Securing wider EU commitment to the elimination of hepatitis C virus.

In 2016, the Hepatitis B and C Public Policy Association (HepBCPPA), gathered all the main stakeholders in the field of hepatitis C virus (HCV) to launch the now landmark HCV Elimination Manifesto, calling for the elimination of HCV in the EU by 2030. Since then, many European countries have made progress towards HCV elimination. Multiple programmes-from the municipality level to the EU level-were launched, resulting in an overall decrease in viremic HCV infections and liver-related mortality. However, as of 2021, most countries are not on track to reach the 2030 HCV elimination targets set by the WHO. Moreover, the COVID-19 pandemic has resulted in a decrease in HCV diagnoses and fewer direct-acting antiviral treatment initiations in 2020. Diagnostic and therapeutic tools to easily diagnose and treat chronic HCV infection are now well established. Treating all patients with chronic HCV infection is more cost-saving than treating and caring for patients with liver-related complications, decompensated cirrhosis or hepatocellular carcinoma. It is more important than ever to reinforce and scale-up action towards HCV elimination. Yet, efforts urgently need the dedicated commitment of policymakers at all governmental and policy levels. Therefore, the third EU Policy Summit, held in March 2021, featured EU parliamentarians and other key decision makers to promote dialogue and take strides towards securing wider EU commitment to advance and achieve HCV elimination by 2030. We have summarized the key action points and reported the 'Call-to-Action' statement supported by all the major relevant European associations in the field.

Immunogenicity of a third dose of the BNT162b2 COVID-19 vaccine in patients with CLL: effects on treatment selection.

Patients with chronic lymphocytic leukemia (CLL) show suboptimal responses to the vaccines against SARS-CoV-2; it has been shown though that a booster dose of the BNT162b2 vaccine may lead to a significant increase in the seroconversion rates of immunocompromised patients. We conducted a prospective, non-interventional study to evaluate the immunogenicity of a third dose of the BNT162b2 vaccine in adult patients with CLL. Sera were tested before the first, after the second, and before and after the third dose for anti-SARS-CoV-2 receptor binding domain (RBD) spike protein IgG (anti-RBD). Thirty-nine patients with CLL were included in the study. The seroconversion rate increased from 28.2% before the third dose to 64.1% after the third dose and was higher in treatment-naïve patients (72.7% versus 47.1% in actively treated patients, p = 0.042). All but one patient achieving a seroconversion after the second dose retained after the third, while eight patients not achieving a seroconversion after the second dose (38.1%), did so after the third. Moreover, patients actively treated with venetoclax had a higher seroconversion rate than those treated with ibrutinib (87.5% versus 14.3%, p = 0.001). This study confirms the beneficial effect of a third dose of the BNT162b2 vaccine on the seroconversion rate in patients with CLL. Our results also strongly suggest that the use of venetoclax is correlated with higher immunogenicity/seroconversion rates than that of ibrutinib, a finding that has been reported by another study. A treatment strategy change during the pandemic favoring the use of venetoclax may be suggested based on our results, although these results should be validated in larger studies.

Safety and immunogenicity of the BNT162b2 mRNA Covid-19 vaccine in patients with chronic lymphocytic leukemia: a prospective study.

