Skip to main content
PMC home page
Gut logoLink to Gut
. 1999 Mar;44(3):417–423. doi: 10.1136/gut.44.3.417

Elevated carboxy terminal cross linked telopeptide of type I collagen in alcoholic cirrhosis: relation to liver and kidney function and bone metabolism

S Moller 1, M Hansen 1, J Hillingso 1, J Jensen 1, J Henriksen 1
PMCID: PMC1727409  PMID: 10026331

Abstract

BACKGROUND—The carboxy terminal cross linked telopeptide of type I collagen (ICTP) has been put forward as a marker of bone resorption. Patients with alcoholic liver disease may have osteodystrophy. 
AIMS—To assess circulating and regional concentrations of ICTP in relation to liver dysfunction, bone metabolism, and fibrosis. 
METHODS—In 15 patients with alcoholic cirrhosis and 20 controls, hepatic venous, renal venous, and femoral arterial concentrations of ICTP, and bone mass and metabolism were measured. 
RESULTS—Circulating ICTP was higher in patients with cirrhosis than in controls. No overall significant hepatic disposal or production was found in the patient or control groups but slightly increased production was found in a subset of patients with advanced disease. Significant renal extraction was observed in the controls, whereas only a borderline significant extraction was observed in the patients. Measurements of bone mass and metabolism indicated only a mild degree of osteodystrophy in the patients with cirrhosis. ICTP correlated significantly in the cirrhotic patients with hepatic and renal dysfunction and fibrosis, but not with measurements of bone mass or metabolism. 
CONCLUSIONS—ICTP is highly elevated in patients with cirrhosis, with no detectable hepatic net production or disposal. No relation between ICTP and markers of bone metabolism was identified, but there was a relation to indicators of liver dysfunction and fibrosis. As the cirrhotic patients conceivably only had mild osteopenia, the elevated ICTP in cirrhosis may therefore primarily reflect liver failure and hepatic fibrosis. 



Keywords: bone mineral density; carboxy terminal cross linked telopeptide of type I collagen; chronic liver disease; fibrosis; hepatic osteodystrophy; portal hypertension

Full Text

The Full Text of this article is available as a PDF (127.4 KB).

Figure 1 .

Figure 1

Open in a new tab

Circulating concentrations of ICTP (A), PICP (B), and PIIINP (C) in 15 patients with alcoholic cirrhosis and 20 control subjects. Bars represent medians and the grey areas are the normal ranges. 


Figure 2 .

Figure 2

Open in a new tab

Concentrations of ICTP in the femoral artery and renal vein in patients with cirrhosis (A; n=13) and subjects with normal liver function (B; n=19). In subjects with normal liver function there was a significant renal extraction of ICTP of 0.15 (p<0.001), whereas the renal extraction of 0.13 in the cirrhotic patients was only of borderline significance (p=0.09). 


Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Chen C. C., Wang S. S., Jeng F. S., Lee S. D. Metabolic bone disease of liver cirrhosis: is it parallel to the clinical severity of cirrhosis? J Gastroenterol Hepatol. 1996 May;11(5):417–421. doi: 10.1111/j.1440-1746.1996.tb00284.x. [DOI] [PubMed] [Google Scholar]
  2. Compston J. E. Hepatic osteodystrophy: vitamin D metabolism in patients with liver disease. Gut. 1986 Sep;27(9):1073–1090. doi: 10.1136/gut.27.9.1073. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Diamond T. H., Stiel D., Lunzer M., McDowall D., Eckstein R. P., Posen S. Hepatic osteodystrophy. Static and dynamic bone histomorphometry and serum bone Gla-protein in 80 patients with chronic liver disease. Gastroenterology. 1989 Jan;96(1):213–221. [PubMed] [Google Scholar]
  4. Diamond T., Stiel D., Lunzer M., Wilkinson M., Posen S. Ethanol reduces bone formation and may cause osteoporosis. Am J Med. 1989 Mar;86(3):282–288. doi: 10.1016/0002-9343(89)90297-0. [DOI] [PubMed] [Google Scholar]
  5. Diamond T., Stiel D., Lunzer M., Wilkinson M., Roche J., Posen S. Osteoporosis and skeletal fractures in chronic liver disease. Gut. 1990 Jan;31(1):82–87. doi: 10.1136/gut.31.1.82. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Ebeling P. R., Peterson J. M., Riggs B. L. Utility of type I procollagen propeptide assays for assessing abnormalities in metabolic bone diseases. J Bone Miner Res. 1992 Nov;7(11):1243–1250. doi: 10.1002/jbmr.5650071118. [DOI] [PubMed] [Google Scholar]
  7. Elomaa I., Virkkunen P., Risteli L., Risteli J. Serum concentration of the cross-linked carboxyterminal telopeptide of type I collagen (ICTP) is a useful prognostic indicator in multiple myeloma. Br J Cancer. 1992 Aug;66(2):337–341. doi: 10.1038/bjc.1992.266. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Epstein M. Hepatorenal syndrome: emerging perspectives of pathophysiology and therapy. J Am Soc Nephrol. 1994 Apr;4(10):1735–1753. doi: 10.1681/ASN.V4101735. [DOI] [PubMed] [Google Scholar]
  9. Eriksen E. F., Charles P., Melsen F., Mosekilde L., Risteli L., Risteli J. Serum markers of type I collagen formation and degradation in metabolic bone disease: correlation with bone histomorphometry. J Bone Miner Res. 1993 Feb;8(2):127–132. doi: 10.1002/jbmr.5650080202. [DOI] [PubMed] [Google Scholar]
  10. Fabris C., Falleti E., Federico E., Toniutto P., Pirisi M. A comparison of four serum markers of fibrosis in the diagnosis of cirrhosis. Ann Clin Biochem. 1997 Mar;34(Pt 2):151–155. doi: 10.1177/000456329703400203. [DOI] [PubMed] [Google Scholar]
  11. Hansen M., Florescu A., Stoltenberg M., Pødenphant J., Pedersen-Zbinden B., Hørslev-Petersen K., Hyldstrup L., Lorenzen I. Bone loss in rheumatoid arthritis. Influence of disease activity, duration of the disease, functional capacity, and corticosteroid treatment. Scand J Rheumatol. 1996;25(6):367–376. doi: 10.3109/03009749609065648. [DOI] [PubMed] [Google Scholar]
  12. Hassager C., Jensen L. T., Johansen J. S., Riis B. J., Melkko J., Pødenphant J., Risteli L., Christiansen C., Risteli J. The carboxy-terminal propeptide of type I procollagen in serum as a marker of bone formation: the effect of nandrolone decanoate and female sex hormones. Metabolism. 1991 Feb;40(2):205–208. doi: 10.1016/0026-0495(91)90176-w. [DOI] [PubMed] [Google Scholar]
  13. Hassager C., Jensen L. T., Pødenphant J., Thomsen K., Christiansen C. The carboxy-terminal pyridinoline cross-linked telopeptide of type I collagen in serum as a marker of bone resorption: the effect of nandrolone decanoate and hormone replacement therapy. Calcif Tissue Int. 1994 Jan;54(1):30–33. doi: 10.1007/BF00316286. [DOI] [PubMed] [Google Scholar]
  14. Henriksen J. H., Grønbaek M., Møller S., Bendtsen F., Becker U. Carbohydrate deficient transferrin (CDT) in alcoholic cirrhosis: a kinetic study. J Hepatol. 1997 Feb;26(2):287–292. doi: 10.1016/s0168-8278(97)80043-8. [DOI] [PubMed] [Google Scholar]
  15. Henriksen J. H., Ring-Larsen H. Hepatorenal disorders: role of the sympathetic nervous system. Semin Liver Dis. 1994 Feb;14(1):35–43. doi: 10.1055/s-2007-1007296. [DOI] [PubMed] [Google Scholar]
  16. Henriksen J. H., Ring-Larsen H., Kanstrup I. L., Christensen N. J. Splanchnic and renal elimination and release of catecholamines in cirrhosis. Evidence of enhanced sympathetic nervous activity in patients with decompensated cirrhosis. Gut. 1984 Oct;25(10):1034–1043. doi: 10.1136/gut.25.10.1034. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Henriksen J. H., Winkler K. Hepatic blood flow determination. A comparison of 99mTc-diethyl-IDA and indocyanine green as hepatic blood flow indicators in man. J Hepatol. 1987 Feb;4(1):66–70. doi: 10.1016/s0168-8278(87)80011-9. [DOI] [PubMed] [Google Scholar]
