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1.
Med Sci Monit ; 26: e927444, 2020 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-33320844

RESUMO

BACKGROUND Alpha-fetoprotein (AFP) is widely used to screen for hepatocellular carcinoma (HCC). However, the use of this biomarker has been challenged due to its low sensitivity and high rate of false negatives. In this study, we evaluated the diagnostic capability of cyclin D2 (CCND2) promoter methylation in patients with HCC related to hepatitis B virus (HBV). MATERIAL AND METHODS Using methylation-specific PCR and quantitative real-time PCR, we measured methylation status and mRNA levels of CCND2 in plasma and peripheral blood mononuclear cells (PBMCs) from 275 subjects: 75 patients with chronic hepatitis B (CHB), 47 with liver cirrhosis (LC), 118 with HCC, and 35 healthy controls (HCs). RESULTS The methylation rate of the CCND2 promoter was significantly higher in HCC patients than in patients without HCC (P<0.001). Furthermore, advanced HCC (TNM III/IV) was associated with a significantly higher frequency of CCND2 methylation and lower CCND2 mRNA levels than early-stage disease (TNM I/II; P<0.05). Combined measurement of CCND2 methylation and AFP yielded significantly higher sensitivity and area under the curve (AUC) than AFP alone in distinguishing patients with HCC from subjects with LC and CHB (P<0.001). CONCLUSIONS CCND2 methylation may be useful for predicting HCC progression. In addition, combined measurement of CCND2 methylation and AFP could serve as a non-invasive diagnostic marker for patients with HBV-related HCC.


Assuntos
Carcinoma Hepatocelular , Ciclina D2/genética , Metilação de DNA , Hepatite B Crônica , Cirrose Hepática , Neoplasias Hepáticas , alfa-Fetoproteínas/análise , Área Sob a Curva , Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Diagnóstico Diferencial , Progressão da Doença , Feminino , Hepatite B Crônica/sangue , Hepatite B Crônica/diagnóstico , Humanos , Leucócitos Mononucleares/patologia , Cirrose Hepática/sangue , Cirrose Hepática/diagnóstico , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Regiões Promotoras Genéticas , RNA Mensageiro/análise , Sensibilidade e Especificidade
2.
Zhonghua Gan Zang Bing Za Zhi ; 28(7): 586-590, 2020 Jul 20.
Artigo em Chinês | MEDLINE | ID: mdl-32791794

RESUMO

Objective: To explore the effect of HBV preC/C and S gene antigen epitope mutations on HBeAg serological status in patients with chronic hepatitis B. Methods: Thirty-five cases with chronic hepatitis B without antiviral therapy were enrolled in this cross-sectional study. Nested PCR-TA cloning-sequencing method was used to screen HBV preC/C and S gene mutation sites related to HBeAg serological status. Then, in the longitudinal study (60 cases), the independent correlation between HBV preC/C and S gene antigen epitopes mutations and HBeAg status was explored by using multiple regression models to correct the correlated confounding factors. Results: In this cross-sectional study, 64.4% of preC/C and 68.2% of S mutations had occurred in the epitope region. There were ten mutation sites (PreC/C50, 55, 79, 84, 103, 126, 145, 184 and s110, s213) correlated with HBeAg negative status (P < 0.05). After adjusting for confounding factors such as age, gender, HBV genotype, serum alanine aminotransferase level and precw28 * mutations in the longitudinal studies, the results showed that TC cell epitope (prec47-56, prec117-125, s208-216) and Th cell epitope (prec176-185) were the main independent risk factors affecting the host HBeAg serological status. Conclusion: HBV preC/C region (PreC47-56, PreC117-125 and PreC176-185) and S region (s208-216) epitope mutations are the main independent factors affecting the host HBeAg status, suggesting that these epitope mutations may be involved in the HBeAg seroconversion.


Assuntos
Antígenos do Núcleo do Vírus da Hepatite B/genética , Antígenos de Superfície da Hepatite B/genética , Antígenos E da Hepatite B/sangue , Vírus da Hepatite B , Hepatite B Crônica/sangue , Estudos Transversais , DNA Viral , Epitopos/genética , Genótipo , Vírus da Hepatite B/genética , Humanos , Estudos Longitudinais , Mutação
3.
Medicine (Baltimore) ; 99(32): e21551, 2020 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-32769895

RESUMO

To explore the association between serum cystatin C (Cys-C) and renal damage in patients with chronic hepatitis B.We retrospectively analyzed the clinical data of 425 patients with chronic hepatitis B virus (HBV) infection. Liver stiffness measured by FibroScan was used to diagnosis liver fibrosis. Cys-C levels were detected via latex-enhanced immunoturbidimetric assay.A total of 425 patients were enrolled. Among them, 217 were patients with CHB with an eGFR > 90 mL/min/1.73 m and 208 with an eGFR ≤90 mL/min/1.73 m. Cys-C levels significantly differed in patients with eGFR > 90 mL/min/1.73 m compared with patients with eGFR ≤90 mL/min/1.73 m (0.81 ±â€Š0.05 vs 1.05 ±â€Š0.06 mg/L, P < .001). Moreover, the Cys-C levels were 0.82 ±â€Š0.04 mg/L in patients without liver fibrosis, 0.98 ±â€Š0.05 mg/L in patients with mild liver fibrosis, 1.05 ±â€Š0.08 mg/L in patients with advanced liver fibrosis, and 1.12 ±â€Š0.07 mg/L in patients with liver cirrhosis (P < .001). Multivariate analyses were conducted to explore the independent factors associated with a decreased eGFR. Multivariate analysis suggested that T2DM (P = .032), liver fibrosis (P = .013), and Cys-C level (P = .035) were the independent factors associated with the decreased eGFR in patients with CHB. While age (P = .020) and Cys-C level (P = .001) were the independent factors associated with the decreased eGFR in patients with CHB-related fibrosis.The fibrosis group had significantly higher Cys-C levels than those without fibrosis. Routine monitoring of Cys-C levels is of positive significance in preventing the development of renal impairment of CHB patients.


