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Noninvasive determination of liver collagen content in chronic hepatitis. Multivariate regression modeling with blood chemical parameters as variables

  • Liver, Pancreas, and Biliary Tract
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Abstract

To evaluate the diagnostic utility of blood biochemical parameters in assessing degree of hepatic fibrosis, serum levels of aminoterminal type III procollagen peptide (P III P), type IV collagen (IV-collagen), 7S domain of type IV collagen (7S-collagen), and hyaluronan (HA) were measured in 54 patients with chronic viral liver disease. Liver collagen content was quantified by a computer-assisted image analysis method. Significant correlations were found between the amount of collagen in the liver and serum levels of P III P (r=0.482;P<0.02), IV-collagen (r=0.705;P<0.001), 7S-collagen (r=0.771;P<0.001), and HA (r=0.595;P<0.001). To optimize diagnostic efficacy, we applied multivariate regression analysis to to the combined results obtained for these blood biochemical parameters and some additional laboratory tests. The correlation coefficient obtained from the application of this model was 0.809. To measure the predictive value of the proposed model, we used it to estimate collagen content in an additional 16 patients with chronic liver disease and compared the estimated to the actual amount of collagen determined by direct measurement. The correlation coefficient was 0.937. These results suggest that application of the model would be useful for the assessment of collagen content of fibrotic liver.

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References

  1. Melkko J, Niemi S, Risteli L, et al. Radioimmunoassay of carboxyterminal propertide of type I procollagen. Clin Chem 1990;36:1328–1332.

    PubMed  CAS  Google Scholar 

  2. Hartman DJ, Trinchet JC, Ricard-Blum S, et al. RAdioimmunoassay of type I collagen that mainly detects degradation product in serum: Application to patients with liver disease. Clin Chem 1990;36:421–426.

    Google Scholar 

  3. Risteli J, Niemi S, Trivedi P, et al. Rapid equilibrium radioimmunoassay for the amino-terminal propeptide of human type III procollagen. Clin Chem 1988;34:715–718.

    PubMed  CAS  Google Scholar 

  4. Schuppan D, Besser M, Schwarting R, et al. Radioimmunoassay for the carboxy-terminal cross-linking domain of type IV (basement membrane) procollagen in body fluids. J Clin Invest 1986;78:241–248.

    Article  PubMed  CAS  Google Scholar 

  5. Hayasaka A, Schuppan D, Ohnishi K, et al. Serum concentration of carboxyterminal cross-linking domain of type IV (NC-1) and the aminoterminal propertide of procollagen type III (P III P) in chronic liver disease. J Hepatol 1990;10:17–22.

    Article  PubMed  CAS  Google Scholar 

  6. Kropf J, Gressner AM, Negwer A. Efficacy of serum laminin measurement for diagnosis of fibrotic disease. Clin Chem 1990;34:2026–2030.

    Google Scholar 

  7. Misaki M, Shima Y, Yano Y, et al. Basement-related and type III procollagen-related antigens in serum of patients with chronic viral liver disease. Clin Chem 1990;36:522–524.

    PubMed  CAS  Google Scholar 

  8. Robert P, Champigneulle B, Kreher I, et al. Evaluation of fibrosis in the Disse space in non-cirrhotic alcohol liver disease. Alcoholism Clin Exp Res 1989;13:176–180.

    Article  CAS  Google Scholar 

  9. Niemelae O, Risteli J, Blake JE, et al. Markers of fibrogenesis and basement membrane formation in alcoholic liver disease. Gastroenterology 1990;98:1612–1619.

    Google Scholar 

  10. Nakano H, Yamamoto Y, Ohnishi S, et al. Serum monoamine oxidase assayed with a synthetic bebzylamine derivative as substrate. Its clinical significance with special reference to hepatic fibrosis. Clin Chim Acta 1978;88:315–319.

    Article  PubMed  CAS  Google Scholar 

  11. Kuutti-Savolainen ER, Risteli J, Miettinen TA, et al. Collagen biosynthesis enzymes in serum and hepatic tissue in liver disease. 1. Prolylhydroxlase. Eur J Clin Chem 1979;9:89–95.

