Improved performance of quantitative collagen parameters versus standard histology in longitudinal assessment of non-advanced liver fibrosis for…

Posted by on 02 Dec 2017 | Tagged as: Hepatitis B Alternative Medicine

Improved performance of quantitative collagen parameters versus standard histology in longitudinal assessment of non-advanced liver fibrosis for chronic hepatitis B. J Viral Hepat. 2017 Nov 29;: Authors: Wang Y, Liang X, Yang J, Wang H, Tan D, Chen S, Cheng J, Chen Y, Sun J, Rong F, Yang W, Liu H, Liu Z, Zheng Y, Liang J, Li S, Liu Z, Hou J Abstract Monitoring longitudinal non-advanced fibrosis is a more common scenario in management of chronic hepatitis B (CHB), for which however, current evaluation methods generally lack sufficient performance. We conducted a proof-of-concept study to evaluate the performance of quantitative fibrous collagen parameters (q-FP) in the assessment. Data sets from a prior CHB trial (NCT00962533) with mostly mild-to-moderate fibrosis participants were used for this study. 301 subjects with paired liver biopsies were consecutively included. Of these, 139 subjects were used to establish the test and the rest for internal validation. Fibrosis change between baseline and week 104 of treatment was blindly assessed with q-FP and was compared with Ishak fibrosis staging. There were 70% and 93% subjects with Ishak F0-2 at baseline and week 104, respectively. For the test of the subjects, q-FP and Ishak staging showed no difference in determining the incidence of fibrosis regression (68% vs. 67%; difference=0.7%, p=1.00). Q-FP demonstrated that the regression was independently associated with the antiviral efficacy endpoint (OR 3.0, 95%CI 1.4-6.5, p=0.005), but Ishak failed the detection (OR 0.6, 95%CI 0.3-1.3, p=0.24). Moreover, q-FP directly revealed a higher fibrosis-resistance to antiviral treatment in virus genotypes C versus B and in males versus females. These results were confirmed in the validation subjects. Additionally, a functional model built on the test subjects showed an accuracy of 82% in stratifying fibrosis-reversibility of the validation subjects. In conclusion, q-FP could have improved efficiency and accuracy in the longitudinal assessment of mild-to-moderate CHB fibrosis, indicating a potential alternative to current evaluation methodologies. This article is protected by copyright. All rights reserved. PMID: 29193542 [PubMed – as supplied by publisher]

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Improved performance of quantitative collagen parameters versus standard histology in longitudinal assessment of non-advanced liver fibrosis for…

Field performance of the Determine HBsAg point-of-care test for diagnosis of hepatitis B virus co-infection among HIV patients in Zambia.

Posted by on 28 Nov 2017 | Tagged as: Hepatitis B Alternative Medicine

Field performance of the Determine HBsAg point-of-care test for diagnosis of hepatitis B virus co-infection among HIV patients in Zambia. J Clin Virol. 2017 Nov 16;98:5-7 Authors: Chisenga CC, Musukuma K, Chilengi R, Zürcher S, Munamunungu V, Siyunda A, Ojok D, Bauer S, Wandeler G, Vinikoor M, for International Epidemiological Databases to Evaluate AIDS in Southern Africa (IeDEA-SA) Institutions Abstract BACKGROUND: We evaluated the field performance of a rapid point-of-care (POC) test for hepatitis B surface antigen (HBsAg) that could support decentralization and scale-up of hepatitis B virus (HBV) diagnosis in Africa. OBJECTIVE: To determine the field performance of the Determine HBsAg POC test for diagnosis of HBV co-infection among HIV patients in Zambia. STUDY DESIGN: Between 2013-2014, we screened HIV-infected adults for HBsAg at two urban clinics in Zambia. A subset were tested with the POC Determine HBsAg (Alere, USA) by finger prick in the clinic and HBsAg serology (Access2Analyzer, Beckman Coulter) at a reference laboratory. If either test was reactive, we determined HBV viral load (VL) and genotype. We described patient demographic and clinical characteristics (including liver fibrosis) and assessed the sensitivity, specificity, positive and negative predictive values (PPV and NPV) of the Determine test. In secondary analyses, we assessed sensitivity among patients with replicating HBV (i.e., VL>20 IU/ml) and with high HBV VL (i.e.,>20,000IU/ml). RESULTS: Among 412 participants with both HBsAg tests, median age was 34 years, 51% were women, and median CD4 was 208 cells/mm3. By serology, 66 (16%) were HBsAg-positive. Overall Determine had 87.9% sensitivity, 99.7% specificity, 98.3% PPV, and 97.7% NPV. Six of 8 patients with false negative results had undetectable HBV VL and no evidence of significant liver fibrosis. Test sensitivity was 95.9% among the 51 with replicating HBV and 100% among the 28 with high HBV VL. CONCLUSIONS: Determine HBsAg is a cheaper alternative HBV testing option compared to the gold standard ELISA and has high specificity and good sensitivity in the field among HIV-infected individuals. PMID: 29175231 [PubMed – as supplied by publisher]

