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1.
Medicine (Baltimore) ; 98(46): e17969, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31725660

RESUMO

Alanine transaminase (ALT) abnormalities are common in chronic hepatitis B (CHB) carriers during postpartum period. Disturbances in cytokines are considered to be associated with hepatitis Flares. There are limited data on cytokines changes in HBeAg positive patients with ALT abnormalities.This is an observational study. Pregnant patients with hepatitis B e-antigen (HBeAg) positive were enrolled from January 2014 to September 2018. Patients were assigned into three groups based on ALT levels in postpartum 6 to 8 weeks: ALT in normal range, ALT in 1 to 2-fold upper limits of normal (ULN) and ALT >2-fold ULN. Serum cytokines, ratios of regulatory T cells, and the concentration of cortisol were collected and compared among the three groups.Of the 135 mothers enrolled, 80.7% (109/135) completed the postpartum 6-week study. 13.8% (15/109) patients had postpartum ALT higher than 2ULN, 27.5% (30/109) patients had ALT in 1 to 2ULN and 58.7% (64/109) patients had ALT in normal range. Compared to control group, patients with ALT >2ULN had a higher IL-10 level (P < .05). No differences of IL-10 levels were found in the comparison of other inter comparison among three groups. No differences were found in the levels of other collected serum cytokines, cortisol, and regulatory T cells among three groups. On multivariate analysis, abnormal IL-10 level was independent risk factor for postpartum ALT elevating >2ULN. At the same time, the incidence of postpartum ALT elevated >2ULN were higher in patients with abnormal elevation IL-10 level than in patients with normal IL-10 level (14/68 vs 1/41, P = .008).CHB patients with postpartum ALT abnormalities show higher IL-10 level and postpartum ALT abnormalities were mainly occurred in patients with abnormal IL-10 level. IL-10 may be an underlying predictor and treatment target of hepatitis B, and further studies are needed.


Assuntos
Alanina Transaminase/sangue , Antígenos E da Hepatite B/sangue , Hepatite B Crônica/sangue , Interleucina-10/sangue , Período Pós-Parto/fisiologia , Adulto , Antivirais/uso terapêutico , Citocinas/sangue , Feminino , Antígenos E da Hepatite B/imunologia , Hepatite B Crônica/tratamento farmacológico , Humanos , Hidrocortisona/sangue
2.
Expert Opin Drug Metab Toxicol ; 15(10): 779-785, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31593639

RESUMO

Introduction: Interferon (IFN) had both antiviral and immunomodulatory effects, and was one of the approved treatments for hepatitis B virus (HBV). Herein, we reviewed the pharmacokinetics and pharmacodynamics of pegylated IFN-α (PegIFN-α) for the treatment of HBV. Areas covered: The steady-state serum levels of PegIFN-α were reached within 5 to 8 weeks, and the week 48 mean trough concentrations were approximately 2-fold higher than week 1. There was also no difference of the pharmacokinetics in male or female, healthy volunteers or patients with hepatitis B or C infection. PegIFN-α did not affect the metabolism of the cytochrome P450 (CYP) isozymes, except inhibition of CYP1A2. There was also no pharmacokinetic interaction between PegIFN-α and HBV nucleot(s)ide analogues (NUCs). Forty-eight weeks of PegIFN-α achieved 32% of HBeAg seroconversion, 32-43% of HBV DNA suppression, 41-59% of ALT normalization, and 3% of HBsAg seroconversion rate with a post-treatment durable response up to 80% in the initial responders. Expert opinion: On-treatment HBsAg titer guided the treatment of HBV with PegIFN-α. The recommendation of PegIFN-α and NUC combination or switch remained controversial. New immunotherapeutic agents are now in development. Although, PegIFN-α should continue to play a role in the treatment of HBV.


