134 research outputs found
European 'NAFLD Preparedness Index' - Is Europe ready to meet the challenge of fatty liver disease?
Background & Aims: Non-alcoholic fatty liver disease (NAFLD), which is closely associated with obesity, metabolic syndrome,
and diabetes, is a highly prevalent emerging condition that can be optimally managed through a multidisciplinary patient centred approach. National preparedness to address NAFLD is essential to ensure that health systems can deliver effective
care. We present a NAFLD Preparedness Index for Europe.
Methods: In June 2019, data were extracted by expert groups from 29 countries to complete a 41-item questionnaire about
NAFLD. Questions were classified into 4 categories: policies/civil society (9 questions), guidelines (16 questions), epidemiology
(4 questions), and care management (12 questions). Based on the responses, national preparedness for each indicator was
classified into low, middle, or high-levels. We then applied a multiple correspondence analysis to obtain a standardised
preparedness score for each country ranging from 0 to 100.
Results: The analysis estimated a summary factor that explained 71.3% of the variation in the dataset. No countries were
found to have yet attained a high-level of preparedness. Currently, the UK (75.5) scored best, although falling within the mid level preparedness band, followed by Spain (56.2), and Denmark (43.4), whereas Luxembourg and Ireland were the lowest
scoring countries with a score of 4.9. Only Spain scored highly in the epidemiology indicator category, whereas the UK was the
only country that scored highly for care management.
Conclusions: The NAFLD Preparedness Index indicates substantial variation between countries’ readiness to address NAFLD.
Notably, even those countries that score relatively highly exhibit deficiencies in key domains, suggesting that structural
changes are needed to optimise NAFLD management and ensure effective public health approaches are in place.
Lay summary: Non-alcoholic fatty liver disease (NAFLD), which is closely associated with obesity, metabolic syndrome, and
diabetes, is a highly prevalent condition that can be optimally managed through a multidisciplinary patient-centred approach.
National preparedness to address NAFLD is essential to allow for effective public health measures aimed at preventing disease
while also ensuring that health systems can deliver effective care to affected populations. This study defined preparedness as
having adequate policies and civil society engagement, guidelines, epidemiology, and care management. NAFLD preparedness
was found to be deficient in all 29 countries studied, with great variation among the countries and the 4 categories studied
Care standards for non-alcoholic fatty liver disease in the United Kingdom 2016: a cross-sectional survey
OBJECTIVE: Guidelines for the assessment of non-alcoholic fatty liver disease (NAFLD) have been published in 2016 by National Institute for Health and Care Excellence and European Associations for the study of the Liver-European Association for the study of Diabetes-European Association for the study of Obesity. Prior to publication of these guidelines, we performed a cross-sectional survey of gastroenterologists and hepatologists regarding NAFLD diagnosis and management. DESIGN: An online survey was circulated to members of British Association for the Study of the Liver and British Society of Gastroenterology between February 2016 and May 2016. RESULTS: 175 gastroenterologists/hepatologists responded, 116 completing the survey, representing 84 UK centres. 22% had local NAFLD guidelines. 45% received >300 referrals per year from primary care for investigation of abnormal liver function tests (LFTs). Clinical assessment tended to be performed in secondary rather than primary care including body mass index (82% vs 26%) and non-invasive liver screen (86% vs 32%) and ultrasound (81% vs 37%). Widely used tools for non-invasive fibrosis risk stratification were aspartate transaminase (AST)/alanine transaminase (ALT) ratio (53%), Fibroscan (50%) and NAFLD fibrosis score (41%). 78% considered liver biopsy in selected cases. 50% recommended 10% weight loss target as first-line treatment. Delivery of lifestyle interventions was mostly handed back to primary care (56%). A minority have direct access to community weight management services (22%). Follow-up was favoured by F3/4 fibrosis (72.9%), and high-risk non-invasive fibrosis tests (51%). Discharge was favoured by simple steatosis at biopsy (30%), and low-risk non-invasive scores (25%). CONCLUSIONS: The survey highlights areas for improvement of service provision for NAFLD assessment including improved recognition of non-alcoholic steatohepatitis in people with type 2 diabetes, streamlining abnormal LFT referral pathways, defining non-invasive liver fibrosis assessment tools, use of liver biopsy, managing metabolic syndrome features and improved access to lifestyle interventions
Lipid Remodeling in Hepatocyte Proliferation and Hepatocellular Carcinoma
