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1.
Antiviral Res ; 226: 105889, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38631661

RESUMEN

Hepatitis B virus (HBV) infections pose a major threat to human health. HBV can upregulate the expression of the transcription factor Yin Yang 1 (YY1) in in vitro cytological experiments, suggesting an association between YY1 and HBV infection. However, data on YY1 expression in chronic hepatitis B (CHB) patients are lacking. In this study, we aimed to assess the correlation between YY1 expression and HBV infection. We detected serum YY1 levels in 420 patients with chronic HBV infection, 30 patients with chronic hepatitis C virus infection, and 32 healthy controls using an enzyme-linked immunosorbent assay. The correlation between YY1 levels and clinical parameters was analyzed. Meanwhile, the changes of YY1 before and after interferon or entecavir treatment were analyzed. YY1 levels in the liver tissues were detected using immunofluorescence staining. The expression of YY1 in HBV-expressing cells was detected through western blotting. Meanwhile, we explored the effects of YY1 on HBV replication and gene expression. We found that YY1 was highly expressed in the serum and liver tissues of CHB patients. Serum YY1 levels positively correlated with HBV DNA and hepatitis B surface antigen (HBsAg). Additionally, HBV DNA levels increased but HBsAg levels decreased after HBV-expressing cells overexpress YY1. In conclusion, our study demonstrates that YY1 plays an important role in HBV replication and gene expression, providing a potential target for the treatment of CHB.


Asunto(s)
ADN Viral , Antígenos de Superficie de la Hepatitis B , Virus de la Hepatitis B , Hepatitis B Crónica , Hígado , Replicación Viral , Factor de Transcripción YY1 , Humanos , Factor de Transcripción YY1/metabolismo , Factor de Transcripción YY1/genética , Hepatitis B Crónica/virología , Hepatitis B Crónica/tratamiento farmacológico , Hepatitis B Crónica/metabolismo , Virus de la Hepatitis B/genética , Virus de la Hepatitis B/fisiología , Masculino , Femenino , Adulto , Persona de Mediana Edad , ADN Viral/genética , ADN Viral/sangre , Antígenos de Superficie de la Hepatitis B/sangre , Antígenos de Superficie de la Hepatitis B/metabolismo , Hígado/virología , Hígado/metabolismo , Guanina/análogos & derivados , Antivirales/uso terapéutico , Antivirales/farmacología , Interferones/metabolismo , Células Hep G2
2.
Afr Health Sci ; 20(2): 579-586, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-33163019

RESUMEN

BACKGROUND: The health of people living with HIV/AIDS becomes progressively worse when co-infected with hepatitis B virus (HBV) and hepatitis C virus (HCV), resulting in shortened life span. The modes of transmission of HIV, HBV and HCV are similar. OBJECTIVE: To determine the prevalence of HBV and HCV co-infection in HIV patients. METHOD: This was a retrospective study of serology test results for hepatitis B surface antigen (HBsAg) and antibodies to HCV (anti-HCV) of HIV positive patients registered from 2008-2013 (6years) at the University of Nigeria Teaching Hospital. Adult patients with confirmed HIV seropositivity were included. Ethical approval was obtained and confidentiality of the patient information was maintained. Laboratory records were reviewed to obtain HBsAg, anti-HCV, and CD4 T-lymphocyte results. Prevalence was determined by the number of positive results over total number of patients tested. Chi-square test was used to determine relationships and p<0.05 was considered to be statistically significant. RESULTS: 4663 HIV patient records were included comprising 3024 (65%) females and 1639 (35%) males. Serology results showed 365/4663 (7.8%) tested HBsAg-positive only; 219/4663 (4.7%) tested anti-HCV-positive only; and 27/4663 (0.58%) tested both HBsAg and anti-HCV-positive. Correlation of age and sex were statistically significant with HBV and HCV (p<0.05) but not CD4 count (p>0.05). CONCLUSION: HBV co-infection was more prevalent than HCV, and triple infection was also observed. Screening for these viral infections in the HIV population is necessary for early identification to enable appropriate, holistic management of these patients.


Asunto(s)
Coinfección/epidemiología , Infecciones por VIH/epidemiología , Hepacivirus/aislamiento & purificación , Virus de la Hepatitis B/aislamiento & purificación , Hepatitis B/epidemiología , Anticuerpos contra la Hepatitis C/sangre , Hepatitis C/epidemiología , Adulto , Recuento de Linfocito CD4 , Coinfección/virología , Ensayo de Inmunoadsorción Enzimática , Femenino , VIH/genética , Infecciones por VIH/sangre , Hepacivirus/genética , Hepatitis B/sangre , Antígenos de Superficie de la Hepatitis B/análisis , Antígenos de Superficie de la Hepatitis B/sangre , Virus de la Hepatitis B/genética , Hepatitis C/sangre , Humanos , Masculino , Persona de Mediana Edad , Nigeria/epidemiología , Prevalencia , ARN Viral/análisis , Estudios Retrospectivos , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa
3.
Viruses ; 12(9)2020 08 25.
Artículo en Inglés | MEDLINE | ID: mdl-32854335

RESUMEN

Over 257 million individuals worldwide are chronically infected with the Hepatitis B Virus (HBV). Nucleos(t)ide analogues (NAs) are the first-line treatment option for most patients. Entecavir (ETV) and tenofovir disoproxil fumarate (TDF) are both potent, safe antiviral agents, have a high barrier to resistance, and are now off patent. They effectively suppress HBV replication to reduce the risk of cirrhosis, liver failure, and hepatocellular carcinoma (HCC). Treatment is continued long-term in most patients, as NA therapy rarely induces HBsAg loss or functional cure. Two diverging paradigms in the treatment of chronic hepatitis B have recently emerged. First, the public health focussed "treat-all" strategy, advocating for early and lifelong antiviral therapy to minimise the risk of HCC as well as the risk of HBV transmission. In LMICs, this strategy may be cost saving compared to monitoring off treatment. Second, the concept of "stopping" NA therapy in patients with HBeAg-negative disease after long-term viral suppression, a personalised treatment strategy aiming for long-term immune control and even HBsAg loss off treatment. In this manuscript, we will briefly review the current standard of care approach to the management of hepatitis B, before discussing emerging evidence to support both the "treat-all" strategy, as well as the "stop" strategy, and how they may both have a role in the management of patients with chronic hepatitis B.


