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1.
Medicine (Baltimore) ; 100(4): e24354, 2021 Jan 29.
Artículo en Inglés | MEDLINE | ID: mdl-33530229

RESUMEN

ABSTRACT: Diabetes mellitus (DM) increases the risk of developing hepatocellular carcinoma (HCC), and how DM affects the prognosis of HCC have not been elucidated. The aim of this study was to compare clinicopathological characteristics and survival between hepatitis B virus (HBV)-related HCC patients with and without DM and to determine risk factors for overall survival after hepatectomy.Among 474 patients with HBV-related HCC, 119 patients had DM. Patients were divided into the diabetic group and nondiabetic group. The short-term and long-term outcomes were evaluated by using propensity score matching analysis.After 1:2 propensity score matching, there were 107 patients in diabetic group, 214 patients in nondiabetic group. The proportion of vessels invasion were higher in diabetic group. The overall survival rate in the diabetic group was 44.7% at 3 years, which was lower than that in the nondiabetic group (56.1%, P = .025). The multivariate analysis indicated that fasting blood glucose >7.0, capsular invasion, microvascular invasion and satellite were independent risk factor of poor prognosis in HCC.DM dose affect the recurrence-free survival and overall survival in HBV-related HCC patients after hepatectomy. One of the more significant findings to emerge from this study is that DM induced higher proportion of major vessel invasion in HCC patients implied unfavorable prognosis.


Asunto(s)
Carcinoma Hepatocelular/mortalidad , Diabetes Mellitus Tipo 2/virología , Virus de la Hepatitis B , Hepatitis B/complicaciones , Neoplasias Hepáticas/mortalidad , Glucemia/análisis , Carcinoma Hepatocelular/cirugía , Carcinoma Hepatocelular/virología , Diabetes Mellitus Tipo 2/sangre , Femenino , Hepatectomía/mortalidad , Hepatitis B/virología , Humanos , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/virología , Masculino , Persona de Mediana Edad , Análisis Multivariante , Pronóstico , Puntaje de Propensión , Factores de Riesgo , Tasa de Supervivencia , Resultado del Tratamiento
2.
Viruses ; 13(1)2021 Jan 12.
Artículo en Inglés | MEDLINE | ID: mdl-33445753

RESUMEN

An estimated two billion people worldwide have been infected with hepatitis B virus (HBV). Despite the high infectivity of HBV in vivo, a lack of easily infectable in vitro culture systems hinders studies of HBV. Overexpression of the sodium taurocholate co-transporting polypeptide (NTCP) bile acid transporter in hepatoma cells improved infection efficiency. We report here a hepatoma cell culture system that does not require dimethyl sulfoxide (DMSO) for HBV infection. We overexpressed NTCP in Huh7.5 cells and allowed these cells to differentiate in a medium supplemented with human serum (HS) instead of fetal bovine serum (FBS). We show that human serum culture enhanced HBV infection in Huh7.5-NTCP cells, e.g., in HS cultures, HBV pgRNA levels were increased by as much as 200-fold in comparison with FBS cultures and 19-fold in comparison with FBS+DMSO cultures. Human serum culture increased levels of hepatocyte differentiation markers, such as albumin secretion, in Huh7.5-NTCP cells to similar levels found in primary human hepatocytes. N-glycosylation of NTCP induced by culture in human serum may contribute to viral entry. Our study demonstrates an in vitro HBV infection of Huh7.5-NTCP cells without the use of potentially toxic DMSO.


Asunto(s)
Virus de la Hepatitis B/fisiología , Hepatitis B/virología , Replicación Viral , Biomarcadores , Línea Celular , Células Cultivadas , Dimetilsulfóxido/farmacología , Expresión Génica , Vectores Genéticos/genética , Virus de la Hepatitis B/efectos de los fármacos , Hepatocitos/efectos de los fármacos , Hepatocitos/metabolismo , Hepatocitos/virología , Humanos , Transportadores de Anión Orgánico Sodio-Dependiente/genética , Simportadores/genética , Internalización del Virus/efectos de los fármacos , Replicación Viral/efectos de los fármacos
3.
Viruses ; 13(1)2021 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-33467678

RESUMEN

While treatment options are available for hepatitis B virus (HBV), there is currently no cure. Anti-HBV nucleoside analogs and interferon-alpha 2b rarely clear HBV covalently closed circular DNA (cccDNA), requiring lifelong treatment. Recently, we identified GLP-26, a glyoxamide derivative which modulates HBV capsid assembly. The impact of GLP-26 on viral replication and integrated DNA was assessed in an HBV nude mouse model bearing HBV transfected AD38 xenografts. At day 45 post-infection, GLP-26 reduced HBV titers by 2.3-3 log10 versus infected placebo-treated mice. Combination therapy with GLP-26 and entecavir reduced HBV log10 titers by 4.6-fold versus placebo. Next, we examined the pharmacokinetics (PK) in cynomolgus monkeys administered GLP-26 via IV (1 mg/kg) or PO (5 mg/kg). GLP-26 was found to have 34% oral bioavailability, with a mean input time of 3.17 h. The oral dose produced a mean peak plasma concentration of 380.7 ng/mL, observed 0.67 h after administration (~30-fold > in vitro EC90 corrected for protein binding), with a mean terminal elimination half-life of 2.4 h and a mean area under the plasma concentration versus time curve of 1660 ng·hr/mL. GLP-26 was 86.7% bound in monkey plasma. Lastly, GLP-26 demonstrated a favorable toxicity profile confirmed in primary human cardiomyocytes. Thus, GLP-26 warrants further preclinical development as an add on to treatment for HBV infection.