Background and Aims: Hepatocytes undergo profound metabolic rewiring when primed to proliferate during compensatory regeneration and in hepatocellular carcinoma (HCC). However, the metabolic control of these processes is not fully understood. In order to capture the metabolic signature of proliferating hepatocytes, we applied state-of-the-art systems biology approaches to models of liver regeneration, pharmacologically and genetically activated cell proliferation, and HCC. Approach and Results: Integrating metabolomics, lipidomics, and transcriptomics, we link changes in the lipidome of proliferating hepatocytes to altered metabolic pathways including lipogenesis, fatty acid desaturation, and generation of phosphatidylcholine (PC). We confirm this altered lipid signature in human HCC and show a positive correlation of monounsaturated PC with hallmarks of cell proliferation and hepatic carcinogenesis. Conclusions: Overall, we demonstrate that specific lipid metabolic pathways are coherently altered when hepatocytes switch to proliferation. These represent a source of targets for the development of therapeutic strategies and prognostic biomarkers of HCC
Staging fibrosis and excluding advanced fibrosis in patients with NAFLD: comparison of non-invasive markers in an interim analysis from a prospective multicentre study
Variants in MARC1 and HSD17B13 reduce severity of NAFLD in children, perturb phospholipid metabolism, and suppress fibrotic pathways
Background & aims: Genome-wide association studies in adults have identified variants in HSD17B13 and MARC1 as protective against NAFLD. It is not known if they are similarly protective in children and, more generally, whether the peri-portal inflammation of pediatric NAFLD and lobular inflammation seen in adults share common genetic influences. Therefore, we aimed to: establish if these variants are associated with NAFLD in children, and to investigate the function of these variants in hepatic metabolism using metabolomics. Methods: 960 children (590 with NAFLD, 394 with liver histology) were genotyped for rs72613567T>TA in HSD17B13, rs2642438G>A in MARC1. Genotype-histology associations were tested using ordinal regression. Untargeted hepatic proteomics and plasma lipidomics were performed in a subset of samples. In silico tools were used to model the effect of rs2642438G>A (p.Ala165Thr) on MARC1. Results: rs72613567T>TA in HSD17B13 was associated with lower odds of NAFLD diagnosis (OR 0.7 (95%CI 0.6-0.9) and lower grade of portal inflammation (PA in MARC1 was associated with lower grade of hepatic steatosis (P=0.02). Proteomics found reduced expression of HSD17B13 in carriers of the protective allele, whereas MARC1 levels were not affected by genotype. Both variants showed downregulation of hepatic fibrotic pathways, upregulation of retinol metabolism and perturbation of phospholipid species. Modelling suggests that p.Ala165Thr would disrupt the stability and metal-binding of MARC1. Conclusions: There are shared genetic mechanisms between pediatric and adult NAFLD, despite their differences in histology. MARC1 and HSD17B13 are involved in phospholipid metabolism and suppress fibrosis in NAFLD
Abundances of neutron-capture elements in G 24-25. A halo-population CH subgiant
The differences between the neutron-capture element abundances of halo stars
are important to our understanding of the nucleosynthesis of elements heavier
than the iron group. We present a detailed abundance analysis of carbon and
twelve neutron-capture elements from Sr up to Pb for a peculiar halo star
G24-25 with [Fe/H] = -1.4 in order to probe its origin. The equivalent widths
of unblended lines are measured from high resolution NOT/FIES spectra and used
to derive abundances based on Kurucz model atmospheres. In the case of CH, Pr,
Eu, Gd, and Pb lines, the abundances are derived by fitting synthetic profiles
to the observed spectra. Abundance analyses are performed both relative to the
Sun and to a normal halo star G16-20 that has similar stellar parameters as
G24-25. We find that G24-25 is a halo subgiant star with an unseen component.
It has large overabundances of carbon and heavy s-process elements and mild
overabundances of Eu and light s-process elements. This abundance distribution
is consistent with that of a typical CH giant. The abundance pattern can be
explained by mass transfer from a former asymptotic giant branch component,
which is now a white dwarf.Comment: 11 pages, 9 figures, accepted for publication in A&
Simple non-invasive fibrosis scores identify patients with nonalcoholic fatty liver disease who progress to advanced fibrosis/cirrhosis: evidence from a large cohort of patients with sequential liver biopsies
Further delineation of fibrosis progression in NAFLD: evidence from a large cohort of patients with sequential biopsies
Novel Fibroscan-Based Score to Diagnose NASH and its severity in A Multi-centre UK Cohort of Patients with Suspected NAFLD
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