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1.
J Ethnopharmacol ; 302(Pt A): 115896, 2023 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-36334815

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Salvia miltiorrhiza (the roots of S. miltiorrhiza Bunge, Danshen in Chinese), a traditional Chinese medicine, has been clinically used to prevent and treat various diseases, such as cardiovascular and cerebrovascular diseases, diabetes, and hepatitis B, in China and some other Asian countries. Lithospermic acid (LA), a polyphenol derived from S. miltiorrhiza, has been reported to exhibit multiple pharmacological properties, such as anti-inflammatory, anti-HIV, and anti-carbon tetrachloride-induced liver injury activities. However, little is known about the anti-hepatitis B virus (HBV) activity of LA. AIM OF THE STUDY: The study was projected to investigate the anti-HBV activity of LA in vitro (HepG2.2.15 and pHBV1.3-transfected HepG2 cells) and in vivo (pAAV-HBV1.2 hydrodynamic injection [HBV-HDI] mice) and explore the potential mechanism as well. MATERIALS AND METHODS: Hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) contents were detected by ELISA kits. HBV DNA and hepatitis B core antigen (HBcAg) levels were evaluated by quantitative real-time polymerase chain reaction and immunohistochemistry assay, respectively. The proteins in autophagy process, lysosomal acidic function, and autophagy-related signaling pathways were examined by Western blot. Transmission electron microscopy was used to observe the number of autophagosomes and autolysosomes. Confocal microscopy was applied to analyze the autophagic flux and lysosomal acidification, using mCherry-enhanced green fluorescent protein (EGFP)-microtubule-associated protein light chain (LC)3 and lysosomal probes, respectively. RESULTS: LA exhibited anti-HBV activity by inhibiting HBV DNA replication in HepG2.2.15 and pHBV-transfected HepG2 cells in dose- and time-dependent manners and hampering HBsAg and HBeAg levels in HepG2.2.15 cells to a certain extent. LA reduced HBV DNA, HBsAg/HBeAg, and HBcAg levels in the serum/liver tissues of HBV-HDI C57BL/6 mice during the 3-week treatment and suppressed the withdrawal rebound of HBV DNA and HBsAg in the mice serum. LA increased LC3-II protein expression and the number of autolysosomes/autophagosomes and promoted the degradation of sequestosome 1(p62) protein in vitro and in vivo. LA enhanced the co-localization of LC3 protein with autolysosomes, further confirming the ability of LA to induce a complete autophagy. Knockdown of autophagy-related gene (Atg) 7 or 5 in vitro and administration of 3-methyladenine (an autophagic inhibitor) in vivo disabled the inhibitory efficacy of LA on HBV DNA replication, suggesting that the anti-HBV efficacy of LA depended on its ability of inducing autophagy. LA could enhance lysosomal acidification and improve the function of lysosomes by promoting the protein expression of lysosomal-associated membrane protein (LAMP)-1, LAMP-2, and mature cathepsin D, which may contribute to the autophagic induction of LA. LA inhibited the activation of AKT and mammalian target of rapamycin (mTOR) induced by HBV, which was reversed by IGF-1 (an agonist of the PI3K/AKT/mTOR signaling pathway), indicating that LA elicited autophagy through hampering the PI3K/AKT/mTOR signaling pathway. CONCLUSION: We revealed the anti-HBV activity and mechanism of LA in vitro and in vivo. This study facilitates a new understanding of the anti-HBV potent components of S. miltiorrhiza and sheds light on LA for further development as an active constituent or candidate used in the therapy against HBV infection.


Assuntos
Hepatite B , Herpesvirus Cercopitecino 1 , Salvia miltiorrhiza , Camundongos , Animais , Vírus da Hepatite B , Antígenos de Superfície da Hepatite B/genética , Antígenos do Núcleo do Vírus da Hepatite B/genética , Polifenóis/metabolismo , Herpesvirus Cercopitecino 1/genética , Herpesvirus Cercopitecino 1/metabolismo , Antígenos E da Hepatite B , DNA Viral/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Replicação Viral/fisiologia , Camundongos Endogâmicos C57BL , Autofagia , Serina-Treonina Quinases TOR/metabolismo , Mamíferos/genética , Mamíferos/metabolismo
2.
J Virol Methods ; 311: 114640, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36332714