Asunto(s)
Antivirales/uso terapéutico , Guanina/análogos & derivados , Hepatitis B Crónica/tratamiento farmacológico , Tenofovir/uso terapéutico , Antivirales/administración & dosificación , Carcinoma Hepatocelular/prevención & control , Duración de la Terapia , Guanina/administración & dosificación , Guanina/uso terapéutico , Antígenos de Superficie de la Hepatitis B/sangre , Antígenos e de la Hepatitis B/sangre , Virus de la Hepatitis B/fisiología , Hepatitis B Crónica/complicaciones , Hepatitis B Crónica/virología , Humanos , Neoplasias Hepáticas/prevención & control , Práctica de Salud Pública , Tenofovir/administración & dosificación , Resultado del Tratamiento , Carga Viral , Privación de Tratamiento
4.
J Dig Dis ; 21(7): 406-415, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-32407579

RESUMEN

OBJECTIVE: In this prospective cohort study, we aimed to evaluate the association between dietary habits and the risk of developing hepatocellular carcinoma (HCC) in hepatitis B surface antigen (HBsAg)-positive carriers in Qidong, an hepatitis B virus (HBV)-epidemic area in China. METHODS: A total of 3199 HBsAg carriers aged 30-70 years in a prospective cohort in Qidong, China from 2007 to 2011 were included in the study. At baseline, all participants self-reported their dietary habits in a questionnaire interview. A follow-up check-up was performed every 6 months to identify HCC cases until November 2017. Cox's regression analysis and an interaction analysis were performed to estimate the relative risks of HCC in terms of baseline diet. RESULTS: Among 3199 HBsAg-positive participants, 270 developed HCC (143.86/100 000 person-years [PYs]). Compared with participants who rarely consume garlic, the risk of HCC in those who consumed it ≥ once per week decreased along with the increase in frequency (HR = 1.00, 0.90 and 0.62 in those who consumed it rarely vs those who consumed it 1-6 times per week and ≥ 7 times per week, respectively). This study found a synergistic effect between garlic and tea consumption on the risk of HCC (P = 0.039 for a multiplicative interaction). CONCLUSIONS: HBsAg carriers should improve their diet. Regular consumption of garlic and tea drinking may reduce the HCC incidence in HBsAg carriers.


Asunto(s)
Carcinoma Hepatocelular , Dieta , Antígenos de Superficie de la Hepatitis B/sangre , Hepatitis B Crónica , Neoplasias Hepáticas , Carcinoma Hepatocelular/epidemiología , China , Ajo , Virus de la Hepatitis B , Hepatitis B Crónica/epidemiología , Humanos , Neoplasias Hepáticas/epidemiología , Estudios Prospectivos , Factores de Riesgo ,
5.
PLoS One ; 15(3): e0230005, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32163475

RESUMEN

BACKGROUND AND AIMS: The Barcelona Clinic Liver Cancer (BCLC) stage C (BCLC C) of hepatocellular carcinoma (HCC) includes a heterogeneous population for which sorafeninb is one of the recommended therapies. We aim to evaluate the real world clinical treatment and survival of BCLC stage C patients in an Asian cohort. METHODS: This is a retrospective cohort study that enrolled 427 consecutive BCLC stage C patients diagnosed between 2011 and 2017 by using the HCC registry data for our hospital. All patients were managed via a multidisciplinary team (MDT) approach. RESULTS: Hepatitis B surface antigen positive was noted in 50.6% of the patients. The patients were classified as performance status (PS)1 alone (n = 83; 19.4%), PS2 alone (n = 23; 5.4%), or macrovascular invasion (MVI) or extrahepatic spread (EHS) (n = 321; 75.2%). The median overall survival (OS) was 11.0 months in the whole cohort. The most frequent treatments were transcatheter arterial embolization (TAE) in the PS1 (45.8%) and PS2 patients (52.2%) and sorafenib (32.4%) in the MVI or EHS patients. The independent prognostic factors were the PS, Child-Pugh class, MVI or EHS, alpha fetoprotein levels, and treatment type. CONCLUSIONS: We reported the real world management in BCLC stage C patients in an Asian cohort through the use of personalized management via a MDT approach.


Asunto(s)
Antineoplásicos/uso terapéutico , Carcinoma Hepatocelular/terapia , Embolización Terapéutica , Neoplasias Hepáticas/terapia , Anciano , Anciano de 80 o más Años , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/patología , Femenino , Antígenos de Superficie de la Hepatitis B/sangre , Humanos , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Sorafenib/uso terapéutico , Análisis de Supervivencia , Neoplasias Vasculares/diagnóstico , Neoplasias Vasculares/secundario , alfa-Fetoproteínas/análisis
6.
J Hepatol ; 72(6): 1088-1096, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-31981727

