Hepatitis delta infection among persons living with HIV in Europe

BACKGROUND AND AIMS: A high prevalence of hepatitis delta virus (HDV) infection, the most severe form of viral hepatitis, has been reported among persons living with HIV (PLWH) in Europe. We analysed data from a large HIV cohort collaboration to characterize HDV epidemiological trends across Europe, as well as its impact on clinical outcomes. METHODS: All PLWH with a positive hepatitis B surface antigen (HBsAg) in the Swiss HIV Cohort Study and EuroSIDA between 1988 and 2019 were tested for anti-HDV antibodies and, if positive, for HDV RNA. Demographic and clinical characteristics at initiation of antiretroviral therapy were compared between HDV-positive and HDV-negative individuals using descriptive statistics. The associations between HDV infection and overall mortality, liver-related mortality as well as hepatocellular carcinoma (HCC) were assessed using cumulative incidence plots and cause-specific multivariable Cox regression. RESULTS: Of 2793 HBsAg-positive participants, 1556 (56%) had stored serum available and were included. The prevalence of HDV coinfection was 15.2% (237/1556, 95% confidence interval [CI]: 13.5%–17.1%) and 66% (132/200) of HDV-positive individuals had active HDV replication. Among persons who inject drugs (PWID), the prevalence of HDV coinfection was 50.5% (182/360, 95% CI: 45.3%–55.7%), with similar estimates across Europe, compared to 4.7% (52/1109, 95% CI: 3.5%–5.9%) among other participants. During a median follow-up of 10.8 years (interquartile range 5.6–17.8), 82 (34.6%) HDV-positive and 265 (20.1%) HDV-negative individuals died. 41.5% (34/82) of deaths were liver-related in HDV-positive individuals compared to 17.7% (47/265) in HDV-negative individuals. HDV infection was associated with overall mortality (adjusted hazard ratio 1.6; 95% CI 1.2–2.1), liver-related death (2.9, 1.6–5.0) and HCC (6.3, 2.5–16.0). CONCLUSION: We found a very high prevalence of hepatitis delta among PWID across Europe. Among PLWH who do not inject drugs, the prevalence was similar to that reported from populations without HIV. HDV coinfection was associated with liver-related mortality and HCC incidence

Targeted Next-Generation Sequencing Analysis of 1,000 Individuals with Intellectual Disability.

To identify genetic causes of intellectual disability (ID), we screened a cohort of 986 individuals with moderate to severe ID for variants in 565 known or candidate ID-associated genes using targeted next-generation sequencing. Likely pathogenic rare variants were found in ∼11% of the cases (113 variants in 107/986 individuals: ∼8% of the individuals had a likely pathogenic loss-of-function [LoF] variant, whereas ∼3% had a known pathogenic missense variant). Variants in SETD5, ATRX, CUL4B, MECP2, and ARID1B were the most common causes of ID. This study assessed the value of sequencing a cohort of probands to provide a molecular diagnosis of ID, without the availability of DNA from both parents for de novo sequence analysis. This modeling is clinically relevant as 28% of all UK families with dependent children are single parent households. In conclusion, to diagnose patients with ID in the absence of parental DNA, we recommend investigation of all LoF variants in known genes that cause ID and assessment of a limited list of proven pathogenic missense variants in these genes. This will provide 11% additional diagnostic yield beyond the 10%-15% yield from array CGH alone.Action Medical Research (SP4640); the Birth Defect Foundation (RG45448); the Cambridge National Institute for Health Research Biomedical Research Centre (RG64219); the NIHR Rare Diseases BioResource (RBAG163); Wellcome Trust award WT091310; The Cell lines and DNA bank of Rett Syndrome, X-linked mental retardation and other genetic diseases (member of the Telethon Network of Genetic Biobanks (project no. GTB12001); the Genetic Origins of Congenital Heart Disease Study (GO-CHD)- funded by British Heart Foundation (BHF)This is the final version of the article. It first appeared from Wiley via http://dx.doi.org/10.1002/humu.2290

Gender differences in the use of cardiovascular interventions in HIV-positive persons; the D:A:D Study

Peer reviewe

Pathophysiology of erectile dysfunction

Introduction. Multiple regulatory systems are involved in normal erectile function. Disruption of psychological, neurological, hormonal, vascular, and cavernosal factors, individually, or in combination, can induced erectile dysfunction (ED). The contribution of neurogenic, vascular, and cavernosal factors was thoroughly reviewed by our committee, while psychological and hormonal factors contributing to ED were evaluated by other committees. Aim. To provide state of the art knowledge on the physiology of ED. Methods. An international consultation in collaboration with the major urology and sexual medicine associations assembled over 200 multidisciplinary experts from 60 countries into 17 committees. Committee members established specific objectives and scopes for various male and female sexual medicine topics. The recommendations concerning state-of-the-art knowledge in the respective sexual medicine topic represent the opinion of experts from five different continents developed in a process over a 2-year period. Concerning the pathophysiology of ED committee, there were seven experts from five different countries. Main Outcome Measure. Expert opinion was based on the grading of evidence-based medical literature, widespread internal committee discussion, public presentation, and debate. Results. The epidemiology and classification of neurogenic ED was reviewed. The evidence for association between vascular ED atherosclerosis/hypercholesterolemia, hypertension and diabetes was evaluated. In addition, the pathophysiological inechanisins implicated in vascular ED were defined, including: arterial remodeling, increased vasoconstriction, impaired neurogenic vasodilatation, and impaired endothelium-dependent vasodilatation. The possible mechanisms underlying the association between chronic renal failure and ED were also evaluated as well as the evidence supporting the association of ED with various classes of medications. Conclusions. A better understanding of how diseases interfere with the physiological mechanisms that regulate penile erection has been achieved over the last few years, which helps establish a strategy for the prevention and treatment of ED