Assuntos
Hepatite B Crônica/tratamento farmacológico , Interferon alfa-2/administração & dosagem , Interferon-alfa/administração & dosagem , Polietilenoglicóis/administração & dosagem , Animais , Antivirais/administração & dosagem , Antivirais/farmacocinética , Antivirais/farmacologia , DNA Viral/efeitos dos fármacos , Interações de Medicamentos , Feminino , Antígenos E da Hepatite B/sangue , Humanos , Interferon alfa-2/farmacocinética , Interferon alfa-2/farmacologia , Interferon-alfa/farmacocinética , Interferon-alfa/farmacologia , Masculino , Polietilenoglicóis/farmacocinética , Polietilenoglicóis/farmacologia , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/farmacocinética , Proteínas Recombinantes/farmacologia
3.
Zhonghua Gan Zang Bing Za Zhi ; 27(8): 594-603, 2019 Aug 20.
Artigo em Chinês | MEDLINE | ID: mdl-31594076

RESUMO

Chronic hepatitis B virus (HBV) infection remains a major world public health problem. Current guidelines for the prevention and treatment of chronic hepatitis B (CHB) have suggested clinical cure (also known as functional cure) as the ideal therapeutic goal, which is associated with decreased risk of cirrhosis and hepatocellular carcinoma. Clinical cure is defined as sustained, undetectable serum HBsAg, HBeAg and HBV DNA with or without seroconversion to anti-HBs, but with the persistence of residual cccDNA, accompanied by resolution of liver injury after the completion of a finite course of treatment. Accumulating data from a series of randomized controlled trials as well as clinical practice have confirmed certain clinical benefit of optimal sequential/ combination strategies of direct acting antiviral drugs (DAA) [such as nucleoside analogues (NA)] or immunomodulators (such as pegylated interferon alpha (Peg-IFN)] for appropriately selected CHB patients. This consensus provides an updated and comprehensive analysis of the data supporting the use of combination therapies and summarizes the roadmap towards clinical cure of CHB to guide decision-making in clinical practice.


Assuntos
Antivirais/uso terapêutico , Hepatite B Crônica/terapia , Consenso , DNA Viral/sangue , Antígenos de Superfície da Hepatite B/sangue , Antígenos E da Hepatite B/sangue , Vírus da Hepatite B , Humanos , Guias de Prática Clínica como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto
4.
Zhonghua Gan Zang Bing Za Zhi ; 27(8): 604-609, 2019 Aug 20.
Artigo em Chinês | MEDLINE | ID: mdl-31594077

