Crônica/imunologia , Interleucinas/sangue , Adulto , Antivirais/uso terapêutico , Linfócitos T CD4-Positivos/imunologia , Estudos de Casos e Controles , Ensaio de Imunoadsorção Enzimática , Feminino , Hepatite B Crônica/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Telbivudina/uso terapêutico , Células Th17/imunologia , Adulto Jovem
2.
Medicine (Baltimore) ; 98(52): e18527, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31876748

RESUMO

This study aim was to evaluate whether plasma D-dimer levels could serve as a novel prognostic biomarker for 1-month mortality in patients with HBV-related decompensated cirrhosis (HBV-DeCi).This was a retrospective study that enrolled 132 HBV-DeCi patients. Univariate and multivariate regression models were used to identify risk factors for mortality. The area under the receiver operating characteristic curve was calculated to estimate and compare the predictive values of different prognostic markers.In the present study, the plasma D-dimer levels were higher in the nonsurviving group than in the surviving group. Additionally, the D-dimer level was positively correlated with the model for end-stage liver disease (MELD) score. The results of multivariate analysis showed that both the MELD score and D-dimer level are independent predictors of 1-month mortality in HBV-DeCi patients (both P < .01).Plasma D-dimer can be considered a new additional prognostic marker for 1-month mortality in HBV-DeCi patients.


Assuntos
Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Hepatite B Crônica/mortalidade , Cirrose Hepática/mortalidade , Adulto , Idoso , Biomarcadores/sangue , Feminino , Hepatite B Crônica/sangue , Hepatite B Crônica/complicações , Hepatite B Crônica/diagnóstico , Humanos , Cirrose Hepática/sangue , Cirrose Hepática/diagnóstico , Cirrose Hepática/etiologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos
3.
Medicine (Baltimore) ; 98(50): e18319, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31852119

RESUMO

Gamma-glutamyl transpeptidase-to-platelet ratio (GPR) and fibrosis-4 (FIB-4) index have been reported to be useful predictors in predicting hepatocellular carcinoma (HCC) development in chronic hepatitis B (CHB) patients. However, their predictive performances on HCC development have not been validated in elderly patients. Thus, the aim of this study was to evaluate the predictive values of the GPR and FIB-4 index on HCC in elderly CHB patients with in China.Between January 2007 and December 2016, 1011 CHB patients older than 60 years were enrolled in the study, and their data were retrospectively analyzed. Receiver-operating characteristic (ROC) curve analysis was used to determine the optimal cutoff points of GPR and the FIB-4 index. Cumulative HCC incidence rates were calculated by the Kaplan-Meier method and compared by the log-rank test. Univariate and multivariate analyses were performed to detect risk factors for HCC development. The prediction performances of GPR and FIB-4 index were compared based on time-dependent ROC analyses.After a median follow-up of 6.8 (interquartile range 3.9-8.4) years, 39 (3.9%) patients developed HCC. The ROC analysis of GPR and the FIB-4 index at the 5-year time point revealed that the optimal cutoff point was 0.23 for GPR and 4.15 for the FIB-4 index. When stratified by low and high GPR values and FIB-4 indices, the patients' subgroups showed significantly different cumulative incidences of HCC. The multivariate analysis revealed that high GPR (hazard ratio [HR] 4.224; 95% confidence interval [CI] 1.891-9.434, P < .001) was an independent risk factor for HCC development, whereas a high FIB-4 index was not (HR 0.470; 95% CI 0.212-1.043; P = .063). In the time-dependent ROC analysis, GPR showed higher area under curve (AUC) values than the FIB-4 index did at all time points and reached statistical significance at the 5-, 7-, and 10-year time points (GPR vs FIB-4 index, AUC 0.725 vs 0.549 at 5 years, P = .005; GPR vs FIB-4 index, AUC 0.733 vs 0.578 at 7 years, P = .001; GPR vs FIB-4 index, AUC 0.837 vs 0.475 at 10 years, P < .001).In conclusion, our study suggests GPR is superior to the FIB-4 index in predicting HCC development in elderly CHB patients in China.


Assuntos
Carcinoma Hepatocelular/sangue , Vírus da Hepatite B , Hepatite B Crônica/complicações , Cirrose Hepática/sangue , Cirrose Hepática/complicações , Neoplasias Hepáticas/sangue , gama-Glutamiltransferase/sangue , Idoso , Biomarcadores Tumorais , Plaquetas/patologia , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/etiologia , China/epidemiologia , Feminino , Seguimentos , Hepatite B Crônica/sangue , Hepatite B Crônica/virologia , Humanos , Incidência , Cirrose Hepática/diagnóstico , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/etiologia , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Curva ROC , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo
4.
Klin Lab Diagn ; 64(10): 588-593, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31742950

RESUMO

At some works, it has been shown there are signs of damage and endothelium dysfunction in patients with chronic viral hepatitis (CVH) and liver cirrhosis of viral etiology the severity of these conditions depends on the severity of the pathological process. Evaluation of the role of angiogenic factors and endothelial dysfunction in persistent of CVH in children and adolescents. 35 patients were examined: of which 11 with chronic hepatitis B (CHB) and 24 with chronic hepatitis C (CHC). The reference group consisted of 120 practically healthy persons of the corresponding age and sex. VEGF-A, angiotensin (ANG), soluble receptors of VEGF-A (sVEGF-R1 и sVEGF-R2) and trombomodulin (TM) have been investigated in serum by enzyme immunoassay using special kits (BCM Diagnostics, USA). Other endothelial dysfunction markers as von Willebrand factor (vWf) was determined in blood plasma by immunoturbidimetry (Siemens, Germany), plasminogen (PLG) was investigated due to extended coagulation. In children with CVH, regardless of etiology, the concentration of VEGF-A was significantly lower, and sVEGF-R2, sVEGF-R1 and TM was higher than in children without liver disease (p <0.001, p <0.05, p <0.01, p <0.001, respectively). The concentration of TM and the level of PLG activity in patients with CHC were slightly higher than in CHB. Decreased level of VEGF-A and increased expression of its soluble receptors indicate enhanced inhibition of angiogenesis in CVH, which may indicate the pathogenetic role of this phenomenon in the development of liver damage in CHC.


