An inverse relationship between markers of fibrogenesis and collagen degradation in patients with or without alcoholic liver disease.

Abstract

OBJECTIVES:

Excessive deposition of collagen leading to cirrhosis is a major complication of alcohol abuse. However, the mechanisms behind the accumulation of the extracellular matrix proteins are poorly understood.

METHODS:

We measured serum markers of collagen degradation (beta-CTx), fibrogenesis (PINP, PIIINP), and pro- and anti-inflammatory cytokines from 84 male heavy drinkers, who were either with (N = 52) or without (N = 32) clinical or histological signs of alcoholic liver disease (ALD), and from 20 healthy nonalcoholic controls.

RESULTS:

Serum beta-CTx levels in ALD patients were significantly lower than in healthy controls or in the alcoholics without liver disease, while PINP and PIIINP, reflecting type I and type III collagen synthesis, respectively, were significantly increased. The alcoholics without liver disease showed values, that were not significantly different from those of healthy controls. Serum beta-CTx correlated negatively with serum PIIINP and proinflammatory cytokines (IL-2, IL-6, IL-8, TNF-alpha), and positively with anti-inflammatory cytokines (IL-1, TGF-beta), whereas serum PIIINP correlated positively with these proinflammatory cytokines and negatively with the anti-inflammatory cytokines. Calculation of PIIINP/beta-CTx ratio was found to yield an excellent sensitivity (94%) and specificity (98%) in differentiating the alcoholics with liver disease.

CONCLUSION:

The present findings indicate a positive relationship between markers of collagen biosynthesis and proinflammatory cytokines, and a negative relationship between these markers and a marker of collagen degradation and anti-inflammatory cytokines, suggesting that a disturbed balance in these cellular responses may facilitate fibrogenesis and play a pivotal role in the pathogenesis of ALD. These findings should also be implicated in the development of noninvasive tools for discriminating individuals at risk for fibrogenesis.

• Authors: Heidi Koivisto, Johanna Hietala, Onni Niemelä
• Journal: The American journal of gastroenterology (Am J Gastroenterol) Vol. 102 Issue 4 Pg. 773-9 (Apr 2007) ISSN: 0002-9270 [Print] United States
• PMID: 17222322 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers
• Cytokines
• Peptide Fragments
• Procollagen
• procollagen Type I N-terminal peptide
• procollagen Type III-N-terminal peptide
• procollagen type I carboxy terminal peptide

Topics

• Analysis of Variance
• Biomarkers (blood)
• Cytokines (blood)
• Enzyme-Linked Immunosorbent Assay
• Humans
• Liver Diseases, Alcoholic (blood)
• Liver Function Tests
• Male
• Middle Aged
• Peptide Fragments (blood)
• Procollagen (blood)
• ROC Curve
• Sensitivity and Specificity