Performance of non-invasive tests and histology for the prediction of clinical outcomes in patients with non-alcoholic fatty liver disease: an individual participant data meta-analysis

BackgroundHistologically assessed liver fibrosis stage has prognostic significance in patients with non-alcoholic fatty liver disease (NAFLD) and is accepted as a surrogate endpoint in clinical trials for non-cirrhotic NAFLD. Our aim was to compare the prognostic performance of non-invasive tests with liver histology in patients with NAFLD.MethodsThis was an individual participant data meta-analysis of the prognostic performance of histologically assessed fibrosis stage (F0–4), liver stiffness measured by vibration-controlled transient elastography (LSM-VCTE), fibrosis-4 index (FIB-4), and NAFLD fibrosis score (NFS) in patients with NAFLD. The literature was searched for a previously published systematic review on the diagnostic accuracy of imaging and simple non-invasive tests and updated to Jan 12, 2022 for this study. Studies were identified through PubMed/MEDLINE, EMBASE, and CENTRAL, and authors were contacted for individual participant data, including outcome data, with a minimum of 12 months of follow-up. The primary outcome was a composite endpoint of all-cause mortality, hepatocellular carcinoma, liver transplantation, or cirrhosis complications (ie, ascites, variceal bleeding, hepatic encephalopathy, or progression to a MELD score ≥15). We calculated aggregated survival curves for trichotomised groups and compared them using stratified log-rank tests (histology: F0–2 vs F3 vs F4; LSM: 2·67; NFS: 0·676), calculated areas under the time-dependent receiver operating characteristic curves (tAUC), and performed Cox proportional-hazards regression to adjust for confounding. This study was registered with PROSPERO, CRD42022312226.FindingsOf 65 eligible studies, we included data on 2518 patients with biopsy-proven NAFLD from 25 studies (1126 [44·7%] were female, median age was 54 years [IQR 44–63), and 1161 [46·1%] had type 2 diabetes). After a median follow-up of 57 months [IQR 33–91], the composite endpoint was observed in 145 (5·8%) patients. Stratified log-rank tests showed significant differences between the trichotomised patient groups (p<0·0001 for all comparisons). The tAUC at 5 years were 0·72 (95% CI 0·62–0·81) for histology, 0·76 (0·70–0·83) for LSM-VCTE, 0·74 (0·64–0·82) for FIB-4, and 0·70 (0·63–0·80) for NFS. All index tests were significant predictors of the primary outcome after adjustment for confounders in the Cox regression.InterpretationSimple non-invasive tests performed as well as histologically assessed fibrosis in predicting clinical outcomes in patients with NAFLD and could be considered as alternatives to liver biopsy in some cases

How does eDNA decay affect metabarcoding experiments?

Este artículo contiene 9 páginas, 2 figuras.The detection of species using environmental DNA (eDNA) relies on our capacity to identify DNA from the sampled environment. Once eDNA is released into the environment, the physical degradation of individual eDNA molecules over time directly affects our ability to detect species (eDNA decay). Therefore, interpreting eDNA data requires an explicit understanding of eDNA decay to accurately infer contemporary presence or absence of a given species in the study ecosystem. Most research to date on eDNA decay has focused on single-species assays (predominantly quantitative PCR), and thus little is known on how eDNA decay affects the interpretation of metabarcoding datasets. Here, we used eDNA metabarcoding (targeting a section of the eukaryotic cytochrome c oxidase subunit I gene) of water samples from controlled tanks to examine eDNA decay in a wide variety of marine metazoan species. After the stocked organisms were removed from these tanks, we observed a sharp decrease in amplicon sequence variant (ASV) richness within the first 48 hours. Furthermore, there was a substantial change in beta diversity between 24 and 48 hours, and after 48 hours, most stocked species became undetectable. Interestingly, the estimated decay rate for each study species, calculated using a linear regression of reads over time, differed across organisms, with up to 2–3-fold difference among species. Our results showed that, for marine temperate species, the most substantial change in eDNA metabarcoding detectability occurred within the first 48 h, and after that, eDNA from several taxa became undetectable. These findings inform the ecological interpretation of metabarcoding datasets and provide estimates of eDNA decay rate that are valuable for both simulation studies and the design of future ecological surveys.LEH was supported by the Natural Environmental Research Council (grant number NE/L002531/).Peer reviewe

A Systematic Scoping Review of Communication Skills Training in Medical Schools between 2000 and 2020

10.1080/0142159X.2022.2054693Medical Teacher449997-100