Assuntos
Hepatite B Crônica/sangue , Hepatite C Crônica/sangue , Cirrose Hepática/virologia , Neovascularização Patológica/sangue , Adolescente , Angiotensinas/sangue , Biomarcadores/sangue , Criança , Humanos , Plasminogênio/análise , Trombomodulina/sangue , Fator A de Crescimento do Endotélio Vascular/sangue , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/sangue , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/sangue , Fator de von Willebrand/análise
5.
Klin Lab Diagn ; 64(10): 635-640, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31742959

RESUMO

To analyze the method for detecting HBV DNA in peripheral blood at low viral load and evaluate its significance in identifying HBsAg-negative viral hepatitis B. In this work, samples of blood and liver tissue biopsy material were used from 128 patients living in the Russian Federation and the Republic of Uzbekistan without CHB and with CHB confirmed detection of circle covalently closed HBV DNA in hepatocytes. Plasma viral load was measured using the «AmpliSens® HBV-Monitor-FL¼ kit. HBV at low viral load was detected by nested PCR. Analytical sensitivity was checked by step dilution. According to our method, at the first stage, an asymmetric PCR is carried out using extended oligonucleotide primers with different melting points, complementary to the hepatitis B different genotypes genomes greatest similarity region. To increase the sensitivity, a second PCR is performed using the first reaction amplification product and internal primers. The sensitivity of the method for DNA extraction from 100 µl of plasma was 5 IU / ml, specificity 100%. Since, in spite of the HBV genotypes characteristic geographical distribution, the detection of "alien" genovariants for certain territories is becoming more frequent, we tested the method in geographically remote but active international relations with the Russian Federation regions with a high frequency of hepatotropic viruses. The developed method for detecting HBV DNA in blood plasma at low viral load based on PCR technology allows the various HBV gene variants identification and genotyping, both characteristic and rare in the Russian Federation, circulating in other world regions. The method can be used to detect HBV in risk groups, in a population, as well as when screening blood donors in order to ensure the blood transfusions safety.


Assuntos
DNA Viral/sangue , Vírus da Hepatite B/isolamento & purificação , Hepatite B Crônica/sangue , Antígenos de Superfície da Hepatite B , Humanos , Reação em Cadeia da Polimerase , Federação Russa , Carga Viral
6.
Zhonghua Gan Zang Bing Za Zhi ; 27(9): 668-672, 2019 Sep 20.
Artigo em Chinês | MEDLINE | ID: mdl-31594089

RESUMO

Objective: To analyze serum HBV-RNA levels in patients with chronic hepatitis B whose serum HBV-DNA has dropped to undetected levels after treatment with entecavir, and to explore the correlation between HBV-RNA level and liver biochemical parameters, which lay the research foundation for the clinical significance of new serological marker HBV-RNA. Methods: HBeAg negatively detected 107 cases with chronic hepatitis B whose serum HBV-DNA test results were lower than detection level for six consecutive months after receiving standard nucleoside therapy for more than 12 months were included. HBV-RNA level was detected by Perkin-Elmer reagent. HBV-DNA level was detected by Roche Cobas. Hitachi automatic biochemical analyzer was used to detect ALT and AST. Architect chemiluminescence analyzer was used to detect HBsAg, HBeAg, anti-HBe and anti-HBc. RStudio software was performed to analyze the correlation between HBV-RNA level and liver biochemical parameters. Logistic regression was used to analyze the independent factors influencing HBV-RNA level. Results: The positive detection rate of serum HBV-RNA in patients with chronic hepatitis B whose serum HBV-DNA had dropped to undetected levels after ETV treatment was 22.43%. HBsAg, ALT and AST levels in HBV-RNA positive group were slightly higher than HBV-RNA negative group, while anti-HBc levels were slightly higher in HBV-RNA negative group. There was no difference in the level of anti-HBe between the HBV-RNA negative and the positive group. Logistic regression analysis showed that anti-HBc was an independent factor influencing the level of HBV-RNA detection (P = 0.021). Conclusion: HBV-RNA can be detected in some patients with chronic hepatitis B whose serum HBV-DNA level has dropped to undetected levels after ETV treatment. Serum HBV-RNA only comes from the direct transcription of cccDNA, so it is better than HBV-DNA and HBsAg to reflect cccDNA level or activity. Anti-HBc, as an independent factor influencing the level of HBV-RNA, may be used in combination as a new marker to predict the efficacy of antiviral therapy.