RESUMEN

BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) may develop in patients with chronic hepatitis (CHB) even after 5 years of oral therapy and cannot be easily predicted. We assessed predictors of HCC development and the need for HCC surveillance in this setting. METHODS: Of 1,951 adult Caucasians with CHB included in the PAGE-B cohort, 1,427 (73%) had completed >5 years of follow-up under therapy without developing HCC by year 5. Median follow-up was 8.4 years from treatment onset. Points-based risk scores were developed to predict HCC risk after year 5. RESULTS: In years 5-12, HCC was diagnosed in 33/1,427 (2.3%) patients with cumulative incidences of 2.4%, 3.2% and 3.8% at 8, 10 and 12 years, respectively. Older age or age >50 years, baseline cirrhosis and liver stiffness (LSM) ≥12 kPa at year 5 were independently associated with increased HCC risk. The HCC incidence was lower in non-cirrhotics than cirrhotics at baseline with year-5 LSM <12; among cirrhotics at baseline, it was lower in those with year-5 LSM <12 than ≥12 kPa. CAGE-B score was based on age at year 5 and baseline cirrhosis in relation to LSM at year 5 and SAGE-B score was based only on age and LSM at year 5 (c-index = 0.809-0.814, 0.805-0.806 after bootstrap validation). Both scores offered 100% negative predictive values for HCC development in their low risk groups. CONCLUSIONS: In Caucasians with CHB, the HCC risk after the first 5 years of antiviral therapy depends on age, baseline cirrhosis status and LSM at year 5. CAGE-B and particularly SAGE-B represent simple and reliable risk scores for HCC prediction and surveillance beyond year 5 of therapy. LAY SUMMARY: In Caucasians with chronic hepatitis B, the risk of hepatocellular carcinoma after the first 5 years of entecavir or tenofovir therapy depends on age, baseline cirrhosis status and liver stiffness at year 5, which can provide simple and reliable risk scores for hepatocellular carcinoma prediction and surveillance beyond year 5. In patients with cirrhosis at baseline, liver stiffness <12 kPa at year 5 is associated with lower HCC risk, but surveillance may be still required.


Asunto(s)
Antivirales/administración & dosificación , Carcinoma Hepatocelular/epidemiología , Guanina/análogos & derivados , Virus de la Hepatitis B/genética , Hepatitis B Crónica/tratamiento farmacológico , Hepatitis B Crónica/etnología , Neoplasias Hepáticas/epidemiología , Tenofovir/administración & dosificación , Población Blanca , Administración Oral , Adulto , Anciano , Carcinoma Hepatocelular/etiología , ADN Viral/sangre , ADN Viral/genética , Femenino , Estudios de Seguimiento , Guanina/administración & dosificación , Antígenos de Superficie de la Hepatitis B/sangre , Hepatitis B Crónica/complicaciones , Hepatitis B Crónica/virología , Humanos , Incidencia , Cirrosis Hepática/complicaciones , Neoplasias Hepáticas/etiología , Masculino , Persona de Mediana Edad , Factores de Riesgo , Resultado del Tratamiento , Adulto Joven
7.
Viruses ; 11(9)2019 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-31480588

RESUMEN

Coffee is hepatoprotective and potentially antiviral; however, its anti-hepatitis B virus (anti-HBV) property is not known in humans. This study investigated the influence of coffee drinking behaviour as well as clinical and biochemical profiles of hepatitis B e antigen (HBeAg) negative participants on circulating HBV DNA and hepatitis B surface antigen (HBsAg) levels at a 24-week interval. Exactly 114 chronically HBV-infected adult participants were enrolled from the University of Malaya Medical Centre (UMMC), Malaysia. A significant reduction of HBV DNA level was observed in those drinking three or more cups of coffee per day, with a median reduction of 523 IU/mL (P = 0.003). Reduction of HBsAg level was observed in those drinking two cups per day, with a median reduction of 37 IU/mL (P < 0.001). Multivariate analysis showed that increased coffee intake (P = 0.015) and lower ALT level (P = 0.033) were the significant predictors for a lower HBV DNA level, whereas increased coffee intake (P = 0.002) and having a family history of HBV infection (P = 0.021) were the significant predictors for a lower HBsAg level. These data suggest that drinking three cups or more coffee per day reduces circulating HBV DNA and HBsAg levels.


Asunto(s)
Café , ADN Viral/sangre , Conducta de Ingestión de Líquido , Antígenos de Superficie de la Hepatitis B/sangre , Hepatitis B Crónica/virología , Anciano , Alanina Transaminasa/sangre , Estudios de Cohortes , Femenino , Virus de la Hepatitis B/genética , Virus de la Hepatitis B/inmunología , Hepatitis B Crónica/sangre , Hepatitis B Crónica/epidemiología , Humanos , Malasia/epidemiología , Masculino , Persona de Mediana Edad , Carga Viral
8.
J Clin Lab Anal ; 33(3): e22725, 2019 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-30461067

RESUMEN

BACKGROUND: The pregnant women often take Elevit as the multivitamin supplement which has a substantial amount of biotin that might potentially interfere with the HBsAg immunoassay performed by the prevalent Sysmex system in clinical laboratories. We therefore wanted to determine this, so that the therapeutic intervention on the hepatitis B virus infection during pregnancy and birth would not be missed. METHODS: Elevit was both serially diluted in vitro and orally taken by healthy volunteers whose blood samples were then taken at different time points. All samples were added to a serum sample with a known result of HBsAg and then measured by Sysmex. The Abbott immunoassay system was used as the control as it involves no streptavidin-biotin binding in the reagent set. Besides, the HBsAg results were compared between the pregnant women taking or not taking Elevit. RESULTS: Biotin at 25 ng/mL in the Elevit started to suppress the HBsAg and reached about 50% suppression at 100 ng/mL on Sysmex. In the volunteers, biotin reached the peak concentration at 2 hours. However, their blood samples showed no suppression on the HBsAg detection by Sysmex. In samples from pregnant women who took Elevit, the HBsAg results by Sysmex were highly correlated with those by Abbott (R2  = 0.96). Comparison of the results from Sysmex between the age- and pregnancy-matched females with and without Elevit intake showed no difference. CONCLUSION: Elevit intake in pregnant women shows no significant interference with HBsAg immunoassay on Sysmex.