RESUMO

HBV cure rates remain low despite prolonged nucleos(t)ide (NrtI) therapy, likely due to persistent residual viral replication and an inability to eliminate covalently closed circular DNA (cccDNA). Therapies with novel mechanisms of action against hepatitis B virus (HBV) are being explored with the goal of achieving sustained off-treatment response and a functional cure without requiring lifelong therapy. Recent studies have indicated that serum HBV DNA levels (a biomarker for viral replication) combined with serum pregenomic RNA (pgRNA) levels (a surrogate for intrahepatic cccDNA transcriptional activity), may provide a better prediction for the risk of liver-related complications. Current HBV DNA assays, such as the COBAS AmpliPrep/COBAS TaqMan HBV test v2.0, quantitate HBV DNA down to 20 IU/mL, but are not able to monitor loss of residual virus in patients on NrtI therapy. There are no commercially available assays approved to detect serum/plasma HBV pgRNA levels. We have developed a multi-assay panel of highly sensitive nucleic acid assays designed to monitor levels of HBV DNA, pgRNA and total nucleic acids (TNA, composite DNA + pgRNA) in clinical specimens and to monitor changes during treatment with new antiviral combination regimens.


Assuntos
Hepatite B Crônica , Hepatite B , Humanos , Hepatite B Crônica/diagnóstico , Hepatite B Crônica/tratamento farmacológico , DNA Viral/genética , Vírus da Hepatite B/genética , DNA Circular/genética , RNA , Antivirais/uso terapêutico
3.
Eur J Gastroenterol Hepatol ; 35(1): 120-126, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36468576

RESUMO

BACKGROUND: To investigate the efficacy of precise hepatectomy in the treatment of patients with intermediate and advanced hepatocellular carcinoma and analyze the risk factors affecting prognosis. METHODS: Totally 104 patients with intermediate and advanced hepatocellular carcinoma from January 2018 to January 2019 were enrolled in this retrospective analysis. Of these, four patients lost to follow-up. Logistic regression was conducted to explore the odds ratio (OR) and 95% confidence interval (CI). RESULTS: Compared with the control group, the precise hepatectomy decreased intraoperative blood loss (331.2928.91 to 203.29 ± 29.34 ml), operation time (198.29 ± 19.38 to 150.28 ± 18.27 min), perioperative blood transfusion volume (376.22 ± 25.93 to 228.29 ± 22.19 ml) (all P < 0.001). Logistic regression analysis of study group showed that hepatitis B infection (OR = 1.746; 95% CI, 1.068-2.976), P = 0.021, Child-Pugh classification (OR = 2.319; 95% CI, 1.428-3.213), P < 0.001, Eastern Cooperative Oncology Group (ECOG) score (OR = 2.287; 95% CI, 1.098-3.876; P = 0.013) and Barcelona-Clinic Liver Cancer (BCLC) staging (OR = 2.029; 95% CI, 1.086-3.671; P = 0.022) were independent risk factors for prognosis of the precise hepatectomy. CONCLUSION: Hepatitis B virus infection, Child-Pugh grade, ECOG score and BCLC staging grade were the independent risk factors affecting the prognosis of precise hepatectomy.


Assuntos
Carcinoma Hepatocelular , Hepatite B , Neoplasias Hepáticas , Humanos , Hepatectomia/efeitos adversos , Prognóstico , Carcinoma Hepatocelular/cirurgia , Estudos Retrospectivos , Neoplasias Hepáticas/cirurgia , Fatores de Risco
4.
Medicine (Baltimore) ; 101(47): e31962, 2022 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-36451458

RESUMO

Risk of hepatitis B virus reactivation (HBVr) in patients with resolved HBV infection receiving immunosuppressive therapy has been a growing concern, particularly in the era of biological and targeted therapies. HBV monitoring versus antiviral prophylaxis against HBVr in those patients remains controversial. The aim of the study was to determine the incidence of HBVr and HBV-related hepatitis in resolved HBV patients who received immunosuppressive therapy with or without antiviral prophylaxis. This retrospective study included 64 patients with resolved HBV infection who received different regimens of immunosuppressive medications, with moderate risk of HBVr, for variable underlying diseases. Patients who had chronic HBV infection or other viral infections were excluded. Patients who received B-cell depleting therapies were ruled out. They were divided into 2 groups: group 1 included 31 patients who received immunosuppressive therapy without antiviral prophylaxis, and group 2 included 33 patients who received antiviral prophylaxis (entecavir) within 2 weeks of commencing the immunosuppressive therapy. HBVr, HBV-related hepatitis, and HBV-unrelated hepatitis were assessed along a 1-year duration. The overall HBVr incidence was 1.56% (1/64). This patient who had HBVr was seen in group 1. There were no significant differences between the 2 groups regarding the incidence of HBVr, HBV-related hepatitis, HBV-unrelated hepatitis, and immunosuppressive therapy interruption along a 1-year duration. Based on this retrospective study, close monitoring was equal to antiviral prophylaxis regarding the outcome of resolved HBV patients who received moderate risk immunosuppressive therapy. HBV treatment should commence once HBVr is confirmed.