Asunto(s)
Cápside/efectos de los fármacos , Cápside/metabolismo , Cardiotoxinas/farmacocinética , Virus de la Hepatitis B/efectos de los fármacos , Virus de la Hepatitis B/fisiología , Compuestos de Sulfonilurea/farmacocinética , Ensamble de Virus/efectos de los fármacos , Animales , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Hepatitis B/tratamiento farmacológico , Hepatitis B/virología , Humanos , Macaca fascicularis , Masculino , Ratones , Miocitos Cardíacos/efectos de los fármacos , Compuestos de Sulfonilurea/efectos adversos , Compuestos de Sulfonilurea/química , Carga Viral
4.
BMC Infect Dis ; 21(1): 41, 2021 Jan 09.
Artículo en Inglés | MEDLINE | ID: mdl-33422017

RESUMEN

BACKGROUND: In order to reduce the burden on organ shortage around the world, using potential infectious donor might be an option. However, scarce evidences have been published on kidney transplantation (KTx) from hepatitis B surface antigen (HBsAg) + donors to HBsAg- recipients [D (HBsAg+)/R(HBsAg-)] without hepatitis B virus (HBV) immunity. Here, we reported the results of D(HBsAg+/HBV DNA- or +)/R(HBsAg-) living KTx recipients with or without HBV immunity. METHODS: We retrospectively identified 83 D(HBsAg+)/R(HBsAg-) living KTx recipients, and 83 hepatitis B core antibody (HBcAb) + living donors to HBcAb- recipients [D(HBcAb+)/R(HBcAb-)] were used as control group by reviewing medical archives and propensity score matching. Treatment failure (defined as any HBV serology conversion, liver injury, graft loss, or recipient death) is the primary endpoint. RESULTS: Twenty-four donors (28.9%) were HBV DNA+, and 20 recipients had no HBV immunity in the D(HBsAg+)/R(HBsAg-) group pre-transplantation. HBV prophylaxis was applied in all D(HBsAg+)/R(HBsAg-) recipients, while none was applied in the D(HBcAb+)/R(HBcAb-) group. We observed a significant higher treatment failure in D(HBsAg+)/R(HBsAg-) than D(HBcAb+)/R(HBcAb-) group (21.7% vs. 10.8%, P < 0.001). Interestingly, no significant difference was found between groups on HBV seroconversion, liver and graft function, rejection, infection, graft loss, or death. However, 2/20 recipients without HBV immunity in the D(HBsAg+)/R(HBsAg-) group developed HBV DNA+ or HBsAg+, while none observed in the D(HBcAb+)/R(HBcAb-) group. HBV DNA+ donor and male recipient were significant risk factors for treatment failure. CONCLUSION: D(HBsAg+)/R(HBsAg-) should be considered for living kidney transplantation, but with extra caution on donors with HBV DNA+ and male candidates.


Asunto(s)
Antígenos de Superficie de la Hepatitis B/genética , Hepatitis B/virología , Trasplante de Riñón/efectos adversos , Complicaciones Posoperatorias/virología , Adulto , Anciano , ADN Viral/genética , Femenino , Hepatitis B/sangre , Hepatitis B/epidemiología , Anticuerpos contra la Hepatitis B/sangre , Antígenos del Núcleo de la Hepatitis B/genética , Antígenos del Núcleo de la Hepatitis B/inmunología , Antígenos de Superficie de la Hepatitis B/inmunología , Virus de la Hepatitis B/genética , Virus de la Hepatitis B/inmunología , Humanos , Riñón/virología , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/sangre , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Estudios Retrospectivos , Factores de Riesgo , Donantes de Tejidos/estadística & datos numéricos , Receptores de Trasplantes/estadística & datos numéricos , Insuficiencia del Tratamiento
5.
BMC Infect Dis ; 21(1): 56, 2021 Jan 12.
Artículo en Inglés | MEDLINE | ID: mdl-33435880

RESUMEN

BACKGROUND: Hepatitis B virus (HBV) infection is a high-risk factor of hepatocellular carcinoma (HCC). Cellular immune responses are essential for HCC development, and the CD4+ and CD8+ T subtypes are identified as the primary anti-tumor immune cells. In the study, we investigated the effect and mechanism of amygdalin in the cellular immune response in HBV-related HCC and HCC progression. METHODS: The cell proliferation was examined by MTT analysis. Cells metastasis ability was detected by Invasion and migration assays. Quantification of apoptotic cells was performed with Flow cytometer assay. The protein levels of p-STAT3, STAT3, p-JAK2, JAK2, caspase-3, cleaved caspase-3 were detected by performing immunoblotting assays. RESULTS: We demonstrate that amygdalin treatment could rescue the HBV-T cell viability and IFN-γ and TNF-αproduction. In HBV-T cells, the MFI levels of CD8+ are lower than that in NC-T cells. Moreover, the phosphorylation levels of STAT3 and JAK2 are higher in HBV-T cells, compared to those in NC-T cells, and then reduced by amygdalin treatment. Co-culture with HBV-T cells could reduce IFN-γ and TNF-α, production while increase IL-6 and IL-10 production in HepG2.2.15 cells; these alterations could be partially reversed by amygdalin pretreatment. Finally, co-culture with HBV-T cells significantly promoted the cell viability, inhibited the apoptosis, and promoted the migration of HepG2.2.15 cells, and these alterations could be partially reversed by amygdalin treatment. CONCLUSION: Our findings provide a rationale for further studies on the functions and mechanism of amygdalin inhibiting HBV-related HCC cell proliferation, invasion, and migration via T cell-mediated tumor immunity.


