Gastroenterologia Japonica

, Volume 26, Issue 4, pp 465–471 | Cite as

Hepatic collagen synthesis in patients with alcoholic and nonalcoholic liver disease

  • Yoshikazu Murawaki
  • Sciichi Kato
  • Chisato Hirayama
Liver, Pancreas and Biliary Tract


To examine the synthesis of hepatic collagen in patients with alcoholic and nonalcoholic liver disease, liver biopsy specimens were incubated in vitro with14C-proline, and the radioactivity of the newly synthesized protein-bound14C-hydroxyproline was measured. Mean hepatic collagen synthesis was 0.82±0.19 pmole of14C-hydroxyproline/g liver/2 h in control subjects without histological liver fibrosis. Hepatic collagen synthesis was increased in patients with alcoholic and nonalcoholic liver diseases, especially in those with alcoholic fibrosis, alcoholic cirrhosis and chronic active hepatitis. The raised collagen synthesis in alcoholic liver disease rapidly decreased after withdrawal of alcohol. When alcoholic liver disease were compared with nonalcoholic liver disease, there was no significant difference in hepatic collagen synthesis.

Key words

alcoholic liver disease hepatic collagen synthesis nonalcoholic liver disease 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Hirayama C, Kimura N, Irisa T, et al: Hepatic collagen and non-collagen protein synthesis in man with and without liver disease. Clin Chim Acta 1968;21:49–54.PubMedCrossRefGoogle Scholar
  2. 2.
    Hirayama C, Kimura N, Masuya T: Anabolic steroid effect on hepatic protein synthesis in patients with liver cirrhosis. Digestion 1970;3:41–47.PubMedGoogle Scholar
  3. 3.
    Chen TSN, Leevy CM: Collagen biosynthesis in liver disease of the alcoholic. J Lab Clin Med 1975;85:103–112.PubMedGoogle Scholar
  4. 4.
    Mann SW, Fuller GC, Rodil JV, et al: Hepatic prolyl hydrox-ylase and collagen synthesis in patients with alcoholic liver disease. Gut 1979;20:825–832.PubMedCrossRefGoogle Scholar
  5. 5.
    Kato S, Murawaki Y, Hirayama C: Effects of ethanol feeding on hepatic collagen synthesis and degradation in rats. Res Commun Chem Pathol Pharmacol 1985;47:163–180.PubMedGoogle Scholar
  6. 6.
    Koda M, Murawaki Y, Hirayama C: Free and small peptide-bound (14C)Hydroxyproline synthesis in rat liver in vitro in CCl4-induced hepatic fibrosis. Biochem Biophys Res Com-mun 1988;151:1128–1135.CrossRefGoogle Scholar
  7. 7.
    Rojkind M, Gonzalez E: An improved method for determining specific radioactivities of proline-l4C and hydroxyproline-14C in collagen and in noncollagenous proteins. Analy Biochem 1974;54:l-7.Google Scholar
  8. 8.
    Murawaki Y, Kato S, Koda M et al: Hepatic collagen degrada-tion system in early stage of ethanol-induced liver injury. In: C Hirayama, KI Kivirikko, eds. Pathobiology of hepatic fibrosis. Excerpta Medica, Amsterdam. 1985;121–129.Google Scholar
  9. 9.
    Knodell RG, Ishak KG, Black WC, et al: Formulation and ap-plication of a numerical scoring system for assessing histological activity in asymptomatic chronic active hepatitis. Hepatology 1981;l:431–435.CrossRefGoogle Scholar
  10. 10.
    Mortimore GE, Woodside KH, Henry JE: Compartmentation of free valine and its relation to protein turnover in perfused rat liver. J Biol Chem 1972;247:2776–2784.PubMedGoogle Scholar
  11. 11.
    Airhart J, Vidrich A, Khairallah EA: Compartmentation of free amino acids for protein synthesis in rat liver. Biochem J 1974;140:539–548.PubMedGoogle Scholar
  12. 12.