Assuntos
Hepatite B Crônica/diagnóstico , RNA Viral/sangue , DNA Viral/sangue , Anticorpos Anti-Hepatite/sangue , Antígenos de Superfície da Hepatite B/sangue , Antígenos E da Hepatite B/sangue , Vírus da Hepatite B , Hepatite B Crônica/sangue , Humanos
7.
Braz J Med Biol Res ; 52(10): e8845, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31576907

RESUMO

Regucalcin is a soluble protein that is principally expressed in hepatocytes. Studies of regucalcin have mainly been conducted in animals due to a lack of commercially available kits. We aimed to develop an enzyme-linked immunosorbent assay (ELISA) to quantify serum regucalcin in patients with hepatitis B virus (HBV)-related disease. High-titer monoclonal antibodies and a polyclonal antibody to regucalcin were produced, a double-antibody sandwich ELISA method was established, and serum regucalcin was determined in 47 chronic hepatitis B (CHB) patients, 91 HBV-related acute-on-chronic liver failure (HBV-ACLF) patients, and 33 healthy controls. The ELISA demonstrated an appropriate linear range, and high levels of reproducibility, sensitivity, specificity, accuracy, and stability. The median serum regucalcin concentrations in HBV-ACLF and CHB patients were 5.46 and 3.76 ng/mL, respectively (P<0.01), which were much higher than in healthy controls (1.72 ng/mL, both P<0.01). For the differentiation of CHB patients and healthy controls, the area under curve (AUC) was 0.86 with a cut-off of 2.42 ng/mL, 85.7% sensitivity, and 78.8% specificity. In contrast, the AUC of alanine aminotransferase (ALT) was lower (AUC=0.80, P=0.01). To differentiate ACLF from CHB, the AUC was 0.72 with a cut-off of 4.26 ng/mL, 77.0% sensitivity, and 61.2% specificity while the AUC of ALT was 0.41 (P=0.07). Thus, we have developed an ELISA that is suitable for measuring serum regucalcin and have shown that serum regucalcin increased with the severity of liver injury due to HBV-related diseases, such that it appears to be more useful than ALT as a marker of liver injury.


Assuntos
Proteínas de Ligação ao Cálcio/sangue , Hepatite B Crônica/sangue , Insuficiência Renal/sangue , Adolescente , Adulto , Idoso , Anticorpos Antivirais/imunologia , Biomarcadores/sangue , Estudos de Casos e Controles , Ensaio de Imunoadsorção Enzimática/métodos , Feminino , Hepatite B Crônica/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência Renal/virologia , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Índice de Gravidade de Doença , Adulto Jovem
8.
Medicine (Baltimore) ; 98(33): e16778, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31415381

RESUMO

BACKGROUND: Tenofovir disoproxil fumarate (TDF) has been widely recommended as a first-line antiviral agent to treat chronic hepatitis B (CHB). Qingzhong and Viread, formulations of TDF commercialized by Jiangsu Chia-tai Tianqing Pharmaceutical Co Ltd and GlaxoSmithKline, respectively, have both been approved by the State Food and Drug Administration, China. This study analyzed the efficacy and safety of these 2 TDF agents in Chinese patients with CHB. METHODS: In this multicenter, randomized, double-blind, double-dummy, noninferiority phase 3 clinical trial (ClinicalTrials.gov identifier: NCT02287857), 330 Chinese patients with CHB [hepatitis B envelope antigen-positive (HBeAg) (+): 232] were randomly assigned to receive Qingzhong (group A: 161 patients) or Viread (group B: 169 patients) 300 mg once daily for 48 weeks. Subsequently, all patients were administered Qingzhong 300 mg once daily from week 49 to week 240. The primary end point was the degree of decline of plasma hepatitis B virus (HBV) DNA levels at week 48 and the secondary endpoints were viral suppression, normalization of alanine aminotransferase (ALT) levels, hepatitis B surface antigen (HBsAg)/HBeAg loss or seroconversion, and virological breakthrough. RESULTS: Among patients with CHB who were HBeAg (+), the mean HBV DNA titer decreased similarly between the groups at week 48. The percentages of patients who achieved undetectable HBV DNA were similar between the groups (85.11% and 82.35% in groups A and B, respectively) and similar losses of HBeAg and HBeAg seroconversion rates were achieved. Moreover, for patients with CHB who were HBeAg (-), reductions in HBV DNA were similar. Among all patients with CHB, the rates of normalization of ALT and the loss of HBsAg were similar. The overall incidence of adverse events was comparable between the groups. CONCLUSION: In conclusion, the 48-week administration of Qingzhong showed noninferior efficacy and safety profiles compared to Viread in Chinese patients with CHB.


Assuntos
Antivirais/uso terapêutico , Hepatite B Crônica/tratamento farmacológico , Tenofovir/uso terapêutico , Adolescente , Adulto , Idoso , Antivirais/administração & dosagem , China , Método Duplo-Cego , Esquema de Medicação , Composição de Medicamentos , Feminino , Antígenos E da Hepatite B/sangue , Hepatite B Crônica/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Tenofovir/administração & dosagem , Resultado do Tratamento , Adulto Jovem
9.
BMC Infect Dis ; 19(1): 640, 2019 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-31324231