Asunto(s)
Suplementos Dietéticos , Antígenos de Superficie de la Hepatitis B/sangre , Inmunoensayo/métodos , Inmunoensayo/normas , Vitaminas/química , Adulto , Femenino , Humanos , Embarazo , Reproducibilidad de los Resultados , Vitaminas/uso terapéutico
9.
BMC Complement Altern Med ; 18(1): 248, 2018 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-30189898

RESUMEN

BACKGROUND: Persistent hepatitis B virus (HBV) infection causes liver cirrhosis and hepatocellular carcinoma and constitutes a major worldwide health problem. Currently, anti-HBV drugs are limited to peginterferon and nucleos(t)ide analogs, which are costly and have considerable side effects; the development of novel, effective anti-HBV agents is crucial. METHODS: Catechins are a major group of compounds found in green tea extract and epigallocatechin gallate (EGCG) has been shown to have antiviral properties, including inhibition of cellular entry by HBV. FRG (Fah-/-/ Rag2-/-/ IL-2Rγ/-) mice were used in this study to generate chimeras carrying human primary hepatocytes, to facilitate investigation of the inhibitory effect of EGCG on HBV infection. RESULTS: Here, we show the inhibitory effect of EGCG on HBV infection and replication in HuS-E/2 cells. The inhibitory effect of EGCG on HBV infection in vivo was confirmed by monitoring HBV DNA and HBsAg in serum and immunostaining the liver tissues of the human liver chimeric mice. CONCLUSIONS: The effects of EGCG suggest a robust strategy for the treatment of HBV infection and EGCG may have therapeutic potential for the treatment of HBV-associated liver diseases.


Asunto(s)
Antivirales/farmacología , Catequina/análogos & derivados , Virus de la Hepatitis B/efectos de los fármacos , Hepatitis B , Animales , Catequina/farmacología , ADN Viral/sangre , Femenino , Células Hep G2 , Hepatitis B/inmunología , Hepatitis B/virología , Antígenos de Superficie de la Hepatitis B/sangre , Humanos , Hígado/efectos de los fármacos , Hígado/virología , Ratones , Replicación Viral/efectos de los fármacos
10.
Cell Physiol Biochem ; 48(2): 633-643, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30025397

RESUMEN

BACKGROUND/AIMS: To investigate the clinical effects of the combination therapy with Bushen Formula (BSF) plus enticavir (ETV) on chronic hepatitis B (CHB) patients with suboptimal response to ETV and explore the regulatory mechanisms of BSF on B cells-mediated humoral immunity. METHODS: Sixty-four HBeAg-positive CHB patients with suboptimal response to ETV were enrolled, and were randomly assigned into control group (C-Group, placebo combined with ETV for 12 months) or treatment group (T-Group, BSF combined with ETV for 12 months). Serum samples from 57 treatment-naïve CHB patients and 15 healthy controls were collected. Serum HBV DNA levels were evaluated by real-time PCR. Characteristics of peripheral blood B-cell subtypes were analyzed by flow cytometry. Serum HBV markers and B cell-activating factor (BAFF) levels were detected by ELISA. Chinese medicine symptom complex score was evaluated and recorded. RESULTS: After treatment, the rates of patients with a reduction of HBsAg > 0.5 log10 IU/ml or 1.0 log10 IU/ml and the rates of HBeAg clearance in T-Group were all higher than those in C-group, with no significant intergroup difference. Only in T-Group, Chinese medicine symptom complex score and the frequency of total B cells were significantly decreased, and the frequencies of Bm1, CD24+CD27-switched B cells and plasma cells were markedly increased after treatment compared with those before treatment. Compared with healthy controls, serum BAFF levels in treatment-naïve CHB patients were increased, and there was a significant positive correlation between serum BAFF and HBsAg levels. However, serum BAFF levels did not differ after treatment in T-Group and C-Group. CONCLUSIONS: The combination therapy with BSF plus ETV promotes the reduction of HBsAg level and the clearance of HBeAg in CHB patients with partial response to ETV through regulating the differentiation of B-cell subsets.


Asunto(s)
Antivirales/farmacología , Diferenciación Celular/efectos de los fármacos , Medicamentos Herbarios Chinos/uso terapéutico , Hepatitis B Crónica/tratamiento farmacológico , Adolescente , Adulto , Anciano , Alanina Transaminasa/sangre , Antivirales/uso terapéutico , Linfocitos B/citología , Linfocitos B/efectos de los fármacos , Linfocitos B/metabolismo , Estudios de Casos y Controles , ADN Viral/sangre , ADN Viral/metabolismo , Quimioterapia Combinada , Medicamentos Herbarios Chinos/farmacología , Femenino , Antígenos de Superficie de la Hepatitis B/sangre , Antígenos e de la Hepatitis B/sangre , Virus de la Hepatitis B/genética , Virus de la Hepatitis B/aislamiento & purificación , Hepatitis B Crónica/diagnóstico , Hepatitis B Crónica/patología , Hepatitis B Crónica/virología , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven
11.
Euro Surveill ; 23(11)2018 03.
Artículo en Inglés | MEDLINE | ID: mdl-29560855

RESUMEN

We evaluated uptake and diagnostic outcomes of voluntary hepatitis B (HBV) and C virus (HCV) screening offered during routine tuberculosis entry screening to migrants in Gelderland and Amsterdam, the Netherlands, between 2013 and 2015. In Amsterdam, HIV screening was also offered. Overall, 54% (461/859) accepted screening. Prevalence of chronic HBV infection (HBsAg-positive) and HCV exposure (anti-HCV-positive) in Gelderland was 4.48% (9/201; 95% confidence interval (CI): 2.37-8.29) and 0.99% (2/203; 95% CI: 0.27-3.52), respectively, all infections were newly diagnosed. Prevalence of chronic HBV infection, HCV exposure and chronic HCV infection (HCV RNA-positive) in Amsterdam was 0.39% (1/256; 95% CI: 0.07-2.18), 1.17% (3/256; 95% CI: 0.40-3.39) and 0.39% (1/256; 95% CI: 0.07-2.18), respectively, with all chronic HBV/HCV infections previously diagnosed. No HIV infections were found. In univariate analyses, newly diagnosed chronic HBV infection was more likely in participants migrating for reasons other than work or study (4.35% vs 0.83%; odds ratio (OR) = 5.45; 95% CI: 1.12-26.60) and was less likely in participants in Amsterdam than Gelderland (0.00% vs 4.48%; OR = 0.04; 95% CI: 0.00-0.69). Regional differences in HBV prevalence might be explained by differences in the populations entering compulsory tuberculosis screening. Prescreening selection of migrants based on risk factors merits further exploration.


