Serum basement membrane and type III procollagen-related antigens in primary biliary cirrhosis

doi:10.1016/S0168-8278(88)80047-3

Journal of Hepatology

Volume 6, Issue 3, 1988, Pages 307-314

https://doi.org/10.1016/S0168-8278(88)80047-3 Get rights and content

Summary

A characteristic histological lesion in early primary biliary cirrhosis (PBC) is disruption of the basement membrane around small bile ducts, which at later stages of the disease is followed by fibrosis. To assess the significance of serum basement membrane- and type III procollagen-related antigens in reflecting such processes, we have measured radioimmunologically the concentrations of serum laminin, type IV collagen and the aminoterminal propeptide of type III procollagen in 22 patients with PBC, classified into four stages according to liver histology. The mean laminin concentration in PBC patients was twice that of the healthy control subjects. Increased concentrations were observed in all patients with stage III or IV of the disease and also in 60% (6/10) of the patients with early stages (I or II). Elevated serum type IV collagen concentrations were found only in four patients, all in the late, fibrotic stages of the disease. The basement membrane protein changes in serum were in accordance with immunohistochemical findings obtained with the antibodies against these proteins. Neither of these serum parameters emerged, however, as a significant predictive factor for survival. The changes in serum aminoterminal propeptide of type III procollagen resembled those in laminin P1. Moreover, the propeptide was also significant as a predictive factor for survival.

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Cited by (26)

Utility of Noninvasive Markers of Fibrosis in Cholestatic Liver Diseases
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Elevated serum aminoterminal procollagen type-III-peptide parallels collagen accumulation in rats with secondary biliary fibrosis
1996, Journal of Hepatology
Background/Aims: The aminoterminal procollagen type-III-peptide, which can be released during collagen type III deposition, has been suggested as a serum marker of fibrogenesis in patients with chronic liver disease. However, longitudinal studies correlating procollagen type-III-peptide concentrations in serum with the evolution of liver fibrosis are still needed. The purpose of the present study was to prove the significance of procollagen type-III-peptide concentrations in serum as a non-invasive marker of liver fibrogenesis in an animal model that best resembles progressive human liver fibrosis.
Methods: In 88 female Wistar rats the biliary system was occluded by double ligation of the choledochal duct followed by retrograde injection of a mixture of prolamine/ethanole (Ethibloc®). Sixteen rats served as controls. Groups of 8–10 rats were sacrificed at days 2, 7, 14, 21, 30, 32, 35, 60 and 90 after bile duct occlusion. In the groups histological staging (fibrosis score), determination of total liver hydroxyproline, measurement of serum procollagen type-III-peptide and routine liver function tests were performed.
Results: First histological signs of liver fibrosis were seen as early as 7 days after bile duct occlusion. Progressive fibrosis was paralleled by an increase of serum procollagen type-III-peptide. There was a significant correlation between serum procollagen type-III-peptide and histological stages of fibrosis (r=0.80; p<0.0001) as well as between serum procollagen type-III-peptide and hydroxyproline in total liver tissue (r=0.85; p<0.0001)
Conclusions: These results indicate that: (1) complete bile duct occlusion in rats produces progressive hepatic fibrosis resembling human secondary biliary fibrosis, and (2) procollagen type-III-peptide concentrations in serum reflect ongoing collagen formation in the liver unrelated to serum markers of cholestasis and inflammation.
The carboxy-terminal cross-linked telopeptide of type I collagen (ICTP) is a potential serum marker of ongoing liver fibrosis
1996, Clinica Chimica Acta
We report for the first time the measurement of the serum concentration of the carboxy-terminal cross-linked telopeptide of type I collagen in patients with various liver diseases. This breakdown product of type I collagen, which is the major collagen type found in fibrotic liver, was measured by a radioimmunoassay in the serum of 149 patients with various liver diseases and in 67 controls. Its concentration is significantly elevated (P < 0.05) above reference intervals in sera from patients with liver diseases, except in patients with chronic active hepatitis of unknown origin and in patients with acute hepatitis A. In the 143 patients with liver fibrosis, the serum level of the carboxy-terminal telopeptide of type I collagen is correlated with the extent of fibrosis, as assessed by a histological scoring system (r = 0.3899, P < 0.0001), but not with inflammation and necrosis.
Glycoprotein metabolism in dimethylnitrosamine induced hepatic fibrosis in rats
1996, International Journal of Biochemistry and Cell Biology
Glycoproteins play a major role in the pathogenesis of hepatic fibrosis by accumulating in the sinusoids and the space of Disse. In order to obtain more information about the altered metabolism of glycoproteins during the development of human hepatic fibroses, the carbohydrate moieties of the glycoproteins were monitored in experimentally induced hepatic fibrosis. The liver injury was induced by injecting dimethyluitrosamine intraperitoneally in male albino rats. The injections were given on the first 3 consecutive days of each week over a period of 21 days. Glycoprotein moieties such as total hexose, hexosamine, fucose and sialic acid were estimated in liver, serum and urine samples on days 7, 14 and 21 of the experiment. The results indicated a significant decrease in total hexose and an increase in fucose levels in the 'liver time during dimethylnitrosamine administration. While protein bound hexose in the serum showed a significant decrease, sialic acid levels were notably increased. The other glycoprotein sties both in liver and serum also showed an increase in the later periods of study, especially on day 21. All glycoprotein moieties exhibited a significant increase in the rate of urinary excretion on the 14th and 21st days, indicating an increased rate of metabolic degradation in the acute phase of hepatic his. The results suggest that glycoproteins undergo changes in both synthesis and the degradation during hepatic fibrosis. The relative alterations in these processes will play a vital role in determining the progression of hepatic fibrosis.
A placebo-controlled trial of primary biliary cirrhosis treatment with colchicine and ursodeoxycholic acid
1995, Gastroenterology
$Background/Aims$ Ursodeoxycholic acid (UDCA) and colchicine have beneficial effects in primary biliary cirrhosis (PBC). The efficacy of colchicine and UDCA in PBC was compared in a 2-year placebo-controlled study (n = 90). $Methods$ Clinical events, laboratory test results, and liver histology were recorded at the beginning and end of the trial. $Results$ There were significantly fewer dropouts for hepatic reasons with UDCA than with placebo. Pruritus was reduced by both active drugs. Colchicine improved liver function test results only modestly, whereas UDCA significantly decreased the serum activities of aminotransferases, alkaline phosphatase, and γ-glutamyltransferase compared with colchicine and placebo. Serum total bilirubin levels were decreased only by UDCA. Both colchicine and UDCA reduced serum cholesterol levels, and UDCA also reduced high-density lipoprotein cholesterol levels. Furthermore, UDCA reduced the serum levels of immunoglobulin (Ig) M and IgG, and colchicine reduced IgG levels compared with placebo. The elevated serum level of aminoterminal propeptide of type III procollagen remained unchanged by colchicine or UDCA, whereas the serum level of carboxyterminal propeptide of type I procollagen was significantly decreased by UDCA. UDCA significantly decreased ductular proliferation compared with colchicine or placebo. $Conclusions$ These data suggest that UDCA frequently is superior to colchicine and especially to placebo in the treatment of PBC.
Relationship between procollagen III aminoterminal propeptide and hyaluronan serum levels and histological fibrosis in primary biliary cirrhosis and chronic viral hepatitis C
1994, Journal of Hepatology
The diagnostic values of aminoterminal propeptide of type III procollagen and hyaluronan serum levels were compared as markers of liver fibrosis in two chronic liver diseases of different etiologies and pathophysiologies, namely primary biliary cirrhosis and chronic viral hepatitis C. The results were analysed in terms of the histological extent of fibrosis. Both serum procollagen-III peptide and hyaluronan were elevated in patients with primary biliary cirrhosis and chronic viral hepatitis C (p<0.0001) relative to control values. A positive correlation was found between serum procollagen-III peptide levels and the histological grade of fibrosis in primary biliary cirrhosis (p<0.001) but not in chronic viral hepatitis C, while a strong correlation was found between serum hyaluronan levels and histological fibrosis in both primary biliary cirrhosis and chronic viral hepatitis C (p<0.001), independent of age. These results suggest that, in chronic liver diseases, serum hyaluronan levels could be an important indicator of the extent of fibrosis and should be assayed to monitor the response to treatment in controlled clinical trials.