Assuntos
Cistatina C/sangue , Vírus da Hepatite B , Hepatite B Crônica/sangue , Insuficiência Renal/sangue , Adulto , Feminino , Taxa de Filtração Glomerular , Hepatite B Crônica/complicações , Hepatite B Crônica/virologia , Humanos , Rim/virologia , Cirrose Hepática/sangue , Cirrose Hepática/virologia , Masculino , Pessoa de Meia-Idade , Insuficiência Renal/virologia , Estudos Retrospectivos
4.
Ann Hematol ; 99(11): 2671-2677, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32737632

RESUMO

Hematopoietic stem cell transplantation (HSCT) is a risk factor for viral hepatitis reactivations because it affects lymphocyte number and functions. Latent hepatitis B virus (HBV) may stay in dormant form in hepatocytes and may be reactivated in prolonged immunosuppression. This study analyzes the incidence of reactivation of HBV infections in HSCT patients in a middle endemic country like Turkey. Five hundred and sixty-one HSCT patients from 1994 to 2015 were retrospectively evaluated. Sixty-six patients had a serologic feature of HBV infection. Fifteen patients were hepatitis B surface antigen (HBsAg)-positive patients (3 allogeneic and 12 autologous) while 51 of them were anti-hepatitis B core IgG (anti-HBc IgG)-positive patients (22 allogeneic and 29 autologous). Although under lamivudine prophylaxis, reactivation was seen in three of 12 (25%) chronic HBV (HBsAg positive) patients who received autologous HSCT and in two of the three HBsAg-positive patients who received allogeneic HSCT. Rate of reactivation in the whole HBsAg-positive group was 33%. Reactivation occurred on median 270th day (range: 60-730). Reverse seroconversion incidence was 10% on 133th day for HBsAg negative, but anti-HBc IgG-positive patients, which increased to 17% on 360th and to 23% on 1500th day. Cumulative incidence increased to 41% on 2280th day for isolated anti-HBc IgG-positive patients. Hepatitis B surface antibodies (anti-HBs) were found to be protective as reactivation did not exceed 11% on 5050th day when anti-HBs was positive. When anti-HBc IgG-positive cases were analyzed according to their transplantation types, allogeneic HSCT was found to have higher cumulative incidence (45% on 3258th day) for HBV reactivation than autologous HSCT (7% on 5050th day). Besides, HBV reactivation in anti-HBc IgG-positive patients who received allogeneic transplantation was related to mortality. Findings of this study suggest that HBV prophylaxis extending over 1 year should be prescribed for HBsAg-positive patients independent of the transplantation type. Prophylaxis should also be given to anti-HBc IgG-positive patients if an allogeneic HSCT is to be performed.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Anticorpos Anti-Hepatite B/sangue , Antígenos de Superfície da Hepatite B/sangue , Vírus da Hepatite B/fisiologia , Hepatite B Crônica/sangue , Imunoglobulina G/sangue , Ativação Viral , Adulto , Aloenxertos , Autoenxertos , Feminino , Hepatite B Crônica/prevenção & controle , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
5.
Aliment Pharmacol Ther ; 52(4): 692-700, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32613672

RESUMO

BACKGROUND: Serum hepatitis B virus (HBV) RNA is a novel biomarker for evaluating treatment response. Detailed information regarding serum HBV RNA kinetics during treatment with nucleos(t)ide analogues (NAs) is limited. AIMS: To ascertain serum HBV RNA kinetics during long-term NA treatment and identify associated factors. METHODS: We enrolled 76 HBeAg-positive chronic hepatitis B patients receiving NA from randomised controlled trials. Laboratory assays were undertaken every 3 months. Factors associated with serum HBV RNA kinetics were identified by generalised estimating equations. RESULTS: Baseline serum HBV RNA was 8.5 ± 1.0 log10  copies/mL. Decline in serum HBV RNA during NA therapy was biphasic: the first phase (HBV DNA detectable) had a fast decrease (median slope, -0.207 log10  copies/mL/month) and was followed by a second phase (HBV DNA undetectable) with slow decrease (median slope, -0.071 log10  copies/mL/month). In the first phase, factors independently associated with lower initial serum HBV RNA were male sex (OR, 0.685, P = 0.044), low baseline HBsAg (OR, 0.525, P = 0.001) and rapid virological response (RVR) (OR, 0.624, P = 0.031). In the second phase, only RVR was independently associated with serum HBV RNA kinetics, including its lower initial level (OR, 0.694, P = 0.043) and greater decline (OR, 0.966, P = 0.002). Based on viral dynamics, time needed to achieve undetectable serum HBV RNA from baseline was 43.56 (IQR: 29.49-66.40) months. CONCLUSION: RVR was a significant determinant for biphasic decline in serum HBV RNA during NA treatment, which significantly influenced the treatment duration required to achieve undetectable serum HBV RNA.