Assuntos
Hepatite A , Hepatite B , Humanos , Estudos Retrospectivos , Hepatite B/tratamento farmacológico , Hepatite B/epidemiologia , Hepatite B/prevenção & controle , Vírus da Hepatite B , Terapia de Imunossupressão/efeitos adversos , Infecção Persistente , Antivirais/uso terapêutico
5.
J Biomed Opt ; 27(7): 075002, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36451700

RESUMO

Significance: The combination of polarized imaging with artificial intelligence (AI) technology has provided a powerful tool for performing an objective and precise diagnosis in medicine. Aim: An approach is proposed for the detection of hepatitis B (HB) virus using a combined Mueller matrix imaging technique and deep learning method. Approach: In the proposed approach, Mueller matrix imaging polarimetry is applied to obtain 4 × 4 Mueller matrix images of 138 HBsAg-containing (positive) serum samples and 136 HBsAg-free (negative) serum samples. The kernel estimation density results show that, of the 16 Mueller matrix elements, elements M 22 and M 33 provide the best discriminatory power between the positive and negative samples. Results: As a result, M 22 and M 33 are taken as the inputs to five different deep learning models: Xception, VGG16, VGG19, ResNet 50, and ResNet150. It is shown that the optimal classification accuracy (94.5%) is obtained using the VGG19 model with element M 22 as the input. Conclusions: Overall, the results confirm that the proposed hybrid Mueller matrix imaging and AI framework provides a simple and effective approach for HB virus detection.


Assuntos
Inteligência Artificial , Hepatite B , Humanos , Hepatite B/diagnóstico por imagem , Diagnóstico por Imagem
6.
PLoS One ; 17(12): e0275238, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36454799

RESUMO

BACKGROUND: Chronic kidney disease (CKD) predispose to viral coinfections in patients submitted to renal replacement therapy (RRT); nevertheless, few reports have been performed to elucidate the current epidemiology within this population in Mexico. AIM: To estimate the prevalence of HBV, HCV, and HIV coinfection and to explore factors associated with prevalent coinfection in patients living with renal failure undergoing to RRT. METHODS: A multicenter cross-sectional recruitment across 21 units at the Mexican Institute of Social Security (IMSS) at the State of Mexico was performed during 2019. A standardized clinical questionnaire was performed to elucidate individual and relatives-related conditions. A treatment facility questionnaire was applied to the chief responsible of each unit to explore treatment facility variables. Serological testing, clinical, biochemical, and anthropometrical parameters were extracted from clinical records. RESULT: In 1,304 patients (57.5% male, mean age 45.5 (SD: 15.6) years, and 95.8% in hemodialysis), the prevalence of any viral coinfection was 3.14% (95% CI: 2.32%-4.23%). The highest viral coinfection prevalence were for HCV, HBV, and HIV, in which men and subjects diagnosed after 2010's had the highest rates. We identify that being submitted to peritoneal dialysis, being treated in a surrogated dialysis center and living with a close relative with prior hepatitis coinfection were associated factors for any viral coinfection. CONCLUSION: In patients submitted to RRT, the prevalence of viral coinfection remains high compared with general population. Screening strategies, medical awareness and targeted public healthcare policies should prioritize better care practices within patients submitted to RRT in Mexico.


Assuntos
Coinfecção , Infecções por HIV , Hepatite B , Hepatite C , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Coinfecção/epidemiologia , Estudos Transversais , México/epidemiologia , Diálise Renal , Hepatite C/complicações , Hepatite C/epidemiologia , Hepacivirus , Hepatite B/complicações , Hepatite B/epidemiologia , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Terapia de Substituição Renal , HIV
7.
BMC Public Health ; 22(1): 2243, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36457005