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Field performance of the Determine HBsAg point-of-care test for diagnosis of hepatitis B virus co-infection among HIV patients in Zambia.

Tenofovir Alafenamide Fumarate: A New Tenofovir Prodrug for the Treatment of Chronic Hepatitis B Infection.

Posted by on 21 Nov 2017 | Tagged as: Hepatitis B Alternative Medicine

Tenofovir Alafenamide Fumarate: A New Tenofovir Prodrug for the Treatment of Chronic Hepatitis B Infection. J Infect Dis. 2017 Nov 16;216(suppl_8):S792-S796 Authors: Buti M, Riveiro-Barciela M, Esteban R Abstract Tenofovir alafenamide fumarate (TAF), a new prodrug of tenofovir and a potential successor of tenofovir disoproxil fumarate (TDF), has been approved in the United States and Europe for treating adolescents and adults with chronic hepatitis B infection. TAF is formulated to deliver the active metabolite to target cells more efficiently than TDF at lower doses, thereby reducing systemic exposure to tenofovir. In patients with chronic hepatitis B, TAF appears to be as effective as TDF, with lower bone and renal toxicity. TAF has the potential advantages that dose adjustment is not required in patients with renal impairment, and monitoring can be less intense because of the better safety profile. Results from 2 large, randomized, phase 3 studies after 48 weeks of therapy have shown that TAF may be a good alternative to TDF for treating chronic hepatitis B. Whether the short-term benefits observed in these 48-week trials will translate into improvements in bone and renal health in patients receiving long-term treatment remains to be seen. PMID: 29156043 [PubMed – in process]

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Tenofovir Alafenamide Fumarate: A New Tenofovir Prodrug for the Treatment of Chronic Hepatitis B Infection.

The future of viral hepatitis testing: innovations in testing technologies and approaches.

Posted by on 17 Nov 2017 | Tagged as: Hepatitis B Alternative Medicine

The future of viral hepatitis testing: innovations in testing technologies and approaches. BMC Infect Dis. 2017 Nov 01;17(Suppl 1):699 Authors: Peeling RW, Boeras DI, Marinucci F, Easterbrook P Abstract A large burden of undiagnosed hepatitis virus cases remains globally. Despite the 257 million people living with chronic hepatitis B virus infection, and 71 million with chronic viraemic HCV infection, most people with hepatitis remain unaware of their infection. Advances in rapid detection technology have created new opportunities for enhancing access to testing and care, as well as monitoring of treatment. This article examines a range of other technological innovations that can be leveraged to provide more affordable and simplified approaches to testing for HBV and HCV infection and monitoring of treatment response. These include improved access to testing through alternative sampling methods (use of dried blood spots, oral fluids, self-testing) and combination rapid diagnostic tests for detection of HIV, HBV and HCV infection; more affordable options for confirmation of virological infection (HBV DNA and HCV RNA) such as point-of-care molecular assays, HCV core antigen and multi-disease polyvalent molecular platforms that make use of existing centralised laboratory based or decentralised TB and HIV instrumentation for viral hepatitis testing; and finally health system improvements such as integration of laboratory services for procurement and sample transportation and enhanced data connectivity to support quality assurance and supply chain management. PMID: 29143676 [PubMed – in process]

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The future of viral hepatitis testing: innovations in testing technologies and approaches.

General practitioners’ perceptions of vaccination controversies: a French nationwide cross-sectional study.