Asunto(s)
Amigdalina/farmacología , Carcinoma Hepatocelular/sangre , Carcinoma Hepatocelular/virología , Progresión de la Enfermedad , Hepatitis B/complicaciones , Janus Quinasa 2/metabolismo , Neoplasias Hepáticas/sangre , Neoplasias Hepáticas/virología , Factor de Transcripción STAT3/metabolismo , Transducción de Señal/efectos de los fármacos , Linfocitos T/efectos de los fármacos , Anciano , Amigdalina/metabolismo , Apoptosis/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Técnicas de Cocultivo , Citocinas/metabolismo , Femenino , Células Hep G2 , Hepatitis B/virología , Virus de la Hepatitis B/fisiología , Humanos , Masculino , Persona de Mediana Edad , Linfocitos T/metabolismo , Linfocitos T/virología
6.
Subcell Biochem ; 96: 451-470, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33252740

RESUMEN

Non-enveloped Nackednaviridae and enveloped hepadnaviridae both have capsids that are formed by related small proteins which evolved more than 430 Mya. In Hepatitis B virus, which belongs to the enveloped hepadnaviridae, this small protein is termed Hepatitis B core protein (Hbc). Its function, as building block of a major human pathogen, triggered extensive research that elucidated the importance of almost every single amino acid for the structural integrity of the capsids and the orderly progression of the viral life cycle. In particular, encapsidation of the genome, envelopment of the capsid, uncoating of the genome and targeting of the different compartments during viral maturation have been a vivid focus of research. HBc has also been developed as a biotechnological tool for the design of nano-containers with tailored properties. These nano-containers can display foreign epitopes on their surfaces and induce a strong immune response, which is attractive for the development of vaccines against other pathogens. This chapter will discuss some of the unique properties of HBc and their significance for the formation of a functional macromolecular capsid.


Asunto(s)
Cápside/química , Virus de la Hepatitis B/química , Proteínas del Núcleo Viral/química , Proteínas de la Cápside/química , Hepatitis B/virología , Humanos
7.
Viruses ; 12(12)2020 12 14.
Artículo en Inglés | MEDLINE | ID: mdl-33327640

RESUMEN

Around 257 million people are living with hepatitis B virus (HBV) chronic infection and 71 million with hepatitis C virus (HCV) chronic infection. Both HBV and HCV infections can lead to liver complications such as cirrhosis and hepatocellular carcinoma (HCC). To take care of these chronically infected patients, one strategy is to diagnose the early stage of fibrosis in order to treat them as soon as possible to decrease the risk of HCC development. microRNAs (or miRNAs) are small non-coding RNAs which regulate many cellular processes in metazoans. Their expressions were frequently modulated by up- or down-regulation during fibrosis progression. In the serum of patients with HBV chronic infection (CHB), miR-122 and miR-185 expressions are increased, while miR-29, -143, -21 and miR-223 expressions are decreased during fibrosis progression. In the serum of patients with HCV chronic infection (CHC), miR-143 and miR-223 expressions are increased, while miR-122 expression is decreased during fibrosis progression. This review aims to summarize current knowledge of principal miRNAs modulation involved in fibrosis progression during chronic hepatitis B/C infections. Furthermore, we also discuss the potential use of miRNAs as non-invasive biomarkers to diagnose fibrosis with the intention of prioritizing patients with advanced fibrosis for treatment and surveillance.


Asunto(s)
Biomarcadores , Hepacivirus , Virus de la Hepatitis B , Hepatitis B/genética , Hepatitis B/virología , Hepatitis C/genética , Hepatitis C/virología , MicroARNs/genética , Progresión de la Enfermedad , Susceptibilidad a Enfermedades , Regulación de la Expresión Génica , Hepatitis B/complicaciones , Hepatitis B/diagnóstico , Hepatitis C/complicaciones , Hepatitis C/diagnóstico , Humanos , Sistema Inmunológico/inmunología , Sistema Inmunológico/metabolismo , Cirrosis Hepática/etiología , Cirrosis Hepática/patología , MicroARNs/sangre , Pronóstico , Replicación Viral
8.
Viruses ; 13(1)2020 12 23.
Artículo en Inglés | MEDLINE | ID: mdl-33374798

RESUMEN

Hepatitis B virus (HBV) is a major focus of antiviral research worldwide. The International Coalition to Eliminate HBV, together with the World Health Organisation (WHO), have prioritised the search for a cure, with the goal of eliminating deaths from viral hepatitis by 2030. We present here a comprehensive model of intracellular HBV infection dynamics that includes all molecular processes currently targeted by drugs and agrees well with the observed outcomes of several clinical studies. The model reveals previously unsuspected kinetic behaviour in the formation of sub-viral particles, which could lead to a better understanding of the immune responses to infection. It also enables rapid comparative assessment of the impact of different treatment options and their potential synergies as combination therapies. A comparison of available and currently developed treatment options reveals that combinations of multiple capsid assembly inhibitors perform best.


