Binge drinking induces an acute burst of markers of hepatic fibrogenesis (PRO-C3)

Nikolaj Torp, Mads Israelsen, Mette Juul Nielsen, Claus Philip Åstrand, Pernille Juhl, Stine Johansen, Camilla Dalby Hansen, Bjørn Madsen, Ida Falk Villesen, Diana Julie Leeming, Maja Thiele, Torben Hansen, Morten Karsdal, Aleksander Krag

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

Background & Aims: Binge drinking is associated with an increased risk of liver disease. Morbidity and mortality of alcohol-related liver disease (ALD) is associated with collagen deposition in the hepatic extracellular matrix (ECM). However, the acute effects of binge drinking on ECM turnover are unknown. We aimed to investigate the effects on hepatic ECM turnover following a binge drinking episode. Methods: We performed a pathophysiological intervention study with 15 non-alcoholic fatty liver disease (NAFLD) patients, 15 ALD patients and 10 healthy controls. We used 40% ethanol in 9 mg/mL NaCl administered through a nasogastric tube to simulate binge drinking. Hepatic vein catheterisation allowed simultaneous hepatic- and systemic vein sampling. Markers of ECM formation and degradation were measured with competitive ELISA. Results: The interstitial matrix formation marker PRO-C3 increased by 1.2 ng/mL (10%, P <.001) 24 hours after binge drinking. In participants with existing liver fibrosis determined by elevated baseline PRO-C3, hepatic levels increased by 0.09 ng/mL (95% CI: 0.03-0.15, P =.005) while systemic PRO-C3 decreased 0.11 ng/mL (95% CI: −0.15 to −0.06, P <.001) in 3 hours. PRO-C8 increased by 30% (+0.9 ng/mL, P =.014) in liver-diseased patients with F0-F1 but not in any other group. Twenty-four-hour changes in systemic C3M and PRO-C3 were not associated (P =.911). Conclusions: Binge drinking induced an acute burst of PRO-C3 in healthy individuals and patients with liver disease. Markers of ECM degradation were not correlated to markers of ECM formation, suggesting that even a single episode of binge drinking promotes excessive hepatic fibrogenesis.

Original languageEnglish
JournalLiver International
Volume42
Issue number1
Pages (from-to)92-101
ISSN1478-3223
DOIs
Publication statusPublished - Jan 2022

Bibliographical note

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Keywords

  • acute intoxication
  • biomarker
  • cirrhosis
  • extracellular matrix
  • fibrosis

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