Introduction: Immunization of patients with chronic lymphocytic leukemia (CLL) with vaccines against several infectious diseases has proven insufficient. Data on seroconversion of patients with CLL after vaccination against severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) are still young, but accumulating evidence shows low seroconversion rates. Methods: We conducted a prospective, noninterventional study evaluating the safety and immunogenicity of two doses of the BNT162b2 mRNA Covid-19 vaccine, administered 21 days apart in consecutive adult patients with CLL. Patients vaccinated with other vaccines against SARS-CoV-2, with a history of confirmed Coronavirus Disease 19 (COVID-19), with known human immunodeficiency virus infection, or with an inability to provide written informed consent were excluded. Sera were tested before the first and after the second dose of the vaccine for anti-SARS-CoV-2 receptor binding domain (RBD) spike protein IgG (anti-RBD), using the Abbott SARS-CoV-2 IgG II Quant assay (Abbott Laboratories, Abbott Park, IL, USA), with a cutoff value for seroconversion at 50 AU/ml. Results: Sixty-one patients (28 males/33 females) with CLL, with a median age of 61 years, were included in the study. The majority of the patients (82.0%) were lower (0-2) stage per the RAI staging system. The seroconversion rate at 14 days after the second dose was 45% and was correlated with RAI stage (0-2 versus 3-4; 51.0% versus 18.3%, p = 0.047), the treatment status (treatment naïve, previously treated, or actively treated patients; 63.0% versus 40.0% versus 26.1%, respectively, p = 0.031), the number of previous treatment lines (0-2 versus >2; 55.3% versus 8.3%, p = 0.004), and the platelet count of the patients (over or under 100 × 109/L; 52.9% versus 10.0%, p = 0.015). Moreover, there was a positive linear relationship between the antibody titers and the gamma-globulin levels (r = 0.182, p = 0.046) and platelet count (r = 0.277, p = 0.002). Finally, patients actively treated with venetoclax had higher antibody titers than those treated with ibrutinib (15.8 AU/ml versus 0.0 AU/ml, p = 0.047). No safety issues were identified while the emergence of adverse events was not correlated with immunogenicity. Discussion: This study confirms results from previous studies on the low seroconversion rates in patients with CLL vaccinated with the BNT162b2 mRNA Covid-19 vaccine and on the detrimental effect of advanced disease and multiple treatment lines on seroconversion, while it is suggested that treatment with venetoclax may offer a chance for higher antibody titers, suggesting a treatment strategy change during the pandemic provided that this result is confirmed by larger studies specifically designed to address this issue.

Tracking missed opportunities for an early HIV diagnosis in a population of people living with HIV with known time of infection.

PURPOSE: The goal of 90-90-90 first requires the expansion of access to HIV testing. Our aim was to record frequencies of HIV indicator conditions (ICs) and identify missed opportunities for an early HIV diagnosis. METHODS: We retrospectively identified ICs in a population of 231 people living with HIV with known infection dates who attended our clinic. The study population was divided into four groups: (1) those self-tested pre-emptively (47/231, 20.3%), (2) those offered targeted testing based on risk factors (67/231, 29%), (3) those tested after an IC (73/231, 31.6%) and (4) those who were not offered testing after an IC (44/231, 19%). HIV acquisition dates were estimated by molecular clock analysis. RESULTS: A total of 169 healthcare contacts (HCCs) were recorded. The most frequent HCC was mononucleosis-like syndrome (20.1%), unexplained weight loss (10.7%) and STIs (10.1%). AIDS-defining conditions were detected in 11.8%. Only 62.4% (73/117) of those with an IC were offered testing after their first HCC. Patients in group 4 had statistically significant delay in diagnosis compared with group 3 (109.1 weeks (IQR 56.4-238.6) vs 71.6 weeks (IQR 32.3-124.6)). The proportion of patients diagnosed as late presenters in each group was: (1) 16/47 (34%), (2) 37/67 (55.2%), (3) 43/73 (58.9%) and (4) 27/44 (61.4%) (p=0.027). CONCLUSIONS: Our study uses a combination of molecular and clinical data and shows evidence that late presentation occurs in a high proportion of patients even in the presence of an IC. Given that risk-based targeted testing has low coverage, IC-guided testing provides a reasonable alternative to facilitate earlier HIV diagnosis and to improve late diagnosis across Europe and globally.

Effects of Nutrition, and Physical Activity Habits and Perceptions on Body Mass Index (BMI) in Children Aged 12-15 Years: A Cross-Sectional Study Comparing Boys and Girls.