Asunto(s)
Virus de la Hepatitis B/fisiología , Hepatitis B/virología , Algoritmos , Antivirales/farmacología , Antivirales/uso terapéutico , Simulación por Computador , Hepatitis B/tratamiento farmacológico , Virus de la Hepatitis B/efectos de los fármacos , Hepatitis B Crónica/tratamiento farmacológico , Hepatitis B Crónica/virología , Humanos , Cinética , Modelos Biológicos , Ensamble de Virus/efectos de los fármacos , Internalización del Virus/efectos de los fármacos , Replicación Viral/efectos de los fármacos
9.
BMC Infect Dis ; 20(1): 957, 2020 Dec 14.
Artículo en Inglés | MEDLINE | ID: mdl-33317454

RESUMEN

BACKGROUND: Chronic Sedentary lifestyles have been linked to increased odds of stress, elevated anxiety and diminished wellbeing, inducing cytokine production and predispose to hypertension and other cardiovascular diseases. In endemic areas, Plasmodium falciparum and hepatitis B virus (HBV) infections can trigger pro-inflammatory cytokine responses. However, the impact of these infections on cytokine response profiles in individuals engaged in chronic sedentary activities is unknown. This study was aimed at addressing these concerns using a predominantly sedentary population of traders in the Tamale metropolis of Ghana. METHOD: Four hundred respondents were categorized, based on their number of working years (< or ≥ 5 years) and number of working hours per day (< or ≥ 10 h), into sedentary (≥5 years + ≥ 10 h) and non-sedentary (≥ 5 years + < 10 h, < 5 years + ≥ 10 h and <  5 years + < 10 h) groups. The participants were tested for P. falciparum and HBV infections using polymerase chain reaction. Blood pressure and cytokines responses were measured. Associations and comparison analysis between variables were determined, and test statistics with p < 0.05 were considered statistically significant. RESULTS: Infection status included: un-infected (93.5%), P. falciparum mono-infected (1.0%), HBV mono-infected (3.0%) or P. falciparum /HBV co-infected (2.5%). Majority of the participants, 57.0% (n = 228) were involved in chronic sedentary life style. That notwithstanding, sedentary lifestyle was independent of the infection groups (χ2 = 7.08, p = 0.629). Hypertension was diagnosed in 53.8% of respondents and was independent of infection status (X 2 = 6.33, p = 0.097). Pro-inflammatory (TNF-α, IL-1ß, IL-6, IL-8 and IL-12) and anti-inflammatory (IL-10, IL-7 and IL-13) cytokine responses were similar among individuals with different sedentary working time and between hypertensive and non-hypertensive individuals (p > 0.05 for all comparisons). Among individuals with different infection status, pro-inflammatory (TNF-α; p = 0.290, IL-1ß; p = 0.442, IL-6; p = 0.686, IFN-γ; p = 0.801, IL-8; p = 0.546, IL-12; p = 0.154) and anti-inflammatory (IL-10; p = 0.201, IL-7; p = 0.190, IL-13; p = 0.763) cytokine responses were similar. CONCLUSION: Our data suggest that asymptomatic infections of P. falciparum and HBV together with a high prevalence of hypertension did not have any significant impact on cytokine response profiles among predominantly sedentary traders in the Tamale metropolis of Ghana.


Asunto(s)
Enfermedades Asintomáticas/epidemiología , Coinfección/epidemiología , Citocinas/sangre , Virus de la Hepatitis B/genética , Hepatitis B/epidemiología , Malaria Falciparum/epidemiología , Plasmodium falciparum/genética , Conducta Sedentaria , Adolescente , Adulto , Coinfección/parasitología , Coinfección/virología , Estudios Transversales , Femenino , Ghana/epidemiología , Hepatitis B/sangre , Hepatitis B/virología , Humanos , Malaria Falciparum/sangre , Malaria Falciparum/parasitología , Masculino , Persona de Mediana Edad , Autoinforme , Adulto Joven
10.
BMC Infect Dis ; 20(1): 839, 2020 Nov 12.
Artículo en Inglés | MEDLINE | ID: mdl-33183254

RESUMEN

BACKGROUND: Hepatitis B virus (HBV) infection is a public health problem in Togo and transmission to the child occurs mainly during childbirth. The objective of this study was to estimate the prevalence of HBV among childbearing women and infants born to HBV positive mothers in Togo. METHODS: A national cross-sectional study was carried out in six cities in Togo in the six health regions in Togo. Mother-child pairs were recruited from immunization centers or pediatric wards in Lomé, Tsévié, Atakpamé, Sokodé, Kara and Dapaong in 2017. Women aged 18 and over with one child of at least 6 months old were included. A standardized questionnaire was used for data collection and HBV screening was performed using Determine® rapid tests. The prevalence of HBV, defined by a positive HBV surface antigen (HBsAg), was estimated in mothers and then in infants of mothers who were positive for HBsAg. Logistic regression model was performed to identify risk factors for HBsAg positivity in mothers. RESULTS: A total of 2105 mothers-pairs child were recruited. The median age of mothers and infants was 29 years, interquartile range (IQR) [25-33] and 2.1 years, IQR [1-3] respectively. About 35% of women were screened for HBV during antenatal care and 85% of infants received three doses of HBV immunization. Among mothers, the prevalence of HBV was 10.6, 95% confidence interval (95% CI) [9.4-12.0%], and 177 had detectable HBV viral load (> 10 IU/mL). Among mothers with positive HBsAg, three infants also had positive HBsAg, a prevalence of 1.3, 95% CI [0.2-3.8%]. In multivariable analysis, HIV-infection (aOR = 2.19; p = 0.018), having at least three pregnancies (aOR = 1.46; p = 0.025) and living in Tsévié (aOR = 0.31; p < 0.001) compared to those living in Lomé, were associated to HBV infection in mothers. CONCLUSION: In this study, one out of 10 childbearing women were infected with HBV, but less than 2% of infant born to HBV positive mothers under 5 years' old who received immunization under the Expanded Program on Immunization were infected. Improving antenatal screening and providing targeted interventions in babies could help eliminate HBV in Togo.