RESUMO

BACKGROUND: Hepatitis B virus (HBV) infection is considered a significant global public health challenge with infectivity as well as estimated potential for transmission more than 50 to 100 times that of HIV. Over time, numerous empirical studies have shown that majority of HBV-related yearly global deaths are secondary to carcinoma of the liver. It is also known that HBV infected Women have the potential to transmit the infection vertically to their infants during pregnancy. This accounts for the WHO reported 3.16% prevalence among children less than 5 years of age in Uganda. This study assessed the predictors of HBV infection prevention practices among eligible consenting pregnant women using Lubaga health facility for antenatal care (ANC). METHODS: A cross-sectional descriptive study employing quantitative data collection based on the constructs of IMB model was used to capture data on the study variables among 385 randomly selected eligible pregnant women attending antenatal care at Lubaga hospital between September 2020 and October 2020. Data derived from the quantitative instrument was analysed by data reduction and transformation to summaries of descriptive statistics using (SPSS version 26) and regression analysis was performed to establish characteristics of the association between the variables with significance level set as (p < 0.05). Chi-square goodness-of-fit test was employed for significant differences in the proportion of dichotomous responses. RESULTS: The findings showed that more than half of the respondents (59%) were between the ages of 18 and 28 and majority of them (42.3%) had secondary education. Furthermore, an average but inadequate knowledge ([Formula: see text] 5.97 ± 6.61; B = 0.57; p < .001), positive perception ([Formula: see text] 17.10 ± 18.31; B = 0.97; p = .014) and good behavioural skills ([Formula: see text] 12.39 ± 13.37; B = 0.56; p < .001) for adopting prevention practices all statistically predicted the averagely acceptable level of prevention practices ([Formula: see text] 15.03 ± 16.20) among the study respondents as measured on rating scales of 12, 33, 21 and 30 respectively. CONCLUSION AND RECOMMENDATION: There were observed gaps in their knowledge about some basic features of the infection like transmission and risk factors as well as some misperceptions about vaccination despite the relatively average score level for both, which is likely to influence their prevention behaviours and predispose them to the risk of the infection if actions are not taken. Therefore, personalized health education is needed during antenatal visits and subsequent health campaign in order to inform better prevention practices among this vulnerable population group.


Assuntos
Hepatite B , Gestantes , Gravidez , Criança , Lactente , Feminino , Humanos , Adolescente , Adulto Jovem , Adulto , Cuidado Pré-Natal , Motivação , Uganda/epidemiologia , Estudos Transversais , Hepatite B/prevenção & controle , Vírus da Hepatite B , Hospitais
8.
AIDS Res Ther ; 19(1): 57, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36457041

RESUMO

BACKGROUND: Although Ethiopia is endemic to viral hepatitis and HIV, data that could guide population-specific interventions are limited. In this study, we determined the seroprevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV) and assessed their associations with HIV-1 viral load suppression among HIV-1 infected patients on antiretroviral therapy (ART) at Mekelle hospital in northern Ethiopia. METHODS: Between February and April 2020, blood samples were collected from 439 participants. Samples were screened for HBsAg and anti-HCV on the immunochromatographic test and confirmed using the Enzyme-Linked Immuno-sorbent assay (Beijing Wantai Co. China). HIV-1 viral load was quantified using reverse transcription-polymerase chain reaction (RT-PCR) on the Abbott platform. Binary and multivariable logistic regression was performed to identify potential predictors. RESULTS: Overall, 10% (44/439) and 3.6% (16/439) of the participants were coinfected with HBV and HCV, respectively. In a multivariate analysis, being illiterate (AOR = 6.57; 95% CI 1.04-41.6), and having a history of sexually transmitted infections (AOR = 4.44; 95% CI 1.31-15.0) and multiple sexual partners (AOR = 29.9; 95% CI 7.82-114.8) were associated with HBV infection. On the other hand, participants with a history of chronic non-communicable diseases (AOR = 10.6, 95% CI 1.61-70.1), and those reporting a history of sexually transmitted infections (AOR = 5.21, 95% CI 1.39-19.5) were more likely to be infected with HCV. In further analysis, HCV infection status was significantly associated with decreased viral load suppression rate (AOR = 7.14; 95% CI 2.18-23.3) whereas no significant association was observed with the HBV infection. CONCLUSIONS: The HBV coinfection rate in our study is high and, as per WHO's standard, corresponds to a hyperendemic level. The HCV coinfection rate is also substantially high and urges attention given its influence on the viral load suppression of HIV patients on ART at our study site. Our findings suggest the need to adopt universal screening and vaccination of people with HIV against HBV and screening for HCV at our study site and in Ethiopia at large, which contributes to Ethiopia's progress towards the 2030 global target of reducing the HBV infection.