RESUMO

BACKGROUND: The virological or clinical relapse is common in chronic hepatitis B (CHB) patients after stopping long-term nucleos(t)ide analogue (NA) therapy. Soluble growth stimulation expressed gene 2 (sST2), one of the Toll-like/interleukin-1 receptor members, is involved in a variety of inflammatory processes and immune responses. However, the expression and function of serum sST2 in CHB patients after stopping NA treatment remains unknown. METHODS: A total of 91 non-cirrhotic Asian patients with CHB who discontinued NA therapy according to international guidelines were prospectively followed up to 240 weeks. All patients were divided into clinical relapse group and non-clinical relapse (including sustained virological response and only virological relapse) group according HBV DNA and ALT levels. The serum levels of sST2 of all participants were determined by ELISA and compared between each two groups. RESULTS: Clinical relapse occurred in 26 patients and virological relapse occurred in 57 patients. We found that there was a positive correlation between sST2 expression and HBsAg, ALT, HBV DNA, and anti-HBc levels in CHB patients after discontinuation of NA treatment. Levels of serum sST2 in clinical relapse patients showed a rising trend and most patients showed peak sST2 levels at the point of clinical relapse. Moreover, the sST2 levels of clinical relapse group at week 12, week 24 and week 48 were relatively higher than non-clinical relapse group. However, the level of sST2 at the end of treatment was not an effective biological marker for the early prediction of clinical relapse after discontinuation of long-term NA therapy. CONCLUSIONS: In conclusion, we found that an increase in sST2 in clinical relapse patients might be associated with an inflammation-related immune response after discontinuation of NA treatment. TRIAL REGISTRATION: The trial was retrospectively registered at Chinese Clinical Trial Registry: ChiCTR-OOC-17013970 . Registration date: December 15, 2017.


Assuntos
Antivirais/uso terapêutico , Hepatite B Crônica/tratamento farmacológico , Proteína 1 Semelhante a Receptor de Interleucina-1/sangue , Adulto , Biomarcadores/sangue , Feminino , Antígenos E da Hepatite B/sangue , Vírus da Hepatite B/genética , Hepatite B Crônica/sangue , Humanos , Masculino , Estudos Prospectivos , Recidiva , Resposta Viral Sustentada , Resultado do Tratamento
10.
Medicine (Baltimore) ; 98(26): e16208, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31261570

RESUMO

The composition of glycan in immunoglobulin G (IgG) has shown to affect various diseases and can be regulated by drugs and preventive vaccination. A hepatitis B surface antigen (HBsAg)-hepatitis B immunoglobulin (HBIG) immune complex (YIC) therapeutic vaccine for chronic hepatitis B (CHB) patients has undergone clinical trials. To explore for markers of CHB, which could be associated with responsiveness to YIC therapeutic vaccine, serum IgG glycosylation in CHB patients was analyzed.Kinetic changes of serum galactosylated IgG in 53 hepatitis Be antigen (HBeAg)-positive CHB patients treated with YIC were monitored by matrix-assisted laser desorption/ionization (MALDI) mass spectrometry (MS) analysis. Whole blood cytokines were assayed by cytokine binding assay kits. All samples were back assayed before treatment, during therapy and follow-up for 6 months from a previous completed clinical trial.During YIC treatment, 26 patients with lower IgG galactosylation level at baseline [galactosylation level (Gal-ratio) = -0.29, 0.18 (mean, SD)] showed sustained increase of serum galactosylated IgG, and responded to YIC treatment by HBeAg seroconversion. While those who did not respond to YIC treatment [Gal-ratio = -0.40, 0.15 (mean, SD)] failed to show similar changes. Furthermore, this kinetic increase of galactosylated IgG correlated with marked up-regulated IL-2 level, confirming that effective cellular immune responses have participated in responsiveness.For HBeAg-positive CHB patients lower serum IgG galactosylation level may serve as an indicator for selecting a suitable subpopulation of candidates for YIC therapeutic vaccination.


Assuntos
Vacinas contra Hepatite B/uso terapêutico , Antígenos E da Hepatite B/sangue , Hepatite B Crônica/imunologia , Hepatite B Crônica/terapia , Imunoglobulina G/sangue , Adulto , Biomarcadores/sangue , Método Duplo-Cego , Feminino , Seguimentos , Galactose/metabolismo , Hepatite B Crônica/sangue , Humanos , Interleucina-2/sangue , Masculino , Soroconversão , Resultado do Tratamento , Vacinação
11.
Zhonghua Gan Zang Bing Za Zhi ; 27(6): 430-435, 2019 Jun 20.
Artigo em Chinês | MEDLINE | ID: mdl-31357758

RESUMO

Objective: To evaluate the using value of FibroTouch and six serological models in detecting the degree of liver fibrosis in patients with chronic hepatitis B, in an attempt to provide reference for accurate diagnosis. Methods: Two hundred and fifty-eight cases with chronic hepatitis B admitted to Xixi Hospital of Hangzhou from September 1, 2015 to September 1, 2017 were selected. All patients underwent liver histopathological examination and FibroTouch measurement to determine liver stiffness (LSM). Serum biochemical parameters were detected and the scoring values of six serological models were calculated. SAS 9.4 statistical software was used for statistical analysis, and the correlation between FibroTouch and the six serological models was analyzed by Spearman correlation. The diagnostic value of FibroTouch and six serological models was analyzed by receiver operating characteristic curve (ROC) based on liver histopathological findings. Results: The median LSM of 258 cases with chronic hepatitis B was 9.4 (6.5-13.8) kPa. In the six serological models, the median value of aspartate transaminase to platelet ratio index (APRI), FIB-4 index, S-index, Forn's index, PRPindex, and FIB-5 were 0.42 (0.28-0.62), 1.27 (0.78-2.03), 0.11 (0.07-0.20), 6.95 (5.89-8.51), 0.000 8 (0.000 6-0.000 9),and 38.59 (36.28-40.97). FibroTouch had positive correlation with APRI, FIB-4, S-index, Forn's index, PRP, fibrosis stage (r= 0.73,P< 0.001) and inflammation grade, and had negative correlation with FIB-5, and both had statistical significance. The area under curve (AUC) of FT-LSM at S≥2, S≥3, S = 4 were 0.89, 0.90 and 0.85, respectively, which was significantly higher than serological models (P< 0.001). The AUC of S-index model at S≥2, S≥3, S = 4 were higher than other five serological models. Conclusion: The diagnostic performance of FibroTouch is significantly better than serological model. S-index model has the best diagnostic performance in the six serological models, and the combination of S-index and FT-LSM may better diagnose the grading of liver fibrosis, and thus can be applied and promoted in clinic.