Asunto(s)
Virus de la Hepatitis B/inmunología , Hepatitis B/epidemiología , Hepatitis B/prevención & control , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Complicaciones Infecciosas del Embarazo/epidemiología , Complicaciones Infecciosas del Embarazo/prevención & control , Vacunación , Adulto , Preescolar , Estudios Transversales , Femenino , VIH , Infecciones por VIH/diagnóstico , Infecciones por VIH/epidemiología , Infecciones por VIH/virología , Hepatitis B/virología , Antígenos de Superficie de la Hepatitis B/sangre , Antígenos de Superficie de la Hepatitis B/inmunología , Virus de la Hepatitis B/genética , Humanos , Lactante , Masculino , Embarazo , Complicaciones Infecciosas del Embarazo/virología , Atención Prenatal , Prevalencia , Togo/epidemiología , Adulto Joven
11.
BMC Infect Dis ; 20(1): 742, 2020 Oct 09.
Artículo en Inglés | MEDLINE | ID: mdl-33036558

RESUMEN

BACKGROUND: The surge of methamphetamine use has been a complicating factor compounding the steeply increasing number of drug overdose deaths in the U.S. Infection from blood-borne viruses including hepatitis B virus (HBV), hepatitis C virus (HCV) and HIV, related to methamphetamine use continue to grow. This study aims to examine the risk factors associated with HBV, HCV and HIV among people who used methamphetamine. METHODS: People who ever used methamphetamine were identified from five National Health and Nutrition Examination Survey (NHANES) cohorts, 2007 to 2016. The outcome was either positive or negative for blood-borne viruses as identified from laboratory tests. Weighted statistics for the combined ten years of data were calculated by multiplying the weighted variable for laboratory measurements by 0.2. We examined the association of sexual activities (sexual partners, sexual identity), drug use behaviors (poly-drug use, injection drug use, frequency of drug use, age started using methamphetamine), demographics, and socio-economic status with blood-borne viruses using bivariate and multivariable logistic regression models. RESULTS: There were 1132 participants representing approximately 11,996,319 persons who ever used methamphetamine in the U.S. Blood-borne viruses' positive rate was 13.0 per 100,000. Multivariable logistic regression analyses showed significant associations of blood-borne infections with age 40-49 years (vs. age 20-29 years, adjusted odds ratio 4.77, 95% CI 1.11-20.55), age 50-59 years (vs. age 20-29 years, 10.25, 2.40-43.82), living within poverty index 1-1.9 (vs. poverty index > = 2, 2.55; 1.19-5.49), living below the poverty threshold (vs. poverty index > = 2, 2.55; 1.11-5.86), having lower than high school education (vs. equal or higher than high school education, 3.13; 1.51-6.46), sexual identity as other than heterosexual (vs. heterosexual, 5.60; 1.72-18.28), using methamphetamine and heroin and cocaine (vs. using methamphetamine alone, 4.24; 1.06-16.92), injection drug use (vs. no injection drug use, 3.15; 1.61-6.16), and started using methamphetamine at age above 25 (vs. started using methamphetamine at age between 10 and 17, 2.09; 1.01-4.35). CONCLUSIONS: Among people who use methamphetamine, those who use polysubstance, or who inject substances, are in urgent need for vaccination and interventions to avoid further harm from blood borne infections.


Asunto(s)
Infecciones por VIH/epidemiología , VIH-1/inmunología , VIH-2/inmunología , Hepacivirus/inmunología , Virus de la Hepatitis B/inmunología , Hepatitis B/epidemiología , Hepatitis C/epidemiología , Metanfetamina , Abuso de Sustancias por Vía Intravenosa , Adulto , Estudios de Cohortes , Estudios Transversales , Femenino , Infecciones por VIH/virología , Hepatitis B/virología , Hepatitis C/virología , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Encuestas Nutricionales , Oportunidad Relativa , Factores de Riesgo , Asunción de Riesgos , Pruebas Serológicas , Conducta Sexual , Parejas Sexuales , Adulto Joven
12.
Medicine (Baltimore) ; 99(41): e22650, 2020 Oct 09.
Artículo en Inglés | MEDLINE | ID: mdl-33031326

RESUMEN

RATIONALE: Hepatitis B virus (HBV) reactivation caused by immunosuppressive therapy or chemotherapy is well known. The administration of direct-acting antiviral agents (DAAs) to treat hepatitis C virus (HCV) infection has also been reported to cause HBV reactivation. We report a rare case of HBV reactivation in a patient with HCV infection after DAA therapy. PATIENT CONCERNS: In 1996, a 53-year-old female was identified as infected with HCV at a medical check-up, following which she visited our hospital. She was infected with HCV genotype 2b, and at follow up in 1997, was found to be hepatitis B surface antigen (HBsAg) and antibody against HBsAg negative, antibody against HBV core positive. She then experienced malignant lymphoma in 2001 at 58 years of age. Complete remission was achieved following chemotherapy and autologous peripheral blood stem cell transplantation. In 2014, she remained negative for HBsAg and antibody against HBsAg but positive for antibody against HBV core. In 2015, 12 weeks of sofosbuvir and ribavirin treatment for HCV was started. Serum HCV RNA levels rapidly decreased, and HCV elimination was confirmed at 24 weeks after cessation of DAA treatment. Acute hepatitis B developed at 15 weeks post- sustained virological response without any symptoms and physical examination findings. DIAGNOSES: This case is speculated to represent HBV reactivation induced by DAA treatment in a patient with previously resolved HBV, based on virologic and clinical status. Genome sequencing revealed the HBV genotype as A2. INTERVENTIONS: The patient was treated with nucleotide analog for HBV reactivation once a day. OUTCOMES: Serum HBV-DNA levels decreased, and serum liver enzymes improved following initiation of nucleotide analog treatment. Also, adverse events of nucleotide analog treatment were not observed. LESSONS: Although the risk may be very low, DAA therapy can cause HBV reactivation in chronic hepatitis C patients with prior HBV infection. Thus, those patients must be closely monitored for serum HBV DNA levels during and after DAA treatment.


