Changing prevalence of chronic hepatitis B virus infection in China between 1973 and 2021: a systematic literature review and meta-analysis of 3740 studies and 231 million people

Objective
China concentrates a large part of the global burden of HBV infection, playing a pivotal role in achieving the WHO 2030 global hepatitis elimination target.

Methods
We searched for studies reporting HBV surface antigen (HBsAg) seroprevalence in five databases until January 2023. Eligible data were pooled using a generalised linear mixed model with random effects to obtain summary HBsAg seroprevalence. Linear regression was used to estimate annual percentage change (APC) and HBsAg prevalence in 2021.

Results
3740 studies, including 231 million subjects, were meta-analysed. HBsAg seroprevalence for the general population decreased from 9.6% (95% CI 8.4 to 10.9%) in 1973–1984 to 3.0% (95% CI 2.1 to 3.9%) in 2021 (APC=–3.77; p

Leggi
Novembre 2023

Chronic Hepatitis B Virus Infection and Risk of Stroke Types: A Prospective Cohort Study of 500 000 Chinese Adults

Stroke, Ahead of Print. BACKGROUND:Stroke is a leading cause of mortality and permanent disability in China, with large and unexplained geographic variations in rates of different stroke types. Chronic hepatitis B virus infection is prevalent among Chinese adults and may play a role in stroke cause.METHODS:The prospective China Kadoorie Biobank included >500 000 adults aged 30 to 79 years who were recruited from 10 (5 urban and 5 rural) geographically diverse areas of China from 2004 to 2008, with determination of hepatitis B surface antigen (HBsAg) positivity at baseline. During 11 years of follow-up, a total of 59 117 incident stroke cases occurred, including 11 318 intracerebral hemorrhage (ICH), 49 971 ischemic stroke, 995 subarachnoid hemorrhage, and 3036 other/unspecified stroke. Cox regression models were used to estimate adjusted hazard ratios (HRs) for risk of stroke types associated with HBsAg positivity. In a subset of 17 833 participants, liver enzymes and lipids levels were measured and compared by HBsAg status.RESULTS:Overall, 3.0% of participants were positive for HBsAg. HBsAg positivity was associated with an increased risk of ICH (adjusted HR, 1.29 [95% CI, 1.16–1.44]), similarly for fatal (n=5982; adjusted HR, 1.36 [95% CI, 1.16–1.59]) and nonfatal (n=5336; adjusted HR, 1.23 [95% CI, 1.06–1.44]) ICH. There were no significant associations of HBsAg positivity with risks of ischemic stroke (adjusted HR, 0.97 [95% CI, 0.92–1.03]), subarachnoid hemorrhage (adjusted HR, 0.87 [95% CI, 0.57–1.33]), or other/unspecified stroke (adjusted HR, 1.12 [95% CI, 0.89–1.42]). Compared with HBsAg-negative counterparts, HBsAg-positive individuals had lower lipid and albumin levels and higher liver enzyme levels. After adjustment for liver enzymes and albumin, the association with ICH from HBsAg positivity attenuated to 1.15 (0.90–1.48), suggesting possible mediation by abnormal liver function.CONCLUSIONS:Among Chinese adults, chronic hepatitis B virus infection is associated with an increased risk of ICH but not other stroke types, which may be mediated through liver dysfunction and altered lipid metabolism.

Leggi
Novembre 2023

Prevalence and determinants of high-risk human papilloma virus among men who have sex with men in Benin: a cross-sectional study embedded in a demonstration project on pre-exposure prophylaxis against HIV

Objectives
This study aims to assess the prevalence and factors associated with anal high-risk human papilloma virus (HR-HPV).

Design
A cross-sectional study conducted from 24 August 2020 to 24 November 2020.

Setting
Primary care, Cotonou, Benin.

Participants
204 HIV-negative men who have sex with men initiating oral pre-exposure prophylaxis.

Primary outcome measure
Anal HR-HPV genotypes using GeneXpert HPV assay. Fourteen HR-HPV were evaluated: HPV-16 and HPV-18/45 in 2 distinct channels and the 11 other genotypes as a pooled result (31, 33, 35, 39, 51, 52, 56, 58, 59, 66 and 68). The potential independent variables analysed included anal gonorrhoea and chlamydia infections, and sociodemographic and sexual behaviour factors. To assess the determinants of HR-HPV, univariate and multivariate Poisson regression models were performed by using SAS V.9.4.