RESUMO

Objective: To investigate the curative effect of antiviral therapy and related factors influencing the curative affect in children with immune-tolerant phase chronic hepatitis B. Methods: From May 2014 to April 2015, 46 children with chronic hepatitis B, aged 1 to 16 years with immune-tolerant phase were enrolled as the treatment group. All cases in the treated group either received interferon alpha (3-5 MIU/m(2), once daily) in lamivudine combination (if HBV DNA decreased < 2 log(10)) or repeatedly received interferon-alpha alone (if HBV DNA decreased >2 log(10)) for 12 weeks. Interferon was discontinued at 72 weeks and followed-up period was continued with lamivudine for 24 weeks. At the same time, data of 23 cases of untreated children with immune-tolerant phase chronic hepatitis B were collected as the control group. The treatment group and the control group were divided into two age groups: 1-7 years old and 7-15 years old. Data measurements were compared using t-test, analysis of variance and single factor analysis methods, and the count data were analyzed by χ (2) test. Multiple logistic regression analysis was used to analyze the effects of different factors on response. Results: (1) There were 22 cases aged 1-7 years in the treatment group (47.8%) and 12 cases aged 1-7 years in the control group (52.2%). The cases of mother-to-child transmission (MTCT) in treatment and control group were 34 (73.9%) and 17 (73.9%), while children with normal baseline ALT in the treatment and control group were 18 (39.1%) and 10 (43.5%). (2) At the end of follow-up, 15 cases in the treatment group (32.6%) had HBeAg serological conversion. Among them, nine (19.6%) cases had HBsAg clearance or HB-Ag seroconversion with anti-HBs, and one (2.2%) case had HBsAg clearance, but both HBeAg and anti-HBe were positive. In the control group, one case had HBV DNA lower than the lower limit of detection level, and one case had HBeAg seroconversion without HBsAg clearance. (3) At the end of follow-up, the seroconversion rates of HBeAg in patients aged 1 to 7 years and patients aged 7 to 15 years were 45.5% and 20.8%, respectively (P = 0.078) and the clearance rates of HBsAg were 36.4% and 8.3% (P = 0.023). The serum conversion rates of normal and abnormal baseline alanine aminotransferase levels were 5.6% and 50.0% (P = 0.005), and the clearance rates of HBsAg were 5.6% and 32.1% (P = 0.077), respectively. There was no statistically significant difference in gender, mother-to-child transmission, HBV DNA genotyping and baseline HBsAg level in antiviral efficacy among children (P > 0.05). (4) HBsAg and HBeAg clearance occurred in 100% of patients at the end of follow-up who had HBsAg < 3 000 IU/ml at 24 weeks of treatment. (5) Multivariate logistic regression analysis showed that serum HBeAg conversion rate had relation with non-MTCT transmission and abnormal baseline alanine aminotransferase. Furthermore, HBsAg clearance rate was associated with the age of children. Conclusion: Sequential combination of interferon and lamivudine with a prolonged course can improve the HBV DNA negative conversion rate, HBeAg seroconversion rate, HBsAg loss rate and mild ALT abnormalities at baseline in children under the age of 7 years with immune-tolerant phase chronic hepatitis B.


Assuntos
Antivirais/uso terapêutico , Hepatite B Crônica/tratamento farmacológico , Interferons/uso terapêutico , Lamivudina/uso terapêutico , Adolescente , Criança , Pré-Escolar , DNA Viral/sangue , Quimioterapia Combinada , Antígenos de Superfície da Hepatite B/sangue , Antígenos E da Hepatite B/sangue , Humanos , Lactente , Transmissão Vertical de Doença Infecciosa , Resultado do Tratamento
5.
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
6.
Medicine (Baltimore) ; 98(36): e17022, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31490387

RESUMO

Pegylated interferon alpha (PEG-IFN-α) is a first-line treatment for patients with chronic hepatitis B (CHB), but its efficacy varies from individual to individual. Early discrimination between responder and non-responder patients is important for optimal clinical management. In addition, low therapeutic efficacy is still a major issue; thus, treatment timing should be optimized.We reviewed our experience with hepatitis B e-antigen (HBeAg)-positive patients treated with PEG-IFN-α, alone or in combination with nucleoside analogues (NAs), from 2009 through 2014. Collected data included both general characteristics of 113 patients and laboratory data at baseline and at treatment weeks 12, 24, 52, and 76. The endpoint was HBeAg seroconversion at week 76.A total of 113 patients with changed to or start of NAs therapy were included in this study. At the end of treatment, 44 (38.9%) patients exhibited HBeAg seroconversion. Patients with HBeAg seroconversion had lower baseline HBeAg (475.5 vs 751.7; P = .007). The incidence of HBeAg seroconversion was significantly higher among patients with HBeAg ≤ 500 signal-to-cutoff ratio (S/CO) (OR = 2.60, 95% CI: 1.16-5.83, P = .02) at baseline, HBeAg S/CO ≤ 20 (OR = 3.37, 95% CI: 1.47-7.73, P = .003), or a higher than 10-fold HBeAg drop (OR = 3.55, 95% CI: 1.50-8.37, P = .003) at week 12 or HBeAg ≤ 15 S/CO (OR = 10.35, 95% CI: 4.09-26.20, P < .001) at week 24. Subgroup analyses demonstrated that in patients with HBeAg >20 S/CO at 24 weeks, the addition of NAs treatment may increase HBeAg seroconversion (23.3% vs 0%, P = .03).HBeAg levels had an impact on the rate of serological conversion in CHB patients receiving PEG-IFN-based treatment. Combination therapy with NAs should be considered in CHB patients maintaining a high HBeAg level after 24 weeks of PEG-IFN monotherapy.


