Liver macrophages revisited: The expanding universe of versatile responses in a spatiotemporal context

Hepatology Communications, Journal Year: 2024, Volume and Issue: 8(7)

Published: July 1, 2024

The liver is a vital organ that continuously adapts to wide and dynamic diversity of self-antigens xenobiotics. This involves the active contribution immune cells, particularly by liver-resident macrophages, Kupffer cells (KCs), which exert variety central functions in homeostasis disease. As such, KCs interact with their microenvironment shape hepatic cellular landscape, control gut-derived signal integration, modulate metabolism. On injury, rapid recruitment bone marrow monocyte-derived macrophages alters this status quo and, when unrestrained, drastically compromises homeostasis, surveillance, tissue organization. Several factors determine functional roles these processes, such as ontogeny, activation/polarization profile importantly, spatial distribution within liver. Loss tolerance adaptability environment may result persistent inflammation, fibrosis, cirrhosis, tumorigenic niche promoting cancer. In review, we aim at providing most recent breakthroughs our understanding macrophage biology, spatiotemporal context, well on potential therapeutic interventions hold key tackling remaining clinical challenges varying etiologies hepatology.

Language: Английский

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Population screening for cirrhosis

Hepatology Communications, Journal Year: 2024, Volume and Issue: 8(9)

Published: Aug. 26, 2024

In response to the growing health crisis of liver-related morbidity and mortality, screening for liver cirrhosis has emerged as a promising strategy early detection timely intervention. By identifying individuals with severe fibrosis or compensated cirrhosis, holds promise enhancing treatment outcomes, delaying disease progression, ultimately improving quality life affected individuals. Clinical practice guidelines from international scientific societies currently recommend targeted strategies, investigating high-risk populations known risk factors disease. While there is good evidence that increases case finding in population, number studies indicate may motivate beneficial lifestyle changes patients steatotic disease, are major gaps knowledge need clarification before programs implemented. Foremost, randomized trials needed ensure leads improved mortality. If not, could be unethical due overdiagnosis, overtreatment, increased care costs, negative psychological consequences screening, futile invasive investigations. Moreover, tests used optimized toward lower false positive rates than FIB-4 while retaining few negatives. Finally, barriers adherence implementation elucidated. This review provides comprehensive overview current landscape strategies promises pitfalls methods detection.

Language: Английский

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Unraveling Metabolic Dysfunction-Associated Steatotic Liver Disease Through the Use of Omics Technologies

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(4), P. 1589 - 1589

Published: Feb. 13, 2025

Non-alcoholic fatty liver disease (NAFLD), now referred to as metabolic dysfunction-associated steatotic (MASLD), is the most prevalent disorder globally, linked obesity, type 2 diabetes, and cardiovascular risk. Understanding its potential progression from simple steatosis cirrhosis hepatocellular carcinoma (HCC) crucial for patient management treatment strategies. The disease's complexity requires innovative approaches early detection personalized care. Omics technologies-such genomics, transcriptomics, proteomics, metabolomics, exposomics-are revolutionizing study of MASLD. These high-throughput techniques allow a deeper exploration molecular mechanisms driving progression. Genomics can identify genetic predispositions, whilst transcriptomics proteomics reveal changes in gene expression protein profiles during evolution. Metabolomics offers insights into alterations associated with MASLD, while exposomics links environmental exposures MASLD pathology. By integrating data various omics platforms, researchers map out intricate biochemical pathways involved This review discusses roles technologies enhancing understanding highlights diagnostic therapeutic targets within spectrum, emphasizing need non-invasive tools staging development.

Language: Английский

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Deep proteome profiling of metabolic dysfunction-associated steatotic liver disease

Communications Medicine, Journal Year: 2025, Volume and Issue: 5(1)

Published: March 3, 2025

Metabolic dysfunction-associated steatotic liver disease (MASLD) affects roughly 1 in 3 adults and is a leading cause of transplants related mortality. A deeper understanding pathogenesis essential to assist developing blood-based biomarkers. Here, we use data-independent acquisition mass spectrometry assess disease-state associated protein profiles human liver, blood plasma, white adipose tissue (WAT). In find that MASLD with an increased abundance proteins involved immune response extracellular matrix (ECM) decrease metabolism. Cell type deconvolution the proteome indicates endothelial hepatic stellate cells are main source ECM rearrangements, hepatocytes major contributor changes blood, several MASLD-associated correlate expression WAT rather than so could serve as suitable predictors multi-protein panel marker. Moreover, our proteomics-based logistic regression models perform better existing methods for predicting fibrosis from samples. Our comprehensive proteomic analysis deepens function pathology by elucidating key cellular mechanisms multi-organ interactions, demonstrates robustness biomarker enhance diagnosis significant fibrosis. common condition affecting about adults. It occurs when there too much fat death people needing transplants. To improve early detection, studied MASLD. revealed certain indicators disease. Some indicated liver. We propose test be more accurate commonly used diagnosing enable better, non-invasive ways detect Boel et al. undertake obese patients Dysfunction-Associated Steatotic Liver Disease (MASLD). Key signatures identified across different organs offer which other diagnostic methods.