Results
Mean age±SD was 25.9±4.8 years. 131/204 men claimed insertive sex procured more pleasure. Thirty-two participants, accounting for 15.7% of the study sample, had gonorrhoea and/or chlamydia. The prevalence of any HR-HPV genotype was 36.3% (95% CI 30.0% to 43.0%). In total, 7.8% of men had HPV-16 and 7.4% had HPV-18/45. The prevalence for the pooled genotypes (31, 33, 35, 39, 51, 52, 56, 58, 59, 66 and 68) was 29.9%. Receptive anal sex during the last 6 months was strongly associated with prevalent HR-HPV infections. The adjusted proportion ratio (aPR) was 1.93 (95% CI 1.31 to 2.83). Gonorrhoea and chlamydia were also associated with the outcome of interest; p value for both infections was

Leggi
Novembre 2023

Abstract 15709: Antagonist of Growth Hormone-Releasing Hormone Receptor Protects Against Cardiopulmonary Injury Induced by rVSV-SARS-CoV-2-S Virus Through Rag2 Regulation

Circulation, Volume 148, Issue Suppl_1, Page A15709-A15709, November 6, 2023. Background:SARS-CoV-2 (COVID-19) transmits a multi-systemic disease that can lead to acute respiratory distress syndrome. Growth hormone-releasing hormone receptor (GHRH-R) and its splice variant are expressed in murine and human lung and heart. GHRH-R antagonist, MIA-602, has been shown to regulate inflammation in animal models and immune cell responses to bleomycin lung injury. Using a BSL2-compatible recombinant VSV-eGFP-SARS-CoV-2-S virus (rVSV-SARS-CoV-2-S) which mimics native SARS-CoV-2 infection in K18 hACE2tg mice, we tested our hypothesis that MIA-602 attenuates COVID-19-induced cardiopulmonary injury by reducing inflammation.Methods:Male and female K18-hACE2tg mice were infected with SARS-CoV-2/USA-WA1/2020, rVSV-SARS-CoV-2-S, or PBS and lung viral load, weight-loss and histopathology were compared (N=8). Mice infected with rVSV-SARS-CoV-2-S were subject to daily subcutaneous injections of 10 μg MIA-602 or vehicle (control) starting at 24h post-infection. Pulmonary function was measured via whole-body plethysmography on day 0, day 3, and day 5 (n=7). Five days after viral infection mice were sacrificed, and blood and tissues collected for histopathological analyses, H&E staining, RNA and protein work. Heart and lung tissues were used for RNASeq (n=3 per group). T-test or One-way ANOVA-test was used for statistical analysis.Results:SARS-CoV-2 and rVSV-SARS-CoV-2-S presented similar pathology for weight loss, infectivity (~60%) and histopathologic changes. Daily treatment with MIA-602 ameliorated weight loss, reduced lung inflammation, pneumonia and pulmonary dysfunction evidenced by rescued respiratory rate, expiratory parameters, and dysregulated airway parameters (p

Leggi
Novembre 2023

Abstract 15748: Association of Clonal Hematopoiesis in the Setting of Human Immunodeficiency Virus Infection With Subclinical Atherosclerosis and Vascular Inflammation

Circulation, Volume 148, Issue Suppl_1, Page A15748-A15748, November 6, 2023. Background:Clonal hematopoiesis of indeterminate potential (CHIP) is associated with cardiovascular disease (CVD) and common in HIV, but whether CHIP contributes to atherosclerosis in HIV is unknown. We hypothesized CHIP is associated with atherosclerosis and arterial inflammation among people with HIV (PWH).Methods:We studied treated, suppressed PWH ages 35-70 years old with ≥1 CVD risk factor. CHIP mutations were detected with a validated targeted sequencing assay. We measured carotid intima-media thickness (IMT) longitudinally with ultrasound and aortic inflammation and lymph node activity using cross-sectional18F-FDG-PET. Inflammatory biomarkers were measured with a multiplex electrochemiluminescence assay. We used linear regression with adjustment for age, sex, nadir CD4 count, smoking, hypertension, diabetes, and hyperlipidemia.Results:We included 231 PWH (52±9 years, 7% female). 32 (14%) had CHIP with median variant allele fraction of 3.1%. Common mutations were in DNM3TA (n=21) and TET2 (n=6). Only age was associated with CHIP (OR 2.3 per decade older, 95%CI 1.2-3.9; p=0.003). Among N=165 (CHIP=22), mean IMT was 1.0 mm with and without CHIP (p=0.63), unchanged after adjustment (Figure). CHIP was not associated with prevalent or incident plaque. Over 3.2 years, IMT progression was faster among those with CHIP (0.033 mm/year; p=0.10), attenuated after adjustment (0.022 mm/year; p=0.27). Among 80 with FDG-PET, CHIP (n=12) was associated with higher lymph node activity (SUV p=0.04) that was attenuated in reference to background activity and adjusted for risk factors. CHIP was not associated with arterial inflammation (p=0.83), inflammatory markers, or viral persistence markers.Conclusions:Among PWH, CHIP mutations were not associated with subclinical atherosclerosis or arterial inflammation, proposed mechanisms of how CHIP could cause CVD. Clinical outcomes studies are needed to ascertain the impact of CHIP on CVD in HIV.