Posted by on 07 Nov 2017 | Tagged as: Hepatitis B Alternative Medicine

Related Articles General practitioners’ perceptions of vaccination controversies: a French nationwide cross-sectional study. Clin Microbiol Infect. 2017 Nov 02;: Authors: le Marechal M, Fressard L, Agrinier N, Verger P, Pulcini C Abstract OBJECTIVES: – We aimed to study general practitioners (GPs) perceptions of vaccines that have been the object of controversies in France. METHODS: – A cross-sectional survey in 2014 asked a representative national sample of GPs, randomly selected from the exhaustive database of health professionals in France, about their perceptions of the likelihood of serious adverse events potentially associated with six different vaccines: for two of them the association was based on some scientific evidence, whereas for the other four this is not the case. We performed a cluster analysis to construct a typology of GPs’ perceptions about the likelihood of these potential six associations. Factors associated with certain clusters of interest were identified using logistic regression models. RESULTS: Overall, 1,582 GPs participated in the questionnaire survey (1582/1712 GPs who agreed to participate, 92%). Cluster analysis identified four groups of GPs according to their susceptibility to vaccine controversies: 1) limited susceptibility to controversies (52%); 2) overall unsure, but rejected the association between Hepatitis B vaccine and multiple sclerosis (32%); 3) highly susceptible to controversies (11%); and 4) unsure (5%). We found that GPs who occasionally practised alternative medicine (OR=2.71 IC95%[1.65-4.45]), and those who considered information provided by mass media as reliable (OR=2.04 IC95%[1.65-3.99]) were more susceptible to controversies. CONCLUSIONS: – GPs had different profiles of susceptibility to vaccination controversies, and most of their perceptions of these controversies were not based on scientific evidence. PMID: 29104170 [PubMed – as supplied by publisher]

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General practitioners’ perceptions of vaccination controversies: a French nationwide cross-sectional study.

Hepatitis B core protein as a therapeutic target.

Posted by on 27 Oct 2017 | Tagged as: Hepatitis B Alternative Medicine

Related Articles Hepatitis B core protein as a therapeutic target. Expert Opin Ther Targets. 2017 Oct 25;: Authors: Mak LY, Wong DK, Seto WK, Lai CL, Yuen MF Abstract INTRODUCTION: Chronic hepatitis B virus (HBV) infection is difficult to cure, due to the presence of covalently-closed-circular DNA and virus-mediated blunting of host immune response. Existing therapies with nucleos(t)ide analogue or pegylated-interferon are not sufficient to achieve a high rate of HBV surface antigen seroclearance, a more desirable treatment outcome. Novel therapeutic agents targeting alternative viral replication steps are being developed. In this review, we will discuss the hepatitis B core antigen (HBcAg) as a therapeutic target. Areas covered: The basic structure and fundamental functions of HBcAg including nucleocapsid assembly, pre-genomic RNA encapsidation, reverse transcription, virion formation, cccDNA amplification, immune response regulation, and HBx protein interaction will be reviewed. Most of these are identified as therapeutic targets and tested in in vitro and in vivo studies, although clinical trials are scanty. Among the different components, the core protein allosteric modulators (CpAM) have been most widely investigated and appear promising in clinical trials. Expert opinion: The multiple and essential functions of HBcAg for HBV life cycle are important and attractive targets for HBV therapeutic interventions. Controlled trials involving CpAM are awaited. Apart from CpAM, drugs directed against different functions of HBcAg may be further explored to maximize the chance of cure. PMID: 29065733 [PubMed – as supplied by publisher]

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Hepatitis B core protein as a therapeutic target.

Serum WFA(+) -M2BP levels for evaluation of early stages of liver fibrosis in patients with chronic hepatitis B virus infection.