Background: The aim of the present study was to examine the effects of socioeconomic status, nutrition and physical activity lifestyle habits and perceptions on Body Mass Index (BMI) in children aged 12-15 years in Greece. Furthermore, to compare the difference between the two sexes. Methods: This is a cross-sectional study conducted on a representative secondary school cohort that included 5144 subjects, aged 12 to 15 years. Students and their parents filled in validated questionnaires evaluating socioeconomic status, nutrition and physical activity. International Obesity Task Force cut offs were used to classify the children. Factor analysis of mixed data and partial proportional ordered logistic models were used to analyze ΒMΙ distributions. All analyses were stratified by gender. Results: Boys were 2.9 (95%CI: 2.592-3.328) times more likely to be overweight/obese than girls. Partial proportional ordinal models indicate significant associations between nutritional and physical habits and perceptions variables but also significant gender differences in socio-demographic, nutritional risk factors as well as physical activity habits and perceptions. Conclusions: A clear understanding of the factors that contribute to the sex differences in nutrition and physical activity habits and perceptions may guide intervention efforts.

Validation of molecular clock inferred HIV infection ages: Evidence for accurate estimation of infection dates.

BACKGROUND: Improving HIV diagnosis, access to care and effective antiretroviral treatment provides our global strategy to reduce HIV incidence. To reach this goal we need to increase our knowledge about local epidemics. HIV infection dates would be an important information towards this goal, but they are largely unknown. To date, methods to estimate the dates of HIV infection are based mainly on laboratory or molecular methods. Our aim was to validate molecular clock inferred infection dates that were estimated by analysing sequences from 145 people living with HIV (PLHIV) with known transmission dates (clinically estimated infection dates). METHODS: All HIV sequences were obtained by Sanger sequencing and were previously found to belong to well-established molecular transmission clusters (MTCs). RESULTS: Our analysis showed that the molecular clock inferred infection dates were correlated with the clinically estimated ones (Spearman's Correlation coefficient = 0.93, p < 0.001) and that there was an agreement between them (Lin's concordance correlation coefficient = 0.92, p < 0.001). For the 61.4% of cases the molecular clock inferred preceded the clinically estimated infection dates. The median difference between clinically and molecularly estimated dates of infection was of 0.18 (IQR: -0.21, 0.89) years. The lowest differences were identified in people who inject drugs of our study population. CONCLUSIONS: The estimated time to more recent common ancestor (tMRCA) of nodes within clusters provides a reliable approximation of HIV infections for PLHIV infected within MTCs. Next-generation sequencing data and molecular clock estimates based on heterochronous sequences provide, probably, more reliable methods for inferring infection dates. However, since these data are not available in most of the HIV clinical laboratories, our approach, under specific conditions, can provide a reliable estimation of HIV infection dates and can be used for HIV public health interventions.

Antibodies against SARS-CoV-2 among health care workers in a country with low burden of COVID-19.

INTRODUCTION: Greece is a country with limited spread of SARS-CoV-2 and cumulative infection attack rate of 0.12% (95% CI 0.06-0.26). Health care workers (HCWs) are a well-recognized risk group for COVID-19. The study aimed to estimate the seroprevalence of antibodies to SARS-CoV-2 in a nosocomial setting and assess potential risk factors. METHODS: HCWs from two hospitals participated in the study. Hospital-1 was a tertiary university affiliated center, involved in the care of COVID-19 patients while hospital-2 was a tertiary specialized cardiac surgery center not involved in the care of these patients. A validated, CE, rapid, IgM/IgG antibody point-of-care test was used. Comparative performance with a reference globally available assay was assessed. RESULTS: 1,495 individuals consented to participate (response rate 77%). The anti-SARS-CoV-2 weighted prevalence was 1.26% (95% CI 0.43, 3.26) overall and 0.53% (95% CI 0.06, 2.78) and 2.70% (95% CI 0.57, 9.19) in hospital-1 and hospital-2, respectively although the study was underpowered to detect statistically significant differences. The overall, hospital-1, and hospital-2 seroprevalence was 10, 4 and 22 times higher than the estimated infection attack rate in general population, respectively. Suboptimal use of personal protective equipment was noted in both hospitals. CONCLUSIONS: These data have implications for the preparedness of a second wave of COVID-19 epidemic, given the low burden of SARS-CoV-2 infection rate, in concordance with national projections.

Economic evaluation of the hepatitis C elimination strategy in Greece in the era of affordable direct-acting antivirals.