Leggi
Novembre 2023

Abstract 15132: Proteomic Signatures of Human Immunodeficiency Virus-Associated Subclinical Left Atrial Dilation

Circulation, Volume 148, Issue Suppl_1, Page A15132-A15132, November 6, 2023. Introduction:Persons living with HIV (PLWH) receiving combination antiretroviral therapy (cART) are at higher risk of heart failure (HF) and preceding cardiac abnormalities, including left atrial (LA) dilation, compared to persons without HIV (PWOH). Mechanisms of this excess risk are unclear. We assessed whether plasma proteomic signatures of immune activation are cross-sectionally associated with LA volume index (LAVi) and augmented among PLWH.Methods:We performed Olink proteomics on plasma obtained concurrently with cardiac magnetic resonance among PLWH and PWOH. Proteins were analyzed individually and as clusters agnostically defined using weighted gene co-expression network analysis. Associations with HIV serostatus and LAVi were estimated using multivariable linear regression with robust variance. We explored protein relationships using annotated enrichment analysis.Results:Among 352 participants (age 55±6 years; 25% female; 70% Black), mean LAVi was 29±9 mL/m2and 60% were PLWH (88% on cART; 73% with undetectable plasma HIV RNA). Of 2594 proteins, 104 were independently associated with LAVi (false discovery rate, FDR

Leggi
Novembre 2023

Abstract 14877: Spike Protein of SARS-CoV-2 Virus Induces Mitochondrial Dysfunction in Swine Heart via Redox Impairment of Heme Proteins and Increasing Superoxide Generation

Circulation, Volume 148, Issue Suppl_1, Page A14877-A14877, November 6, 2023. The cellular entry of the SARS-CoV-2 virus depends on the binding of spike (S) protein to its biological ligand, ACE2. Although the virus commonly causes respiratory distress, cardiac injury can occur in COVID-19 patients, which is consistent with the expression of ACE2 in myocytes. Previous reports indicate SARS-CoV-2 proteins can target cardiac mitochondria and suppress mitochondrial function via enhancing MPTP pore opening and perturbing cardiac bioenergetics. To explore the underlying mechanism of the effect of SARS-CoV-2 on cardiac mitochondria, we measured the interactions of SARS-CoV-2 proteins with swine heart mitochondria in vitro. Incubation of recombinant S protein with isolated mitochondria significantly decreased state-3 oxygen consumption rate (OCR, 95.10 vs 65.68 nmol/min/mg) and FCCP uncoupling OCR (82.94 vs 66.95 nmol/min/mg). We further detected that S protein impaired the enzymatic activities of electron transport chain (ETC) (by 15.62% to 34.44%). However, S protein had no effect on TCA cycle enzymes, indicating the involvement of mitochondrial membrane components in decreased OCR by S proteins. Recombinant nucleocapsid (N) protein of SAR-CoV-2 had no effect on the OCR and ETC activities of swine mitochondria. S proteins decreased the intensity of mitochondrial heme spectrum determined by dithionite reduction with UV/VIS spectroscopy (by 17.52% hemea, 15.82% hemec1). The results were further assessed using isolated complex III (Cx3) and complex IV (Cx4). Treatment of isolated Cx3 and Cx4 with S protein decreased the spectral intensities of hemeaand hemec1. The spectra of both Cx3 and Cx4 were not affected by N protein. The results suggested S protein downregulates redox potentials of ETC in swine mitochondria. Treatment of swine mitochondria with S proteins enhanced superoxide (.O2–) generation by Cx1 (by 43.7%) and by Cx3 (by 10.9-fold) assessed by EPR and cytochromecreduction assays. However, we detected S proteins modestly decreased.O2–generation by swine mitochondria under state-2 condition (by 9.52%), indicating impairing pH gradient by S protein. In conclusion, the spike protein of SARS-CoV-2 virus mediates mitochondrial dysfunction of swine heart via impairing the redox function and increasing.O2–generation.

Leggi
Novembre 2023