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Connective tissue components of the normal and fibrotic human liver

II. Clinical aspects

Das Bindegewebe der normalen und fibrotischen menschlichen Leber

II: Klinische Aspekte

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Summary

In this second part, clinical aspects of connective tissue metabolism in the liver will be described and two main aspects considered. The first is the possibility to monitor the activity of fibrosis by the use of metabolites and enzymes of connective tissue metabolism. In recent studies the qualification for this purpose of enzymes such as procollagen prolyl hydroxylase and lysosomal N-Acetyl-β-glucosaminidase and the N-terminal peptide of procollagen type III has been tested. The serum activities or concentrations of these substances in patients with chronic active liver diseases increase in due relation to the histologically estimated activity of liver fibrosis.

The second aspect deals with therapeutic approaches to fibrosis in the liver by using connective tissue specific agents. So far none of the antifibrotic substances such as proline analogues, colchicine, lathyrogens and penicillamine has been used in longer-term antifibrotic treatment.

Zusammenfassung

Im zweiten Teil dieser Übersicht werden die klinischen Aspekte des Bindegewebsstoffwechsels in der fibrotischen Leber dargestellt. Besonders eingegangen wird auf die Möglichkeit, die Aktivität der Leberfibrose durch neuere Laborproben zur Erfassung von Enzymen und Metaboliten des Bindegewebsstoffwechsels zu verfolgen. Für diesen Zweck geeignet erscheinen die Enzyme Prokollagen-Prolyl-Hydroxylase, die lysosomale N-Acetyl-β-Glucosaminidase und das N-terminale Peptid vom Prokollagen Typ III. Die Aktivitäten bzw. Konzentrationen im Serum von Patienten mit chronisch aktiven Leberkrankheiten korrelieren gut mit der histologisch geschätzten Aktivität der Fibrose im punktierten Lebergewebe der gleichen Patienten. Weiterhin werden die therapeutischen Versuche zur Behandlung der Leberfibrose mit bindegewebsspezifischen Substanzen besprochen.

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References

  1. Alexander M, Wille G (1974) D-Penicillamin Therapie bei Leberkrankheiten. Münch Med Wochenschr 116:211–216

    Google Scholar 

  2. Ackermann W, Pott G, Voss B, Müller KM, Gerlach U (1981) Concentration of procollagen III peptide and activity of N-Acetyl-β-glucosaminidase in diagnosis of the activity of liver fibrosis in patients with chronic active liver diseases. Clin Chim Acta 112:365–369

    Google Scholar 

  3. Anthony PP, Ishak KG, Nayak NC, Poulsen HE, Scheuer PJ, Sobin LH (1977) The morphology of cirrhosis: definition, nomenclature, and classification. Bull WHO 55:521–540

    Google Scholar 

  4. Baggenstoss AH (1975) Morphological features: Their usefullness in the diagnosis, prognosis and management of cirrhosis. Clin Gastroenterol 2:227–264

    Google Scholar 

  5. Bianchi L (1970) Zum Problem der Leberfibrose. Schweiz Med Wochenschr 100:1214–1215

    Google Scholar 

  6. Castor CW, Whitney L (1978) Connective tissue activation XIII. Stimulation of sulfated glycosaminoglycan synthesis in human connective tissue cells by peptide mediators from lymphocytes and platelets. J Lab Clin Med 16:811–821

    Google Scholar 

  7. Chen TSN, Leevy CM (1975) Collagen biosynthesis in liver disease of the alcoholic. J Lab Clin Med 85:103–112

    Google Scholar 

  8. Cutroneo KR, Stassen FLH, Cardinale GJ (1975) Antiinflammatory steroids and collagen metabolism: Glucocorticoid-mediated decrease of prolylhydroxylase. Mol Pharmacol 11:44–51

    Google Scholar 

  9. Chvapil M (1977) Pharmacology of fibrosis: Definition, limits and perspectives. Life Sci 16:1345–1362

    Google Scholar 

  10. Feinman L, Lieber CS (1972) Hepatic collagen metabolism: effect of alcohol consumption in rats and baboons. Science 176:795