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^*: This study was supported in part by grants from the Finnish Foundation for Alcohol Studies and the Medical Research Council of the Academy of Finland. Part of this work was presented and published in abstract form at the 37th Annual Meeting of the American Association for the Study of Liver Diseases (Hepatology 1986; 6: 1105) and at the IVth International Symposium on Renal Basement Membranes (Paris 1987; A61).

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Research PaperSerum basement membrane and type III procollagen-related antigens in primary biliary cirrhosis*

Summary

J Hepatol

Int Rev Connect Tissue Res

J Hepatol

Gastroenterology

Clin Chim Acta

J Hepatol

Radioimmunoassays for monitoring connective tissue metabolism

Rheumatology

Collagen metabolism in liver disease

Radioimmunoassay for type III procollagen peptide and its application to human liver disease

Eur J Clin Invest

The blue glass and the predictive value of serum amino-terminal propeptide of type III procollagen as a marker of liver fibrosis

Hepatology

Type IV collagen and laminin-related antigens in human serum in alcoholic liver disease

Eur J Clin Invest

Serum concentrations of N-terminal propeptide of type III procollagen and laminin in the outflow of fibrotic livers compared with liver-distal regions

Hepatogastroenterology

Serum type III procollagen and basement membrane proteins as noninvasive markers of hepatic pathology in Indian childhood cirrhosis

Hepatology

Primary biliary cirrhosis: chronic non-suppurative destructive cholangitis

Am J Pathol

Research Paper
Serum basement membrane and type III procollagen-related antigens in primary biliary cirrhosis*