- MeSH
- hepatitida B - antigeny povrchové krev MeSH
- hepatitida C - protilátky krev MeSH
- krevní plazma imunologie MeSH
- látky proti HIV krev MeSH
- lidé MeSH
- řízení kvality MeSH
- sérologické testy * MeSH
- testování odbornosti laboratoří statistika a číselné údaje MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- zprávy MeSH
INTRODUCTION AND AIMS: Viral hepatitis, which appears most frequently at birth or during childhood, is a disease whose transmission routes include tears, bile, sexual fluids, sweat, milk, urine, feces, and saliva. The aim of the present study was to analyze the specificity of the immunochromatographic and ELISA diagnostic tests for hepatitis B surface antigen and compare them with PCR testing. MATERIALS AND METHODS: The study sample was made up of 140 men and 60 women referred to the Urmia Medical University hospital to undergo PCR testing for HBV diagnosis. The ELISA test was performed using the Pioneer Medicine Company kit (Tehran, Iran). RESULTS: The results of the HBs-Ag rapid test and the ELISA test were compared with the PCR test. The HBs-Ag rapid test had 97% sensitivity and 91% specificity, whereas the ELISA test had 78% sensitivity and 76% specificity. DISCUSSION AND CONCLUSION: According to our results, the immunochromatographic test was accurate for diagnosing HBs-Ag in blood and the ELISA test had acceptable sensitivity and specificity, compared with PCR testing.
- MeSH
- chromatografie afinitní MeSH
- diagnostické testy rutinní MeSH
- ELISA MeSH
- hepatitida B - antigeny povrchové * MeSH
- hepatitida B * diagnóza MeSH
- lidé MeSH
- novorozenec MeSH
- polymerázová řetězová reakce MeSH
- virus hepatitidy B genetika MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- novorozenec MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
- Geografické názvy
- Írán MeSH
BACKGROUND AND AIMS: Sustained off-treatment immune control is achievable in a proportion of patients with chronic hepatitis B treated with peginterferon alfa-2a. We evaluated on-treatment predictors of hepatitis B surface antigen (HBsAg) clearance 3 years after peginterferon alfa-2a treatment and determined the incidence of hepatocellular carcinoma. METHODS: A prospective, international, multicenter, observational study in patients with chronic hepatitis B who have been prescribed peginterferon alfa-2a (40KD) in a real-world setting. The primary endpoint was HBsAg clearance after 3 years' follow-up. RESULTS: The modified intention-to-treat population comprised 844 hepatitis B e antigen (HBeAg)-positive patients (540 [64%] completed 3 years' follow-up), and 872 HBeAg-negative patients (614 [70%] completed 3 years' follow-up). At 3 years' follow-up, HBsAg clearance rates in HBeAg-positive and HBeAg-negative populations, respectively, were 2% (16/844) and 5% (41/872) in the modified intention-to-treat population and 5% [16/328] and 10% [41/394] in those with available data. In HBeAg-positive patients with data, Week 12 HBsAg levels <1500, 1500-20,000, and >20,000 IU/mL were associated with HBsAg clearance rates at 3 years' follow-up of 11%, 1%, and 5%, respectively (Week 24 predictability was similar). In HBeAg-negative patients with available data, a ≥10% decline vs a <10% decline in HBsAg at Week 12 was associated with HBsAg clearance rates of 16% vs 4%. Hepatocellular carcinoma incidence was lower than REACH-B (Risk Estimation for Hepatocellular Carcinoma in Chronic Hepatitis B) model predictions. CONCLUSIONS: Sustained off-treatment immune control is achieved with peginterferon alfa-2a in a real-world setting. HBsAg clearance 3 years after completion of peginterferon alfa-2a can be predicted on the basis of on-treatment HBsAg kinetics.
- MeSH
- bezpečnost MeSH
- chronická hepatitida B farmakoterapie metabolismus MeSH
- dospělí MeSH
- hepatitida B - antigeny e metabolismus MeSH
- hepatitida B - antigeny povrchové metabolismus MeSH
- interferon alfa škodlivé účinky terapeutické užití MeSH
- internacionalita * MeSH
- lidé MeSH
- polyethylenglykoly škodlivé účinky terapeutické užití MeSH
- rekombinantní proteiny škodlivé účinky terapeutické užití MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- pozorovací studie MeSH
- práce podpořená grantem MeSH
We describe here the anti-HBV activity of natural and synthetic retinoids in primary human hepatocytes (PHHs). The most potent compounds inhibited HBsAg, HBeAg, viral RNA and DNA production by HBV infected cells with EC50 values ranging from 0.4 to 2.6 μM. The activity was independent of PHH donor and HBV genotype used in testing. 13-cis retinoic acid (Accutane) was selected for further evaluation in the PXB chimeric mouse model of HBV infection at doses allowing to achieve Accutane peak serum concentrations near its antiviral EC90 and exposures ∼5-fold higher than a typical clinical dose. While these supraclinical exposures of 100 mg/kg/day were well-tolerated by regular Balb/c mice, PXB mice were more sensitive and even a lower those of 60 mg/kg/day led to significant weight loss. Despite dosing at this maximal tolerated dose for 28 days, Accutane failed to show any anti-HBV activity. RAR target engagement was verified using transcriptome analysis of liver samples from treated versus vehicle groups. However, gene expression changes in PXB liver samples were vastly muted when compared to the in vitro PHH system. When comparing transcriptional changes associated with the conditioning of fresh hepatocytes toward enabling HBV infection, we also observed a large number of changes. Noticeably, a significant number of genes that were up- or down-regulated by the conditioning process were down- or up-regulated by HBV infected PHH treatment with Accutane, respectively. While the lack of efficacy in the PXB model may have many explanations, the observed, opposing transcriptional changes upon conditioning PHH and treating these cultured, HBV-infected PHH with Accutane allow for the possibility that the PHH system may yield artificial anti-HBV hits.