    CAS  Google Scholar 

  12. Kuutti-Savolainen ER, Anttinen H, Miettinen TA, et al. Collagen biosynthesis enzyms in serum and hepatic tissue in liver disease. 2. Galactosyl hydroxylysyl glucosyltransferase. Eur J Clin Invest 1979;9:97–101.

    Article  PubMed  CAS  Google Scholar 

  13. Siegel RC, Chen KH, Greenspan JS, et al. Biochemical and immunochemical study of lysyl oxidase in experimental hepatic fibrosis in the rat. Proc Natl Acad Sci USA 1978;75:2945–2949.

    Article  PubMed  CAS  Google Scholar 

  14. Engstöem-Laurent A, Lööf L, Nyberg A, et al. Increased serum levels of hyaluronate in liver disease. Hepatology 1985;5:638–642.

    Article  Google Scholar 

  15. Nyberg A, Engstöem-Laurent A, Lööf L. Serum hyluronate in primary biliary cirrhosis. A biochemical marker for progressive liver damage. Hepatology 1988;8:142–146.

    Article  PubMed  CAS  Google Scholar 

  16. León AL-D, Rojkind M. A simple micromethod for collagen and total protein determination in formalin-fixed paraffin-embedded sections. J Histochem Cytochem 1985;33:737–743.

    Google Scholar 

  17. Jimenez W, Parés A, Caballería J, et al. Measurement of fibrosis in needle liver biopsy: Evaluation of a colorimetric method. Hepatology 1985;5:815–818.

    Article  PubMed  CAS  Google Scholar 

  18. Nakabayashi H, Takamatsu S, Nakano H. A simple estimation of liver collagen content by the computed color image analyzer using Sirius red stained section (in Japanese with English abstract). Acta Hepat Jap 1993;34:212–218.

    Google Scholar 

  19. Rohde H, Vargas L, Kalbfleisch H, et al. Radioimmunoassay for type III procollagen peptide and its application to human liver disease. Eur J Clin Invest 1979;9:451–459.

    Article  PubMed  CAS  Google Scholar 

  20. Yamada S, Suou T, Kawasaki H, et al. Clinical significance of serum 7S collagen levels in various liver diseases. Clin Biochem 1992;25:467–470.

    Article  PubMed  CAS  Google Scholar 

  21. Obata K, Iwata K, Ichida T, et al. One-step sandwich enzyme immunoassay for human type IV collagen using monoclonal antibodies. Clin Chim Acta 1989;181:293–304.

    Article  PubMed  CAS  Google Scholar 

  22. Sakamoto Y, Ishiguro M, Kitagawa G. Johoryotokeigaku. Tokyo: Kyoritsu Shuppan, 1983; 42–64.

    Google Scholar 

  23. Koizumi T, Mitsutani N, Kagawa H, et al. N-acetyl-β-glucosaminidase activity in hepatic fibrosis. Lab Invest 1964; 13:752–756.

    PubMed  CAS  Google Scholar 

  24. Frei A, Zimmerman A, Weigand K. The N-terminal propeptide of collagen type III in serum reflects activity and degree of fibrosis in patients with chronic liver disease. Hepatology 1984;4:830–834.

    Article  PubMed  CAS  Google Scholar 

  25. Galambos MR, Collins DC, Galambos JT. A radioimmunoassay procedure for type III procollagen: Its use in the detection of hepatic fibrosis. Hepatology 1985;5:38–42.

    Article  PubMed  CAS  Google Scholar 

  26. Nakano H, Kawasaki T, Miyamura M, et al. Serum levels of N-terminal type III procollagen peptide in normal subjects and comparison to hepatic fibrosis. Acta Hepatol Jap 1983;24:1230–1234.

    Google Scholar 

  27. Tsutsumi M, Urashima S, Matsuda Y, et al. Change in type IV collagen content in livers of patients with alcoholic liver disease. Hepatology 1993;17:820–827.