Assuntos
Antivirais/uso terapêutico , Hepatite B Crônica/tratamento farmacológico , Interferon-alfa/uso terapêutico , Nucleosídeos/uso terapêutico , Adolescente , Adulto , Quimioterapia Combinada , Feminino , Antígenos E da Hepatite B/sangue , Hepatite B Crônica/imunologia , Humanos , Masculino , Estudos Retrospectivos , Soroconversão , Adulto Jovem
7.
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
8.
BMC Pregnancy Childbirth ; 19(1): 275, 2019 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-31375078

RESUMO

BACKGROUND: Our study aims to describe how obstetricians manage pregnant women infected with chronic hepatitis B in a region with a large high-risk population. METHODS: We performed a cross-sectional study among practicing obstetricians in Santa Clara County, California. All obstetricians practicing in Santa Clara County were invited to participate in the study. Obstetricians were recruited in person or by mail to complete a voluntary, multiple choice survey on hepatitis B (HBV). Survey questions assessed basic HBV knowledge and obstetricians' self-reported clinical practices of the management of HBV-infected pregnant women. Pooled descriptive analyses were calculated for the cohort, as well as, correlation coefficients to evaluate the association between reported clinical practices and hepatitis B knowledge. RESULTS: Among 138 obstetricians who completed the survey, 94% reported routinely testing pregnant women for hepatitis B surface antigen (HBsAg) with each pregnancy. Only 60.9% routinely advised HBsAg-positive patients to seek specialist evaluation for antiviral treatment and monitoring and fewer than half (48.6%) routinely provided them with HBV information. While most respondents recognized the potential complications of chronic HBV (94.2%), only 21% were aware that chronic HBV carries a 25% risk of liver related death when left unmonitored and untreated, and only 25% were aware of the high prevalence of chronic HBV in the foreign-born Asian, Native Hawaiian and Pacific Islander population. Obstetricians aware of the high risk of perinatal HBV transmission were more likely to test pregnant women for HBV DNA or hepatitis B e-antigen in HBV-infected women (r = 0.18, p = 0.033). Obstetricians who demonstrated knowledge of the long-term consequences of untreated HBV infection were no more likely to refer HBV-infected women to specialists for care (r = 0.02, p = 0.831). CONCLUSION: Our study identified clear gaps in the practice patterns of obstetricians that can be readily addressed to enhance the care they provide to HBV-infected pregnant women.


Assuntos
Competência Clínica , Hepatite B Crônica/terapia , Obstetrícia , Padrões de Prática Médica , Complicações Infecciosas na Gravidez/terapia , Encaminhamento e Consulta , Adulto , Antivirais/uso terapêutico , Estudos Transversais , DNA Viral/sangue , Gerenciamento Clínico , Feminino , Antígenos de Superfície da Hepatite B/sangue , Antígenos E da Hepatite B/sangue , Hepatite B Crônica/sangue , Hepatite B Crônica/diagnóstico , Hepatite B Crônica/etnologia , Humanos , Transmissão Vertical de Doença Infecciosa , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Gravidez , Complicações Infecciosas na Gravidez/sangue , Complicações Infecciosas na Gravidez/diagnóstico , Complicações Infecciosas na Gravidez/etnologia
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.
Virus Genes ; 55(5): 610-618, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31359359