Assuntos
Biomarcadores , Hepatite B Crônica , Cirrose Hepática , Aspartato Aminotransferases/sangue , Biomarcadores/sangue , Hepatite B Crônica/sangue , Hepatite B Crônica/complicações , Hepatite B Crônica/diagnóstico , Hepatite B Crônica/patologia , Humanos , Cirrose Hepática/sangue , Cirrose Hepática/complicações , Cirrose Hepática/diagnóstico , Cirrose Hepática/patologia , Curva ROC
12.
Medicine (Baltimore) ; 98(23): e15924, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31169710

RESUMO

To explore interleukin-17 (IL-17) and its epigenetic regulation during the progression of chronic hepatitis B virus (HBV) infection.A total of 162 patients with chronic HBV infection, including 75 with chronic hepatitis B (CHB), 54 with hepatitis B-associated liver cirrhosis and 33 with hepatitis B-associated hepatocellular carcinoma (HBV-HCC), were enrolled in this study. Thirty healthy adults of the same ethnicity were enrolled in the control group. Whole venous blood was obtained from the patients and normal controls (n = 30). Clinical and laboratory parameters were assessed, and we performed enzyme-linked immunosorbent assay and quantitative real-time PCR to measure the serum levels and relative mRNA expression of IL-17, respectively. IL-17 promoter methylation in peripheral blood mononuclear cells was assessed by methylation-specific PCR. We analyzed the serum and mRNA levels of IL-17 and IL-17 promoter methylation in the 4 groups as well as the effect of methylation on serum IL-17 levels. Correlations between the IL-17 promoter methylation status and clinical parameters were analyzed by Spearman correlation analysis.Compared to the normal control group, the patient groups exhibited significantly higher serum and relative mRNA levels of IL-17. The methylation distribution among the patients was significantly lower than that among the normal controls (P < .05), with the HBV-HCC group showing the lowest IL-17 gene methylation frequency. The average IL-17 promoter CG methylation level was negatively correlated with IL-17 mRNA expression (r = -0.39, P = .03), and negative correlations between IL-17 promoter methylation and prothrombin time activity (r = -0.585, P = .035), alanine aminotransferase (r = -0.522, P < .01), aspartate aminotransferase (r = -0.315, P < .05), and the model for end-stage liver disease score (r = -0.461, P < .05) were observed. IL-17 serum levels in the methylated-promoter groups were significantly lower than those in the unmethylated-promoter groups.IL-17 expression and promoter methylation were associated with chronic HBV infection progression, especially in the HBV-HCC group. The IL-17 promoter status may help clinicians initiate the correct treatment strategy at the CHB stage.


Assuntos
Progressão da Doença , Vírus da Hepatite B , Hepatite B Crônica/genética , Interleucina-17/sangue , Regiões Promotoras Genéticas/genética , Adulto , Idoso , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/virologia , Metilação de DNA , Epigênese Genética , Feminino , Hepatite B Crônica/sangue , Hepatite B Crônica/virologia , Humanos , Cirrose Hepática/sangue , Cirrose Hepática/genética , Cirrose Hepática/virologia , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade
13.
BMC Infect Dis ; 19(1): 523, 2019 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-31200663

RESUMO

BACKGROUND: Due to no clinical symptoms in the compensated stage of cirrhosis, it is usually diagnosed when decompensated complications occur. In this study, the noninvasive circulating biomarkers for early detection to compensated stage of cirrhosis in patients with chronic HBV (hepatitis B virus) infection was explored. METHODS: According to the Guideline of Prevention and Treatment of Chronic Hepatitis B (2015 Update), 78 patients with CHB (chronic hepatitis B) were divided into mild group, moderate-to-advanced group, while 73 patients with HBV-related cirrhosis were divided into compensated group and decompensated group. Nineteen cytokines and chemokines, four serum liver fibrosis markers were measured using chemiluminescence. The expression of CCL5 in liver tissue was determined with immunohistochemistry. RESULTS: The CCL5 expression level in serum increased in CHB patients with aggravated liver injury and significantly decreased in cirrhosis patients with advanced liver fibrosis. ROC analysis revealed that the serum levels of CCL5, HA and MIP-1ß were effective in distinguishing patients with cirrhosis from patients with CHB, especially for CCL5. Increasing serum level of CCL5 in CHB patients was severely associated with disease progression. CONCLUSIONS: The serum levels of CCL5, HA and MIP-1ß maybe used to distinguish cirrhosis from CHB patients, moreover, CCL5 was the most reliable marker. The increasing serum levels of CCL5 were significantly related to disease progression in CHB patients.