Posted by on 25 Oct 2017 | Tagged as: Hepatitis B Alternative Medicine

Related Articles Serum WFA(+) -M2BP levels for evaluation of early stages of liver fibrosis in patients with chronic hepatitis B virus infection. Liver Int. 2017 Jan;37(1):35-44 Authors: Zou X, Zhu MY, Yu DM, Li W, Zhang DH, Lu FJ, Gong QM, Liu F, Jiang JH, Zheng MH, Kuno A, Narimatsu H, Zhang Y, Zhang XX Abstract BACKGROUND & AIMS: Accurate evaluation of liver fibrosis is crucial for predicting progression of chronic hepatitis B virus (HBV) infection. We assessed the utility of a novel fibrosis glycobiomarker Wisteria floribunda agglutinin-positive Mac-2-binding protein (WFA(+) -M2BP) for evaluating liver fibrosis and disease progression in patients with chronic HBV infection. METHODS: We enrolled 774 patients with chronic HBV infection, with or without fibrosis, diagnosed by liver biopsy/FibroScan. Patients who underwent liver biopsy (n = 297) were divided into training (n = 221) and validation (n = 76) groups. Serum WFA(+) -M2BP values were measured and compared with FIB-4 index, aspartate aminotransferase (AST)-to-platelet ratio (APRI) and AST-to-alanine aminotransferase ratio (AAR) using receiver-operating characteristic (ROC) analysis. RESULTS: Serum WFA(+) -M2BP levels increased significantly with fibrosis progression (P < 0.0001). Area under the ROC curve of WFA(+) -M2BP for diagnosing significant fibrosis was higher than that of FIB-4 (P = 0.198), APRI (P = 0.017) and AAR (P < 0.001), with sensitivity and specificity in the training set of 60.5% and 79.8% and validation set of 59.5% and 82.1%, respectively. Serum WFA(+) -M2BP levels were significantly correlated with FibroScan values (P < 0.0001) and improved the accuracy of FibroScan in assessing significant fibrosis. Changes in WFA(+) -M2BP levels were parallel with those in FibroScan values during nucleot(s)ide analogues therapy in patients with chronic HBV infection. CONCLUSIONS: WFA(+) -M2BP is an accurate serum indicator for assessing early stages of liver fibrosis and may monitor regression of fibrosis during the treatment of chronic HBV infection. WFA(+) -M2BP provides a simple and reliable alternative or complementary method to liver biopsy and FibroScan. PMID: 27300763 [PubMed – indexed for MEDLINE]

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Serum WFA(+) -M2BP levels for evaluation of early stages of liver fibrosis in patients with chronic hepatitis B virus infection.

Screening for HIV, hepatitis B and syphilis on dried blood spots: A promising method to better reach hidden high-risk populations with self-collected…

Posted by on 21 Oct 2017 | Tagged as: Hepatitis B Alternative Medicine

Related Articles Screening for HIV, hepatitis B and syphilis on dried blood spots: A promising method to better reach hidden high-risk populations with self-collected sampling. PLoS One. 2017;12(10):e0186722 Authors: van Loo IHM, Dukers-Muijrers NHTM, Heuts R, van der Sande MAB, Hoebe CJPA Abstract INTRODUCTION: Many people at high risk for sexually transmitted infections (STIs), e.g., men who have sex with men (MSM), are not optimally reached by current sexual health care systems with testing. To facilitate testing by home-based sampling or sampling in outreach setting we evaluated dried blood spots (DBS), a method for self-collected blood sampling for serological screening of HIV, hepatitis B (HBV) and syphilis. The aims of this study were to assess the acceptability and feasibility of self-collected DBS and to compare the test results for screening of HIV, HBV and syphilis from DBS with blood drawn by venous puncture. METHODS: DBS were collected from men who have sex with men (MSM), visiting the STI clinic of the public health service South Limburg (n = 183) and HIV positive and HBV positive patients (n = 34), visiting the outpatient clinics of the Maastricht University Medical Centre in the period January 2012-April 2015. The 93 first participating MSM visiting the STI clinic were asked to fill in a questionnaire about the feasibility and acceptability about self-collection of DBS in a setting without going to a health care facility and were asked to collect the DBS themselves. Serological screening tests for HIV (HIV combi PT, Roche), HBV (HBsAg, Roche) and syphilis (Treponema pallidum Ig, Biokit 3.0) were performed on DBS and on blood drawn by venous puncture, which was routinely taken for screening. RESULTS: In total 217 participants were included in the study with a median age of 40 years (range between 17-80). Of MSM 84% agreed that it was clear and easy to do the finger-prick, while 53% agreed that it was clear and easy to apply the blood onto the DBS card. Also, 80% of MSM would use the bloodspot test again. In 91% (198) of DBS, sufficient material was collected to perform the three tests. No difference was observed in DBS quality between self-collected DBS and health care worker collected DBS. For HIV (n = 195 DBS-serum pairs) sensitivity and specificity were 100%. For HBV the sensitivity for HBsAg (n = 202) was 90% and specificity was 99%. For syphilis (n = 191) the sensitivity of the DBS was 93% with a specificity of 99%. Analysis of the DBS of HIV positive participants (n = 38) did show similar test performance for HBV and syphilis as in HIV negatives. CONCLUSION: DBS is an acceptable self-sampling method for MSM, as there was no difference in DBS quality in self-collected and health care worker collected DBS. Test performance, i.e., its high sensitivity (>90%) and specificity (>99%) measures show that DBS is a valid alternative for venous blood puncture. Especially when DBS is combined with home-collected sampling for Chlamydia trachomatis and Neisseria gonorrhoeae, complete STI screening can be done in outreach setting and/or home-collected sampling in MSM. PMID: 29053737 [PubMed – in process]

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Screening for HIV, hepatitis B and syphilis on dried blood spots: A promising method to better reach hidden high-risk populations with self-collected…

Accurate quantification of within- and between-host HBV evolutionary rates requires explicit transmission chain modelling.