    PubMed  CAS  Google Scholar 

  28. Ueno T, Inuzuka S, Torimura T, et al. Significance of serum type-IV collagen levels in various liver diseases. Measurement with a one-step sandwich enzyme immunoassay using monoclonal antibodies with specificity for pepsin-solubilized type-IV collagen. Scand J Gastroenterol 1992;27:513–520.

    Article  PubMed  CAS  Google Scholar 

  29. Yamada S, Kishimoto Y, Suou T, et al. Heterogeneity of antigens related to 7S domain of type IV collagen in serum: Application to patients with chronic liver disease. Clin Chim Acta 1992;212:73–78.

    Article  PubMed  CAS  Google Scholar 

  30. Timple R, Glanvill RW. The aminopeptidase of collagen. Clin Orthop 1981;158:224–242.

    Google Scholar 

  31. McCullough AJ, Stanssen WN, Wiesner RH, et al. Serum type III procollagen peptide concentrations in severe chronic active hepatitis: Relationship to cirrhosis and disease activity. Hepatology 1987;7:49–54.

    Article  PubMed  CAS  Google Scholar 

  32. Surrenti C, Casini A, Milani S, et al. Is determination of serum N-terminal procollagen type III peptide (sP III P) a marker of hepatic fibrosis? Dig Dis Sci 1987;32:705–709.

    Article  PubMed  CAS  Google Scholar 

  33. Annoni G, Colombo M, Cantaluppi MC, et al. Serum type III procollagen peptide and laminin (lam-P1) detect alcoholic hepatitis in chronic alcohol abusers. Hepatology 1989;9:693–697.

    Article  PubMed  CAS  Google Scholar 

  34. Schaffner F, Popper H. Capillarization of hepatic sinusoids in man. Gastroenterology 1963;44:239–242.

    PubMed  CAS  Google Scholar 

  35. Fukutomi T, Sakamoto S, Isobe H, et al. Clinical significance of serum levels of the 7S domain of type IV collagen in patients with primary biliary cirrhosis. J Gastroenterol Hepatol 1992;7: 596–601.

    Article  PubMed  CAS  Google Scholar 

  36. Matsumoto E, Muragaki Y, Ooshima A. Increased amount of serum type IV collagen peptide in human liver fibrosis as determined by enzyme immunoassay with monoclonal antibodies. Acta Pathol Jap 1989;39:217–223.

    CAS  Google Scholar 

  37. Eriksson S, Franser JRE, Laurent TC, et al. Endothelial cells are a site of uptake and degradation of hyaluronic acid in the liver. Exp Cell Res 1983;144:223–228.

    Article  PubMed  CAS  Google Scholar 

  38. Smedsrod B, Pertoft H, Eriksson S, et al. Studies in vitro on the uptake and degradation of sodium hyaluronate in rat liver endothelial cells. Biochem J 1984;223:617–626.

    PubMed  CAS  Google Scholar 

  39. Ueno T, Inuzuka S, Torimura T, et al. Serum hyaluronate reflects hepatic sinusoidal capillarization. Gastroenterology 1993;105: 475–481.

    PubMed  CAS  Google Scholar 

  40. Deaciuc IV, Bagby GJ, Lang CH, et al. Hyaluronic acid uptake by the isolated, perfused rat liver: An index of hepatic sinusoidal endothelial cell function. Hepatology 1993;17:266–272.

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Clinico-Laboratory Diagnostics, Nara Medical University, 840, Shijo, 634, Kashihara, Nara, Japan

    Seigo Takamatsu, Hitomi Nakabayashi, Yasuyuki Okamoto & Hiroshi Nakano

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  1. Seigo Takamatsu
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  2. Hitomi Nakabayashi
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  3. Yasuyuki Okamoto
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  4. Hiroshi Nakano
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Takamatsu, S., Nakabayashi, H., Okamoto, Y. et al. Noninvasive determination of liver collagen content in chronic hepatitis. Multivariate regression modeling with blood chemical parameters as variables. J Gastroenterol 32, 355–360 (1997). https://doi.org/10.1007/BF02934493

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  • DOI: https://doi.org/10.1007/BF02934493

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