Assuntos
Antivirais/uso terapêutico , Vírus da Hepatite B/genética , Hepatite B Crônica/tratamento farmacológico , Nucleosídeos/uso terapêutico , Nucleotídeos/uso terapêutico , RNA Viral/sangue , Adulto , Biomarcadores/análise , Biomarcadores/sangue , Testes Diagnósticos de Rotina , Feminino , Seguimentos , Antígenos de Superfície da Hepatite B/sangue , Antígenos E da Hepatite B/sangue , Vírus da Hepatite B/efeitos dos fármacos , Vírus da Hepatite B/isolamento & purificação , Hepatite B Crônica/sangue , Hepatite B Crônica/diagnóstico , Hepatite B Crônica/virologia , Humanos , Cinética , Masculino , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Nucleosídeos/análogos & derivados , RNA Viral/análise , RNA Viral/isolamento & purificação , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
6.
BMC Infect Dis ; 20(1): 509, 2020 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-32664850

RESUMO

BACKGROUND: Complete clearance of intracellular viruses depends on effector cells of innate and adaptive immune systems. This study aimed to identify the relationships among antiviral cytokines produced by natural killer (NK) and T cells and clinical-virological characteristics in untreated chronic hepatitis B (CHB) patients. METHODS: We measured antiviral cytokines interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), and interleukin-2 (IL-2) produced by T, NK and natural killer T (NKT) cells, respectively, in a cohort with chronic hepatitis B virus (HBV) infection (CHB). We also correlated these cytokines with clinical-virological characteristics using a linear regression model. RESULTS: levels of IFN-γ+ and TNF-α+ CD4+ and CD8+ T cells were significantly higher in immune active (IA) phase than in other phases. Immune tolerant (IT) patients showed the lowest expression of IFN-γ by NK and NKT cells, and TNF-α by NK cells. IFN-γ+, TNF-α+ and IL-2+ CD4+ and CD8+ T cells frequencies were similar between IA and gray zone (GZ) phases. Principal component analysis based on cytokines confirmed that most IT patients significantly differed from inactive carriers (IC) and IA patients, while GZ patients were widely scattered. Multivariate analysis showed both T and NK cells producing IFN-γ and TNF-α, but not IL-2, had significant association with serum alanine aminotransferase (ALT). Moreover, IFN-γ+ NKT cells were associated with HBV DNA, while IFN-γ+ CD4+ and CD8+ T cells were correlated with age. CONCLUSION: HBV clinical phases are characterized by distinct cytokine signatures, which showed relationship to viral features in these untreated CHB patients.


Assuntos
Imunidade Adaptativa , Citocinas/metabolismo , Vírus da Hepatite B/genética , Vírus da Hepatite B/imunologia , Hepatite B Crônica/sangue , Hepatite B Crônica/imunologia , Imunidade Inata , Adulto , Alanina Transaminase/sangue , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Estudos de Coortes , DNA Viral/sangue , Feminino , Antígenos de Superfície da Hepatite B/sangue , Hepatite B Crônica/virologia , Humanos , Células Matadoras Naturais/imunologia , Masculino , Células T Matadoras Naturais/imunologia , Adulto Jovem
7.
BMC Infect Dis ; 20(1): 485, 2020 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-32641006

RESUMO

BACKGROUND: Bhutan is committed to eliminating hepatitis B and hepatitis C, though recent baseline estimates of disease burden in the general population are unknown. In 2017, we carried out a biomarker survey in the general population to estimate the prevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV) biomarkers to evaluate the impact of immunization and guide further efforts. METHODS: In 2017, a cross-sectional, population-based, three-stage cluster survey was undertaken of the general population (1-17 and 20+ years of age). We visited households, collected blood specimens and administered a standard questionnaire. Specimens were collected for hepatitis B surface antigen (HBsAg) and hepatitis C virus antibody (anti-HCV) testing. We calculated prevalence of infection and selected characteristics, along with confidence intervals (CIs). RESULTS: Of 1372 individuals approached, 1358 (99%) participated. Of those, 1321 (97%) had a specimen tested for HBsAg, and among 1173 enrolled individuals 5 years of age or older, 1150 (98%) individuals were tested for anti-HCV. The prevalence of HBsAg was 2.0% in 775 persons 20 years of age or older (95% CI: 1.0-4.0) and 0.5% in 546 persons 1-17 years of age (95% CI: 0.1-1.8). The prevalence of anti-HCV was 0.3% (95% CI: 0.1-0.8) among persons ≥5 years. CONCLUSIONS: Universal hepatitis B immunization of infants has resulted in a low prevalence of chronic HBV infection in persons 1-17 years of age and the prevalence of anti-HCV is low among persons aged ≥5 years. Efforts should continue to reach high coverage of the timely birth dose along with completion of the hepatitis B vaccine series. To reduce the chronic liver disease burden among adults, HBV and HCV testing and treatment as indicated might be restricted to pregnant women, blood donors, individuals with chronic liver diseases, and other groups with history of high-risk exposures.


Assuntos
Hepacivirus/imunologia , Vírus da Hepatite B/imunologia , Hepatite B Crônica/epidemiologia , Hepatite B Crônica/prevenção & controle , Hepatite C/epidemiologia , Hepatite C/prevenção & controle , Vacinação , Adolescente , Adulto , Butão/epidemiologia , Biomarcadores/sangue , Criança , Pré-Escolar , Análise por Conglomerados , Estudos Transversais , Feminino , Antígenos de Superfície da Hepatite B/sangue , Hepatite B Crônica/sangue , Hepatite B Crônica/transmissão , Hepatite C/sangue , Hepatite C/transmissão , Anticorpos Anti-Hepatite C/sangue , Humanos , Lactente , Transmissão Vertical de Doença Infecciosa/prevenção & controle , Masculino , Prevalência , Inquéritos e Questionários , Adulto Jovem
8.
BMC Infect Dis ; 20(1): 547, 2020 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-32711465