Language: Английский

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Recompensation in Cirrhosis: Biomarkers and Strategies

Seminars in Liver Disease, Journal Year: 2025, Volume and Issue: unknown

Published: April 3, 2025

The onset of decompensation in advanced chronic liver disease (ACLD) is a hallmark natural history, with poor prognosis and significantly increased liver-related mortality. Etiological treatments for viral hepatitis or abstinence cirrhosis due to alcohol abuse have demonstrated that some patients experience partial complete clinical analytical improvement, stage termed “recompensation.” Although recompensation primarily defined clinically based on treatable etiologies, it still evolving conditions like metabolic dysfunction-associated steatotic (MASLD). Despite the need specific biomarkers hepatic recompensation, no been thoroughly studied this context. Biomarkers identified compensated ACLD (cACLD) following etiological treatment might be explored recompensation. pathophysiology mechanisms underlying remain unclear, understanding mechanism involved could help identify potential targets This review provides an update concept, examines existing data invasive non-invasive biomarkers, mainly cACLD after cure, raised explores future therapeutic process.

Language: Английский

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Antifibrotic Therapies for Metabolic Dysfunction-associated Steatotic Liver Disease

JHEP Reports, Journal Year: 2025, Volume and Issue: unknown, P. 101421 - 101421

Published: April 1, 2025

Language: Английский

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Precision Medicine in Immunoradiotherapy

Published: Jan. 1, 2025

Language: Английский

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Proteomic signatures for fibrosis in MASLD: a biopsy-proven dual-cohort study

Scandinavian Journal of Gastroenterology, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 9

Published: April 16, 2025

Predicting disease progression in metabolic dysfunction-associated steatotic liver (MASLD) is challenging, and current non-invasive tests (NITs) lack the precision to replace biopsy. This study aimed identify plasma biomarkers for different stages of fibrosis using affinity-based proteomics two biopsy-proven cohorts. The primary objective was capable distinguishing between low-to-no (F0-1) significant (F2-4) MASLD. Participants discovery cohort were recruited from Uppsala University Hospital Swedish CArdioPulmonary bioImage Study (SCAPIS), while validation included Linköping Hospital. All participants diagnosed with MASLD underwent biopsy categorized by stage (F0-1 or F2-4). A total 276 proteins analyzed Olink® panels, identified through ordinal logistic regression, random forest (RF) analysis Boruta algorithm. 60 participants, 60% having F0-1 40% F2-4. had 59 whom 35 (59.3%) 24 F2-4 (40.7%). Five significantly associated cohort, four confirmed cohort. model combining angiotensin converting enzyme-2 (ACE2), hepatocyte growth factor (HGF) insulin-like factor-binding protein-7 (IGFBP-7) demonstrated strong predictive performance (c-statistics 0.82-0.83), outperforming fibrosis-4 (FIB-4) 0.61-0.72). biomarker including ACE2, HGF IGFBP7 shows promise low-stage fibrosis.

Language: Английский

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Unique metabolomics characteristics for distinguishing cirrhosis related to different liver diseases: A systematic review and meta-analysis

Diabetes & Metabolic Syndrome Clinical Research & Reviews, Journal Year: 2024, Volume and Issue: 18(6), P. 103068 - 103068

Published: June 1, 2024

Language: Английский

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The 2024 Report on the Human Proteome from the HUPO Human Proteome Project

Journal of Proteome Research, Journal Year: 2024, Volume and Issue: 23(12), P. 5296 - 5311

Published: Nov. 8, 2024

The Human Proteome Project (HPP), the flagship initiative of Organization (HUPO), has pursued two goals: (1) to credibly identify at least one isoform every protein-coding gene and (2) make proteomics an integral part multiomics studies human health disease. past year seen major transitions for HPP. neXtProt was retired as official HPP knowledge base, UniProtKB became reference proteome Ensembl-GENCODE provides protein target list. A function evidence FE1–5 scoring system been developed functional annotation proteins, parallel PE1–5 UniProtKB/neXtProt scheme expression. This report includes updates from (version 2023–09) release 2024_04, with expression detected (PE1) 18138 19411 GENCODE genes (93%). number non-PE1 proteins ("missing proteins") is now 1273. transition a net reduction 367 (19,411 instead 19,778 PE1–4 last in neXtProt). We include reports Biology Disease-driven HPP, Protein Atlas, Grand Challenge Project. expect new Functional Evidence energize throughout global community, including π-HuB China.

Language: Английский

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