BACKGROUND: Hepatitis C virus (HCV) is a leading cause of worldwide liver-related morbidity and mortality. The World Health Organization released an integrated strategy targeting HCV-elimination by 2030. This study aims to estimate the required interventions to achieve elimination using updated information for direct-acting antiviral (DAA) treatment coverage, to compute the total costs (including indirect/societal costs) of the strategy and to identify whether the elimination strategy is cost-effective/cost-saving in Greece. AIM: To estimate the required interventions and subsequent costs to achieve HCV elimination in Greece. METHODS: A previously validated mathematical model was adapted to the Greek HCV-infected population to compare the outcomes of DAA treatment without the additional implementation of awareness or screening campaigns versus an HCV elimination strategy, which includes a sufficient number of treated patients. We estimated the total costs (direct and indirect costs), the disability-adjusted life years and the incremental cost-effectiveness ratio using two different price scenarios. RESULTS: Without the implementation of awareness or screening campaigns, approximately 20000 patients would be diagnosed and treated with DAAs by 2030. This strategy would result in a 19.6% increase in HCV-related mortality in 2030 compared to 2015. To achieve the elimination goal, 90000 patients need to be treated by 2030. Under the elimination scenario, viremic cases would decrease by 78.8% in 2030 compared to 2015. The cumulative direct costs to eliminate the disease would range from 2.1-2.3 billion euros (€) by 2030, while the indirect costs would be €1.1 billion. The total elimination cost in Greece would range from €3.2-3.4 billion by 2030. The cost per averted disability-adjusted life year is estimated between €10100 and €13380, indicating that the elimination strategy is very cost-effective. Furthermore, HCV elimination strategy would save €560-895 million by 2035. CONCLUSION: Without large screening programs, elimination of HCV cannot be achieved. The HCV elimination strategy is feasible and cost-saving despite the uncertainty of the future cost of DAAs in Greece.

Immunomodulatory Function of HBeAg Related to Short-Sighted Evolution, Transmissibility, and Clinical Manifestation of Hepatitis B Virus.

Hepatitis B virus (HBV) infection, a global public health problem can be asymptomatic, acute or chronic and can lead to serious consequences of infection, including cirrhosis, and hepatocellular carcinoma. HBV, a partially double stranded DNA virus, belongs to the family Hepadnaviridae, and replicates via reverse transcription of an RNA intermediate. This reverse transcription is catalyzed by a virus-encoded polymerase that lacks proof reading ability, which leads to sequence heterogeneity. HBV is classified into nine genotypes and at least 35 subgenotypes, which may be characterized by distinct geographical distributions. This HBV diversification and distinct geographical distribution has been proposed to be the result of the co-expansion of HBV with modern humans, after their out-of-Africa migration. HBeAg is a non-particulate protein of HBV that has immunomodulatory properties as a tolerogen that allows the virus to establish HBV infection in vivo. During the natural course of infection, there is seroconversion from a HBeAg-positive phase to a HBeAg-negative, anti-HBe-positive phase. During this seroconversion, there is loss of tolerance to infection and immune escape-HBeAg-negative mutants can be selected in response to the host immune response. The different genotypes and, in some cases, subgenotypes develop different mutations that can affect HBeAg expression at the transcriptional, translational and post-translational levels. The ability to develop mutations, affecting HBeAg expression, can influence the length of the HBeAg-positive phase, which is important in determining both the mode of transmission and the clinical course of HBV infection. Thus, the different genotypes/subgenotypes have evolved in such a way that they exhibit different modes of transmission and clinical manifestation of infection. Loss of HBeAg may be a sign of short-sighted evolution because there is loss of tolerogenic ability of HBeAg and HBeAg-negative virions are less transmissible. Depending on their ability to lead to HBeAg seroconversion, the genotype/subgenotypes exhibit varying degrees of short-sighted evolution. The "arms race" between HBV and the immune response to HBeAg is multifaceted and its elucidation intricate, with transmissibility and persistence being important for the survival of the virus. We attempt to shed some light on this complex interplay between host and virus.