Asunto(s)
Prestación Integrada de Atención de Salud , Infecciones por VIH/diagnóstico , Hepatitis B/diagnóstico , Hepatitis C/diagnóstico , Tamizaje Masivo/métodos , Migrantes , Tuberculosis/diagnóstico , Adolescente , Adulto , África/etnología , Anticuerpos Antivirales/sangre , Asia Sudoriental/etnología , Región del Caribe/etnología , Europa Oriental , Femenino , Infecciones por VIH/epidemiología , Infecciones por VIH/etnología , Hepatitis B/epidemiología , Hepatitis B/etnología , Antígenos de Superficie de la Hepatitis B/sangre , Hepatitis C/epidemiología , Hepatitis C/etnología , Anticuerpos contra la Hepatitis C/sangre , Humanos , América Latina/etnología , Masculino , Región Mediterránea , Persona de Mediana Edad , Países Bajos/epidemiología , Prevalencia , Pruebas Serológicas , Tuberculosis/epidemiología , Tuberculosis/etnología , Adulto Joven
12.
Hum Vaccin Immunother ; 14(6): 1417-1422, 2018 06 03.
Artículo en Inglés | MEDLINE | ID: mdl-29388874

RESUMEN

Pre-clinical models mimicking persistent hepatitis B virus (HBV) expression are seldom, do not capture all features of a human chronic infection and due to their complexity, are subject to variability. We report a meta-analysis of seven experiments performed with TG1050, an HBV-targeted immunotherapeutic, 1 in an HBV-persistent mouse model based on the transduction of mice by an adeno-associated virus coding for an infectious HBV genome (AAV-HBV). To mimic the clinical diversity seen in HBV chronically infected patients, AAV-HBV transduced mice displaying variable HBsAg levels were treated with TG1050. Overall mean percentages of responder mice, displaying decrease in important clinical parameters i.e. HBV-DNA (viremia) and HBsAg levels, were 52% and 51% in TG1050 treated mice, compared with 8% and 22%, respectively, in untreated mice. No significant impact of HBsAg level at baseline on response to TG1050 treatment was found. TG1050-treated mice displayed a significant shorter Time to Response (decline in viral parameters) with an Hazard Ratio (HR) of 8.3 for viremia and 2.6 for serum HBsAg. The mean predicted decrease for TG1050-treated mice was 0.5 log for viremia and 0.8 log for HBsAg, at the end of mice follow-up, compared to no decrease for viremia and 0.3 log HBsAg decrease for untreated mice. For mice receiving TG1050, a higher decline of circulating viremia and serum HBsAg level over time was detected by interaction term meta-analysis with a significant treatment effect (p = 0.002 and p<0.001 respectively). This meta-analysis confirms the therapeutic value of TG1050, capable of exerting potent antiviral effects in an HBV-persistent model mimicking clinical situations.


Asunto(s)
Antivirales/uso terapéutico , Hepatitis B Crónica/terapia , Factores Inmunológicos/uso terapéutico , Animales , ADN Viral/sangre , Modelos Animales de Enfermedad , Evaluación Preclínica de Medicamentos , Femenino , Antígenos de Superficie de la Hepatitis B/sangre , Ratones Endogámicos C57BL , Resultado del Tratamiento , Carga Viral
13.
BMC Cancer ; 17(1): 645, 2017 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-28899349

RESUMEN

BACKGROUND: Sorafenib and transarterial chemoembolization (TACE) are recommended therapies for advanced hepatocellular carcinoma (HCC), but their combined efficacy remains unclear. METHODS: Between August 2004 and November 2014, 104 patients with BCLC stage B/C HCC were enrolled at the Affiliated Tumor Hospital of Guangxi Medical University, China. Forty-eight patients were treated with sorafenib alone (sorafenib group) and 56 with TACE plus sorafenib (TACE + sorafenib group). Baseline demographic/clinical data were collected. The primary outcomes were median overall survival (OS) and progression-free survival (PFS). Secondary outcomes were overall response rate (ORR) and sorafenib-related adverse events (AEs). Baseline characteristics associated with disease prognosis were identified using multivariate Cox hazards regression. RESULTS: The mean age of the 104 patients (94 males; 90.38%) was 49.02 ± 12.29 years. Of the baseline data, only albumin level (P = 0.028) and Child-Pugh class (P = 0.017) differed significantly between groups. Median OS did not differ significantly between the sorafenib and TACE + sorafenib groups (18.0 vs. 22.0 months, P = 0.223). Median PFS was significantly shorter in the sorafenib group than that in the TACE + sorafenib group (6.0 vs. 8.0 months, P = 0.004). Six months after treatments, the ORRs were similar between the sorafenib and TACE + sorafenib groups (12.50% vs. 18.75%, P = 0.425). The rates of grade III-IV adverse events in sorafenib and TACE + sorafenib groups were 29.2% vs. 23.2%, respectively. TACE plus sorafenib treatment (HR = 0.498, 95% CI = 0.278-0.892), no vascular invasion (HR = 0.354, 95% CI = 0.183-0.685) and Child-Pugh class A (HR = 0.308, 95% CI = 0.141-0.674) were significantly associated with better OS, while a larger tumor number was predictive of poorer OS (HR = 1.286, 95% CI = 1.031-1.604). TACE plus sorafenib treatment (HR = 0.461, 95% CI = 0.273-0.780) and no vascular invasion (HR = 0.557, 95% CI = 0.314-0.988) were significantly associated with better PFS. CONCLUSIONS: Compared with sorafenib alone, combining TACE with sorafenib might prolong survival and delay disease progression in patients with advanced HCC.


