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


CONCLUSIONS
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.
Koivisto
Heidi
H
Department of Laboratory Medicine and Medical Research Unit, Seinäjoki Central Hospital, and University of Tampere, FIN-60220 Seinäjoki, Finland.
Hietala
Johanna
J
Niemelä
Onni
O
D000704:Analysis of Variance; D015415:Biomarkers / Q000097:blood*; D016207:Cytokines / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D008108:Liver Diseases, Alcoholic / Q000097:blood*; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000097:blood; D011347:Procollagen / Q000097:blood; D012372:ROC Curve; D012680:Sensitivity and Specificity
D015415:Biomarkers; D016207:Cytokines; D010446:Peptide Fragments; D011347:Procollagen; C047202:procollagen Type I N-terminal peptide; C041876:procollagen Type III-N-terminal peptide; C042813:procollagen type I carboxy terminal peptide