The comprehensive outcomes of hepatitis C virus infection: A multi-faceted chronic disease.

Treatment of hepatitis C virus (HCV) infection has been revolutionized with the introduction of pangenotypic, interferon- and ribavirin-free regimens associated with high cure rates and a low side effect profile. Additionally, there is evidence that HCV cure reduces HCV complications, improves patient-reported outcomes and is cost-saving in most western countries in the long term. This is a review of the comprehensive burden of HCV and the value of eliminating HCV infection. With the introduction of the interferon-free all-oral, once a day pill treatment regimen for the cure of HCV, the potential to eliminate HCV by 2030 has become a possibility for some regions of the world. Nevertheless, there are barriers to screening, linkage to care, and treatment in many countries that must be overcome in order to reach this goal. In conclusion, globally, work must continue to ensure national policies are in place to support screening, linkage to care and affordable treatment in order to eliminate HCV.

Human Endogenous Retrovirus-K HML-2 integration within RASGRF2 is associated with intravenous drug abuse and modulates transcription in a cell-line model.

HERV-K HML-2 (HK2) has been proliferating in the germ line of humans at least as recently as 250,000 years ago, with some integrations that remain polymorphic in the modern human population. One of the solitary HK2 LTR polymorphic integrations lies between exons 17 and 18 of RASGRF2, a gene that affects dopaminergic activity and is thus related to addiction. Here we show that this antisense HK2 integration (namely RASGRF2-int) is found more frequently in persons who inject drugs compared with the general population. In a Greek HIV-1-positive population (n = 202), we found RASGRF2-int 2.5 times (14 versus 6%) more frequently in patients infected through i.v. drug use compared with other transmission route controls (P = 0.03). Independently, in a United Kingdom-based hepatitis C virus-positive population (n = 184), we found RASGRF2-int 3.6 times (34 versus 9.5%) more frequently in patients infected during chronic drug abuse compared with controls (P < 0.001). We then tested whether RASGRF2-int could be mechanistically responsible for this association by modulating transcription of RASGRF2 We show that the CRISPR/Cas9-mediated insertion of HK2 in HEK293 cells in the exact RASGRF2 intronic position found in the population resulted in significant transcriptional and phenotypic changes. We also explored mechanistic features of other intronic HK2 integrations and show that HK2 LTRs can be responsible for generation of cis-natural antisense transcripts, which could interfere with the transcription of nearby genes. Our findings suggest that RASGRF2-int is a strong candidate for dopaminergic manipulation, and emphasize the importance of accurate mapping of neglected HERV polymorphisms in human genomic studies.

Impact of Interferon-α Receptor-1 Promoter Polymorphisms on the Transcriptome of the Hepatitis B Virus-Associated Hepatocellular Carcinoma.

Background and aims: Genetic polymorphisms within the promoter of interferon-α receptor type-1 (IFNAR1) have been associated with the susceptibility to and the outcome of chronic hepatitis B virus (HBV) infection. However, the impact of these polymorphisms in the transcriptome of the HBV-associated hepatocellular carcinoma (HCC) remains largely unexplored. Methods: Using whole-genome and exome sequencing data from The Cancer Genome Atlas project, we characterized three single-nucleotide polymorphisms (SNPs: -568G/C, -408C/T, -3C/T) and one variable number tandem repeat [VNTR: -77(GT)n] within the IFNAR1 promoter sequence in 49 HCC patients. RNAseq data from 10 genotyped HCC samples were grouped according to their -77VNTR or -3SNP genotype to evaluate the impact of these polymorphisms on the differential expression on the HCC transcriptome. Results: There is a fourfold higher impact of the -77VNTR on the HCC transcriptome compared to the -3SNP (q < 0.1, p < 0.001). The expression of the primary IFNAR1 transcript is not affected by these polymorphisms but a secondary, HCC-specific transcript is expressed only in homozygous -77VNTR ≤8/≤8(GT)n samples (p < 0.05). At the same time, patients carrying at least one -77VNTR >8(GT) allele, presented a strong upregulation of the fibronectin-1 (FN-1) gene, which has been associated with the development of HCC. Gene Ontology and pathway enrichment analysis of the differentially expressed genes revealed a strong disruption of the PI3K-AKT signaling pathway, which can be partially triggered by the extracellular matrix FN-1. Conclusion: The IFNAR-1 promoter polymorphisms are not involved in the expression levels of the main IFNAR-1 transcript. The -77VNTR has a regulatory role on the expression of a secondary, truncated, HCC-specific transcript, which in turn coincides with disruptions in cancer-associated pathways and in FN-1 expression modifications.