Asunto(s)
Antivirales/efectos adversos , Virus de la Hepatitis B/aislamiento & purificación , Hepatitis C/tratamiento farmacológico , Ribavirina/efectos adversos , Sofosbuvir/efectos adversos , Femenino , Hepatitis B/virología , Humanos , Persona de Mediana Edad , Recurrencia
13.
PLoS Pathog ; 16(9): e1008744, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32898182

RESUMEN

In HIV-hepatitis B virus (HBV) co-infection, adverse liver outcomes including liver fibrosis occur at higher frequency than in HBV-mono-infection, even following antiretroviral therapy (ART) that suppresses both HIV and HBV replication. To determine whether liver disease was associated with intrahepatic or circulating markers of inflammation or burden of HIV or HBV, liver biopsies and blood were collected from HIV-HBV co-infected individuals (n = 39) living in Bangkok, Thailand and naïve to ART. Transient elastography (TE) was performed. Intrahepatic and circulating markers of inflammation and microbial translocation were quantified by ELISA and bead arrays and HIV and HBV infection quantified by PCR. Liver fibrosis (measured by both transient elastography and liver biopsy) was statistically significantly associated with intrahepatic mRNA for CXCL10 and CXCR3 using linear and logistic regression analyses adjusted for CD4 T-cell count. There was no evidence of a relationship between liver fibrosis and circulating HBV DNA, qHBsAg, plasma HIV RNA or circulating cell-associated HIV RNA or DNA. Using immunohistochemistry of liver biopsies from this cohort, intrahepatic CXCL10 was detected in hepatocytes associated with inflammatory liver infiltrates in the portal tracts. In an in vitro model, we infected an HBV-infected hepatocyte cell line with HIV, followed by interferon-γ stimulation. HBV-infected cells lines produced significantly more CXCL10 than uninfected cells lines and this significantly increased in the presence of an increasing multiplicity of HIV infection. Conclusion: Enhanced production of CXCL10 following co-infection of hepatocytes with both HIV and HBV may contribute to accelerated liver disease in the setting of HIV-HBV co-infection.


Asunto(s)
Quimiocina CXCL10/metabolismo , Coinfección/complicaciones , Infecciones por VIH/complicaciones , VIH/aislamiento & purificación , Virus de la Hepatitis B/aislamiento & purificación , Hepatitis B/complicaciones , Cirrosis Hepática/epidemiología , Adulto , Australia/epidemiología , Estudios de Cohortes , Coinfección/virología , Femenino , Infecciones por VIH/virología , Hepatitis B/virología , Humanos , Incidencia , Cirrosis Hepática/metabolismo , Cirrosis Hepática/virología , Masculino , Países Bajos/epidemiología , Pronóstico , Tailandia/epidemiología
14.
PLoS One ; 15(9): e0238839, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32915862

RESUMEN

In patients who are HIV infected, hepatitis B virus (HBV) infection is an important co-morbidity. However, antiretroviral options for HIV/HBV co-infected children are limited and, at the time of this study, only included lamivudine. These children may remain on this regimen for many years until late adolescence. They are at high risk of developing HBV drug resistance and uncontrolled HBV disease. The aim of this study was to characterize HBV infection in HIV/HBV co-infected children. Known HIV-infected/HBsAg-positive children, previously exposed to lamivudine monotherapy against HBV, and their mothers were recruited at the Katutura Hospital paediatric HIV clinic in Windhoek, Namibia. Dried blood spot and serum samples were collected for HBV characterization and serological testing, respectively. Fifteen children and six mothers participated in the study. Eight of the 15 children (53.3%) tested HBV DNA positive; all eight children were on lamivudine-based ART. Lamivudine-associated resistance variants, together with immune escape mutants in the surface gene, were identified in all eight children. Resistance mutations included rtL80I, rtV173L, rtL180M, rtM204I/V and the overlapping sE164D, sW182*, sI195M and sW196LS variants. HBV strains belonged to genotypes E (6/8, 75%) and D3 (2/8, 25%). Further analysis of the HBV core promoter region revealed mutations associated with reduced expression of HBeAg protein and hepatocarcinogenesis. All six mothers, on HBV-active ART containing tenofovir and lamivudine, tested HBV DNA negative. This study confirms the importance of screening HIV-infected children for HBV and ensuring equity of drug access to effective HBV treatment if co-infected.


Asunto(s)
Coinfección/epidemiología , Farmacorresistencia Viral/genética , Infecciones por VIH/epidemiología , Hepatitis B/epidemiología , Mutación , Proteínas del Núcleo Viral/genética , Carga Viral , Adolescente , Adulto , Antirretrovirales/uso terapéutico , Niño , Estudios de Cohortes , Coinfección/genética , Coinfección/virología , Estudios Transversales , ADN Viral/análisis , Femenino , VIH/efectos de los fármacos , VIH/aislamiento & purificación , Infecciones por VIH/complicaciones , Infecciones por VIH/genética , Infecciones por VIH/virología , Hepatitis B/complicaciones , Hepatitis B/genética , Hepatitis B/virología , Virus de la Hepatitis B/efectos de los fármacos , Virus de la Hepatitis B/aislamiento & purificación , Humanos , Masculino , Namibia/epidemiología , Adulto Joven
15.
Medicine (Baltimore) ; 99(37): e22065, 2020 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-32925741