RESUMO

BACKGROUND: Monitoring hepatitis B surveillance data is important for evaluating progress towards global hepatitis B elimination goals. Accurate classification of acute and chronic hepatitis infections is essential for assessing program effectiveness. METHODS: We evaluated hepatitis B case-reporting at six hospitals in Fujian, Hainan and Gansu provinces in 2015 to assess the accuracy of case classification. We linked National Notifiable Disease Reporting System (NNDRS) HBV case-reports with hospital information systems and extracted information on age, gender, admission ward and viral hepatitis diagnosis from medical records. To assess accuracy, we compared NNDRS reported case-classifications with the national HBV case definitions. Multivariable logistic regression was used to identify factors associated with misclassification. RESULTS: Of the 1420 HBV cases reported to NNDRS, 23 (6.5%) of the 352 acute reports and 648 (60.7%) of the 1068 chronic reports were correctly classified. Of the remaining, 318 (22.4%) were misclassified and 431 (30.4%) could not be classified due to the lack of supporting information. Based on the multivariable analysis, HBV cases reported from Hainan (aOR = 1.8; 95% CI: 1.3-2.4) and Gansu (aOR = 12.7; 95% CI: 7.7-20.1) along with reports from grade 2 hospitals (aOR = 1.6; 95% CI:1.2-2.2) and those from non-HBV related departments (aOR = 5.3; 95% CI: 4.1-7.0) were independently associated with being 'misclassified' in NNDRS. CONCLUSIONS: We identified discrepancies in the accuracy of HBV case-reporting in the project hospitals. Onsite training on the use of anti-HBc IgM testing as well as on HBV case definitions and reporting procedures are needed to accurately assess program effectiveness and ensure case-patients are referred to appropriate treatment and care. Routine surveillance evaluations such as this can be useful for improving data quality and monitoring program effectiveness.


Assuntos
Monitoramento Epidemiológico , Vírus da Hepatite B/imunologia , Hepatite B Crônica/epidemiologia , Avaliação de Programas e Projetos de Saúde , Doença Aguda , Adolescente , Adulto , Criança , Pré-Escolar , China/epidemiologia , Confiabilidade dos Dados , Feminino , Anticorpos Anti-Hepatite B/sangue , Antígenos de Superfície da Hepatite B/sangue , Hepatite B Crônica/sangue , Hepatite B Crônica/virologia , Hospitais , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Adulto Jovem
9.
Aliment Pharmacol Ther ; 52(4): 682-691, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32573827

RESUMO

BACKGROUND: Chronic hepatitis B virus (HBV) infection is a great health burden with geographical variations. AIMS: To explore genetic variants associated with chronic HBV infection. METHODS: The study included 15 352 participants seropositive for HBV core antibodies in Taiwan Biobank. Among them, 2591 (16.9%) seropositive for HBV surface antigen (HBsAg) were defined as having chronic HBV infection. All participants were examined for whole-genome genotyping by Axiom-Taiwan Biobank Array. The human leucocyte antigen (HLA) imputation was performed after identification of the variants within the region. Logistic regressions were used to estimate odds ratios (ORs) with 95% confidence intervals. Correlations of different HLA allele frequencies with HBsAg seroprevalence were evaluated across worldwide populations by Pearson correlation coefficients. Epitope prediction was performed for HLA alleles using NetMHCIIpan method. RESULTS: Located within a cluster of 450 single nucleotide polymorphisms in HLA class II, rs7770370 (P = 2.73 × 10-35 ) was significantly associated with HBV chronicity (Pcorrected  < 8.6 × 10-8 ). Imputation analyses showed that HLA-DPA1*02:02 and HLA-DPB1*05:01 were associated with chronic HBV, with adjusted ORs of 1.43 (1.09-1.89) and 1.61 (1.29-2.01). These allele frequencies were positively correlated with global HBsAg seroprevalence, with R of 0.75 and 0.62 respectively (P < 0.05). HLA-DRB1*13:02, HLA-DQA1* 01:02 and HLA-DQB1*06:09 associated with HBV chronicity negatively, with adjusted ORs of 0.31 (0.17-0.58), 0.70 (0.56-0.87) and 0.33 (0.18-0.63). These HLA alleles had various binding affinities to the predicted epitopes derived from HBV nucleocapsid protein. CONCLUSIONS: HLA class II variants are relevant for chronicity after HBV acquisition.


Assuntos
Genes MHC da Classe II/genética , Estudo de Associação Genômica Ampla , Hepatite B Crônica/epidemiologia , Hepatite B Crônica/genética , Polimorfismo de Nucleotídeo Único , Adulto , Idoso , Alelos , Bancos de Espécimes Biológicos/estatística & dados numéricos , Feminino , Frequência do Gene , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla/métodos , Anticorpos Anti-Hepatite B/sangue , Antígenos de Superfície da Hepatite B/sangue , Antígenos de Superfície da Hepatite B/imunologia , Hepatite B Crônica/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Soroepidemiológicos , Taiwan/epidemiologia
10.
Medicine (Baltimore) ; 99(24): e20583, 2020 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-32541488