Factors Associated with HIV Testing and HIV Treatment Adherence: A Systematic Review.

BACKGROUND: The impact of the global economic crisis on HIV-related access and care remains unclear. The objective of this systematic review of the literature was to evaluate the association between socioeconomic factors and HIV diagnosis, and adherence to treatment, following the 2008 global economic crisis. METHOD: A systematic search of PubMed and Scopus for studies published between January 2008 and October 2016 was conducted. Studies providing data on social, demographic, economic and cultural barriers associated with HIV diagnosis and treatment were included. RESULTS: Of 33 studies included, 22 evaluated HIV testing and 11 evaluated treatment adherence. Medical history of a sexually transmitted disease, knowledge of HIV-related risks, and age, were significantly associated with HIV testing in most of the included studies. Absence of social support, and alcohol or substance use, were the most common factors associated with adherence. Financial factors were not as commonly found to be related to access to HIV diagnosis and HIV treatment adherence, compared to knowledge of HIV-related risks and social support. CONCLUSION: The identification of persons who are less likely to test for HIV, and to adhere to HIV treatment, may serve as a guide for public health interventions, especially in resource-limited areas.

Is elimination of HCV possible in a country with low diagnostic rate and moderate HCV prevalence?: The case of Greece.

BACKGROUND AND AIM: The treatment of hepatitis C (HCV) with interferon (IFN)-free direct-acting antivirals (DAAs) is anticipated to change the future burden of disease. The aim of this study is to quantify the impact of IFN-free DAAs on HCV-related morbidity and mortality in Greece under different scenarios concerning treatment coverage and primary prevention, including the proposed by World Health Organization Global Hepatitis Strategy. METHODS: A previously described model was used to project the future disease burden up to 2030 under scenarios, which includes treatment based on the combination of pegylated-IFN with ribavirin (base case) and scenarios using DAAs therapies. RESULTS: Under the base case scenario, an increase in HCV-related morbidity and mortality is predicted in Greece (mortality in 2030: +23.6% compared with 2015). If DAAs are used with the same treatment coverage, the number of hepatocellular carcinoma cases and of liver related deaths are predicted to be lower by 4-7% compared with 2015. Under increased treatment coverage (from 2000 treated/year to approximately 5000/year in 2015-2020 and 2500/year subsequently), morbidity and mortality will decrease by 43-53% in 2030 compared with 2015. To achieve the WHO Global Hepatitis Strategy goals, a total number of 86 500 chronic hepatitis C patients will have to be treated during 2015-2030. CONCLUSIONS: Elimination of HCV in Greece by 2030 necessitates great improvements in primary prevention, implementation of large screening programs and high treatment coverage.

Reducing HIV infection in people who inject drugs is impossible without targeting recently-infected subjects.

OBJECTIVE: Although our understanding of viral transmission among people who inject drugs (PWID) has improved, we still know little about when and how many times each injector transmits HIV throughout the duration of infection. We describe HIV dynamics in PWID to evaluate which preventive strategies can be efficient. DESIGN: Due to the notably scarce interventions, HIV-1 spread explosively in Russia and Ukraine in 1990s. By studying this epidemic between 1995 and 2005, we characterized naturally occurring transmission dynamics of HIV among PWID. METHOD: We combined publicly available HIV pol and env sequences with prevalence estimates from Russia and Ukraine under an evolutionary epidemiology framework to characterize HIV transmissibility between PWID. We then constructed compartmental models to simulate HIV spread among PWID. RESULTS: In the absence of interventions, each injector transmits on average to 10 others. Half of the transmissions take place within 1 month after primary infection, suggesting that the epidemic will expand even after blocking all the post-first month transmissions. Primary prevention can realistically target the first month of infection, and we show that it is very efficient to control the spread of HIV-1 in PWID. Treating acutely infected on top of primary prevention is notably effective. CONCLUSION: As a large proportion of transmissions among PWID occur within 1 month after infection, reducing and delaying transmissions through scale-up of harm reduction programmes should always form the backbone of HIV control strategies in PWID. Growing PWID populations in the developing world, where primary prevention is scarce, constitutes a public health time bomb.