  18. Idilman R., de Maria N., Uzunalimoglu O., van Thiel D. H. Hepatic osteodystrophy: a review. Hepatogastroenterology. 1997 Mar-Apr;44(14):574–581. [PubMed] [Google Scholar]
  19. Kalef-Ezra J. A., Merkouropoulos M. H., Challa A., Hatzikonstantinou J., Karantanas A. H., Tsianos E. V. Amount and composition of bone minerals in chronic liver disease. Dig Dis Sci. 1996 May;41(5):1008–1013. doi: 10.1007/BF02091545. [DOI] [PubMed] [Google Scholar]
  20. Lund B., Lund B., Sørensen O. H. Measurement of circulating 1,25-dihydroxyvitamin D in man. Changes in serum concentrations during treatment with 1 alpha-hydroxycholecalciferol. Acta Endocrinol (Copenh) 1979 Jun;91(2):338–350. doi: 10.1530/acta.0.0910338. [DOI] [PubMed] [Google Scholar]
  21. Lund B., Sørensen O. H. Measurement of 25-hydroxyvitamin D in serum and its relation to sunshine, age and vitamin D intake in the Danish population. Scand J Clin Lab Invest. 1979 Feb;39(1):23–30. doi: 10.3109/00365517909104935. [DOI] [PubMed] [Google Scholar]
  22. Melkko J., Niemi S., Risteli L., Risteli J. Radioimmunoassay of the carboxyterminal propeptide of human type I procollagen. Clin Chem. 1990 Jul;36(7):1328–1332. [PubMed] [Google Scholar]
  23. Monegal A., Navasa M., Guañabens N., Peris P., Pons F., Martinez de Osaba M. J., Rimola A., Rodés J., Muñoz-Gómez J. Osteoporosis and bone mineral metabolism disorders in cirrhotic patients referred for orthotopic liver transplantation. Calcif Tissue Int. 1997 Feb;60(2):148–154. doi: 10.1007/s002239900205. [DOI] [PubMed] [Google Scholar]
  24. Parfitt A. M., Simon L. S., Villanueva A. R., Krane S. M. Procollagen type I carboxy-terminal extension peptide in serum as a marker of collagen biosynthesis in bone. Correlation with Iliac bone formation rates and comparison with total alkaline phosphatase. J Bone Miner Res. 1987 Oct;2(5):427–436. doi: 10.1002/jbmr.5650020510. [DOI] [PubMed] [Google Scholar]
  25. Ricard-Blum S., Bresson-Hadni S., Guerret S., Grenard P., Volle P. J., Risteli L., Grimaud J. A., Vuitton D. A. Mechanism of collagen network stabilization in human irreversible granulomatous liver fibrosis. Gastroenterology. 1996 Jul;111(1):172–182. doi: 10.1053/gast.1996.v111.pm8698196. [DOI] [PubMed] [Google Scholar]
  26. Ricard-Blum S., Chossegros P., Guerret S., Trepo C., Grimaud J. A., Chevallier M. The carboxy-terminal cross-linked telopeptide of type I collagen (ICTP) is a potential serum marker of ongoing liver fibrosis. Clin Chim Acta. 1996 Apr 30;248(2):187–195. doi: 10.1016/0009-8981(95)06253-x. [DOI] [PubMed] [Google Scholar]
  27. Rico H. Alcohol and bone disease. Alcohol Alcohol. 1990;25(4):345–352. [PubMed] [Google Scholar]
  28. Ring-Larsen H., Hesse B., Henriksen J. H., Christensen N. J. Sympathetic nervous activity and renal and systemic hemodynamics in cirrhosis: plasma norepinephrine concentration, hepatic extraction, and renal release. Hepatology. 1982 May-Jun;2(3):304–310. doi: 10.1002/hep.1840020303. [DOI] [PubMed] [Google Scholar]
  29. Risteli J., Elomaa I., Niemi S., Novamo A., Risteli L. Radioimmunoassay for the pyridinoline cross-linked carboxy-terminal telopeptide of type I collagen: a new serum marker of bone collagen degradation. Clin Chem. 1993 Apr;39(4):635–640. [PubMed] [Google Scholar]
  30. Risteli J., Niemi S., Trivedi P., Mäentausta O., Mowat A. P., Risteli L. Rapid equilibrium radioimmunoassay for the amino-terminal propeptide of human type III procollagen. Clin Chem. 1988 Apr;34(4):715–718. [PubMed] [Google Scholar]
  31. Rublo M., Caballería J., Deulofeu R., Caballería L., Gassó M., Parés A., Vilella A., Giménez A., Ballesta A., Rodés J. Carbohydrate-deficient transferrin as a marker of alcohol consumption in male patients with liver disease. Alcohol Clin Exp Res. 1997 Aug;21(5):923–927. doi: 10.1111/j.1530-0277.1997.tb03859.x. [DOI] [PubMed] [Google Scholar]
  32. Sampson H. W. Alcohol, osteoporosis, and bone regulating hormones. Alcohol Clin Exp Res. 1997 May;21(3):400–403. doi: 10.1111/j.1530-0277.1997.tb03782.x. [DOI] [PubMed] [Google Scholar]
  33. Trinchet J. C., Hartmann D. J., Pateron D., Laarif M., Callard P., Ville G., Beaugrand M. Serum type I collagen and N-terminal peptide of type III procollagen in chronic hepatitis. Relationship to liver histology and conventional liver tests. J Hepatol. 1991 Mar;12(2):139–144. doi: 10.1016/0168-8278(91)90929-6. [DOI] [PubMed] [Google Scholar]

Articles from Gut are provided here courtesy of BMJ Publishing Group

RESOURCES