RESUMO

To observe the efficacy of telbivudine in chronic hepatitis B (CHB) women with high viral load during pregnancy and the long-term effects on intelligence, growth, and development of the newborns.A total of 87 patients were included. Forty-two patients received telbivudine orally 600 mg per day and treatment initiated from 12 weeks after gestation until the 12th postpartum week. Forty-five patients were untreated according to principle of informed consent. All infants received injection of hepatitis B immune globulin (HBIG; 200 IU) and were vaccinated with recombinant HBV vaccine. Wechsler preschool intelligence scale was used to assess mental and neuropsychological developments of these children till they were 6 years old. Data including serum HBV DNA viral load, Apgar score, and scores of Wechsler preschool intelligence scale were analyzed and compared.Levels of both serum HBV DNA and ALT in patients who received telbivudine were significantly decreased at the 12th week after delivery, compared with baseline levels (P < .01). No significant changes were observed in patients not receiving telbivudine (P > .05). Serum HBV DNA and ALT levels at the 12th week after delivery in the telbivudine group were significantly lower than those of patients without telbivudine (P < .01). The serum HBsAg-positive rate in neonates 7 months of age was 0%, which was significantly lower than that in control group (11.11%) (P < .05). No statistical differences were observed between the 2 groups regarding maternal cesarean section rate, adverse pregnancy rate, postpartum bleeding rate, neonatal body mass, Apgar score, neonatal malformation incidence, or intelligence development of newborn.Telbivudine is effective to reduce the viral load in CHB mothers with high viral load and could lower the perinatal transmission rate. Both mental and physical development in neonates with exposure to telbivudine during perinatal period were similar to those without telbivudine exposure.


Assuntos
Antivirais/uso terapêutico , Hepatite B Crônica/prevenção & controle , Hepatite B Crônica/transmissão , Transmissão Vertical de Doença Infecciosa/prevenção & controle , Telbivudina/uso terapêutico , Adulto , Antivirais/efeitos adversos , Feminino , Hepatite B Crônica/sangue , Hepatite B Crônica/tratamento farmacológico , Humanos , Recém-Nascido , Gravidez , Complicações Infecciosas na Gravidez/tratamento farmacológico , Telbivudina/efeitos adversos , Resultado do Tratamento , Carga Viral , Adulto Jovem
11.
Medicine (Baltimore) ; 99(23): e20638, 2020 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-32502047

RESUMO

To evaluate the diagnostic power of red cell distribution width-to-lymphocyte ratio (RLR) for HBV-related liver cirrhosis via a retrospective cohort study.Seven hundred fifty healthy controls, 327 chronic hepatitis B (CHB) patients, and 410 patients with HBV-related liver cirrhosis (HBV-LC) were enrolled in this study. RLR, lymphocyte-to-monocyte ratio (LMR), neutrophil-to-lymphocyte ratio (NLR), red cell distribution width (RDW), AST to platelet ratio index (APRI), and fibrosis index based on the 4 factors (FIB-4) were compared between the 3 groups. The predictive powers of RLR and RDW for HBV-related liver cirrhosis and patient prognosis were evaluated using AUROC.Patients with HBV-related liver cirrhosis had higher RLR, FIB-4, NLR, RDW, APRI, and lower LMR compared with the control and CHB groups. RLR in the HBV-LC group was significantly higher than both CHB and control groups (both P < .05). While RLR in the CHB group was also higher than the control group, the difference was not statistically significant (P > .05). The AUROC of RLR for predicting HBV-related liver cirrhosis was 0.87, and was superior to RDW (0.81), FIB-4 (0.79), and APRI (0.60). With an optimized cut-off value (10.87), RLR had the highest sensitivity (0.88) and specificity (0.72), and was superior to RDW (0.86, 0.64), FIB-4 (0.80, 0.65), and APRI (0.85, 0.48) as a biomarker. For all 3 groups, RLR was negatively correlated (all P < .05) with serum platelet (PLT) and was positively correlated (all P < .05) with FIB-4 and APRI. There was no significant statistical difference in RLR for patients in HBV-LC group who had different prognosis (P > .05).The RLR, a routinely available, inexpensive, and easily calculated measure, can be used as a predictor of HBV-related liver cirrhosis, but not as a predictor of prognosis for patients with liver cirrhosis. Use of RLR may reduce the need for frequent liver biopsies in CHB patients.


Assuntos
Índices de Eritrócitos , Hepatite B Crônica/sangue , Cirrose Hepática/sangue , Contagem de Linfócitos , Biomarcadores/sangue , Estudos de Casos e Controles , Hepatite B Crônica/complicações , Humanos , Cirrose Hepática/etiologia , Valor Preditivo dos Testes
12.
Aliment Pharmacol Ther ; 51(11): 1180-1187, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32363582

RESUMO

BACKGROUND: Soluble programmed death-1 (sPD-1) and soluble programmed death-ligand 1 (sPD-L1) play a role in immune regulation of chronic hepatitis B virus (HBV) infection. AIM: To investigate the profiles of serum sPD-1 and sPD-L1 in chronic HBV-infected patients with different disease phases and after anti-viral treatment. METHODS: A total of 99 chronic HBV-infected patients were enrolled and divided into HBeAg-positive chronic HBV infection (EPI) group, HBeAg-positive chronic hepatitis B (EPH) group, HBeAg-negative chronic hepatitis B (ENH) group and HBeAg-negative chronic HBV infection (ENI) group. Eleven healthy subjects were included as healthy controls (HCs). Thirty-two EPH patients received anti-viral treatment with nucleos(t)ide analogues and were followed up to 5 years. Serum sPD-1 and sPD-L1 levels were detected by Multiplex Immunoassays. RESULTS: Serum sPD-1 and sPD-L1 levels of chronic HBV infected patients were significantly higher than that of HCs (P < 0.01). Patients in EPH, ENH and EPI groups had higher serum sPD-1 and sPD-L1 levels than that in HCs (P < 0.01). After anti-viral treatment, serum sPD-1 and sPD-L1 levels declined rapidly. EPH patients with HBeAg clearance after 2 years of anti-viral treatment showed lower baseline HBeAg and sPD-1 levels compared to those without HBeAg clearance. CONCLUSIONS: Serum sPD-1 and sPD-L1 levels varied among chronic HBV infected patients with different disease phases. Lower baseline sPD-1 levels were associated with HBeAg clearance after 2 years of anti-viral treatment in EPH patients.