Assuntos
Coinfecção , Infecções por HIV , Soropositividade para HIV , HIV-1 , Hepatite B , Humanos , Coinfecção/epidemiologia , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Carga Viral , Estudos Soroepidemiológicos , Etiópia/epidemiologia , Hepatite B/epidemiologia , Vírus da Hepatite B/genética , Hepacivirus/genética , Hospitais
9.
Front Immunol ; 13: 1075916, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36466821

RESUMO

Hepatitis B virus (HBV) is a hepatotropic virus, which damage to hepatocytes is not direct, but through the immune system. HBV specific CD4+ T cells can induce HBV specific B cells and CD8+ T cells. HBV specific B cells produce antibodies to control HBV infection, while HBV specific CD8+ T cells destroy infected hepatocytes. One of the reasons for the chronicity of HBV infection is that it cannot effectively activate adoptive immunity and the function of virus specific immune cells is exhausted. Among them, virus antigens (including HBV surface antigen, e antigen, core antigen, etc.) can inhibit the function of immune cells and induce immune tolerance. Long term nucleos(t)ide analogues (NAs) treatment and inactive HBsAg carriers with low HBsAg level may "wake up" immune cells with abnormal function due to the decrease of viral antigen level in blood and liver, and the specific immune function of HBV will recover to a certain extent, thus becoming the "dominant population" for functional cure. In turn, the functional cure will further promote the recovery of HBV specific immune function, which is also the theoretical basis for complete cure of hepatitis B. In the future, the complete cure of chronic HBV infection must be the combination of three drugs: inhibiting virus replication, reducing surface antigen levels and specific immune regulation, among which specific immunotherapy is indispensable. Here we review the relationship, mechanism and clinical significance between the cure of hepatitis B and immune system.


Assuntos
Antígenos de Superfície da Hepatite B , Hepatite B , Humanos , Linfócitos T CD8-Positivos , Hepatite B/tratamento farmacológico , Vírus da Hepatite B , Imunidade Adaptativa , Antígenos Virais
10.
BMC Public Health ; 22(1): 2260, 2022 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-36463162

RESUMO

Healthcare-associated transmission was the second most common hepatitis B (HBV) and hepatitis C (HCV) transmission route according to 2006-2012 European surveillance data, but data quality and completeness issues hinder comprehensive characterisation of this important issue. We carried out a systematic review of published literature on healthcare-associated transmission of HBV or HCV in European Union (EU) and European Economic Area (EEA) countries and the United Kingdom to complement surveillance data and identify higher-risk settings. We searched the PubMed and Embase databases and grey literature over the period January 2006 to September 2021, for publications reporting transmission events after 2000 in the EU/EEA and UK related to a healthcare setting or procedure. We collected data on the country, number of patients, setting type and route of transmission. In 65 publications from 16 countries, 43 HBV and 48 HCV events were identified resulting in 442 newly infected patients. Most events were reported from Italy (7 HBV and 12 HCV), Germany (8 HBV and 5 HCV) and the United Kingdom (8 HBV and 5 HCV). The number of patients infected from a single source within an event ranged from 1 to 53. Five large outbreaks of over 20 cases were identified, including two in Poland and one each in Belgium, Hungary and Slovakia. The majority of transmission events occurred through blood transfusions or in dialysis units. However, there were a number of outbreaks in seemingly low risk settings such as CT/MRI scanning units. A failure to adequately follow infection prevention control (IPC) precautions was reported in 30% of included studies. Healthcare-associated transmission of hepatitis B and C continues to occur in a range of community and hospital settings across EU/EEA countries and often results in large outbreaks, although the true extent of the situation cannot be fully determined due to under-reporting. Strict IPC precautions should be implemented across all healthcare settings and regularly audited, and surveillance systems strengthened and standardised to allow for comprehensive and consistent reporting of nosocomial transmission of hepatitis across the EU.


Assuntos
Hepatite B , Hepatite C , Humanos , União Europeia , Surtos de Doenças , Hepatite B/epidemiologia , Hepatite C/epidemiologia , Hepacivirus , Reino Unido/epidemiologia , Atenção à Saúde
11.
Pan Afr Med J ; 42: 252, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36338549

RESUMO

Introduction: adequate knowledge on hepatitis B virus (HBV) infection is important among patients with the infection as this impacts their health-seeking behavior. This study therefore assessed the knowledge and attitude among patients infected with HBV in The Gambia. Methods: this cross-sectional study was conducted at the main liver clinic, Medical Research Council Gambia at London School of Hygiene and Tropical Medicine (MRCG@LSHTM). A questionnaire was administered on a one-on-one basis to assess the level of knowledge and attitude of people with chronic HBV. Results: a total of 152 HBV patients were recruited into the study. Majority of the participants were male 136 (89.5%), within the 30-39 years age group. Sixty-four (42.1%) of the patients attained secondary education and 72 (47.4%) were working as civil servants. The mean knowledge score was 11.09/20 (standard deviation = 4.89). HBV patients having tertiary level education (p-value =0.001) or HBV diagnosis greater than 1 year (p-value =0.031) were more likely to have adequate knowledge of HBV infection. No significant associations were found between the socio-demographic and clinical characteristic variables and attitude. However, majority of the participants (56.6%) reported been worried about having HBV infection ever since being diagnosed. Conclusion: this study has highlighted the need for more patient health education especially for those with lower levels of education and newly diagnosed patients. It also further confirms the need for cultural and appropriate language consideration in providing education and information for HBV patients in The Gambia at the point of diagnosis.