Utility and applicability of the "Childhood Obesity Risk Evaluation" (CORE)-index in predicting obesity in childhood and adolescence in Greece from early life: the "National Action Plan for Public Health".

Early identification of infants being at high risk to become obese at their later childhood or adolescence can be of vital importance in any obesity prevention initiative. The aim of the present study was to examine the utility and applicability of the "Childhood Obesity Risk Evaluation (CORE)" index as a screening tool for the early prediction of obesity in childhood and adolescence. Anthropometric, socio-demographic data were collected cross-sectionally and retrospectively from a representative sample of 5946 children, and adolescents and were combined for calculating the CORE-index score. Logistic regression analyses were performed to examine the associations of the CORE-index score with obesity by gender and age group, and cut-off point analysis was also applied to identify the optimal value of the CORE-index score that differentiates obese from non-obese children. Mean CORE-index score in the total sample was 3.06 (sd 1.92) units (range 0-11 units). Each unit increase in the CORE-index score was found to be associated with a 30 % (95 % C.I. 1.24-1.36) increased likelihood for obesity in childhood or adolescence, while the optimal cut-off value of the CORE-index score that predicted obesity with the highest possible sensitivity and specificity was found to be 3.5. CONCLUSION: The present study supports the utility and applicability of the CORE-index as a screening tool for the early identification of infants that are potentially at a higher risk for becoming obese at their childhood and adolescence. This tool could be routinely used by health professionals to identify infants at high risk and provide appropriate counselling to their parents and caregivers so as to maximize the effectiveness of early obesity prevention initiatives. What is known? • Childhood obesity has reached epidemic proportions worldwide. • Certain perinatal and socio-demographic indices that were previously identified as correlates of childhood obesity in children were combined to develop the CORE-index, a screening tool that estimates obesity risk in 9-13 year-old children. What is new? • The utility and applicability of the CORE-index as screening tool can be extended to the age range of 6-15 years. • The CORE-index is a cost-effective screening tool that can assist health professionals in initiating obesity preventive measures from early life.

A contaminant-free assessment of Endogenous Retroviral RNA in human plasma.

Endogenous retroviruses (ERVs) comprise 6-8% of the human genome. HERVs are silenced in most normal tissues, up-regulated in stem cells and in placenta but also in cancer and HIV-1 infection. Crucially, there are conflicting reports on detecting HERV RNA in non-cellular clinical samples such as plasma that suggest the study of HERV RNA can be daunting. Indeed, we find that the use of real-time PCR in a quality assured clinical laboratory setting can be sensitive to low-level proviral contamination. We developed a mathematical model for low-level contamination that allowed us to design a laboratory protocol and standard operating procedures for robust measurement of HERV RNA. We focus on one family, HERV-K HML-2 (HK2) that has been most recently active even though they invaded our ancestral genomes almost 30 millions ago. We extensively validated our experimental design on a model cell culture system showing high sensitivity and specificity, totally eliminating the proviral contamination. We then tested 236 plasma samples from patients infected with HIV-1, HCV or HBV and found them to be negative. The study of HERV RNA for human translational studies should be performed with extensively validated protocols and standard operating procedures to control the widespread low-level human DNA contamination.

Strategies to control hepatitis B: Public policy, epidemiology, vaccine and drugs.