Assuntos
Antivirais/uso terapêutico , Antígeno B7-H1/sangue , Hepatite B Crônica/sangue , Hepatite B Crônica/tratamento farmacológico , Receptor de Morte Celular Programada 1/sangue , Adulto , Estudos de Casos e Controles , Progressão da Doença , Feminino , Vírus da Hepatite B/fisiologia , Hepatite B Crônica/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Tempo
13.
Aliment Pharmacol Ther ; 52(2): 382-389, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32432816

RESUMO

BACKGROUND: Chronic hepatitis B infection is an important contributor to mortality in the United States, yet impact of available and effective oral antivirals on mortality among infected individuals is unknown. AIMS: To compare risks and predictors of mortality in a recent time period between those with chronic, prior and no hepatitis B infection. METHODS: This is a population-based cohort study of National Health and Nutrition Examination Surveys participants between 1999 and 2014 linked to National Death Index data. Adults aged 20 years or older with hepatitis B serologic testing were included. Outcomes of all-cause and liver-related mortality were evaluated using Cox regression. RESULTS: Of 39 206 participants, 192 (0.5%) had chronic and 2694 (6.9%) had prior hepatitis B infection. The all-cause age/sex-standardised mortality rates for chronic, prior and uninfected were 21.4, 15.1 and 11.8 per 1000 person-years respectively. Liver-related mortality occurred at respective rates of 4.1, 0.3 and 0.1 per 1000 person-years. In multivariable analyses, those with chronic infection had 1.9-fold (95% CI 1.1-3.3) increased hazard of all-cause mortality and 13.3-fold (95% CI 3.9-45.5) increased hazard of liver-related mortality compared to uninfected. Predictors of all-cause mortality among chronic infection included heavy alcohol use (HR 18.3, 95% CI 3.3-100.6) and higher alanine aminotransferase (HR 1.02, 95% CI 1.00-1.03). CONCLUSIONS: Mortality among adults living with chronic hepatitis B infection still exceeds that of uninfected despite availability of improved therapeutics. Identification of chronic infection, initiation of treatment among eligible and modulation of co-factors for disease progression are needed to improve survival.


Assuntos
Hepatite B Crônica/mortalidade , Alanina Transaminase/sangue , Consumo de Bebidas Alcoólicas/sangue , Consumo de Bebidas Alcoólicas/mortalidade , Estudos de Coortes , Feminino , Hepatite B Crônica/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Estados Unidos/epidemiologia
14.
Am J Gastroenterol ; 115(8): 1217-1225, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32355123

RESUMO

INTRODUCTION: Chronic hepatitis B (CHB) remains a major worldwide public health concern. Besifovir dipivoxil maleate (BSV) is a new promising treatment for CHB. However, long-term efficacy and safety have not yet been evaluated. Therefore, the goal of the study is to determine the antiviral efficacy and safety of BSV treatment over a 144-week duration (BSV-BSV) in comparison with those of a sequential treatment with tenofovir disoproxil fumarate (TDF) followed by a 96-week duration BSV administration (TDF-BSV). METHODS: After 48 weeks of a double-blind comparison between BSV and TDF treatments, patients continued the open-label BSV study. We evaluated antiviral efficacy and drug safety up to 144 weeks for BSV-BSV and TDF-BSV groups. The primary endpoint was a virological response (hepatitis B virus DNA < 69 IU/mL). RESULTS: Among the 197 patients enrolled, 170 and 158 patients entered the second-year and third-year open-label phase extensional study, respectively, whereas 153 patients completed the 144-week follow-up. The virological response rate over the 144-week period was 87.7% and 92.1% in BSV-BSV and TDF-BSV groups, respectively (P = 0.36). The rates of ALT normalization and HBeAg seroconversion were similar between the groups. No drug-resistant mutations to BSV were noted. Bone mineral density and renal function were well preserved in the BSV-BSV group and were significantly improved after switching therapy in TDF-BSV patients. DISCUSSION: This extensional study of a phase 3 trial (NCT01937806) suggests that BSV treatment is efficacious and safe for long-term use in treatment-naïve and TDF-experienced patients with CHB.


Assuntos
Antivirais/uso terapêutico , Guanina/análogos & derivados , Hepatite B Crônica/tratamento farmacológico , Organofosfonatos/uso terapêutico , Adulto , Antivirais/administração & dosagem , Densidade Óssea , Método Duplo-Cego , Esquema de Medicação , Feminino , Guanina/administração & dosagem , Guanina/uso terapêutico , Vírus da Hepatite B , Hepatite B Crônica/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Organofosfonatos/administração & dosagem , República da Coreia , Tenofovir/administração & dosagem , Tenofovir/uso terapêutico , Resultado do Tratamento , Carga Viral
15.
Aliment Pharmacol Ther ; 51(11): 1169-1179, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32291781

RESUMO

BACKGROUND: Studies have shown a higher risk of hepatocellular carcinoma (HCC) with higher baseline serum hepatitis B virus (HBV) DNA levels in chronic hepatitis B (CHB) patients. However, the association between very high HBV DNA levels (>6 log10 IU/mL) and HCC risk remains unclear, especially in middle-aged and old HBeAg-positive patients. AIM: To identify the association between broad-range HBV DNA levels and HCC risk. METHODS: We conducted a historical cohort study in Korea involving 6949 non-cirrhotic, treatment-naïve CHB patients with alanine aminotransferase (ALT) <2× upper limit of normal for >1 year. HBV DNA was >6 log10 IU/mL in 2029 (29.2%) patients. Follow-up was censored when the antiviral therapy was initiated. RESULTS: The mean age of the patients was 45 years. During 8.0 years of median follow-up, 363 patients (5.2%) developed HCC. By multivariable Cox regression analysis, HCC risk was highest with baseline HBV DNA levels of 6-7 log10 IU/mL (adjusted hazard ratio [aHR] 4.98; P < 0.001), and lowest with >8 log10 IU/mL (aHR 0.90; P = 0.71) and ≤4 log10 IU/mL (aHR 1.00; reference), which was independent of other predictive factors. The similar association between HBV DNA levels and HCC risk was consistently observed in all age subgroups (age <40, 40-49 and ≥ 50 years). CONCLUSIONS: HCC risk was highest with moderate serum HBV DNA levels of 6-7 log10 IU/mL in CHB patients without significant ALT elevation. Extending treatment indication to CHB patients with moderate levels of HBV DNA may be considered to further prevent HCC, regardless of ALT levels.


