scholarly journals An Intracellular Model of Hepatitis B Viral Infection: An In Silico Platform for Comparing Therapeutic Strategies

Viruses ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 11
Author(s):  
Farzad Fatehi ◽  
Richard J. Bingham ◽  
Eric C. Dykeman ◽  
Nikesh Patel ◽  
Peter G. Stockley ◽  
...  
Keyword(s):  
Hepatitis B ◽  
Treatment Options ◽  
World Health Organisation ◽  
World Health ◽  
Major Focus ◽  
Infection Dynamics ◽  
Viral Particles ◽  
B Virus ◽  
Hepatitis B Viral Infection ◽  
The Impact

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.

scholarly journals Hepatitis B virus (HBV) viral load, liver and renal function in adults treated with tenofovir disoproxil fumarate (TDF) vs. untreated: a retrospective longitudinal UK cohort study

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Tingyan Wang ◽  
David A. Smith ◽  
Cori Campbell ◽  
Jolynne Mokaya ◽  
Oliver Freeman ◽  
...  
Keyword(s):  
Viral Load ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Renal Impairment ◽  
Clinical Guidelines ◽  
Untreated Group ◽  
Liver Inflammation ◽  
B Virus ◽  
The Impact

Abstract Background Current clinical guidelines recommend treating chronic hepatitis B virus (HBV) infection in a minority of cases, but there are relatively scarce data on evolution or progression of liver inflammation and fibrosis in cases of chronic HBV (CHB) that do not meet treatment criteria. We aimed to assess the impact of TDF on liver disease, and the risk of renal impairment in treated CHB patients in comparison to untreated patients. Methods We studied a longitudinal ethnically diverse CHB cohort in the UK attending out-patient clinics between 2005 and 2018. We examined TDF treatment (vs. untreated) as the main exposure, with HBV DNA viral load (VL), ALT, elastography scores and eGFR as the main outcomes, using paired tests and mixed effects model for longitudinal measurements. Additionally, decline of eGFR during follow-up was quantified within individuals by thresholds based on clinical guidelines. Baseline was defined as treatment initiation for TDF group and the beginning of clinical follow-up for untreated group respectively. Results We included 206 adults (60 on TDF, 146 untreated), with a median ± IQR follow-up duration of 3.3 ± 2.8 years. The TDF group was significantly older (median age 39 vs. 35 years, p = 0.004) and more likely to be male (63% vs. 47%, p = 0.04) compared to the untreated group. Baseline difference between TDF and untreated groups reflected treatment eligibility criteria. As expected, VL and ALT declined significantly over time in TDF-treated patients. Elastography scores normalised during treatment in the TDF group reflecting regression of inflammation and/or fibrosis. However, 6/81 (7.4%) of untreated patients had a progression of fibrosis stage from F0-F1 to F2 or F3. There was no evidence of difference in rates or incidence of renal impairment during follow-up in the TDF vs. untreated group. Conclusions Risk of liver inflammation and fibrosis may be raised in untreated patients compared to those receiving TDF, and TDF may benefit a larger percentage of the CHB population.

scholarly journals The Impact of Ultraviolet Radiation on the Aetiology and Development of Uveal Melanoma

Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1700
Author(s):  
Melissa Chalada ◽  
Charmaine A. Ramlogan-Steel ◽  
Bijay P. Dhungel ◽  
Christopher J. Layton ◽  
Jason C. Steel
Keyword(s):  
Risk Factors ◽  
Ultraviolet Radiation ◽  
Uveal Melanoma ◽  
World Health Organisation ◽  
World Health ◽  
Genetic Mutations ◽  
High Incidence ◽  
The World ◽  
The Impact