Asunto(s)
Carcinoma Hepatocelular/tratamiento farmacológico , Quimioembolización Terapéutica/métodos , Neoplasias Hepáticas/tratamiento farmacológico , Niacinamida/análogos & derivados , Compuestos de Fenilurea/administración & dosificación , Adulto , Anciano , Carcinoma Hepatocelular/sangre , Carcinoma Hepatocelular/patología , Quimioembolización Terapéutica/efectos adversos , Terapia Combinada , Supervivencia sin Enfermedad , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/clasificación , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/patología , Femenino , Antígenos de Superficie de la Hepatitis B/sangre , Humanos , Neoplasias Hepáticas/sangre , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Niacinamida/administración & dosificación , Niacinamida/efectos adversos , Compuestos de Fenilurea/efectos adversos , Pronóstico , Sorafenib , Resultado del Tratamiento
14.
Mol Med Rep ; 16(5): 7416-7422, 2017 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-28944901

RESUMEN

The present study aimed to investigate the possible mechanisms underlying the effect of modified Xiaochaihu decoction (mXCHD) in the treatment of chronic hepatitis B (CHB). Patients with CHB, in addition to liver stagnation and spleen deficiency syndrome were randomly assigned to receive either Chinese (mXCHD) or western (entecavir) treatment, with 30 cases in each group. Serum was collected following treatment with mXCHD or entecavir for 7 days. A healthy group of 30 individuals was also included. HepG2.2.15 cells were cultured in vitro and randomly divided into four groups: Healthy; entecavir­treated; 10% mXCHD­treated; and 20% mXCHD­treated. The HepG2.2.15 cells in the four groups were treated with either serum from the healthy volunteers, entecavir­containing serum, or mXCHD­containing serum at different concentrations (10 or 20%, respectively). Following treatment with the corresponding serum, cell proliferation was examined using an MTT assay, and the expression of hepatitis B surface antigen (HBsAg) in the cell supernatant was detected using an enzyme­linked immunosorbent assay. The mRNA and protein expression levels of Janus kinase (JAK)2 and signal transducer and activator of transcription (STAT)3 were measured using reverse transcription­quantitative polymerase chain reaction and western blot analyses, respectively. The results indicated that the most effective treatment for the promotion of HepG2.2.15 cell proliferation was a 20% concentration of mXCHD serum. The expression of HBsAg was significantly decreased in the groups treated with 10 and 20% mXCHD 48 h following intervention (P<0.01). The mRNA and protein expression levels of STAT3 in the 20% mXCHD serum group were significantly increased, compared with those in the healthy group (P<0.01 and P<0.05, respectively), whereas no significant difference was observed in the expression of JAK2 among the four groups. These results indicated that mXCHD suppressed the hepatitis B virus, and treatment of the cells with mXCHD­containing serum promoted HepG2.2.15 cell proliferation via modulating the expression of STAT3, which may contribute to the clinical efficacy of mXCHD against CHB.


Asunto(s)
Medicamentos Herbarios Chinos/farmacología , Hepatitis B Crónica/tratamiento farmacológico , Transducción de Señal/efectos de los fármacos , Antivirales/farmacología , Antivirales/uso terapéutico , Estudios de Casos y Controles , Supervivencia Celular/efectos de los fármacos , Medios de Cultivo/química , Regulación hacia Abajo/efectos de los fármacos , Medicamentos Herbarios Chinos/uso terapéutico , Ensayo de Inmunoadsorción Enzimática , Guanina/análogos & derivados , Guanina/farmacología , Guanina/uso terapéutico , Células Hep G2 , Antígenos de Superficie de la Hepatitis B/sangre , Virus de la Hepatitis B/aislamiento & purificación , Virus de la Hepatitis B/metabolismo , Hepatitis B Crónica/diagnóstico , Hepatitis B Crónica/virología , Humanos , Janus Quinasa 2/genética , Janus Quinasa 2/metabolismo , ARN Mensajero/metabolismo , Factor de Transcripción STAT3/genética , Factor de Transcripción STAT3/metabolismo
15.
BMC Infect Dis ; 16: 249, 2016 06 06.
Artículo en Inglés | MEDLINE | ID: mdl-27267370

RESUMEN

BACKGROUND: Prisoners represent a vulnerable population for blood-borne and sexually transmitted infections which can potentially lead to liver fibrosis and ultimately cirrhosis. However, little is known about the prevalence of liver fibrosis and associated risk factors among inmates in sub-Saharan Africa. METHODS: Screening of liver fibrosis was undertaken in a randomly selected sample of male inmates incarcerated in Lome, Togo and in Dakar, Senegal using transient elastography. A liver stiffness measurement ≥9.5 KPa was retained to define the presence of a severe liver fibrosis. All included inmates were also screened for HIV, Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) infection. Substances abuse including alcohol, tobacco and cannabis use were assessed during face-to-face interviews. Odds Ratio (OR) estimates were computed with their 95 % Confidence Interval (CI) to identify factors associated with severe liver fibrosis. RESULTS: Overall, 680 inmates were included with a median age of 30 years [interquartile range: 24-35]. The prevalence of severe fibrosis was 3.1 % (4.9 % in Lome and 1.2 % in Dakar). Infections with HIV, HBV and HCV were identified in 2.6 %, 12.5 % and 0.5 % of inmates, respectively. Factors associated with a severe liver fibrosis were HIV infection (OR = 7.6; CI 1.8-32.1), HBV infection (OR = 4.8; CI 1.8-12.8), HCV infection (OR = 52.6; CI 4.1-673.8), use of traditional medicines (OR = 3.7; CI 1.4-10.1) and being incarcerated in Lome (OR = 3.3; CI 1.1-9.8) compared to Dakar. CONCLUSIONS: HIV infection and viral hepatitis infections were identified as important and independent determinants of severe liver fibrosis. While access to active antiviral therapies against HIV and viral hepatitis expands in Africa, adapted strategies for the monitoring of liver disease need to be explored, especially in vulnerable populations such as inmates.