Assuntos
Carcinoma Hepatocelular/diagnóstico , DNA Viral/sangue , Vírus da Hepatite B/genética , Hepatite B Crônica/sangue , Neoplasias Hepáticas/diagnóstico , Adulto , Idoso , Alanina Transaminase/sangue , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/virologia , Transformação Celular Viral , Estudos de Coortes , Progressão da Doença , Feminino , Seguimentos , Antígenos E da Hepatite B/sangue , Vírus da Hepatite B/isolamento & purificação , Hepatite B Crônica/complicações , Hepatite B Crônica/diagnóstico , Hepatite B Crônica/patologia , Humanos , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , República da Coreia , Fatores de Risco
16.
Zhonghua Gan Zang Bing Za Zhi ; 28(3): 247-253, 2020 Mar 20.
Artigo em Chinês | MEDLINE | ID: mdl-32306658

RESUMO

Objective: To investigate the application value of reactive oxygen species (ROS) and adiponectin (ADPN) in the judgment of liver inflammation in chronic hepatitis B virus infection combined with nonalcoholic fatty liver disease (NAFLD). Methods: A total of 159 cases with NAFLD (21 cases), chronic hepatitis B virus infection (57 cases), and chronic hepatitis B virus infection combined with NAFLD (81 cases) were collected between June 2016 to December 2018, and the visited patients diagnosis were confirmed by histopathological examination of the liver. ROS and ADPN level retained in serum was determined by enzyme-linked immunosorbent assay. Histopathological examination of liver tissue was used as the gold standard to discuss the diagnostic value of the serum in patients with chronic hepatitis B virus infection combined with NAFLD for the occurrence of nonalcoholic steatohepatitis. One-way analysis of variance was used for the comparison among multiple groups, and LSD-t test was used for pairwise comparison between groups. Measurement data for non-normal distributions were expressed as M (P25, P75). Comparisons between groups were performed using the Mann-Whitney U or Kruskal-Wallis H test. Chi-square test was used to compare the count data between groups. Correlation analysis was performed using Spearman correlation analysis. Histopathological grouping of liver tissue was used as the gold standard, and the area under the receiver operating characteristic curve was used to evaluate the diagnostic efficacy of the regression formula. Results: (1) In patients with chronic hepatitis B virus infection combined with NAFLD, the levels of ROS in the non-hepatic steatosis group and the mild hepatic steatosis group were significantly lower than those in the moderate and severe hepatic steatosis group, while the ADPN level in the non-hepatic steatosis group was significantly higher than liver steatosis group, P < 0.05. (2) The results of correlation analysis showed that ROS was significantly correlated with NAS score, change in the degree of fatty liver and lobular inflammation (all P < 0.05).There was a significant negative correlation between ADPN and the change in the degree of fatty liver (P < 0.05). (3) Logistic regression analysis results showed that the diagnostic formula for chronic hepatitis B virus infection combined with nonalcoholic steatohepatitis was 0.02 × controlled attenuation index + 0.584 × white blood cells/10(9) + 0.587 × ROS-10.982. The area under receiver operating characteristic curve of the subject was = 0.896. The sensitivity, specificity, positive and negative predictive value were 97.1%, 71.2%, 64.2%, and 97.9%. Conclusion: ADPN and ROS have certain reference value in differentiating the change in the degree of fatty liver and inflammation in chronic hepatitis B virus infection combined with NAFLD and the diagnostic formula has higher application value in the diagnosis and exclusion of chronic hepatitis B virus infection combined with nonalcoholic steatohepatitis.


Assuntos
Adiponectina/sangue , Hepatite B Crônica/sangue , Hepatopatia Gordurosa não Alcoólica/sangue , Hepatopatia Gordurosa não Alcoólica/virologia , Espécies Reativas de Oxigênio/sangue , Biópsia , Vírus da Hepatite B , Hepatite B Crônica/complicações , Humanos , Fígado
18.
Acta Biochim Pol ; 67(1): 7-14, 2020 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-32191420

RESUMO

Previous studies detected higher Golgi protein 73 levels in the serum of patients with chronic liver disease. The Beta-2 microglobulin levels were also observed to be higher in patients with chronic hepatitis B infection compared to the inactive carriers and the protein plays an important role in the response to viral infections. The aim of the present study was to assess the liver fibrosis through non-invasive methods in chronic hepatitis B patients. Three groups were included in the study. The first group comprised of the patients who were admitted to the Infectious Diseases and Clinical Microbiology clinic to undergo a liver biopsy, while the second group included the patients who were admitted inactive hepatitis B carriers. The third group comprised the healthy controls. The Golgi p-73 and Beta-2 microglobulin levels in the plasma were determined using the ELISA method. Beta-2 microglobulin level was highest in the patients group and the difference was statistically significant. No significant difference was observed between the carriers group and the group of healthy controls. The Golgi P-73 values were significantly higher in the patients group in comparison to both other groups. However, the mean Golgi p-73 value was also significantly higher in the carrier group compared to the control group. In patients who are followed up with the diagnosis of chronic hepatitis B and who have undergone biopsies as candidates for treatment, the Beta-2 microglobulin and Golgi p-73 values may be important markers since they indicate the extent of the liver damage.