Assuntos
Quimiocina CCL4/sangue , Quimiocina CCL5/sangue , Hepatite B Crônica/diagnóstico , Ácido Hialurônico/sangue , Cirrose Hepática/diagnóstico , Adulto , Biomarcadores/sangue , Progressão da Doença , Diagnóstico Precoce , Feminino , Hepatite B Crônica/sangue , Hepatite B Crônica/patologia , Humanos , Cirrose Hepática/sangue , Cirrose Hepática/patologia , Masculino , Pessoa de Meia-Idade , Curva ROC
14.
BMC Public Health ; 19(1): 829, 2019 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-31242901

RESUMO

BACKGROUND: International sustainable development goals for the elimination of viral hepatitis as a public health problem by 2030 highlight the need to optimize strategies for prevention, diagnosis and treatment of hepatitis B virus (HBV) infection. An important priority for Africa is to have affordable, accessible and sustainable prevention of mother to child transmission (PMTCT) programmes, delivering screening and treatment for antenatal women and implementing timely administration of HBV vaccine for their babies. METHODS: We developed a decision-analytic model simulating 10,000 singleton pregnancies to assess the cost-effectiveness of three possible strategies for deployment of tenofovir in pregnancy, in combination with routine infant vaccination: S1: no screening nor antiviral therapy; S2: screening and antiviral prophylaxis for all women who test HBsAg-positive; S3: screening for HBsAg, followed by HBeAg testing and antiviral prophylaxis for women who are HBsAg-positive and HBeAg-positive. Our outcome was cost per infant HBV infection avoided and the analysis followed a healthcare perspective. RESULTS: Based on 10,000 pregnancies, S1 predicts 45 infants would be HBV-infected at six months of age, compared to 21 and 28 infants in S2 and S3, respectively. Relative to S1, S2 had an incremental cost of $3940 per infection avoided. S3 led to more infections and higher costs. CONCLUSION: Given the long-term health burden for individuals and economic burden for society associated with chronic HBV infection, screening pregnant women and providing tenofovir for all who test HBsAg+ may be a cost-effective strategy for South Africa and other low/middle income settings.


Assuntos
Antivirais/uso terapêutico , Análise Custo-Benefício , Vírus da Hepatite B/imunologia , Hepatite B/tratamento farmacológico , Transmissão Vertical de Doença Infecciosa/prevenção & controle , Complicações Infecciosas na Gravidez/tratamento farmacológico , Tenofovir/uso terapêutico , Adulto , Criança , Países em Desenvolvimento , Feminino , Hepatite B/sangue , Hepatite B/diagnóstico , Hepatite B/virologia , Antígenos de Superfície da Hepatite B/sangue , Vacinas contra Hepatite B/administração & dosagem , Antígenos E da Hepatite B/sangue , Hepatite B Crônica/sangue , Hepatite B Crônica/diagnóstico , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/virologia , Humanos , Lactente , Programas de Rastreamento , Modelos Biológicos , Gravidez , Complicações Infecciosas na Gravidez/sangue , Complicações Infecciosas na Gravidez/diagnóstico , Complicações Infecciosas na Gravidez/virologia , África do Sul , Tenofovir/economia , Vacinação , Adulto Jovem
15.
Bioanalysis ; 11(10): 1003-1013, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31218896

RESUMO

Aim: In order to differential diagnosis of chronic hepatitis B (HBV-I) and hepatocellular carcinoma (HCC), a UPLC-MS/MS method for measuring purine metabolites was developed. Methodology & results: serum samples from 26 HBV-I and 35 HCC patients were collected. Ten purine metabolites were simultaneously quantified by UPLC-MS/MS with tubercidin and uric acid-1,3-15N2 as internal standards. The method was validated to meet the requirements of clinical sample analysis. A logistic equation was established for differential diagnosis of HBV-I and HCC by combination of xanthosine and guanine with the area under the receiver operating characteristic curve of 0.885. Conclusion: Guanine and xanthosine are intermediates in the metabolism of purine, which play an important role in gene synthesis, and metabolism regulation. The alteration of serum purine metabolite may contribute to differential diagnosis of HBV-I and HCC.


Assuntos
Análise Química do Sangue/métodos , Carcinoma Hepatocelular/diagnóstico , Hepatite B Crônica/diagnóstico , Neoplasias Hepáticas/diagnóstico , Purinas/sangue , Purinas/metabolismo , Adulto , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/metabolismo , Cromatografia Líquida de Alta Pressão , Diagnóstico Diferencial , Feminino , Hepatite B Crônica/sangue , Hepatite B Crônica/metabolismo , Humanos , Interações Hidrofóbicas e Hidrofílicas , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/metabolismo , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Curva ROC , Espectrometria de Massas em Tandem
16.
Zhonghua Gan Zang Bing Za Zhi ; 27(4): 256-260, 2019 Apr 20.
Artigo em Chinês | MEDLINE | ID: mdl-31082335

RESUMO

Objective: To explore the prognostic value of model for end-stage liver disease (MELD) combined with arterial blood lactate (Lac) in admitted patients with hepatitis B virus-associated acute- on-chronic liver failure (HBV-ACLF). Methods: Clinical data of 97 cases with hepatitis B virus-associated acute- on-chronic liver failure (HBV-ACLF) admitted to the First Affiliated Hospital of Suzhou University between March 2016 and March 2018 was retrospectively analyzed. Age, gender, complications, MELD score, lactic acid (Lac), total bilirubin (TBil), creatinine (Cr), serum albumin (Alb), high-sensitivity C-reactive protein (CRP), white blood cell count (WBC), platelet count (PLT), hematocrit (Hct), quantification of HBV DNA and HBsAg, and organ support treatment (artificial liver support system, renal replacement therapy and mechanical ventilation ) were documented after admission. The primary endpoint of treatment was death due to ineffective medical treatment during hospitalization, abandonment of medical treatment due to deterioration of the health condition, and switch to liver transplantation for patients with poor medical treatment. The risk factors for primary endpoint of treatment were analyzed by binary logistic regression. Hosmer-Lemeshow test was used to evaluate the goodness of fit for the scoring system, and the ROC to predict the prognosis of MELD-Lac. Results: Ninety-seven cases with HBV-ACLF were included, 56 cases had good prognosis, and 41 cases had bad prognosis (including two cases with poor medical treatment and liver transplantation). The overall improvement rate was 57.7%. MELD score and Lac value in treated group was significantly lower than non-treated group. Bivariable and multivariable logistic regression analysis showed that the MELD score [odds ratio (OR = 1.806)], and Lac score [odds ratio (OR = 1.820)] was the risk factor for hospitalization and mortality in patients with liver failure (P < 0.05). The area under the ROC curve (AUC) and the 95% confidence interval (95% CI) of prognostic patients with MELD-Lac were significantly better than Lac and MELD scores [0.923 (0.84 to 1.00) vs. 0.804 (0.067 to 0.942) and 0.864 (0.75). 0.977)], P < 0.05. When the MELD-Lac Youden index was set at 0.746, the optimal threshold was 18.36, and the sensitivity and specificity were 91.3% and 83.3%, respectively. Conclusion: MELD-Lac score has a high prognostic value in HBV-ACLF patients.