Assuntos
Hepatite B , Humanos , Masculino , Feminino , Gâmbia , Estudos Transversais , Hepatite B/epidemiologia , Hepatite B/diagnóstico , Vírus da Hepatite B , Conhecimentos, Atitudes e Prática em Saúde
12.
Front Immunol ; 13: 1018053, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36325353

RESUMO

Human hepatitis B virus (HBV) is a small, enveloped DNA virus that causes acute and chronic hepatitis. Chronic hepatitis B (CHB) is associated with hepatocellular carcinoma pathogenesis. Interferons (IFNs) have been used for the treatment of CHB for a long time, with advantages including less treatment duration and sustained virological response. Presently, various evidence suggests that epigenetic modification of the viral covalently closed circular DNA (cccDNA) and the host genome is crucial for the regulation of viral activity. This modification includes histone acetylation, DNA methylation, N6-methyladenosine, and non-coding RNA modification. IFN treatment for CHB can stimulate multiple IFN-stimulated genes for inhibiting virus replication. IFNs can also affect the HBV life cycle through epigenetic modulation. In this review, we summarized the different mechanisms through which IFN-α inhibits HBV replication, including epigenetic regulation. Moreover, the mechanisms underlying IFN activity are discussed, which indicated its potential as a novel treatment for CHB. It is proposed that epigenetic changes such as histone acetylation, DNA methylation, m6A methylation could be the targets of IFN, which may offer a novel approach to HBV treatment.


Assuntos
Vírus da Hepatite B , Hepatite B , Humanos , Vírus da Hepatite B/genética , Vírus da Hepatite B/metabolismo , Epigênese Genética , Histonas/metabolismo , Hepatite B/tratamento farmacológico , Hepatite B/genética , Antivirais/uso terapêutico , Antivirais/farmacologia , DNA Viral/genética , Interferon-alfa/metabolismo
13.
Medicine (Baltimore) ; 101(43): e31325, 2022 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-36316942

RESUMO

The selection criterion for liver resection (LR) in intermediate-stage (IM) hepatocellular carcinoma (HCC) is still controversial. This study aims to compare LR and transarterial chemoembolization (TACE) in the range of predicted death risk The multivariable Cox regression model (MVR) was estimated to predict mortality at 5 year. The cutoff values were determined by a 2-piece-wise linear regression model, decision curve analysis with MVR model, and hazard ratio curve for treatment plotted against the predicted mortality. 825 IM-hepatocellular carcinoma (IM-HCC) with hepatitis B cirrhosis were included for analysis (TACE, n = 622; LR, n = 203). The 5-year overall survival (OS) rate of LR patients was higher than the TACE group (52.8% vs 20.8%; P < .0001). The line of LR and TACE were crossing with predicted death risk at 100% (P for interaction = .008). The benefit of LR versus TACE decreased progressively as predicted death risk > 0.55 (95%CI: 0.45, 0.62). When predicted death risk over 0.7, decision curve analysis suggested that LR and TACE did not increase net benefit. Patients were then divided into 4 subgroups by the cutoff values (<0.45, 0.45≥/<0.62, 0.62≥/<0.7, ≥0.7). The stratified analysis of treatment in different subgroups, hazard ratios were 0.39 (95%CI: 0.27, 0.56), 0.36 (95%CI: 0.23, 0.56), 0.51 (95%CI: 0.27, 0.98), and 0.46 (95%CI: 0.27, 0.80), respectively. LR reached the maximal relative utility in the interval of 0.45 to 0.62, and both LR and TACE did not increase net benefit at the 5-year death risk over 0.7.