Assuntos
Hepatite B Crônica/patologia , Proteína Tumoral p73/sangue , Microglobulina beta-2/sangue , Adulto , Biomarcadores/sangue , Estudos de Casos e Controles , Feminino , Hepatite B Crônica/sangue , Hepatite B Crônica/diagnóstico , Humanos , Cirrose Hepática/sangue , Masculino , Pessoa de Meia-Idade , Prognóstico
19.
Sci Rep ; 10(1): 2014, 2020 02 06.
Artigo em Inglês | MEDLINE | ID: mdl-32029790

RESUMO

Our study purpose was to evaluate mitochondrial (mt)DNA and RNA in peripheral blood mononuclear cells (PBMCs) and body shape changes (BSC) in HBV-infected patients. mtDNA and mtRNA were measured in PBMCs. The presence of BSC was evaluated through a questionnaire and clinical evaluation. A total of 157 subjects were enrolled, of these 107 were HBV-infected patients, 54 receiving nucleoside analogues (NAs, Group A), 53 naive to antivirals (Group B) and 50 age-sex matched controls (Group C). All HBV-treated patients had negative HBV-DNA. Twenty (37,0%) received lamivudine + adefovir, 20 (37.0%) tenofovir, 2 (3.7%) lamivudine and 12 (22.2%) entecavir. Therapy median duration was 38 months (IQR 20-60) in NA-treated patients. Group A showed significantly higher mtDNA/nuclear (n) DNA ratio (p = 0.000008) compared to Group C and Group B (p = 0.002). Group B showed significantly higher mtDNA/nDNA ratio compared to Group C (p = 0.017). Group A and B had significantly lower mtRNA/nRNA ratio compared to Group C (p = 0.00003 and p = 0.00006, respectively). Tenofovir and entecavir showed less impact compared to lamivudine + adefovir. mtDNA/nDNA ratio positively (Rho = 0.34, p < 0.05) and mtRNA/nRNA ratio negatively (Rho = -0.34, p < 0.05) correlated with therapy duration. BSC were significantly more frequent in Group A [10/54 (18.5%)] compared to Group B [3/53 (5.6%, p = 0.04)] and Group C [0/50, (p = 0.0009)]. In conclusion, long-term NA therapy was associated both to mitochondrial toxicity and BSC, showing significant differences in mtDNA and mtRNA levels. Tenofovir and entecavir showed lower impact on alterations, compared to 1st generation NA.


Assuntos
Adiposidade/efeitos dos fármacos , Antivirais/efeitos adversos , Hepatite B Crônica/tratamento farmacológico , Mitocôndrias/efeitos dos fármacos , Adenina/efeitos adversos , Adenina/análogos & derivados , Estudos Transversais , DNA Mitocondrial/isolamento & purificação , DNA Viral/isolamento & purificação , Farmacorresistência Viral , Quimioterapia Combinada/efeitos adversos , Quimioterapia Combinada/métodos , Feminino , Guanina/efeitos adversos , Guanina/análogos & derivados , Vírus da Hepatite B/genética , Vírus da Hepatite B/isolamento & purificação , Hepatite B Crônica/sangue , Hepatite B Crônica/virologia , Humanos , Lamivudina/efeitos adversos , Leucócitos Mononucleares/citologia , Leucócitos Mononucleares/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Mitocôndrias/genética , Organofosfonatos/efeitos adversos , RNA Mitocondrial/isolamento & purificação , Tenofovir/efeitos adversos
20.
Sci Rep ; 10(1): 1835, 2020 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-32020034

RESUMO

Chronic hepatitis B (CHB) infection functional cure is defined as sustained loss of HBsAg and several therapeutic strategies are in clinical development designed to pharmacologically reduce serum HBsAg, break immune tolerance, and increase functional cure rates. However, little is known about pre-treatment HBsAg levels as an indicator of HBV immune potential. Here, we compared the phenotypes and HBV-specific response of lymphocytes in CHB patients stratified by serum HBsAg levels <500 (HBslo) or >50,000 IU/ml (HBshi) using immunological assays (flow cytometry, ICS, ELISPOT). HBshi patients had significantly higher expression of inhibitory PD-1 on CD4+ T cells, particularly among TEMRA subset, and higher FcRL5 expression on B cells. Upon HBcAg(core) or HBsAg(env)-stimulation, 85% and 60% of HBslo patients had IFNγ+TNFα+ and IFNγ+ IL2+ CD4+ T cell responses respectively, in comparison to 33% and 13% of HBshi patients. Checkpoint blockade with αPD-1 improved HBV-specific CD4+ T cell function only in HBslo patients. HBsAg-specific antibody-secreting cells (ASCs) response was not different between these groups, yet αPD-1 treatment resulted in significantly higher fold change in ASCs among patients with HBsAg <100 IU/ml compared to patients with HBsAg >5,000 IU/ml. Thus, serum HBsAg correlates with inhibitory receptor expression, HBV-specific CD4+ T cell responses, and augmentation by checkpoint blockade.


Assuntos
Linfócitos B/imunologia , Antígenos de Superfície da Hepatite B/sangue , Vírus da Hepatite B/imunologia , Hepatite B Crônica/imunologia , Linfócitos T/imunologia , Biomarcadores/sangue , Citometria de Fluxo , Hepatite B Crônica/sangue , Humanos , Receptor de Morte Celular Programada 1/metabolismo
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