ArticleAlimentary pharmacology & therapeutics2021
Progressive alcohol-related liver fibrosis is characterised by imbalanced collagen formation and degradation.
Article in Alimentary pharmacology & therapeutics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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18 citing papers in PubMed, 37 citations in OpenAlex.
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- Ability of soluble TREM2 and PRO-C3 as biomarkers to predict changes in MASLD activity.JHEP reports : innovation in hepatology · 2025Article
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- Decellularization Techniques for Tissue Engineering: Towards Replicating Native Extracellular Matrix Architecture in Liver Regeneration.Journal of functional biomaterials · 2023Review
- Article
- PRO-C3 is a predictor of clinical outcomes in distinct cohorts of patients with advanced liver disease.JHEP reports : innovation in hepatology · 2023Article
- Collagen matrix scaffolds: Future perspectives for the management of chronic liver diseases.World journal of clinical cases · 2023Review
- Mechanical homeostasis imbalance in hepatic stellate cells activation and hepatic fibrosis.Frontiers in molecular biosciences · 2023Review
- Identification of biomarkers co-associated with M1 macrophages, ferroptosis and cuproptosis in alcoholic hepatitis by bioinformatics and experimental verification.Frontiers in immunology · 2023Article
- Novel potential biomarkers for severe alcoholic liver disease.Frontiers in immunology · 2022Article
- Progressive alcohol-related liver fibrosis is characterised by imbalanced collagen formation and degradation.Alimentary pharmacology & therapeutics · 2021Article
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14 authors at 4 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
backgroundLiver fibrosis accumulation is considered a turnover disease, with formation exceeding degradation, although this hypothesis has never been tested in humans.
aimsTo investigate extracellular matrix (ECM) remodelling in a biopsy-controlled study of alcohol-related liver disease (ALD) patients.
methodsWe evaluated the relationship between formation and degradation of four collagens as a function of histological fibrosis, inflammation and steatosis in 281 patients with ALD and 50 matched healthy controls. Post hoc, we tested the findings in a cohort of patients with alcohol-related cirrhosis and assessed the collagens' prognostic accuracy. We assessed the fibrillar collagens type III (PRO-C3/C3M) and V (PRO-C5/C5M), the basement membrane collagen IV (PRO-C4/C4M), and the microfilament interface collagen VI (PRO-C6/C6M).
resultsMean age was 54 ± 6 years, 74% male, fibrosis stage F0/1/2/3/4 = 33/98/84/18/48. Compared to controls, patients with ALD had higher levels of type III collagen formation and degradation, with the highest concentrations in those with cirrhosis (PRO-C3 = 8.2 ± 1.7 ng/mL in controls, 14.6 ± 13.5 in ALD, 34.8 ± 23.1 in cirrhosis; C3M 7.4 ± 1.9 in controls, 9.3 ± 4.4 in ALD, 14.0 ± 5 in cirrhosis). ECM remodelling became increasingly imbalanced in higher stages of liver fibrosis, with formation progressively superseding degradation. This was particularly pronounced for type III collagen. We observed similar imbalance for inflammatory severity, but not steatosis.
conclusionsALD is characterised by both elevated collagen formation and degradation, which becomes increasingly imbalanced with more severe disease. Net increase in fibrillar collagens contributes to fibrosis progression. This has important implications for monitoring and very early identification of patients at highest risk of progressing to cirrhosis.
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