Progressive alcohol‐related liver fibrosis is characterised by imbalanced collagen formation and degradation. Issue 8 (24th August 2021)

• Record Type: Journal Article
• Authors: Thiele, Maja; Johansen, Stine; Gudmann, Natasja S.; Madsen, Bjørn; Kjærgaard, Maria; Nielsen, Mette Juul; Leeming, Diana J.; Jacobsen, Suganya; Bendtsen, Flemming; Møller, Søren; Detlefsen, Sönke; Karsdal, Morten; Krag, Aleksander
• Other Names: Arumugam Manimozhian investigator.; Bork Peer investigator.; Hansen Torben investigator.; Anastasiadou Ema investigator.; Hartoft Christina investigator.; Israelsen Hans investigator.; Legido‐Quigley Cristina investigator.; Melberg Hans Olav investigator.; Trebicka Jonel investigator.
• Is Part Of: Alimentary pharmacology & therapeutics. Volume 54:Issue 8(2021)
• Page Start: 1070
• Page End: 1080
• Publication Date: 2021-08-24
• Subjects: Digestive organs -- Diseases -- Treatment -- Periodicals; Digestive organs -- Effect of drugs on -- Periodicals; Gastrointestinal system -- Diseases -- Treatment -- Periodicals; Gastrointestinal system -- Effect of drugs on -- Periodicals; 615.73
• DOI: 10.1111/apt.16567
• Languages: English
• ISSNs: 0269-2813

Abstract

Summary: Background: Liver fibrosis accumulation is considered a turnover disease, with formation exceeding degradation, although this hypothesis has never been tested in humans. Aims: To investigate extracellular matrix (ECM) remodelling in a biopsy‐controlled study of alcohol‐related liver disease (ALD) patients. Methods: We 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). Results: Mean 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. Conclusions: ALD 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. Abstract : Alcohol‐related liver fibrosis is characterised by both elevated collagen formation and degradation, which becomes increasingly imbalanced with more severe disease.