Assuntos
Insuficiência Hepática Crônica Agudizada/sangue , Insuficiência Hepática Crônica Agudizada/virologia , Vírus da Hepatite B/isolamento & purificação , Hepatite B Crônica/complicações , Ácido Láctico/sangue , Insuficiência Hepática Crônica Agudizada/diagnóstico , Hepatite B Crônica/sangue , Hepatite B Crônica/virologia , Humanos , Prognóstico , Estudos Retrospectivos
17.
Zhonghua Gan Zang Bing Za Zhi ; 27(4): 261-266, 2019 Apr 20.
Artigo em Chinês | MEDLINE | ID: mdl-31082336

RESUMO

Objective: To observe the changes of liver function, virology and serology and the safety of drug withdrawal in pregnant women who are chronic hepatitis B virus (HBV) carriers. Methods: A prospective clinical cohort was established to enroll pregnant women who are chronic HBV carriers and they were divided into the nucleoside/nucleotide analogs (NAs) intervention group and the non-NAs intervention group according to patients' wishes. Liver function, HBV DNA and HBV serological markers were detected at gestation, postpartum 6 weeks, 12 weeks, 24 weeks, 36 weeks and 48 weeks. Results: 351 patients were enrolled, 320 in the NAs intervention group and 31 in the non-NAs intervention group. The proportion of postpartum hepatitis flares in both groups was higher than that in pregnancy (39.4% vs 12.5%, P < 0.001; 38.7% vs 3.2%, P = 0.001). Six weeks postpartum was the peak period of hepatitis flares, and 96.0% (121/126) of the hepatitis flares occurred within 24 weeks postpartum. At 6 weeks postpartum, there were 6 cases of alanine aminotransferase (ALT) ≥ 10 times upper limit of normal (ULN) in the NAs intervention group. The rate of the hepatitis flare after drug withdrawal was 16.7% (34/203). Conclusion: Regardless of the presence or absence of NAs intervention, pregnant women who are chronic HBV carriers have a certain proportion of hepatitis flares during pregnancy and postpartum, and the hepatitis flare even have a tendency to be severe. Therefore, drug withdrawal after delivery is not always safe, which requires close observation and classification. At 6 weeks postpartum, the incidence of hepatitis flares was high, and those who meet the treatment indications can get better therapeutic effects if given appropriate treatment. The vast majority (96%) of postpartum hepatitis flares occur within 24 weeks, so it is recommended to follow up to at least 24 weeks postpartum after discontinuation.


Assuntos
Antivirais/administração & dosagem , Vírus da Hepatite B/isolamento & purificação , Hepatite B Crônica/tratamento farmacológico , Fígado/fisiologia , Complicações Infecciosas na Gravidez/tratamento farmacológico , Complicações Infecciosas na Gravidez/virologia , Alanina Transaminase/sangue , Antivirais/uso terapêutico , DNA Viral , Feminino , Antígenos E da Hepatite B/sangue , Vírus da Hepatite B/genética , Hepatite B Crônica/sangue , Hepatite B Crônica/patologia , Humanos , Período Pós-Parto , Gravidez , Estudos Prospectivos
18.
BMC Gastroenterol ; 19(1): 65, 2019 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-31046700

RESUMO

BACKGROUND: Pegylated interferon (PEG-IFN) alfa-2b is recommended for chronic hepatitis B (CHB). We aimed to investigate the sustainability of off-treatment responses among Chinese HBeAg-positive CHB patients treated with PEG-IFN alfa-2b from a randomized trial. METHODS: Eligible Chinese patients (n = 322) were followed up by one visit after a median of 6 years (LTFU) following their participation in a randomized trial evaluating the efficacy of three PEG-IFN alfa-2b dosing regimens (1.0 or 1.5 µg/kg/wk. 24 weeks or 1.5 µg/kg/wk. 48 weeks). Primary endpoints at the LTFU were sustained SR and CR (SR/CR at the end of original study [EOS] and at the LTFU). SR was defined as HBeAg loss and seroconversion to anti-HBe and CR as HBeAg loss and seroconversion to anti-HBe and HBV-DNA < 2000 IU/mL. RESULTS: The proportions of patients achieving sustained SR among patients who had SR at EOS were high in three treatment groups (61.9, 65.5, 76.5%, respectively, p = 0.46); treatment with PEG-IFN alfa-2b 1.5 µg/kg/wk. 48 weeks had the highest proportion of a sustained CR among patients who had CR at EOS (75.0%, p = 0.05). A considerable number of patients achieved sustained SR (18.2-29.9%) and sustained CR (14.8-18.3%) after EOS despite no further NA treatment. At the LTFU, rates of SR and CR were less than 70.0 and 50.0%, respectively, among all enrolled patients regardless of additional nucleos(t)ide analogs before the LTFU. CONCLUSIONS: PEG IFN alfa-2b therapy had considerable off-treatment sustainability in Chinese HBeAg positive chronic hepatitis B patients with serological and complete responses.