    Kershemobich D, Fierro FJ, Rojkind M: The relationship be-tween the free pool of proline and collagen content in human liver dirrhosis. J Clin Invest 1970;49:2246–2249.Google Scholar
  13. 13.
    Sakakibara K, Saito M, Ueda M, et al: Native collagen forma-tion by liver parenchymal cells in culture. Nature 1976;262:316–318.CrossRefGoogle Scholar
  14. 14.
    Diegelmann RF, Guzellian PS, Gay R, et al: Collagen formation by the hepatocytes in primary monlayer culture and in vivo. Science 1983;219:1343–1344.PubMedCrossRefGoogle Scholar
  15. 15.
    Tseng SCG, Lee PC, Ells PF, et al: Collagen production by rat hepatocytes and sinusoidal cells in primary monolayer culture. Hepatology 1982;2:13–18.PubMedCrossRefGoogle Scholar
  16. 16.
    Tseng SCG, Smuckler EA, Stern R: Types of collagen synthe-sized by normal rat liver hepatocytes in primary culture. Hep-atology 1983;3:955–963.Google Scholar
  17. 17.
    Hata R, Ninomiya U, Sano J, et al: Activation of collagen syn-thesis in primary culture of rat liver parenchymal cells (Hepato-cytes). J Cell Physiol1985;122:333–342.PubMedCrossRefGoogle Scholar
  18. 18.
    Friedman SL, Roll FJ, Boyles J, et al: Hepatic lipocytes: The principal collagen-producing cells of normal rat liver. Proc Natl Acad Sci USA 1985;82:8681–8685.PubMedCrossRefGoogle Scholar
  19. 19.
    Kawase T, Shiratori Y, Sugimoto T: Collagen production by rat liver fat-storing cells in primary culture. Exp Cell Biol 1986;54: 183–192.PubMedGoogle Scholar
  20. 20.
    Hirayama C, Morotomi K, Hiroshige K: Quantative and metabolic changes of hepatic collagcns in rats after carbon tetrachloride poisoning. Biochem J 1970;118:229–232.PubMedGoogle Scholar
  21. 21.
    Kimura K: Clinical and experimental studies on liver prolyl hydroxylase at various atages of liver disease. J Nara Med Ass 1980;31:76–89. (in Japanese)Google Scholar
  22. 22.
    Annoni G, Weiner FR, Colombo J, et al: albumin and collagen gene regulation in alcohol- and virus-induced human liver disease. Gastroenterology 1990;98:197–202.PubMedGoogle Scholar
  23. 23.
    Mezey E, Protter JJ, Maddrey WC: Hepatic collagen proline hydroxylase activity in alcoholic liver disease. Clin Chim Acta 1976;68:313–320.PubMedCrossRefGoogle Scholar
  24. 24.
    Stern R, Tseng SCG: The fibrosis of chronic alcoholic liver dis-ease. In: PD Berk, TC Chalmers, ets. Frontiers in Liver Dis-ease. Thieme-Stratton, New York 1981:144–155.Google Scholar
  25. 25.
    Arai M, Leo MA, Nakano M, et al: Biological and morpho-logical alteration of baboon hepatic mitochondria after chronic ethanol consumption. Hepatology 1984;4:165–174.PubMedCrossRefGoogle Scholar
  26. 26.
    Videla LA, Valenzuela A: Alcohol ingestion, liver glutathione and lipoperoxidation: Metabolic interrelations and pathologi-cal implications. Life Sci 1982;31:2395–2407.PubMedCrossRefGoogle Scholar
  27. 27.
    Hirayama C, Kishimoto Y, Wakushima T, et al: Mechanism of the protective action of thiol compounds in ethanol-induced liver injury. Biochem Pharmacol 1983;32:321–325.PubMedCrossRefGoogle Scholar
  28. 28.
    Hussain MZ, Watson JA, Bhathgar Rs: Increased prolyl hy-droxylase activity and collagen synthesis in hepatocyte cultures exposed to Superoxide. Hepatology 1987;7:502–507.PubMedCrossRefGoogle Scholar

Copyright information

© The Japanese Society of Gastroenterology 1991

Authors and Affiliations

  • Yoshikazu Murawaki
    • 1
  • Sciichi Kato
    • 1
  • Chisato Hirayama
    • 1
  1. 1.Second Department of Internal MedicineTottori University School of MedicineYonagoJapan

Personalised recommendations