- MeSH
- antivirové látky krev farmakologie MeSH
- DNA virů metabolismus MeSH
- down regulace MeSH
- exprese genu účinky léků MeSH
- hepatitida B - antigeny e účinky léků MeSH
- hepatitida B - antigeny povrchové účinky léků MeSH
- hepatitida B farmakoterapie virologie MeSH
- hepatocyty metabolismus virologie MeSH
- isotretinoin farmakologie MeSH
- lidé MeSH
- modely nemocí na zvířatech MeSH
- myši inbrední BALB C MeSH
- myši MeSH
- replikace viru účinky léků MeSH
- retinoidy krev farmakologie MeSH
- RNA virová metabolismus MeSH
- upregulace MeSH
- viabilita buněk účinky léků MeSH
- virus hepatitidy B účinky léků genetika MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND & AIMS: Robust data on hepatocellular carcinoma (HCC) incidence among HIV/hepatitis B virus (HBV)-coinfected individuals on antiretroviral therapy (ART) are needed to inform HCC screening strategies. We aimed to evaluate the incidence and risk factors of HCC among HIV/HBV-coinfected individuals on tenofovir disoproxil fumarate (TDF)-containing ART in a large multi-cohort study. METHODS: We included all HIV-infected adults with a positive hepatitis B surface antigen test followed in 4 prospective European cohorts. The primary outcome was the occurrence of HCC. Demographic and clinical information was retrieved from routinely collected data, and liver cirrhosis was defined according to results from liver biopsy or non-invasive measurements. Multivariable Poisson regression was used to assess HCC risk factors. RESULTS: A total of 3,625 HIV/HBV-coinfected patients were included, of whom 72% had started TDF-containing ART. Over 32,673 patient-years (py), 60 individuals (1.7%) developed an HCC. The incidence of HCC remained stable over time among individuals on TDF, whereas it increased steadily among those not on TDF. Among individuals on TDF, the incidence of HCC was 5.9 per 1,000 py (95% CI 3.60-9.10) in cirrhotics and 1.17 per 1,000 py (0.56-2.14) among non-cirrhotics. Age at initiation of TDF (adjusted incidence rate ratio per 10-year increase: 2.2, 95% CI 1.6-3.0) and the presence of liver cirrhosis (4.5, 2.3-8.9) were predictors of HCC. Among non-cirrhotic individuals, the incidence of HCC was only above the commonly used screening threshold of 2 cases per 1,000 py in patients aged >45 years old at TDF initiation. CONCLUSIONS: Whereas the incidence of HCC was high in cirrhotic HIV/HBV-coinfected individuals, it remained below the HCC screening threshold in patients without cirrhosis who started TDF aged <46 years old. LAY SUMMARY: We investigated the incidence of hepatocellular carcinoma in HIV/hepatitis B virus-coinfected individuals from a large multi-cohort study in Europe. Over 32,673 patient-years, 60 individuals (1.7%) developed hepatocellular carcinoma. The incidence of hepatocellular carcinoma remained low in patients without cirrhosis, who started on tenofovir disoproxil fumarate when aged <46 years old.
- MeSH
- dospělí MeSH
- hepatitida B - antigeny povrchové analýza MeSH
- hepatitida B farmakoterapie virologie MeSH
- hepatocelulární karcinom epidemiologie MeSH
- HIV * MeSH
- incidence MeSH
- koinfekce farmakoterapie virologie MeSH
- látky proti HIV terapeutické užití MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádory jater epidemiologie MeSH
- následné studie MeSH
- oportunní infekce doprovázející AIDS farmakoterapie virologie MeSH
- prospektivní studie MeSH
- tenofovir terapeutické užití MeSH
- virus hepatitidy B imunologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- MeSH
- chronická hepatitida B diagnóza MeSH
- hepatitida B - antigeny povrchové analýza krev MeSH
- hepatitida B - antigeny * analýza krev MeSH
- hepatitida B * diagnóza terapie MeSH
- klinické laboratorní techniky * MeSH
- laboratorní automatizace MeSH
- lidé MeSH
- senzitivita a specificita MeSH
- sérologické testy MeSH
- Check Tag
- lidé MeSH
- MeSH
- hepatitida B - antigeny povrchové izolace a purifikace krev MeSH
- hepatitida C - protilátky izolace a purifikace krev MeSH
- lidé MeSH
- mikrobiologické techniky statistika a číselné údaje MeSH
- referenční standardy MeSH
- řízení kvality MeSH
- sérologické testy při AIDS MeSH
- sérologické testy * statistika a číselné údaje MeSH
- testování odbornosti laboratoří * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- tabulky MeSH