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

• Published in: Liver international Vol. 42; no. 1; pp. 92 - 101
• Main Authors: Torp, Nikolaj, Israelsen, Mads, Nielsen, Mette J., Åstrand, Claus P., Juhl, Pernille, Johansen, Stine, Hansen, Camilla D., Madsen, Bjørn, Villesen, Ida F., Leeming, Diana J., Thiele, Maja, Hansen, Torben, Karsdal, Morten, Krag, Aleksander
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.01.2022
• Subjects: Acute effects; acute intoxication; Atomic layer epitaxy; Binge drinking; Binge Drinking - complications; biomarker; cirrhosis; Collagen (type I); Complement C3 - analysis; Degradation; Drinking behavior; Ethanol; Ethanol - adverse effects; Extracellular matrix; Fatty liver; Fibrosis; Health risks; Hepatic vein; Humans; Liver; Liver diseases; Markers; Morbidity; Non-alcoholic Fatty Liver Disease; Sodium chloride; fibrosis; acute intoxication; biomarker; cirrhosis; extracellular matrix
• ISSN: 1478-3223; 1478-3231
• DOI: 10.1111/liv.15120

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. Overview of study design and main finding where PRO‐C3 increased in all study groups following a single binge drinking episode. Permission to reproduce material from other sources: Graphical created with BioRender.com reproduced with permission.