Assuntos
Antivirais/uso terapêutico , Antígenos E da Hepatite B/sangue , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/virologia , Interferon alfa-2/uso terapêutico , Interferon-alfa/uso terapêutico , Polietilenoglicóis/uso terapêutico , Resposta Viral Sustentada , Adulto , Antivirais/administração & dosagem , China , Feminino , Seguimentos , Hepatite B Crônica/sangue , Humanos , Interferon alfa-2/administração & dosagem , Interferon-alfa/administração & dosagem , Masculino , Polietilenoglicóis/administração & dosagem , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/uso terapêutico , Adulto Jovem
19.
Zhonghua Zhong Liu Za Zhi ; 41(5): 351-356, 2019 May 23.
Artigo em Chinês | MEDLINE | ID: mdl-31137168

RESUMO

Objective: To establish a quantitative assay of serum Golgi protein 73 (GP73) using xMAP technology and evaluate its performance. Methods: Monoclonal antibodies against GP73 were prepared and purified, and antibody pair screening was performed by double-antibody sandwich enzyme-linked immunosorbent assay. The screened antibodies were used to construct a Luminex liquid chip detection system, and the analysis performance of the detection system was evaluated. The serum levels of GP73 were detected in 90 clinical samples from healthy controls and patients with chronic hepatitis B infection (CHB) and hepatocellular carcinoma (HCC). Results: Five anti-GP73 monoclonal antibodies were prepared and purified, and 5 antibody pairs were successfully screened. The Luminex liquid chip detection system of GP73 was successfully constructed using 8F10D1 and 10B9F11 antibody pairs. The analytical performance evaluation showed that the sensitivity of this system was 0.25 ng/ml and the dynamic range was 0.25-100 ng/ml. No cross reactivity was observed. The intra- and inter-assay variation for GP73 was <8% and <11%, respectively. The recovery was 83%-92%. The linear regression equation was y=1.141x+ 6.436 (r(2)=0.998 4, P<0.001). The GP73 concentrations in the serum samples of healthy control, CHB group, and HCC group were 42.8 (38.68, 55.90) ng/ml, 61.49 (43.59, 81) ng/ml, and 122.78 (49.36 liter, 264.55) ng/ml, respectively. The levels of GP73 in HCC group were significantly higher than those in CHB group and healthy controls (P<0.05). Moreover, the levels of GP73 in CHB group were significantly higher than those in healthy controls (P<0.05). Conclusions: A liquid chip detection system of GP73 was successfully constructed. It provides a powerful tool for the clinical application of GP73 in the future.


Assuntos
Carcinoma Hepatocelular/sangue , Hepatite B Crônica/sangue , Ensaios de Triagem em Larga Escala/métodos , Neoplasias Hepáticas/sangue , Proteínas de Membrana/sangue , Ensaio de Imunoadsorção Enzimática , Ensaios de Triagem em Larga Escala/normas , Humanos
20.
PLoS Pathog ; 15(4): e1007715, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30998783

RESUMO

Hepatitis B virus (HBV) persists with global and virus-specific T-cell dysfunction, without T-cell based correlates of outcomes. To determine if γδT-cells are altered in HBV infection relative to clinical status, we examined the frequency, phenotype and function of peripheral blood Vδ1+ and Vδ2+γδT-cells by multi-parameter cytometry in a clinically diverse North American cohort of chronic hepatitis B (CHB), acute hepatitis B (AHB) and uninfected control subjects. We show that circulating γδT-cells were comprised predominantly of CD3hiCD4- Vδ2+γδT-cells with frequencies that were 2-3 fold higher among Asian than non-Asian Americans and inversely correlated with age, but without differences between CHB, AHB and control subjects. However, compared to control subjects, CHB was associated with increased TbethiEomesdim phenotype in Vδ2+γδT-cells whereas AHB was associated with increased TbethiEomesdim phenotype in Vδ1+γδT-cells, with significant correlations between Tbet/Eomes expression in γδT-cells with their expression of NK and T-cell activation and regulatory markers. As for effector functions, IFNγ/TNF responses to phosphoantigens or PMA/Ionomycin in Vδ2+γδT-cells were weaker in AHB but preserved in CHB, without significant differences for Vδ1+γδT-cells. Furthermore, early IFNγ/TNF responses in Vδ2+ γδT-cells to brief PMA/Ionomycin stimulation correlated inversely with serum ALT but not HBV DNA. Accordingly, IFNγ/TNF responses in Vδ2+γδT-cells were weaker in patients with CHB with hepatitis flare compared to those without hepatitis flares, and this functional deficit persisted beyond clinical resolution of CHB flare. We conclude that circulating γδT-cells show distinct activation and differentiatiation in acute and chronic HBV infection as part of lymphoid stress surveillance with potential role in clinical outcomes.


Assuntos
Vírus da Hepatite B/imunologia , Hepatite B Crônica/imunologia , Ativação Linfocitária/imunologia , Receptores de Antígenos de Linfócitos T gama-delta/imunologia , Linfócitos T/imunologia , Adolescente , Adulto , Idoso , Biomarcadores/análise , Estudos de Coortes , Feminino , Hepatite B Crônica/sangue , Hepatite B Crônica/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Receptores de Antígenos de Linfócitos T gama-delta/sangue , Adulto Jovem
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