Uveal melanoma (UM) is currently classified by the World Health Organisation as a melanoma caused by risk factors other than cumulative solar damage. However, factors relating to ultraviolet radiation (UVR) susceptibility such as light-coloured skin and eyes, propensity to burn, and proximity to the equator, frequently correlate with higher risk of UM. These risk factors echo those of the far more common cutaneous melanoma (CM), which is widely accepted to be caused by excessive UVR exposure, suggesting a role of UVR in the development and progression of a proportion of UM. Indeed, this could mean that countries, such as Australia, with high UVR exposure and the highest incidences of CM would represent a similarly high incidence of UM if UVR exposure is truly involved. Most cases of UM lack the typical genetic mutations that are related to UVR damage, although recent evidence in a small minority of cases has shown otherwise. This review therefore reassesses statistical, environmental, anatomical, and physiological evidence for and against the role of UVR in the aetiology of UM.

scholarly journals Hepatitis B Vaccination in Senegalese Children: Coverage, Timeliness, and Sociodemographic Determinants of Non-Adherence to Immunisation Schedules (ANRS 12356 AmBASS Survey)

Vaccines ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 510
Author(s):  
Lauren Périères ◽  
Fabienne Marcellin ◽  
Gora Lo ◽  
Camelia Protopopescu ◽  
El Ba ◽  
...  
Keyword(s):  
Hepatitis B ◽  
Dose Schedule ◽  
World Health Organisation ◽  
Sub Saharan Africa ◽  
World Health ◽  
Hepatitis B Vaccination ◽  
Detailed Knowledge ◽  
Cross Sectional Survey ◽  
Cross Sectional ◽  
Hbv Vaccination

Detailed knowledge about hepatitis B virus (HBV) vaccination coverage and timeliness for sub-Saharan Africa is scarce. We used data from a community-based cross-sectional survey conducted in 2018–2019 in the area of Niakhar, Senegal, to estimate coverage, timeliness, and factors associated with non-adherence to the World Health Organisation-recommended vaccination schedules in children born in 2016 (year of the birth dose (BD) introduction in Senegal) and 2017–2018. Vaccination status was assessed from vaccination cards, surveillance data, and healthcare post vaccination records. Among 241 children with available data, for 2016 and 2017–2018, respectively, 31.0% and 66.8% received the BD within 24 h of birth (BD schedule), and 24.3% and 53.7% received the BD plus at least two pentavalent vaccine doses within the recommended timeframes (three-dose schedule). In logistic regression models, home birth, dry season birth, and birth in 2016 were all associated with non-adherence to the recommended BD and three-dose schedules. Living over three kilometres from the nearest healthcare post, being the firstborn, and living in an agriculturally poorer household were only associated with non-adherence to the three-dose schedule. The substantial proportion of children not vaccinated according to recommended schedules highlights the importance of considering vaccination timeliness when evaluating vaccination programme effectiveness. Outreach vaccination activities and incentives to bring children born at home to healthcare facilities within 24 h of birth, must be strengthened to improve timely HBV vaccination.

scholarly journals Riding the waves: the ongoing impact of COVID-19 on a national surgical training cohort

2021 ◽  
Author(s):  
Orla Hennessy ◽  
Amy Lee Fowler ◽  
Conor Hennessy ◽  
David Brinkman ◽  
Aisling Hogan ◽  
...  
Keyword(s):  
Surgical Training ◽  
World Health Organisation ◽  
World Health ◽  
Training Methods ◽  
Viral Spread ◽  
Surgical Services ◽  
Global Pandemic ◽  
Surgical Trainees ◽  
Secondary Survey ◽  
The Impact