RESUMO

Current data of hepatitis B virus (HBV) variants associated with treatment outcome identified by next generation sequencing (NGS) are limited. This study was aimed at determining the role of baseline sequence variations in the enhancer II (EnhII), basal core promotor (BCP) and pre-core (PC) regions of HBV genotype C in patients treated with pegylated interferon (PEG-IFN). Patients with HBeAg-positive chronic hepatitis B (CHB) treated with 48-week PEG-IFN were enrolled. Combined response (CR) at week 96 was defined by HBeAg seroconversion plus HBV DNA < 2000 IU/mL and HBsAg < 1000 IU/mL. Pre-treatment viral mutations were characterized by Sanger sequencing and NGS (Miseq Illumina platform). Among 47 patients (32 male, mean age 32.4 years), CR was achieved in 12 (25.5%) individuals. Overall, NGS was superior to Sanger sequencing in detecting mutations (61.7% vs. 38.3%, P < 0.001). Based on NGS, the prevalence of T1753V (T1753C/A/G) and A1762T/G1764A variants were significantly lower in responders compared to non-responders (8.3% vs. 51.4%, P = 0.009 and 33.3% vs. 68.6%, P = 0.032, respectively). No significant difference between groups was found regarding C1653T and G1896A mutants. The absence of T1753V and A1762T/G1764A mutations were factors associated with CR (OR 11.65, 95%CI 1.36-100.16, P = 0.025, and OR 4.36, 95%CI 1.08-17.63, P = 0.039, respectively). The existence of pre-treatment T1753V, A1762T/G1764A mutations and their combination yielded negative predictive values of 94.7%, 85.7% and 93.8%, respectively. The presence of HBV mutants in the BCP region determined by NGS at baseline was associated with poor treatment outcome in patients with HBeAg-positive CHB receiving PEG-IFN.


Assuntos
Antivirais/uso terapêutico , Variação Genética , Vírus da Hepatite B/genética , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/virologia , Interferons/uso terapêutico , Mutação , Adolescente , Adulto , Feminino , Genótipo , Antígenos do Núcleo do Vírus da Hepatite B/genética , Antígenos E da Hepatite B/sangue , Vírus da Hepatite B/isolamento & purificação , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Regiões Promotoras Genéticas , Resultado do Tratamento , Adulto Jovem
12.
Zhongguo Zhong Yao Za Zhi ; 44(13): 2858-2864, 2019 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-31359701

RESUMO

To evaluate the efficacy and safety of Gantaishu Capsules in the treatment of viral B hepatitis. The randomized controlled trials( RCT) retrieved from Cochrane Library,PubMed,Sino Med,CNKI,Wan Fang and VIP were enrolled. The methodology quality of the included studies was evaluated,and a Meta-analysis was performed using Rev Man 5. 3 software. A total of six randomized controlled trials were included. Meta-analysis results showed that the similarities in the negative conversion rate of HBe Ag( RR = 2. 09,95%CI[0. 90,4. 85],P = 0. 09,I2= 0%),the HBV-DNA negative rate( RR = 1. 49,95% CI[0. 56,3. 95],P = 0. 43,I2= 0%) and the changes in ALT levels before and after treatment( RR =-6. 28,95%CI[-72. 83,60. 27],P = 0. 85,I2= 99%),with no statistical difference. In terms of quality of life,Gantaishu Capsules can significantly alleviate the symptoms of hepatitis B patients,with less adverse reactions. Gantaishu Capsules and Dongbao Gantai Tablets were similar in antiviral effect. In this term,Gantaishu Capsules was superior to Dangfei Liganning Capsules. It can significantly alleviate the symptoms of chronic hepatitis B patients,with a good clinical safety.Therefore,it can be applied in the case of syndrome differentiation and treatment. In view of the low quality of the included studies,more high-quality clinical trials were required to confirm its efficacy.