    Google Scholar 

  11. Fuller, GC, Nolan JC, Fink S, Rodil JV (1976) Prolylhydroxylase activity in normal and diseased human liver. Proc Soc Exp Biol Med 151:61–64

    Google Scholar 

  12. Galambos JT, Shapira R (1973) Natural history of alcoholic hepatitis. IV. Glycosaminoglycuronans and collagen in the hepatic connective tissue. J Clin Invest 52:2952–2962

    Google Scholar 

  13. Galambos JT, Hollingsworth MA, Falek A, Warren WD, McCain JR (1977) The rate of synthesis of glycosaminoglycans and collagen by fibroblasts cultured from adult human liver biopsies. J Clin Invest 60:107–111

    Google Scholar 

  14. McGee JO'D, O'Hara RP, Patrick RS (1973) Stimulation of the collagen biosynthetic pathway by factors isolated from experimentally-injured liver. Nature 248:121–123

    Google Scholar 

  15. McGee JO'D, Patrick RS, Rodger MC, Luty CM (1974) Collagen proline hydroxylase activity and S-35 sulphate uptake in human liver biopsies. Gut 15:260–267

    Google Scholar 

  16. Gerok W, Sickinger K (1975) Arzneimittel und Leber. Schattauer, Stuttgart New York

    Google Scholar 

  17. Gottesmann Th, Moeschlin S (1978) Langzeiterfolge der immunsuppressiven Therapie bei der chronisch-aggressiven Heptatitis. D Med Wochenschr 103:1989–1993

    Google Scholar 

  18. Hahn E, Wick G, Pencev D, Timpl R (1980) Distribution of basement membrane proteins in normal and fibrotic human liver: collagen type IV, laminin and fibronectin. Gut 21:63–71

    Google Scholar 

  19. Hahn EG, Ott U, Martini GA (1980) Die Leberfibrose, Teil 1 und 2. Z. Gastroenterologie 18:453–469; 507–523

    Google Scholar 

  20. Hahn EG, Martini GA (1980). Diagnostische Parameter der Kollagenbiosynthese. Internist 21:195–201

    Google Scholar 

  21. Harris ED, Krane SM (1974) Collagenases (first of three parts). N Engl J Med 291:557–563

    Google Scholar 

  22. Hasebe K (1968) Biochemical studies on synovial fluid. I. Mucopolysaccharase activities in synovial fluid of rheumatoid arthritis. Fukushima J Med Sci 15:35–44

    Google Scholar 

  23. Hauss WH, Junge-Hülsing G, Manitz G, König F (1963) Über die Aktivität des Mesenchymstoffwechsels bei krankhaften Prozessen in der Leber. Dtsch Med Wochenschr 88:811–814

    Google Scholar 

  24. Hickman S, Neufeld EF (1972) A hypothesis for I cell disease: Defective hydrolases that do not enter lysosomes. Biochem Biophys Res Commun 49:992–999

    Google Scholar 

  25. Hirayama C, Yoshkikawa T, Tada H (1961) Serum galactosamine. A diagnostic index of liver fibrosis in liver disease. Lancet I:532

    Google Scholar 

  26. Hirayama C, Kawabe M, Morotomi I, Kimura N (1972) Serum collagen-like protein in patients with chronic liver diseases. Digestion 5:31–39

    Google Scholar 

  27. Hutterer F, Eisenstadt M, Rubin E (1970) Turnover of hepatic collagen in reversible and irreversible fibrosis. Experientia 26:244–245

    Google Scholar 

  28. Kuutti-Savolainen ER, Risteli J, Miettinen TA, Kivirikko KI (1979) Collagen biosynthesis enzymes in serum and hepatic tissue in liver disease. I. Prolylhydroxylase. Eur J Clin Invest 9:89–95

    Google Scholar 

  29. Kuutti-Savolainen ER, Anttinen H, Miettinen TA, Kivirikko KI (1979) Collagen biosynthesis enzymes in serum and hepatic tissue in liver disease. II. Galactosylhydroxylysyl glucosyltransferase. Eur J Clin Invest 9:97–101