Posted by on 15 Oct 2017 | Tagged as: Hepatitis B Alternative Medicine

Related Articles Accurate quantification of within- and between-host HBV evolutionary rates requires explicit transmission chain modelling. Virus Evol. 2017 Jul;3(2):vex028 Authors: Vrancken B, Suchard MA, Lemey P Abstract Analyses of virus evolution in known transmission chains have the potential to elucidate the impact of transmission dynamics on the viral evolutionary rate and its difference within and between hosts. Lin et al. (2015, Journal of Virology, 89/7: 3512-22) recently investigated the evolutionary history of hepatitis B virus in a transmission chain and postulated that the ‘colonization-adaptation-transmission’ model can explain the differential impact of transmission on synonymous and non-synonymous substitution rates. Here, we revisit this dataset using a full probabilistic Bayesian phylogenetic framework that adequately accounts for the non-independence of sequence data when estimating evolutionary parameters. Examination of the transmission chain data under a flexible coalescent prior reveals a general inconsistency between the estimated timings and clustering patterns and the known transmission history, highlighting the need to incorporate host transmission information in the analysis. Using an explicit genealogical transmission chain model, we find strong support for a transmission-associated decrease of the overall evolutionary rate. However, in contrast to the initially reported larger transmission effect on non-synonymous substitution rate, we find a similar decrease in both non-synonymous and synonymous substitution rates that cannot be adequately explained by the colonization-adaptation-transmission model. An alternative explanation may involve a transmission/establishment advantage of hepatitis B virus variants that have accumulated fewer within-host substitutions, perhaps by spending more time in the covalently closed circular DNA state between each round of viral replication. More generally, this study illustrates that ignoring phylogenetic relationships can lead to misleading evolutionary estimates. PMID: 29026650 [PubMed]

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Accurate quantification of within- and between-host HBV evolutionary rates requires explicit transmission chain modelling.

In-vivo monitoring of infectious diseases in living animals using bioluminescence imaging.

Posted by on 30 Sep 2017 | Tagged as: Hepatitis B Alternative Medicine

In-vivo monitoring of infectious diseases in living animals using bioluminescence imaging. Virulence. 2017 Sep 29;:0 Authors: Gupta A, Avci P, Karimi M, Sadasivam M, Antunes-Melo WC, Carrasco E, Hamblin MR Abstract Traditional methods of localizing and quantifying the presence of pathogenic microorganisms in living experimental animal models of infections have mostly relied on sacrificing the animals, dissociating the tissue and counting the number of colony forming units. However the discovery of several varieties of the light producing enzyme, luciferase, and the genetic engineering of bacteria, fungi, parasites and mice to make them emit light, either after administration of the luciferase substrate, or in the case of the bacterial lux operon without any exogenous substrate, has provided a new alternative. Dedicated bioluminescence imaging (BLI) cameras can record the light emitted from living animals in real time allowing non-invasive, longitudinal monitoring of the anatomical location and growth of infectious microorganisms as measured by strength of the BLI signal. BLI technology has been used to follow bacterial infections in traumatic skin wounds and burns, osteomyelitis, infections in intestines, Mycobacterial infections, otitis media, lung infections, biofilm and endodontic infections and meningitis. Fungi that have been engineered to be bioluminescent have been used to study infections caused by yeasts (Candida) and by filamentous fungi. Parasitic infections caused by malaria, Leishmania, trypanosomes and toxoplasma have all been monitored by BLI. Viruses such as vaccinia, herpes simplex, hepatitis B and C and influenza, have been studied using BLI. This rapidly growing technology is expected to continue to provide much useful information, while drastically reducing the numbers of animals needed in experimental studies. PMID: 28960132 [PubMed – as supplied by publisher]

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In-vivo monitoring of infectious diseases in living animals using bioluminescence imaging.

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