Assuntos
Antivirais/uso terapêutico , Medicamentos de Ervas Chinesas/uso terapêutico , Hepatite B Crônica/tratamento farmacológico , Cápsulas , DNA Viral/sangue , Antígenos E da Hepatite B/sangue , Humanos , Qualidade de Vida
13.
Int J Infect Dis ; 85: 150-157, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31202910

RESUMO

BACKGROUND: Hepatitis B virus (HBV) infection is a major cause of morbidity and mortality; however, little is known about the prevalence and distribution of HBV in some populations and regions. METHODS: A total of 9791 participants, 15-49 years old, were enrolled in a household survey in KwaZulu-Natal, South Africa. Peripheral blood samples were tested for markers of HBV (hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg), antibody to HBeAg (anti-HBe)) and analysed, accounting for multilevel sampling and weighted to represent the population. RESULTS: Overall HBsAg prevalence was 4.0% (95% confidence interval (CI) 3.4-4.5%): 4.8% (95% CI 3.8-5.8%) in men and 3.2% (95% CI 2.5-3.9%) in women (p=0.01). Among HBsAg-positive participants, 35.2% (95% CI 29.2-41.2%) were HBeAg-positive and 66.3% (95% CI 60.1-72.4%) were anti-HBe-positive. HBsAg prevalence was 6.4% (95% CI 5.3-7.5%) among HIV-positive participants compared to 2.6% (95% CI 1.9-3.2%) among HIV-negative participants (p<0.01), and was higher among HIV-positive men (8.7%, 95% CI 6.3-11.2%) than among HIV-positive women (5.0%, 95% CI 3.8-6.2%) (p<0.01). CONCLUSIONS: HBV infection among HIV-positive men remains an important public health problem in communities in KwaZulu-Natal, South Africa. The prevalence of HBsAg and HBeAg highlight the importance of surveillance and an important missed opportunity for the scale-up of programmes to achieve the goal of controlling HBV for public health benefit.


Assuntos
Anticorpos Anti-Hepatite B/sangue , Hepatite B/epidemiologia , Adolescente , Adulto , Coinfecção , Feminino , Soropositividade para HIV/complicações , Hepatite B/complicações , Antígenos de Superfície da Hepatite B/sangue , Antígenos E da Hepatite B/sangue , Antígenos E da Hepatite B/imunologia , Vírus da Hepatite B/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Soroepidemiológicos , África do Sul/epidemiologia , Inquéritos e Questionários , Adulto Jovem
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.
Med Sci Monit ; 25: 4665-4674, 2019 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-31230063

RESUMO

BACKGROUND High rates of HBeAg and/or HBsAg seroconversion or clearance have been achieved in chronic hepatitis B (CHB) patients receiving pegylated interferon (pegIFN) in addition to ongoing nucleos(t)ide analogue (NUC) treatment. In the present study, we aimed to evaluate HBsAg kinetics to predict HBeAg seroconversion and HBsAg clearance in these patients. MATERIAL AND METHODS A total of 33 HBeAg-positive and 17 HBeAg-negative patients were enrolled between January 2010 and January 2018. At the end of pegIFN treatment, 9 of 50 patients achieved HBsAg clearance, and 9 of 33 HBeAg-positive patients achieved HBeAg seroconversion. RESULTS The cutoff value of 0.41 log10 IU/mL in HBsAg decline at week 12 had a positive predictive value (PPV) of 58.3% and a negative predictive value (NPV) of 94.6% for HBsAg clearance. The cutoff value of 1.94 log10 IU/mL in HBsAg decline at week 24 had a PPV of 80.0% and an NPV of 97.5% for HBsAg clearance. The cutoff value of 0.47 log10 IU/mL in HBsAg decline at week 12 had a PPV of 83.3% and an NPV of 85.2% for HBeAg seroconversion. The cutoff value of 1.29 log10 IU/mL in in HBsAg decline at week 24 had a PPV of 85.7% and an NPV of 88.5% for HBeAg seroconversion. CONCLUSIONS Early HBsAg drop has a high predictive value for HBsAg clearance and HBeAg seroconversion in patients who were treated with combination therapy of pegIFN and NUCs.