Asunto(s)
Infecciones por VIH/epidemiología , Hepatitis B/epidemiología , Hepatitis C/epidemiología , Cirrosis Hepática/epidemiología , Prisioneros/estadística & datos numéricos , Adulto , África Occidental/epidemiología , Alanina Transaminasa/sangre , Aspartato Aminotransferasas/sangre , Coinfección/epidemiología , Comorbilidad , ADN Viral/sangre , Diagnóstico por Imagen de Elasticidad , Hepatitis B/sangre , Antígenos de Superficie de la Hepatitis B/sangre , Virus de la Hepatitis B/genética , Hepatitis C/sangre , Hepatitis C/inmunología , Anticuerpos contra la Hepatitis C/inmunología , Humanos , Hígado/diagnóstico por imagen , Cirrosis Hepática/diagnóstico por imagen , Masculino , Medicinas Tradicionales Africanas/estadística & datos numéricos , Oportunidad Relativa , Prevalencia , Factores de Riesgo , Senegal/epidemiología , Índice de Severidad de la Enfermedad , Factores de Tiempo , Togo/epidemiología , Carga Viral , Adulto Joven
16.
Zhonghua Liu Xing Bing Xue Za Zhi ; 37(4): 455-9, 2016 Apr.
Artículo en Chino | MEDLINE | ID: mdl-27087205

RESUMEN

OBJECTIVE: To analyze the characteristics of health-seeking behaviors and related influencing factors of the community-based hepatitis B surface antigen (HBsAg) positive adults, in China. METHODS: Based on the cohort formed by the HBsAg positive patients, in the national sero-survey project in 2006, we conducted a follow-up programs in 2010 and 2014. In the latest follow-up project, we carried out a cross-sectional study to collect information on health-seeking behaviors of the patients. Questionnaires would include information on clinic visits, diagnosis, regular physical examination and treatments,etc. We used the SPSS 18.0 software for data analysis. RESULTS: Totally, 2 478 HBsAg positive adults (≥18 years old) were followed through, with 34.4% (853/2 478) of them had visited the doctors and diagnosed after they were informed the status of HBsAg positivity, in the 2006-sero-survey program. Among patients who ever visiting the clinic, 51.2% (372/727) of them underwent at least medical examination once a year, with 31.5% (229/727) of them received treatment. Furthermore, 34.5% (79/229) of the treated patients adopted the traditional Chinese medicine or medicine for ' liver protection'. 56.8% (130/229) of the treated patients received antiviral drugs. Data from the binary logistic regression showed that the major influencing factors on clinic visits would include: age, level of education received and residencial areas (rural/urban). CONCLUSIONS: Consciousness on health was low in those community-based HBsAg positive people. Standerdized management and clinical treatment programs should be set up accordingly.


Asunto(s)
Pueblo Asiatico/psicología , Hepatitis B/sangre , Hepatitis B/psicología , Adulto , China/epidemiología , Estudios Transversales , Atención a la Salud , Hepatitis B/diagnóstico , Hepatitis B/etnología , Anticuerpos contra la Hepatitis B/sangre , Antígenos de Superficie de la Hepatitis B/sangre , Humanos , Modelos Logísticos , Características de la Residencia , Población Rural , Estudios Seroepidemiológicos , Encuestas y Cuestionarios
17.
Eur J Nutr ; 55(5): 1823-9, 2016 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-26208687

RESUMEN

PURPOSE: The World Health Report identifies zinc deficiency as one of the major causes of disease in developing countries, and infants are at particular risk. We aimed to investigate the effect of maternal zinc supplementation on the infant's immune function in a population at risk of deficiency. METHODS: In a randomized, double-blind placebo-controlled trial, mothers were supplemented either with 20 mg/day of elemental zinc (n = 20) or placebo (n = 19) at the beginning of second trimester, which continued until 6 months postpartum. Indicators of the infants' immune function measured included interleukin (IL)-7, thymic size and response to hepatitis B vaccination. RESULTS: Infants born from mothers receiving zinc supplements during pregnancy and postpartum had significantly lower plasma zinc (p < 0.05) but marginally higher IL-7 and antibody responses to hepatitis B vaccination (p < 0.10) than infants born from mothers not receiving zinc. Maternal zinc supplementation showed no negative impact on copper status of mothers or their infants. Maternal zinc supplementation did not influence infant thymic size, but cord blood IL-7 was found positively associated with thymus size at 1 month of age (r = 0.392) and with hepatitis B vaccine response at 6 months of age (r = 0.386). CONCLUSION: Prenatal and postnatal zinc supplementation marginally improved T cell-dependent antibody responses in infants along with IL-7, a cytokine involved in human T cell development and maintaining homeostasis.


Asunto(s)
Suplementos Dietéticos , Hepatitis B/inmunología , Fenómenos Fisiologicos Nutricionales Maternos , Zinc/administración & dosificación , Zinc/sangre , Cobre/sangre , Método Doble Ciego , Femenino , Hepatitis B/sangre , Hepatitis B/tratamiento farmacológico , Anticuerpos contra la Hepatitis B/sangre , Antígenos de Superficie de la Hepatitis B/sangre , Antígenos de Superficie de la Hepatitis B/inmunología , Vacunas contra Hepatitis B/administración & dosificación , Vacunas contra Hepatitis B/uso terapéutico , Humanos , Inmunidad Innata , Inmunoglobulina G/sangre , Lactante , Interleucina-7/sangre , Masculino , Atención Posnatal , Periodo Posparto/sangre , Atención Prenatal , Linfocitos T/inmunología , Linfocitos T/metabolismo , Adulto Joven
18.
Zhongguo Zhong Yao Za Zhi ; 40(15): 3047-52, 2015 Aug.
Artículo en Chino | MEDLINE | ID: mdl-26677709

RESUMEN

To verify the effect of echinacoside on replication and antigen expression of hepatitis B virus (HBV) by using HBV-transfected HepG2. 2. 15 cells as the in vitro model. The ELISA method was used to determine HBeAg and HBsAg levels in cellular supernatants. The effect of echinacoside on HBV replication was studied by using HBV transgenic mice as the in vivo model. First of all, the HBV DNA level in hepatic tissues was quantified with PCR method. Meanwhile, the serum transaminase levels and hepatic pathological changes were also evaluated. Subsequently, HBV transgenic mice were divided into five groups: the control group, the lamivudine group (50 mg · kg(-1)) and echinacoside high, medium and low dose group (50, 25 and 12.5 mg · kg(-1)). The mice were orally administered with drugs once per day for 30 days. At the 31st day, the mice serum was separated to measure HBsAg, HBeAg and HBV DNA. Additionally, the liver HBV DNA level and histopathological change were detected. The results indicated that echinacoside at 50 and 100 mg · L(-1) suppressed significantly HBsAg and HBeAg expressions on the sixth day, with the maximum inhibition ratios of 42.68% and 46.29%; And echinacoside at 100 mg · L(-1) also showed an inhibitory effect on HBV DNA. Besides, echinacoside at 50 mg · kg(-1) inhibited significantly HBsAg and HBeAg expressions of HBV transgenic mice, with the inhibition ratios of 42.82% and 29.12%, and reduced markedly the serum HBV DNA level in HBV transgenic mice. In conclusion, the study suggested that echinacoside has a strong effect against HBV replication and antigen expression.