Assuntos
Carcinoma Hepatocelular , Quimioembolização Terapêutica , Hepatite B , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/cirurgia , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/patologia , Estudos de Coortes , Resultado do Tratamento , Hepatectomia , Hepatite B/terapia , Cirrose Hepática/cirurgia , Estudos Retrospectivos
16.
World J Gastroenterol ; 28(40): 5784-5800, 2022 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-36353205

RESUMO

Hepatitis B virus (HBV) infection is a global public health issue. Interferon-α (IFN-α) treatment has been used to treat hepatitis B for over 20 years, but fewer than 5% of Asians receiving IFN-α treatment achieve functional cure. Thus, IFN-α retreatment has been introduced to enhance antiviral function. In recent years, immune-related studies have found that the complex interactions between immune cells and cytokines could modulate immune response networks, in-cluding both innate and adaptive immunity, triggering immune responses that control HBV replication. However, heterogeneity of the immune system to control HBV infection, particularly HBV-specific CD8+ T cell heterogeneity, has consequ-ential effects on T cell-based immunotherapy for treating HBV infection. Altogether, the host's genetic variants, negative-feedback regulators and HBV components affecting the immune system's ability to control HBV. In this study, we reviewed the literature on potential immune mechanisms affecting the immune control of HBV and the clinical effects of IFN-α treatment and retreatment.


Assuntos
Hepatite B Crônica , Hepatite B , Humanos , Interferon-alfa/uso terapêutico , Interferon-alfa/farmacologia , Vírus da Hepatite B , Antígenos de Superfície da Hepatite B , Hepatite B/tratamento farmacológico , Antivirais/farmacologia , Retratamento , Replicação Viral
17.
Front Immunol ; 13: 973993, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36341438

RESUMO

Objective: Hepatocellular carcinoma (HCC) is the sixth most commonly occurring cancer and ranks third in mortality among all malignant tumors; as a result, HCC represents a major human health issue. Although aberrant glycosylation is clearly implicated in HCC, changes in serum immunoglobulin (Ig)G and IgM glycosylation have not been comprehensively characterized. In this study, we used lectin microarrays to evaluate differences in serum IgG and IgM glycosylation among patients with HCC, hepatitis B cirrhosis (HBC), or chronic hepatitis B (CHB), and healthy normal controls (NC) and aimed to establish a model to improve the diagnostic accuracy of HCC. Methods: In total, 207 serum samples collected in 2019-2020 were used for lectin microarray analyses, including 97 cases of HCC, 50 cases of HBC, 30 cases of CHB, and 30 cases of NC. Samples were randomly divided into training and validation groups at a 2:1 ratio. Training group data were used to investigate the diagnostic value of the relative signal intensity for the lectin probe combined with alpha-fetoprotein (AFP). The efficacy of models for HCC diagnosis were analyzed by receiver operating characteristic (ROC) curves. Results: In terms of IgG, a model combining three lectins and AFP had good diagnostic accuracy for HCC. The area under the ROC curve was 0.96 (P < 0.05), the sensitivity was 82.54%, and the specificity was 100%. In terms of IgM, a model including one lectin combined with AFP had an area under the curve of 0.90 (P < 0.05), sensitivity of 75.41%, and specificity of 100%. Conclusion: Estimation of serum IgG and IgM glycosylation could act as complementary techniques to improve diagnosis and shed light on the occurrence and development of the HCC.


Assuntos
Carcinoma Hepatocelular , Hepatite B , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patologia , alfa-Fetoproteínas , Neoplasias Hepáticas/patologia , Lectinas , Biomarcadores Tumorais , Cirrose Hepática , Imunoglobulina M , Imunoglobulina G
18.
East Mediterr Health J ; 28(10): 768-775, 2022 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-36382732

RESUMO

Background: The detection of hepatitis B surface antigen positivity in pregnant women before delivery is crucial to preventing mother-to-child transmission of hepatitis B virus. Aims: This study aimed to evaluate the status and rate of testing for hepatitis B surface antigen, rate of hepatitis B surface antigen positivity, hepatitis B surface antigen positivity distribution rate by age, and changes in hepatitis B surface antigen positivity rate in pregnant women over the study period. Methods: We conducted a multicentre, cross-sectional, descriptive study covering the period January 2005 to June 2019 for 2 145 668 pregnant women from 27 provinces in all 7 regions of Turkey, collected using Microsoft Excel before statistical analysis. Results: We found that 1 012 593 (47.1%) pregnant women were tested for hepatitis B surface antigen over the 15-year period, out of which 11 471 (1.1%) were hepatitis B surface antigen-positive. Overall, 97% of the hepatitis B surface antigen positive women were born before 1998, the year that national HBV vaccination was launched in Turkey. The rate of hepatitis B surface antigen positivity in that group was 1.1%, compared with 0.3% among women born after 1998. Conclusion: There was a downward trend in the hepatitis B surface antigen positivity rate among pregnant women in the younger age groups, especially among those born after universal hepatitis B vaccination was inaugurated, and low rate of HBsAg testing during pregnancy.