RESUMEN

BACKGROUND: Liuweiwuling (LWWL) tablet, a kind of plant-derived traditional Chinese medicine preparation, has been widely applied as a promising adjunctive drug for hepatitis B virus-related cirrhosis (HBVC). However, its exact clinical efficacy and safety is still not well investigated. In this study, we aimed to summarize the efficacy of LWWL tablet on biochemical and virological parameters, and quality of life (QoL) in patients with HBVC through the meta-analysis. METHODS: All available randomized controlled trials and high-quality prospective cohort studies that investigated the efficacy and safety of LWWL for patients with HBVC were searched from the following electronic databases: PubMed, Medline, Cochrane Library, Google Scholar, Web of Science, Excerpt Medica Database, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, China Scientific Journal Database, and Wanfang Database. Papers in Chinese or English published from January 2000 to August 2020 will be included without any restrictions.Study selection and data extraction will be performed independently by 2 authors. The clinical outcomes including biochemical (liver function and fibrosis indexes) and virological parameters, QoL, immune function and adverse events, were systematically evaluated. Review Manager 5.3 and Stata 14.0 were used for data synthesis, sensitivity analysis, meta regression, subgroup analysis, and risk of bias assessment. RESULTS: The results of this study will be published in a peer-reviewed journal, and provide a helpful evidence for clinicians to formulate the best postoperative adjuvant treatment strategy for HBVC patients. CONCLUSION: Our study will draw an objective conclusion of the efficacy of LWWL on biochemical and virological parameters, and QoL in patients with HBVC. INPLASY REGISTRATION NUMBER: INPLASY202080010.


Asunto(s)
Medicamentos Herbarios Chinos/uso terapéutico , Hepatitis B/complicaciones , Cirrosis Hepática/tratamiento farmacológico , Cirrosis Hepática/virología , Metaanálisis como Asunto , Calidad de Vida , Revisiones Sistemáticas como Asunto , Medicamentos Herbarios Chinos/efectos adversos , Hepatitis B/virología , Humanos , Comprimidos , Resultado del Tratamiento
16.
BMC Infect Dis ; 20(1): 565, 2020 Aug 03.
Artículo en Inglés | MEDLINE | ID: mdl-32746807

RESUMEN

BACKGROUND: Patients coinfected with HBV and hepatitis D virus (HDV) have a greater risk of HCC and cirrhosis. The current study was undertaken to assess HDV genotype distribution and determine clinical characteristics of hepatitis delta virus (HDV) among HBsAg positive individuals in Shanghai. METHOD: This retrospective study involved 225 serum samples from HBsAg positive hospitalized patients from October 2010 to April 2013. HDV-specific RT-nested PCR was used to amplify HDV RNA. HDV genotypes were characterized by Next-generation sequencing (NGS), followed by phylogenetic analyses. HDV/HBV co-infected patients and HBV mono-infected patients were compared clinically and virologically. RESULTS: Out of the 225 HBsAg-positive serum samples with elevated transaminases, HDV-RNA was identified in 11 (4.9%) patients. The HBV loads in the HDV positive group were significantly lower than the HDV negative HBV-infected patients. The aminotransferase enzymes were significantly higher in HDV/HBV co-infected compared to HDV negative patients (P < 0.05). Phylogenetic analyses indicated that HDV-2 genotype being the predominant genotype, other HDV genotypes were not observed. HDV/HBV patients were significantly associated with a rather unfavourable clinical outcome. CONCLUSION: In summary, the prevalence of HDV infection in patients with elevated transaminases is not low and the predominance of HDV genotype 2 infection in Shanghai. This finding helps us to better understand the correlation of HDV/HBV co-infection. Moreover, Next-generation sequencing (NGS) technologies provide a rapid, precise method for generating HDV genomes to define infecting genotypes.


Asunto(s)
Hepatitis D/diagnóstico , Virus de la Hepatitis Delta/genética , Adulto , Secuencia de Aminoácidos , China/epidemiología , Coinfección , Femenino , Genotipo , Hepatitis B/diagnóstico , Hepatitis B/virología , Antígenos de Superficie de la Hepatitis B/sangre , Hepatitis D/epidemiología , Hepatitis D/virología , Virus de la Hepatitis Delta/clasificación , Virus de la Hepatitis Delta/aislamiento & purificación , Humanos , Masculino , Persona de Mediana Edad , Filogenia , Prevalencia , ARN Viral/química , ARN Viral/metabolismo , Estudios Retrospectivos , Factores de Riesgo , Carga Viral , Adulto Joven
17.
Arch Virol ; 165(10): 2361-2365, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32743697

RESUMEN

In this study, we investigated the seroprevalence of anti-hepatitis D virus (HDV) antibodies in hepatitis B surface antigen (HBsAg)-positive children after 25 years of obligatory vaccination of infants against hepatitis B virus. This cross-sectional study included 120 treatment-naïve HBsAg-positive children, with a male-to-female ratio of 1.8:1 and a mean age of 7.8 ± 3.8 years (range, 1-17 years). Mothers were positive for HBsAg in 96.6% of the cases. HBeAg-positive chronic infection was observed in 60% of the cases, HBeAg-positive chronic hepatitis in 12.5%, and HBeAg-negative chronic infection in 26.7%. Anti-HDV antibodies were not detected in any of the cases. Thus, there is a lack of anti-HDV antibodies in HBsAg-positive children, despite the current burden in adults.