Abstract Background The World Health Organisation declared a global pandemic on the 11 March 2020 resulting in implementation of methods to contain viral spread, including curtailment of all elective and non-emergent interventions. Many institutions have experienced changes in rostering practices and redeployment of trainees to non-surgical services. Examinations, study days, courses, and conferences have been cancelled. These changes have the potential to significantly impact the education and training of surgical trainees. Aim To investigate the impact of the COVID-19 pandemic on training, educational, and operative experiences of Irish surgical trainees. Methods Surgical trainees were surveyed anonymously regarding changes in working and educational practices since the declaration of the COVID-19 pandemic on 11 March 2020. The survey was circulated in May 2020 to both core and higher RCSI surgical trainees, when restrictions were at level five. Questions included previous and current access to operative sessions as well as operative cases, previous and current educational activities, access to senior-led training, and access to simulation-/practical-based training methods. A repeat survey was carried out in October 2020 when restrictions were at level two. Results Overall, primary and secondary survey response rates were 29% (n = 98/340) and 19.1% (n = 65/340), respectively. At the time of circulation of the second survey, the number of operative sessions attended and cases performed had significantly improved to numbers experienced pre-pandemic (p < 0.0001). Exposure to formal teaching and education sessions returned to pre-COVID levels (p < 0.0001). Initially, 23% of trainees had an examination cancelled; 53% of these trainees have subsequently sat these examinations. Of note 27.7% had courses cancelled, and 97% of these had not been rescheduled. Conclusion Surgical training and education have been significantly impacted in light of COVID-19. This is likely to continue to fluctuate in line with subsequent waves. Significant efforts have to be made to enable trainees to meet educational and operative targets.

scholarly journals Hepatitis B Virus Infection in Pregnancy: Immunological Response, Natural Course and Pregnancy Outcomes

2021 ◽  
Vol 10 (13) ◽  
pp. 2926
Author(s):  
Sirinart Sirilert ◽  
Theera Tongsong
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Pregnancy Outcomes ◽  
Natural Course ◽  
Hbv Infection ◽  
Chronic Hbv Infection ◽  
B Virus ◽  
Chronic Hbv ◽  
Adverse Pregnancy ◽  
The Impact

This review aimed to provide an update on the impact of pregnancy on the natural course of hepatitis B virus (HBV) infection and also on the impact of HBV infection on adverse pregnancy outcomes, including mother-to-child transmission (MTCT). For the literature review, original research articles, review articles, and guidelines were narratively reviewed and comprehensively validated. The databases of PubMed, EMBASE, and CINAHL were carefully searched for articles in English on topics related to HBV infection, pregnancy, and vertical transmission from 1960 to May 2021. Immunological changes during pregnancy such as suppression of Th1 response and induction of Th2 immunity lead to an impaired immune reaction to HBV and stimulate viral activity along with the reduction of CD8 T cells to escape immune detection. The impact of pregnancy on the natural course of chronic HBV infection seems to be minimal, while pregnancy can increase morbidity and mortality in the case of advanced HBV hepatitis or cirrhosis. Importantly, hepatitis flare or alanine aminotransferase (ALT) flare can occur during pregnancy and is more common during the postpartum period due to the interaction between HBV and the immune response. Interestingly, the impact of HBV infection on adverse pregnancy outcomes is more serious than ever thought. Updated evidence indicates that pregnancies with chronic HBV infection increase the risk of preterm birth and gestational diabetes, especially in cases of positive hepatitis e antigen (HBeAg).

“Air pollution arrested not imprisoned”: The impact of laws invoked on Covid-19 city lockdowns

2021 ◽  
Vol 2 (4) ◽  
Author(s):  
Emmanuel Mensah Aboagye ◽  
◽  
Nana Osei Owusu ◽  
Keyword(s):  
Air Pollution ◽  
Environmental Problem ◽  
World Health Organisation ◽  
Developed Countries ◽  
World Health ◽  
Economic Activities ◽  
Global Pandemic ◽  
Depth Study ◽  
The Government ◽  
The Impact

Air pollution continues to be an environmental problem that poses a lot of health risks to the young and aged. Developed countries have invested heavily to curb this environmental problem, causing severe threats to human lives, yet the results do not look convincing. In developing countries, the situation is difficult than they can imagine, resulting in governments borrowing to fight what looks like a lost battle [1-3]. The in-depth study of this environmental menace - air pollution, suggests that the government enacts stringent measures to help fight this battle. This is because air pollution has natural (volcanic eruption) and anthropogenic (human activities) causes. In December 2019, the deadly Coronavirus (Covid-19) outbreak was soon declared as a global pandemic by the World Health Organisation (WHO) [4]. Majority of countries have had their share of the impact of this outbreak. Many countries resorted to city lockdown to strictly control the movement of people and economic activities as recommended by WHO.