    Google Scholar 

  30. Langness U, Clausnitzer H, Verspohl M, Grasedyck K (1978) Die Prolylhydroxylaseaktivität in Leberpunktaten bei chronischen Lebererkrankungen. Med Klin 73:1179–1182

    Google Scholar 

  31. Leevy CM, Tygstrup N (1976) Standardisation of nomenclature, diagnostic criteria and diagnostic methodology for diseases of the liver and biliary tract. Karger, Basel

    Google Scholar 

  32. Lee JES, Yoshida A (1976) Purification and chemical characterisation of human hexosaminidases A and B. Biochem J 159:535–539

    Google Scholar 

  33. Lieber CS (1975) Liver disease and alcohol: fatty liver alcoholic hepatitis, cirrhosis, and their interrelationships. Ann NY Acad Sci 252:63–84

    Google Scholar 

  34. Martini GA (1974) Klinik der Arzneimittelschäden der Leber. In: Gerok W, Sickinger K (Hrsg) Aktuelle Hepatologie. Demeter, Gräfeling

    Google Scholar 

  35. Meyer zum Büschenfelde K.-H. (1978) Immunsuppressive Therapie der HBs-Antigen-positiven und -negativen chronischaktiven Hepatitis. Dtsch Med Wochenschr 103:887–892

    Google Scholar 

  36. Mosesson MW (1977) Cold-Insoluble Globulin (ClG), a circulating cell surface protein. Thromb Haemost 38:742–750

    Google Scholar 

  37. Neufeld EF, Sando GN, Garvin AJ, Rome LH (1977) The transport of lysosomal enzymes. J Supram Struct 6:95–101

    Google Scholar 

  38. Okazaki J, Maruyama K (1974) Collagenase activity in experimental hepatic fibrosis. Nature 252:49–50

    Google Scholar 

  39. Pequinot G (1958) Enquete par interrogatoire sur les circonstances dietetiques de la cirrhose alcoolique en France. Bull Inst Nat Hyg 13:719–739

    Google Scholar 

  40. Platt D, Leinweber B (1969) Untersuchungen zum katabolen Mucopolysaccharidstoffwechsel bei Lebererkrankungen. (Catabolic mucopolysaccharide metabolism in liver diseases). Acta Hepatogastroenterol 16:324–330

    Google Scholar 

  41. Popper H, Udenfriend S (1970) Hepatic fibrosis, correlation of biochemical and morphologic investigations. Am J Med 49:707–721

    Google Scholar 

  42. Popper H, Becker K (1975) Collagen metabolism in the liver. Grune and Stratton, New York

    Google Scholar 

  43. Popper H, Kent G (1975) Cirrhosis. Clin Gastroenterol 2:225–463

    Google Scholar 

  44. Popper H, Piez KA (1978) Collagen metabolism in the liver. Dig Dis 23:641–659

    Google Scholar 

  45. Pott G, Chi-Boesler D, Gerlach U (1978) Isoenzymes of N-Acetyl-β-glucosaminidase from human liver and serum. Separation by electrofocusing in thin layers of polyacrylamide gel. J Clin Chem Clin Biochem 16:15–18

    Google Scholar 

  46. Pott G, Eberhardt G, Gerlach U (1979) Activity of procollagen-prolylhydroxylase and N-Acetyl-β-glucosaminidase in human fibrosis. Klin Wochenschr 57:587–588

    Google Scholar 

  47. Pott G, Rauterberg J, Voss B, Allam S, Brehmer U, Liehr H, Gerlach U (1980) Connective tissue metabolism and lysosomal glycosidases in non-parenchymal cells from normal and fibrotic human livers and from livers of galactosamine-treated rats. In: Liehr H, Grün M (eds) The reticuloendothelial system and the pathogenesis of liver disease. Elsevier-North-Holland, Amsterdam, pp 205–210

    Google Scholar 

  48. Pott G, Gerlach U (1980) Diagnostic significance of connective tissue enzymes. Enzyme 25:394–406

    Google Scholar 

  49. Pott G, Voss B, Meyering M, Karges HE, Sieber A (1980) Plasma concentrations of fibronectin in human diseases. I. Rapid determination of fibronectin by lasernephelometry. J Clin Chem Clin Biochem 18:893–895