The last 50 years of hepatitis B research has resulted in the development of effective screening assays for surveillance, vaccines for prevention and antiviral drugs that significantly improve patient clinical outcomes. Not surprisingly then, the global epidemiology of hepatitis B virus (HBV) is set to change dramatically over the next decade. For example, the success and the high coverage of universal HBV vaccination and the ageing cohorts of patients with chronic hepatitis B (CHB) will result in reductions of incidence and prevalence of chronic hepatitis, cirrhosis and probably hepatocellular carcinoma. This will be further accelerated by the impressive progress in the treatment outcomes for patients with CHB. In spite of this success, challenges remain, such as planning for the impact of migration from countries with high prevalence rates to those countries with low rates of HBV infection. The recent establishment of the World Health Organisation Global Hepatitis Program with the provision of a framework for global action has become the cornerstone for all countries to now frame their own particular national responses to control hepatitis B. An effective policy framework can prevent new infections, ensure people can access clinical care, and in doing so reduce the burden of infection at an individual, country and regional level. These developments present a real opportunity to reduce the significant, social and economic burden of global hepatitis B, ultimately the critical next steps to render the world hepatitis B free.

Time of acquisition of HCV infection in renal transplant recipients: a major prognostic factor for disease progression.

BACKGROUND: This study aims to identify crucial factors affecting the evolution of liver disease in HCV-infected renal transplant recipients. METHODS: Forty-two HCV-infected recipients with known time of HCV acquisition were followed up for a mean (SD) of 7.6 ± 3.4 yr after transplantation with consecutive liver biopsies. Hepatitis progression was defined by: a) fibrosis progression ≥ 0.2 stages/yr and/or b) development of a cholestatic syndrome. RESULTS: Twenty-three patients (54.8%) displayed benign and 19 (45.2%) aggressive hepatitis progression. Hepatitis course was aggressive in 9.1% and 85% of the patients infected pre- and peri/post-transplantation, respectively (p < 0.001). In multivariate analysis, patients who acquired HCV infection peri- or after transplantation had an increased risk of an adverse outcome compared with those infected before transplantation (p = 0.001). HCV RNA levels at the time of first liver biopsy were lower in patients showing a benign course compared with those with aggressive evolution (p = 0.052). CONCLUSIONS: Time of acquisition of HCV infection is a major prognostic factor for hepatitis progression in the setting of renal transplantation. Immunosuppression was found to be determinant in the progression of HCV infection acquired peri- or post-transplantation. High viral load seems to be crucial in the pathogenetic process.

Significance of liver histology in HBsAg-positive, IgM anti-HBc-negative acute hepatitis B virus-related hepatitis.

AIMS: The natural course of HBsAg-positive, IgM anti-HBc-negative acute hepatitis B virus (HBV)-related hepatitis is unclear. The aim of this study was to evaluate the prognostic significance of histological features and hepatic expression of HBV antigens in such patients. METHODS AND RESULTS: Fifty patients with HBsAg-positive, IgM anti-HBc-negative acute hepatitis B who underwent liver biopsy during the acute hepatitis episode were studied [HBeAg seroconversion (n = 16), persistently positive for HBeAg (n = 9), and persistently negative for HBeAg (n = 25)]. Twenty-six cases had features of typical acute hepatitis only (group A), and 24 cases had changes suggesting pre-existing chronic hepatitis (group B). HBcAg and/or HBsAg immunoreactivity was detected less frequently in group A than in group B (31% versus 79%, P = 0.01). HBsAg clearance was observed in 24% of patients, almost exclusively in cases with HBeAg seroconversion. HBsAg loss was significantly more frequent in group A than in group B (52% versus 0%, P < 0.001), and in cases without rather than with immunohistochemical expression of HBV antigens (55% versus 0%, P < 0.001). In group A, HBsAg clearance was observed in 80%, 54% and 0% of patients with mild, moderate or severe acute hepatitis, respectively (P < 0.034). CONCLUSIONS: Histological information is very important for the prognosis of HBsAg-positive, IgM anti-HBc-negative acute hepatitis B. HBeAg seroconversion with underlying typical acute hepatitis changes of mild to moderate severity without hepatic expression of HBV antigens strongly predicts subsequent HBsAg loss.