Original Contribution
The American Journal of Gastroenterology (2007) 102, 773–779; doi:10.1111/j.1572-0241.2006.01036.x
An Inverse Relationship Between Markers of Fibrogenesis and Collagen Degradation in Patients With or Without Alcoholic Liver Disease
Heidi Koivisto MSci, Johanna Hietala MSci and Onni Niemelä MD, PhD
Department of Laboratory Medicine and Medical Research Unit, Seinäjoki Central Hospital, and University of Tampere, FIN-60220 Seinäjoki, Finland
Correspondence: Onni Niemelä, MD, PhD, Department of Laboratory Medicine and Medical Research Unit, Seinäjoki Central Hospital, FIN-60220 Seinäjoki, Finland.
Received 1 August 2006; Accepted 19 October 2006.
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 (
-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 -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 -CTx correlated negatively with serum PIIINP and proinflammatory cytokines (IL-2, IL-6, IL-8, TNF-
), and positively with anti-inflammatory cytokines (IL-1, TGF-), whereas serum PIIINP correlated positively with these proinflammatory cytokines and negatively with the anti-inflammatory cytokines. Calculation of PIIINP/-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.