    Google Scholar 

  50. Prockop DJ, Kivirikko KI, Tuderman L, Guzman NA (1979) The biosynthesis of collagen and its disorders. Part I and II. N Engl J Med 301:13–24; 77–85

    Google Scholar 

  51. Riede UN, Staubesand J (1977) A unifying concept for the role of matrix vesicles and lysosomes in the normal pathogenesis of diseases of connective tissues and blood vessels. Beitr Pathol 160:3–37

    Google Scholar 

  52. Rhode H, Hahn E, Timpl R (1978) Radioimmunoassay for aminoterminal procollagen peptides in liver disease. Fresenius Z Analyt Chem 290:151–152

    Google Scholar 

  53. Rhode H, Vargas L, Hahn E, Kalbfleisch H, Bruguera M, Timpl R (1979) Radioimmunoassay for type III procollagen peptide and its application to human liver disease. Eur J Clin Invest 9:451–459

    Google Scholar 

  54. Rönnemaa T, Pelliniemi TT, Kulonen E (1976) Factor stimulating collagen synthesis from the livers of hypercholesterolemic rats. Atherosclerosis 24:311–321

    Google Scholar 

  55. Rönnemaa T, Vihersaari T, Ranta H (1977) Identification of glutamine as a hepatic factor which influences the synthesis of collagen by freshly isolated fibroblasts. Scand J Clin Lab Invest 37:351–356

    Google Scholar 

  56. Rojkind M (1973) Inhibition of liver fibrosis by L-Azetidine-2-Carboxylic acid in rats treated with carbon tetrachloride. J Clin Invest 52:2451–2456

    Google Scholar 

  57. Rojkind M, Dunn MA (1979) Hepatic fibrosis. Gastroenterology 76:849–863

    Google Scholar 

  58. Schmidt E, Schmidt FW (1963) Enzymbestimmungen im Serum bei Lebererkrankungen. Enzym Biol Clin 3:1–52

    Google Scholar 

  59. Schneider M, Pott G, Voß B, Abreu C, Gerlach U 1981 Determination of N-Acetyl-β-glucosaminidase isoenzymes A and B by immunoprecipitation using monospecific antibodies. (submitted)

  60. Stein DH, Keiser HR, Sjoerdsma A (1970) Proline-hydroxylase activity in human blood. Lancet I:3–11

    Google Scholar 

  61. Sternlieb I (1975) Penicillamine and hepatic fibrosis. The beneficial and adverse effects of penicillamine. In: Popper H, Becker K (eds) Collagen metabolism in the liver. Stratton, New York

    Google Scholar 

  62. Summerskill WHJ, Korman MG, Ammon HV, Baggenstoss AH (1975) Prednisone for chronic active liver disease: dose titration, standard dose, and combination with azathioprine compared. Gut 16:876–883

    Google Scholar 

  63. Taubman MB, Goldberg B, Sherr CJ (1974) Radioimmunoassay for human procollagen. Science 186:1115–1117

    Google Scholar 

  64. Voss B, Allam S, Rauterberg J, Ullrich K, Gieselmann V, Figura K von (1979) Primary cultures of rat hepatocytes synthesize fibronectin. Biochem Biophys Res Commun 90:1348–1354

    Google Scholar 

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Authors and Affiliations

  1. Medizinische Univ.-Klinik Münster Dirketor, Germany

    G. Pott, J. Rauterberg, B. Voss & U. Gerlach

  2. Institut für Arterioskleroseforschung an der Universität Münster, Germany

    G. Pott, J. Rauterberg, B. Voss & U. Gerlach

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  1. G. Pott
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  2. J. Rauterberg
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  3. B. Voss
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  4. U. Gerlach
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Dedicated to Prof. Dr. J. Staubesand on the ocasion of his 60th birthday

Supported by grants from Deutsche Forschungsgemeinschaft (SFB 104, A4)

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Pott, G., Rauterberg, J., Voss, B. et al. Connective tissue components of the normal and fibrotic human liver. Klin Wochenschr 60, 1–7 (1982). https://doi.org/10.1007/BF01721581

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  • DOI: https://doi.org/10.1007/BF01721581

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