Higher levels of serum aminoterminal type III procollagen peptide, and laminin in alcoholic than in nonalcoholic cirrhosis of equal severity.
In vitro models have shown that metabolites of ethanol (acetaldehyde and lactate) stimulate collagen synthesis, thereby, suggesting that they may be important as fibrogenic mediators. The relevance of these findings for fibrogenesis in the human liver in vivo, however, has not as yet been demonstrated. Serum markers for collagen (PIIINP, using radioimmunoassays employing polyclonal antibodies and Fab-fragments (PIIINP-Fab), respectively) and basement membrane (laminin) metabolism were therefore investigated in 25 alcoholic cirrhotics (Pugh-Score: 6.7 +/- 1.9 S.D.) and in 19 comparable nonalcoholic cirrhotics (Pugh-Score: 6.3 +/- 1.5, n.s.) with only slight evidence for inflammation: GOT 28 +/- 22 vs. 24 +/- 21 U/l; GPT 24 +/- 23 vs. 31 +/- 28 U/l; gamma-globulins 24 +/- 8 vs. 22 +/- 5%, respectively (all n.s.). Severity of the disease was assessed by quantitative liver function tests. Levels of PIIINP, PIIINP-Fab and laminin measured by RIA were 21 +/- 19 micrograms/l, 90 +/- 42 micrograms/l and 2.5 +/- 0.8 U/ml in alcoholic cirrhosis and 10 +/- 6 micrograms/l, 61 +/- 10 micrograms/l and 1.9 +/- 0.4 U/ml in nonalcoholic cirrhosis, respectively (all p less than 0.01). Differences on PIIINP and PIIINP-Fab remained significant even after accurate matching for galactose elimination capacity, aminopyrine breath test and hepatic sorbitol clearance. Laminin levels were higher in alcoholic cirrhosis only after matching for the hepatic sorbitol clearance (p less than 0.01). The higher levels of serum markers for collagen and basement membrane metabolism in alcoholic vs. nonalcoholic patients with cirrhosis at equal severity of the disease and with only minimal signs of inflammation may be the clinical reflection of a specific fibrogenic effect of ethanol metabolites.
Lotterer
E
E
Department of Clinical Pharmacology, University of Goettingen, Federal Republic of Germany.
Gressner
A M
AM
Kropf
J
J
Grobe
E
E
von Knebel
D
D
Bircher
J
J
D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D005260:Female; D005690:Galactose / Q000493:pharmacokinetics; D006801:Humans; D007797:Laminin / Q000097:blood*; D008103:Liver Cirrhosis / Q000097:blood* / Q000503:physiopathology; D008104:Liver Cirrhosis, Alcoholic / Q000097:blood* / Q000503:physiopathology; D008297:Male; D008657:Metabolic Clearance Rate / Q000502:physiology; D008875:Middle Aged; D010446:Peptide Fragments / Q000097:blood*; D011347:Procollagen / Q000097:blood*; D011863:Radioimmunoassay; D012720:Severity of Illness Index; D013012:Sorbitol / Q000493:pharmacokinetics
D015415:Biomarkers; D007797:Laminin; D010446:Peptide Fragments; D011347:Procollagen; C041876:procollagen Type III-N-terminal peptide; D013012:Sorbitol; D005690:Galactose