Assuntos
Hepatite B , Complicações Infecciosas na Gravidez , Feminino , Gravidez , Humanos , Antígenos de Superfície da Hepatite B , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Hepatite B/epidemiologia , Hepatite B/prevenção & controle , Hepatite B/diagnóstico , Complicações Infecciosas na Gravidez/epidemiologia , Complicações Infecciosas na Gravidez/prevenção & controle , Gestantes , Estudos Transversais , Turquia/epidemiologia , Vírus da Hepatite B , Vacinação , Vacinas contra Hepatite B
19.
Sci Rep ; 12(1): 19257, 2022 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-36357472

RESUMO

Innovative testing approaches and care pathways are required to meet HIV, hepatitis B (HBV) and hepatitis C (HCV) elimination goals. Routine testing for blood-borne viruses (BBVs) within emergency departments (EDs) is suggested by the European Centre for Disease Prevention and Control but there is a paucity of supporting evidence. We evaluated the introduction of routine BBV testing in EDs at a large teaching hospital in northern England. In October 2018, we modified the electronic laboratory ordering system to reflex opt-out HIV, HBV and HCV testing for all ED attendees aged 16-65 years who had a routine blood test for urea and electrolytes (U&Es). Linkage to care (LTC) was attempted for newly diagnosed patients, those never referred and those who had previously disengaged from care. The project operated for 18 months, here we present evaluation of the initial nine months (2 October 2018-1 July 2019). We analysed testing uptake, BBV seropositivity, LTC and treatment initiation within six months post-diagnosis. Over 9 months, 17,026/28,178 (60.4%) ED attendees who had U&Es performed were tested for ≥ 1 BBV. 299 active BBV infections were identified: 70 HIV Ab/Ag-positive (0.4% seroprevalence), 73 HBsAg-positive (0.4%) and 156 HCV RNA-positive (1.0%). Only 24.3% (17/70) HIV Ab/Ag-positive individuals required LTC, compared to 94.9% (148/156) HCV RNA-positive and 53.4% (39/73) HBsAg-positive individuals. LTC was successful in 94.1% (16/17) HIV Ab/Ag-positive and 69.3% (27/39) HBsAg-positive individuals. However, at 6 months LTC was just 39.2% (58/148) for HCV RNA-positive individuals, with 64% (37/58) of these commencing treatment. Universal opt-out ED BBV testing proved feasible and effective in identifying active BBV infections, especially among marginalised populations with reduced healthcare access. Our integrated approach achieved good LTC rates although further service development is necessary, particularly for HCV RNA-positive people who inject drugs.


Assuntos
Infecções por HIV , Hepatite B , Hepatite C , Humanos , Antígenos de Superfície da Hepatite B , Estudos Soroepidemiológicos , Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia , Hepatite C/diagnóstico , Hepatite C/epidemiologia , Hepatite B/diagnóstico , Hepatite B/epidemiologia , Hepacivirus , Serviço Hospitalar de Emergência , Resultado do Tratamento , Reino Unido , RNA
20.
BMC Infect Dis ; 22(1): 819, 2022 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-36344923

RESUMO

BACKGROUND: Hepatitis B virus (HBV) infection is a global public-health problem. Since the introduction of an effective vaccine, the epidemiology of HBV infection is changing. We aimed to estimate the prevalence of HBV infection in the Gulf Cooperation Council (GCC) region and delineate any variation in member-countries, special sub-groups, and over time. METHODS: This is a systematic review and meta-analysis to review studies of HBV prevalence in the GCC region. Databases were searched and all studies from inception to July 31st, 2021, were considered for inclusion. The pooled HBV prevalence was analyzed using the random-effect model after assessment for heterogeneity. True prevalence was adjusted using the Rogan-Gladen estimator. Pre-defined subgroup analysis was performed, and publication bias was assessed. RESULTS: Overall, 99 studies (n = 1,944,200 participants) met the inclusion criteria. The overall HBV apparent prevalence was 3.05% (95% CI 2.60, 3.52) and the true prevalence was 1.67% (95% CI 1.66, 1.68). The apparent prevalence varied between subgroups. Over time, the apparent prevalence of HBV infection has declined from 9.38% (95% CI 7.26, 11.74) before 1990 to 1.56% (95% CI 1.07, 2.12) during the period 2010 to 2020. CONCLUSION: Over the last four decades the overall prevalence of HBV infection in the GCC region has decreased from high- to low-endemicity level. However, due to poor methodology of the included studies, further high-quality community-based studies are needed to obtain more precise estimate of HBV infection in this region.


Assuntos
Vírus da Hepatite B , Hepatite B , Humanos , Prevalência , Hepatite B/epidemiologia , Antígenos de Superfície da Hepatite B
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