Opportunities and barriers in omics-based biomarker discovery for steatotic liver diseases

Journal of Hepatology, Journal Year: 2024, Volume and Issue: 81(2), P. 345 - 359

Published: March 28, 2024

The rising prevalence of liver diseases related to obesity and excessive use alcohol is fuelling an increasing demand for accurate biomarkers aimed at community screening, diagnosis steatohepatitis significant fibrosis, monitoring, prognostication prediction treatment efficacy. Breakthroughs in omics methodologies the power bioinformatics have created excellent opportunity apply technological advances clinical needs, instance development precision personalised medicine. Via technologies, biological processes from genes circulating protein, as well microbiome - including bacteria, viruses fungi, can be investigated on axis. However, there are important barriers omics-based biomarker discovery validation, semi-quantitative measurements untargeted platforms, which may exhibit high analytical, inter- intra-individual variance. Standardising methods need validate them across diverse populations presents a challenge, partly due disease complexity dynamic nature expression different stages. Lack validity causes lost opportunities when studies fail provide knowledge needed regulatory approvals, all contributes delayed translation these discoveries into practice. While no matured implementation, extent data generated has enabled hypothesis-free plethora candidate that warrant further validation. To explore many hepatologists detailed commonalities differences between various layers, both advantages approaches.

Language: Английский

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Tauroursodeoxycholic acid inhibits intestinal inflammation and barrier disruption in mice with non‐alcoholic fatty liver disease

British Journal of Pharmacology, Journal Year: 2017, Volume and Issue: 175(3), P. 469 - 484

Published: Nov. 15, 2017

The gut-liver axis is associated with the progression of non-alcoholic fatty liver disease (NAFLD). Targeting and bile acid-based pharmaceuticals are potential therapies for NAFLD. effect tauroursodeoxycholic acid (TUDCA), a candidate drug NAFLD, on intestinal barrier function, inflammation, gut lipid transport microbiota composition was analysed in murine model NAFLD.The NAFLD mouse established by feeding mice high-fat diet (HFD) 16 weeks. TUDCA administered p.o. during last 4 expression levels tight junction genes, metabolic inflammatory genes were determined quantitative PCR. Tissue inflammation evaluated haematoxylin eosin staining. 16S rRNA gene sequencing.TUDCA administration attenuated HFD-induced hepatic steatosis, responses, obesity insulin resistance mice. Moreover, responses as manifested decreased histopathology scores cytokine levels. In addition, improved function increasing molecules solid chemical barrier. components involved ileum also reduced HFD-fed Finally, TUDCA-treated showed different compared that but similar to normal chow diet-fed mice.TUDCA attenuates ameliorating improving decreasing fat modulating composition.

Language: Английский

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Metabolic liver disease in diabetes – From mechanisms to clinical trials

Metabolism, Journal Year: 2020, Volume and Issue: 111, P. 154299 - 154299

Published: June 20, 2020

Non-alcoholic fatty liver disease (NAFLD) comprises (steatosis), non-alcoholic steatohepatitis (NASH) and fibrosis/cirrhosis may lead to end-stage failure or hepatocellular carcinoma. NAFLD is tightly associated with the most frequent metabolic disorders, such as obesity, syndrome, type 2 diabetes mellitus (T2DM). Both multisystem diseases share several common mechanisms. Alterations of tissue communications include excessive lipid later cytokine release by dysfunctional adipose tissue, intestinal dysbiosis ectopic fat deposition in skeletal muscle. On level, this leads insulin resistance due abnormal handling mitochondrial function. Over time, cellular oxidative stress activation inflammatory pathways, again supported multiorgan crosstalk, determine progression. Recent studies show that particularly severe resistant (SIRD) subgroup (cluster) associates its accelerated progression increases risk diabetes-related cardiovascular kidney diseases, underpinning critical role resistance. Consequently, lifestyle modification certain drug classes used treat T2DM have demonstrated effectiveness for treating NAFLD, but also some novel therapeutic concepts be beneficial both T2DM. This review addresses bidirectional relationship between mechanisms underlying relevance biomarkers improving diagnostic modalities identification subgroups at specific Also, metabolism-related drugs discussed light recent clinical trials. Finally, highlights challenges addressed future on context

Language: Английский

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Prenatal Exposure to Perfluoroalkyl Substances Associated With Increased Susceptibility to Liver Injury in Children

Hepatology, Journal Year: 2020, Volume and Issue: 72(5), P. 1758 - 1770

Published: Aug. 1, 2020

Background and Aims Per‐ polyfluoroalkyl substances (PFAS) are widespread persistent pollutants that have been shown to hepatotoxic effects in animal models. However, human evidence is scarce. We evaluated how prenatal exposure PFAS associates with established serum biomarkers of liver injury alterations metabolome children. Approach Results used data from 1,105 mothers their children (median age, 8.2 years; interquartile range, 6.6‐9.1) the European Human Early‐Life Exposome cohort (consisting six existing population‐based birth cohorts France, Greece, Lithuania, Norway, Spain, United Kingdom). measured concentrations perfluorooctane sulfonate, perfluorooctanoate, perfluorononanoate, perfluorohexane perfluoroundecanoate maternal blood. assessed alanine aminotransferase, aspartate gamma‐glutamyltransferase child serum. Using Bayesian kernel machine regression, we found higher during pregnancy was associated enzyme levels also metabolomics through a targeted assay significant perturbations amino acid glycerophospholipid metabolism PFAS. A latent variable analysis identified profile at high risk (odds ratio, 1.56; 95% confidence interval, 1.21‐1.92) characterized by increased branched‐chain acids (valine, leucine, isoleucine), aromatic (tryptophan phenylalanine), glycerophospholipids (phosphatidylcholine [PC] aa C36:1 Lyso‐PC C18:1). Conclusions Developmental can contribute pediatric injury.

Language: Английский

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Peroxisome Proliferator-Activated Receptors and Their Novel Ligands as Candidates for the Treatment of Non-Alcoholic Fatty Liver Disease

Cells, Journal Year: 2020, Volume and Issue: 9(7), P. 1638 - 1638

Published: July 8, 2020

Non-alcoholic fatty liver disease (NAFLD) is a major health issue worldwide, frequently associated with obesity and type 2 diabetes. Steatosis the initial stage of disease, which characterized by lipid accumulation in hepatocytes, can progress to non-alcoholic steatohepatitis (NASH) inflammation various levels fibrosis that further increase risk developing cirrhosis hepatocellular carcinoma. The pathogenesis NAFLD influenced interactions between genetic environmental factors involves several biological processes multiple organs. No effective therapy currently available for treatment NAFLD. Peroxisome proliferator-activated receptors (PPARs) are nuclear regulate many functions disturbed NAFLD, including glucose metabolism, as well inflammation. Thus, they represent relevant clinical targets In this review, we describe determinants mechanisms underlying its progression complications, current therapeutic strategies employed. We also focus on complementary distinct roles PPAR isotypes effects first-generation agonists. Finally, review novel safe agonists improved efficacy their potential use

Language: Английский

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