Assuntos
Antígenos de Superfície da Hepatite B/análise , Hepatite B Crônica/tratamento farmacológico , Adulto , Antivirais/uso terapêutico , Biomarcadores Farmacológicos/sangue , DNA Viral/sangue , Feminino , Guanina/análogos & derivados , Antígenos de Superfície da Hepatite B/sangue , Antígenos de Superfície da Hepatite B/metabolismo , Antígenos E da Hepatite B/sangue , Antígenos E da Hepatite B/metabolismo , Vírus da Hepatite B/genética , Hepatite B Crônica/sangue , Humanos , Interferon alfa-2/farmacocinética , Interferon alfa-2/farmacologia , Interferon-alfa/farmacologia , Masculino , Pessoa de Meia-Idade , Polietilenoglicóis/farmacologia , Proteínas Recombinantes/farmacologia , Soroconversão , Resultado do Tratamento
16.
Biomed Environ Sci ; 32(5): 315-323, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31217048

RESUMO

OBJECTIVE: To investigate the relationship between maternal peripheral blood mononuclear cells (PBMC) hepatitis B virus (HBV) covalenty closed circular deoxyribonucleic acid (cccDNA) and other HBV serological markers and its effects on HBV intrauterine transmission. METHODS: We enrolled 290 newborns and their hepatitis B surface antigen (HBsAg) positive mothers. HBV cccDNA in PBMC and HBV DNA in serum were detected by a real-time PCR-TaqMan probe while HBV serological markers were detected with an electrochemiluminescence immunoassay. RESULTS: There was a positive correlation between the levels of PBMC HBV cccDNA and serum HBV DNA and HBeAg (r = 0.436 and 0.403, P < 0.001). The detection rate of pattern A ['HBsAg (+), HBeAg (+), and anti-HBc (+)'] was significantly higher in the PBMC HBV cccDNA positive group than in the control group (χ2 = 48.48, P < 0.001). There was a significant association between HBV intrauterine transmission and PBMC HBV cccDNA (χ2 = 9.28, P = 0.002). In the presence of serum HBV DNA, HBeAg, and PBMC HBV cccDNA, the risk of HBV intrauterine transmission was three times higher (OR = 3.69, 95% CI: 1.30-10.42) than that observed in their absence. The risk of HBV intrauterine transmission was the greatest (OR = 5.89, 95% CI: 2.35-14.72) when both PBMC HBV cccDNA and pattern A were present. A Bayesian network model showed that maternal PBMC HBV cccDNA was directly related to HBV intrauterine transmission. CONCLUSION: PBMC HBV cccDNA may be a direct risk factor for HBV intrauterine transmission. Our study suggests that serological markers could be combined with PBMC-related markers in prenatal testing.


Assuntos
DNA Viral/sangue , Transmissão de Doença Infecciosa , Antígenos E da Hepatite B/sangue , Hepatite B/transmissão , Leucócitos Mononucleares/virologia , Adolescente , Adulto , Feminino , Hepatite B/congênito , Humanos , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Adulto Jovem
17.
Int J Med Sci ; 16(5): 720-728, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31217740

RESUMO

Objective: This study aims to clarify the changes and clinical significance of red cell distribution width (RDW) during HBV-related chronic diseases, including inactive hepatitis B virus (HBV) carriers, HBV immune tolerant individuals, chronic hepatitis B (CHB) patients and HBV-related hepatocirrhosis patients. Methods: RDW was measured 288 CHB patients, 100 patients with hepatitis B e antigen(HBeAg)-negative chronic HBV infection (inactive carriers), 92 patients with HBeAg-positive chronic HBV infection (immune tolerant), and 272 patients with HBV-related hepatocirrhosis. Their RDW changes were compared with 160 healthy controls. Correlations between RDW and clinical indicators were conducted. For HBeAg+ CHB patients, RDW was measured before and after antiviral therapy. The efficiency of RDW to distinguish hepatocirrhosis from CHB and/or inactive carriers was evaluated by receiver operating characteristic (ROC) curves. Results: RDW was higher in hepatocirrhosis patients than other groups of patients and healthy controls. Besides, HBeAg+ CHB patients possessed higher RDW than HBeAg- CHB patients. For HBeAg+ patients that underwent HBeAg seroconversion after antiviral therapy, RDW was decreased. RDW was positively correlated with total bilirubin and Child-Pugh scores and negatively correlated with albumin among hepatocirrhosis patients. The areas under the curve (AUC) of ROC curves to distinguish hepatocirrhosis from CHB patients was 0.7040 for RDW-standard deviation (RDW-SD) and 0.6650 for RDW-coefficient of variation (RDW-CV), and AUC to distinguish hepatocirrhosis from inactive carriers was 0.7805 for RDW-SD and 0.7991 for RDW-CV. Conclusions: RDW is significantly increased in HBeAg+ CHB patients and patients with HBV-related hepatocirrhosis and could reflect their severity. RDW could help to distinguish hepatocirrhosis from CHB patients and inactive HBV carriers.