Discovery of novel hepatitis B virus (HBV) antivirals and analysis of mechanisms of action of HBV-targeting agents

2017 ◽  
Author(s):  
◽  
Andrew Douglas Huber
Keyword(s):  
Hepatocellular Carcinoma ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Treatment Options ◽  
Mechanisms Of Action ◽  
Hbv Infection ◽  
Viral Inhibition ◽  
University Of Missouri ◽  
Chronic Hepatitis B Virus ◽  
B Virus

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] Chronic hepatitis B virus (HBV) infection leads to liver disease, cirrhosis, and hepatocellular carcinoma. Globally, an estimated 50% of all hepatocellular carcinoma cases are linked to chronic HBV infection. More than 240 million people are chronically infected, and there are 0.5-1 million deaths per year due to HBVrelated liver conditions. HBV treatment options rarely cure infections and are associated with adverse side effects that often outweigh the potential benefits of treatment. New treatments, therefore, are highly desired for HBV therapy. Towards this goal, we have developed novel compounds targeting two viral targets and assessed the mechanisms of action by which these compounds act. We have developed systems for the discovery and evaluation of compounds that inhibit 2 distinct steps in the HBV life cycle. Using these systems, we have developed potent inhibitors of HBV replication that have potential to become clinically used HBV drugs. Furthermore, we have used our methods to evaluate which properties of these compounds are likely to result in better viral inhibition. The work described in this thesis has led to at least 2 new compound groups for potential use as HBV antivirals and provides insight into mechanisms by which potent antivirals can be achieved.

scholarly journals Live wildlife trade in markets - a scoping review to inform risk assessment of emerging infectious diseases

2021 ◽  
Author(s):  
Victoria J Brookes ◽  
Okta Wismandanu ◽  
Etih Sudarnika ◽  
Justin A Roby ◽  
Lynne Hayes ◽  
...  
Keyword(s):  
Risk Assessment ◽  
Infectious Diseases ◽  
Scoping Review ◽  
Epistemic Uncertainty ◽  
Mammalian Species ◽  
Emerging Infectious Diseases ◽  
World Health Organisation ◽  
World Health ◽  
Wildlife Trade ◽  
The Impact

Wet markets are important for food security in many regions worldwide but have come under scrutiny due to their potential role in the emergence of infectious diseases. The sale of live wildlife has been highlighted as a particular risk, and the World Health Organisation has called for the banning of live, wild-caught mammalian species in markets unless risk assessment and effective regulations are in place. Following PRISMA guidelines, we conducted a global scoping review of peer-reviewed information about the sale of live, terrestrial wildlife in markets that are likely to sell fresh food, and collated data about the characteristics of such markets, activities involving live wildlife, the species sold, their purpose, and animal, human, and environmental health risks that were identified. Of the 59 peer-reviewed records within scope, only 25% (n = 14) focussed on disease risks; the rest focused on the impact of wildlife sale on conservation. Although there were some global patterns (for example, the types of markets and purpose of sale of wildlife), there was wide diversity and huge epistemic uncertainty in all aspects associated with live, terrestrial wildlife sale in markets such that the feasibility of accurate assessment of the risk of emerging infectious disease associated with live wildlife trade in markets is limited. Given the value of both wet markets and wildlife trade and the need to support food affordability and accessibility, conservation, public health, and the social and economic aspects of livelihoods of often vulnerable people, there are major information gaps that need to be addressed to develop evidence-based policy in this environment. This review identifies these gaps and provides a foundation from which information for risk assessments can be collected.

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