October 2017

Monthly Archive

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.