Early detection of liver fibrosis is crucial to select the correct care path for patients with non-alcoholic fatty liver disease (NAFLD). Here, we systematically review the evidence on the... Show moreEarly detection of liver fibrosis is crucial to select the correct care path for patients with non-alcoholic fatty liver disease (NAFLD). Here, we systematically review the evidence on the performance of FibroMeter versions in detecting different levels of fibrosis in patients with NAFLD. We searched four databases (Medline, Embase, the Cochrane library, and Web of Science) to find studies that included adults with NAFLD and biopsy-confirmed fibrosis (F1 to F4), compared with any version of FibroMeter. Two independent researchers screened the references, collected the data, and assessed the methodological quality of the included studies. We used a bivariate logit-normal random effects model to produce meta-analyses. From 273 references, 12 studies were eligible for inclusion, encompassing data from 3425 patients. Meta-analyses of the accuracy in detecting advanced fibrosis (F >= 3) were conducted for FibroMeter Virus second generation (V2G), NAFLD, and vibration controlled transient elaFS3stography (VCTE). FibroMeter VCTE showed the best diagnostic accuracy in detecting advanced fibrosis (sensitivity: 83.5% (95%CI 0.58-0.94); specificity: 91.1% (95%CI 0.89-0.93)), followed by FibroMeter V2G (sensitivity: 83.1% (95%CI 0.73-0.90); specificity: 84.4% (95%CI 0.62-0.95)) and FibroMeter NAFLD (sensitivity: 71.7% (95%CI 0.63-0.79); specificity: 82.8% (95%CI 0.71-0.91)). No statistically significant differences were found between the different FibroMeter versions. FibroMeter tests showed acceptable sensitivity and specificity in detecting advanced fibrosis in patients with NAFLD, but an urge to conduct head-to-head comparison studies in patients with NAFLD of the different FibroMeter tests remains. Show less
Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here... Show moreGlycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P < 5 x 10(-8)), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution.A trans-ancestry meta-analysis of GWAS of glycemic traits in up to 281,416 individuals identifies 99 novel loci, of which one quarter was found due to the multi-ancestry approach, which also improves fine-mapping of credible variant sets. Show less