Assuntos
Antígenos E da Hepatite B/sangue , Vírus da Hepatite B/patogenicidade , Hepatite B Crônica/sangue , Cirrose Hepática/sangue , Adulto , Diagnóstico Diferencial , Índices de Eritrócitos/imunologia , Feminino , Antígenos E da Hepatite B/imunologia , Vírus da Hepatite B/imunologia , Vírus da Hepatite B/metabolismo , Hepatite B Crônica/imunologia , Hepatite B Crônica/patologia , Hepatite B Crônica/virologia , Humanos , Cirrose Hepática/imunologia , Cirrose Hepática/patologia , Cirrose Hepática/virologia , Masculino , Pessoa de Meia-Idade
18.
Virol J ; 16(1): 61, 2019 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-31064399

RESUMO

BACKGROUND: Hepatitis B e antigen (HBeAg) seroconversion represents an endpoint of treatment of chronic hepatitis B virus (HBV) infections. METHODS: We have studied whether levels of serum hepatitis B virus ribonucleic acid (HBV RNA) during pegylated interferon alfa-2a treatment might be helpful for predicting HBeAg seroconversion. 61 HBeAg-positive chronic hepatitis B (CHB) patients treated with pegylated interferon alfa-2a alone or in combination with adefovir (10 mg/day) for 48 weeks were included in this retrospective analysis. Response was defined as HBeAg seroconversion at 24 weeks posttreatment. Receiver operating characteristic analyses were used to identify baseline and on-treatment HBV RNA levels associated with response. RESULTS: Twenty-two of 61 (36.1%) patients achieved a response. Baseline HBV RNA levels were lower in responders than in nonresponders (4.55 ± 1.19 and 5.90 ± 1.13 copies/mL, respectively, P = 0.001). Baseline HBV RNA cut off level (200,000 copies/mL) provided a positive predictive value (PPV) of 56.0% and a negative predictive value (NPV) of 77.8%. HBV RNA level (3000 copies/mL) at week 12 provide a PPV of 75.0% and a NPV of 82.8%. Moreover, HBeAg seroconversion rates at 24 weeks posttreatment were significantly higher in patients with HBV RNA ≤ 200,000 copies/mL at baseline and HBV RNA ≤ 3000 copies/mL at week 12 (92.9%) versus others (12.5%) (All P < 0.05). CONCLUSIONS: In Conclusions, serum HBV RNA levels may serve as a novel tool for prediction of HBeAg seroconversion during therapy with pegylated interferon alfa-2a in HBeAg-positive CHB patients.


Assuntos
Antivirais/uso terapêutico , DNA Viral/sangue , Antígenos E da Hepatite B/sangue , Hepatite B Crônica/tratamento farmacológico , Interferon-alfa/uso terapêutico , Polietilenoglicóis/uso terapêutico , Adenina/análogos & derivados , Adenina/uso terapêutico , Adulto , Feminino , Vírus da Hepatite B/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Organofosfonatos/uso terapêutico , Curva ROC , Proteínas Recombinantes/uso terapêutico , Estudos Retrospectivos , Soroconversão , Adulto Jovem
19.
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
20.
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
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