Asunto(s)
Anticuerpos Antihepatitis/sangre , Antígenos de Superficie de la Hepatitis B/sangre , Vacunas contra Hepatitis B/administración & dosificación , Virus de la Hepatitis B/inmunología , Hepatitis B/epidemiología , Hepatitis D Crónica/epidemiología , Virus de la Hepatitis Delta/inmunología , Adolescente , Niño , Preescolar , Coinfección , Estudios Transversales , Egipto/epidemiología , Femenino , Hepatitis B/inmunología , Hepatitis B/prevención & control , Hepatitis B/virología , Virus de la Hepatitis B/efectos de los fármacos , Virus de la Hepatitis B/patogenicidad , Hepatitis D Crónica/sangre , Hepatitis D Crónica/inmunología , Hepatitis D Crónica/virología , Virus de la Hepatitis Delta/patogenicidad , Humanos , Lactante , Masculino , Estudios Seroepidemiológicos
18.
PLoS One ; 15(8): e0237586, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32785260

RESUMEN

This study investigated the kinetics of estimated glomerular filtration rate (eGFR) and quantitative hepatitis B surface antigen (qHBsAg) in telbivudine (LdT)-treated chronic hepatitis B (CHB) patients whose treatment was subsequently adjusted with the adding on adefovir or by switching to tenofovir disoproxil fumarate (TDF) as rescue. Of 295 CHB patients initially treated with LdT, 102 of them who subsequently receiving either adding-on adefovir (group A, n = 58) or switching to TDF (group B, n = 44) for more than 24 months were enrolled. Serial eGFR and qHBsAg levels (3 to 6 monthly) in both LdT monotherapy and rescue therapy periods were analyzed retrospectively. Subsequent decline of qHBsAg especially in rescue therapy period were noted (p<0.001 and p = 0.068 in group A and B). However, patients in group B achieved a significant increase of eGFR (p = 0.010) in LdT monotherapy period but had a significant decline of eGFR (p<0.001) in rescue therapy period. In contrast, patients in group A maintained eGFR levels in both periods. Meanwhile, switch to TDF (hazard ratio: 3.036; 95% confidence interval: 1.040-8.861; p = 0.042) was the sole factor related to the decrease of eGFR>20% from baseline. Both rescue therapies achieved subsequent declines of qHBsAg over time but caused different changes in eGFR. LdT-based rescue therapy maintained eGFR but TDF switching therapy descended eGFR. Therefore, it is essential to monitor patient's renal function intensively when switching from LdT to TDF as a rescue strategy.


Asunto(s)
Antivirales/farmacología , Tasa de Filtración Glomerular/efectos de los fármacos , Antígenos de Superficie de la Hepatitis B/metabolismo , Virus de la Hepatitis B/metabolismo , Hepatitis B/patología , Telbivudina/farmacología , Femenino , Estudios de Seguimiento , Hepatitis B/metabolismo , Hepatitis B/virología , Virus de la Hepatitis B/efectos de los fármacos , Humanos , Cinética , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos
19.
PLoS Pathog ; 16(8): e1008802, 2020 08.
Artículo en Inglés | MEDLINE | ID: mdl-32822428

RESUMEN

Hepatitis B virus (HBV) is a worldwide health problem without curative treatments. Investigation of the regulation of HBV biosynthesis by class I and II histone deacetylases (HDACs) demonstrated that catalytically active HDAC5 upregulates HBV biosynthesis. HDAC5 expression increased both the stability and splicing of the HBV 3.5 kb RNA without altering the translational efficiency of the viral pregenomic or spliced 2.2 kb RNAs. Together, these observations point to a broader role of HDAC5 in regulating RNA splicing and transcript stability while specifically identifying a potentially novel approach toward antiviral HBV therapeutic development.


Asunto(s)
Genoma Viral , Virus de la Hepatitis B/metabolismo , Hepatitis B/virología , Histona Desacetilasas/metabolismo , Estabilidad del ARN , ARN Viral/biosíntesis , ARN Viral/química , Regulación Viral de la Expresión Génica , Células Hep G2 , Virus de la Hepatitis B/genética , Histona Desacetilasas/genética , Humanos , Transcripción Genética , Replicación Viral
20.
PLoS One ; 15(8): e0237525, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32776972

RESUMEN

Hepatitis B is a global epidemic that requires carefully orchestrated vaccination initiatives in geographical regions of medium to high endemicity to reach the World Health Organization's elimination targets by 2030. This study compares two widely-used deterministic hepatitis B models-the Imperial HBV model and the CDA Foundation's PRoGReSs-based on their predicted outcomes in four countries. The impact of scaling up of the timely birth dose of the hepatitis B vaccine is also investigated. The two models predicted largely similar outcomes for the impact of vaccination programmes on the projected numbers of new cases and deaths under high levels of the infant hepatitis B vaccine series. However, scenarios for the scaling up of the infant hepatitis B vaccine series had a larger impact in the PRoGReSs model than in the Imperial model due to the infant vaccine series directly leading to the reduction of perinatal transmission in the PRoGReSs model, but not in the Imperial model. Meanwhile, scaling up of the timely birth dose vaccine had a greater impact on the outcomes of the Imperial hepatitis B model than in the PRoGReSs model due to the greater protection that the birth dose vaccine confers to infants in the Imperial model compared to the PRoGReSs model. These differences underlie the differences in projections made by the models under some circumstances. Both sets of assumptions are consistent with available data and reveal a structural uncertainty that was not apparent in either model in isolation. Those relying on projections from models should consider outputs from both models and this analysis provides further evidence of the benefits of systematic model comparison for enhancing modelling analyses.


Asunto(s)
Vacunas contra Hepatitis B/administración & dosificación , Virus de la Hepatitis B/efectos de los fármacos , Hepatitis B/prevención & control , Programas de Inmunización/estadística & datos numéricos , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Modelos Estadísticos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Femenino , Salud Global , Hepatitis B/epidemiología , Hepatitis B/virología , Humanos , Lactante , Recién Nacido , Persona de Mediana Edad , Embarazo , Organización Mundial de la Salud , Adulto Joven
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