Asunto(s)
Glicósidos/farmacología , Virus de la Hepatitis B/efectos de los fármacos , Replicación Viral/efectos de los fármacos , Animales , ADN Viral/sangre , Femenino , Células Hep G2 , Antígenos de Superficie de la Hepatitis B/sangre , Antígenos e de la Hepatitis B/sangre , Virus de la Hepatitis B/fisiología , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL
19.
Virol J ; 12: 204, 2015 Dec 02.
Artículo en Inglés | MEDLINE | ID: mdl-26626263

RESUMEN

BACKGROUND: Viral hepatitis is a life-threatening liver disease that has become important public health issue in developing countries including Ethiopia. This study was undertaken to determine the seroprevalence of HBsAgs and anti-HCV antibodies and what socio-demographic factors are associated with sero-positivity of Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) infections among pregnant women attending maternity ward of Felege Hiwot Referral Hospital, northwest, Ethiopia. METHODS: Hospital based cross-sectional study was conducted from November 2013 to January 2014. Blood samples were randomly collected from 384 pregnant women. Data on socio-demographic characteristics, obstetric and potential risk factors were collected using semi-structured questionnaire. Chromatographic kits were used to detect the presence of HBsAg and antibodies against HCV in serum samples of the studied subjects. Chi-square test was used for assessing the association between socio-demographic variables and HBV and HCV status. Logistic regression analysis was done to determine the strength of association between risk factors and HBV or HCV infection. P-values less than 0.05 were considered as significant. RESULTS: Seroprevalnce of hepatitis B and C virus infections were found to be 4.4 and 0.26 %, respectively. None of the pregnant women were co-infected by these two viruses. Amongst the potential risk factors, previous history of dental procedure (AOR = 4.104, CI = 1.276-13.201, P = 0.018), house hold contact (AOR = 5.475, CI = 1.472-20.368, P = 0.011), multiple sexual exposure (AOR = 5.041, CI = 1.580-16.076, P = 0.006), and delivery at traditional birth attendants (AOR = 4.100, CI = 0.195-86.129, P = 0.024) were significantly associated with and important predictors of hepatitis B infection. CONCLUSIONS: This study found an intermediate endemicity (4.4 %) of HBV infection in pregnant women whereas seroprevalence of anti-HCV antibody was very small, but this needs to be confirmed by other similar studies with larger sample size. Thus, scaling up of the screening of pregnant women for HBV and HCV infections and provision of health education about the risk factors, the mode of transmissions and prevention is recommended.


Asunto(s)
Antígenos de Superficie de la Hepatitis B/sangre , Hepatitis B/epidemiología , Anticuerpos contra la Hepatitis C/sangre , Hepatitis C/epidemiología , Complicaciones Infecciosas del Embarazo/epidemiología , Adolescente , Adulto , Estudios Transversales , Demografía , Etiopía/epidemiología , Femenino , Hospitales , Humanos , Embarazo , Factores de Riesgo , Estudios Seroepidemiológicos , Factores Socioeconómicos , Adulto Joven
20.
Infect Control Hosp Epidemiol ; 36(5): 529-33, 2015 May.
Artículo en Inglés | MEDLINE | ID: mdl-25643863

RESUMEN

OBJECTIVE: To determine whether a difference in antibody to hepatitis B surface antigen (anti-HBs) response to a hepatitis B vaccine challenge dose existed among persons with a baseline anti-HBs level of 0 mIU/mL (group 1) and those with "non-zero" levels of 0.1-4.9 (group 2) and 5.0-9.9 (group 3) mIU/mL, according to the VITROS ECi anti-HBs assay. DESIGN: Subanalysis of randomized clinical trial. Response was defined as a postchallenge anti-HBs level of at least 10 mIU/mL and 4-fold rise in anti-HBs level 2 weeks after a single challenge dose of 10 vs 20 µg Engerix-B. Baseline was defined as the anti-HBs level immediately before administration of the challenge dose. SETTING: Pediatric integrated healthcare system near Houston, Texas. PARTICIPANTS: Three hundred nineteen US-born 16-19-year-olds who completed the hepatitis B vaccine series during the first year of life. RESULTS: One hundred seventy-eight persons had zero (group 1) and 141 (114 group 2 and 27 group 3) had non-zero anti-HBs levels at baseline. Response to the challenge dose was significantly higher among those with non-zero vs zero anti-HBs levels, irrespective of challenge dosage; only 1 person with a non-zero anti-HBs level failed to respond to the challenge dose (group 3, 27/27 [100%] vs group 2, 113/114 [99%] vs group 1, 145/178 [82%]; P<.0001). CONCLUSIONS: Among participants with residual anti-HBs levels less than 10 mIU/mL 16-19 years after primary hepatitis B vaccination during infancy, non-zero anti-HBs levels, with rare exception, indicated persistence of immune memory to HBsAg. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01341275


Asunto(s)
Antígenos de Superficie de la Hepatitis B/inmunología , Vacunas contra Hepatitis B/uso terapéutico , Hepatitis B/prevención & control , Adolescente , Femenino , Hepatitis B/inmunología , Antígenos de Superficie de la Hepatitis B/sangre , Vacunas contra Hepatitis B/inmunología , Humanos , Memoria Inmunológica/inmunología , Lactante , Masculino , Adulto Joven
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