Correspondence

Prediction of Liver Fibrosis According to Serum Collagen VI Level in Children with Cystic Fibrosis

N Engl J Med 1997; 336:1611-1612May 29, 1997

Article

To the Editor:

Chronic fibrotic liver disease accounts for virtually all nonpulmonary causes of mortality in patients with cystic fibrosis. Therefore, along with lung disease and nutritional status, liver fibrosis is an important predictor of the outcome of cystic fibrosis.1 Until now, histologic staging of fibrosis has been the only method for assessing liver fibrosis. Noninvasive markers for diagnosis and follow-up of fibrotic liver disease are urgently needed, and in children these markers must be unaffected by growth velocity.2 Circulating collagen VI resulting from collagen degradation3 has been found to be elevated in adults with fibrosis and cirrhosis of the liver,4,5 but the diagnostic or prognostic value of this marker in children with chronic liver disease, especially those with cystic fibrosis, is not known.

We studied serum collagen VI levels in 224 healthy children (age range, birth to 18 years), 54 children with biopsy-verified hepatic fibrosis of various causes (age range, 1 month to 18 years), and 163 children with cystic fibrosis (age range, 2 to 18 years), 133 of whom had no clinical or laboratory signs of liver disease (normal liver size, normal results on routine liver-function tests, and a serum bile acid level of <10 μmol per liter) and 30 of whom had biopsy-verified liver fibrosis. Circulating collagen VI was measured without knowledge of the findings on liver biopsy by an inhibition enzyme-linked immunosorbent assay.3 The groups were compared with use of the Mann–Whitney U test. The intraassay and interassay coefficients of variation were 2.7 and 3.9 percent, respectively.

The results are shown in Figure 1Figure 1Serum Collagen VI Levels in 224 Healthy Children (the Controls), 54 Children with Liver Fibrosis, 133 with Cystic Fibrosis but No Overt Liver Disease, and 30 with Cystic Fibrosis and Liver Fibrosis.. In the healthy children, serum collagen VI levels were independent of age. The levels were elevated in all the patients with liver fibrosis, with no overlap between these values and those in the healthy controls. All the children with cystic fibrosis and no signs of liver disease had normal collagen VI levels, whereas the levels were significantly elevated in all the patients with cystic fibrosis and fibrotic liver disease.

Our data indicate that collagen VI is a highly sensitive and specific serum marker for the detection of liver fibrosis in children and that it is independent of age. Among children with cystic fibrosis, the serum collagen VI level differentiates those with liver fibrosis from those without fibrotic liver disease. Other fibrosing conditions (e.g., those of the lungs) do not influence collagen VI levels. Longitudinal studies are needed to evaluate serum collagen VI levels in the long-term follow-up of fibrotic liver diseases.

Burkard Gerling, M.D.
Michael Becker, M.D.
Doris Staab, M.D.
Humboldt University of Berlin, D-13353 Berlin, Germany

Detlef Schuppan, M.D., Ph.D.
Free University of Berlin, D-12200 Berlin, Germany

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Citing Articles (9)

Citing Articles

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   Richard J. Thompson, Bernard C. Portmann, Eve A. Roberts. 2012. Genetic and metabolic liver disease. , 157-259.
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   Christian Freise, Ulrike Erben, Marion Muche, Richard Farndale, Martin Zeitz, Rajan Somasundaram, Martin Ruehl. (2009) The alpha 2 chain of collagen type VI sequesters latent proforms of matrix-metalloproteinases and modulates their activation and activity. Matrix Biology 28:8, 480-489
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   Vidhya R. Rao, Raghu R. Krishnamoorthy, Thomas Yorio. (2008) Endothelin-1 mediated regulation of extracellular matrix collagens in cells of human lamina cribrosa. Experimental Eye Research 86:6, 886-894
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   Dariusz M. Lebensztejn, Maria E. Sobaniec-Łotowska, Michael Bauer, Maciej Kaczmarski, Michael Voelker, Detlef Schuppan. (2005) Serum fibrosis markers as predictors of an antifibrotic effect of interferon alfa in children with chronic hepatitis B. European Journal of Gastroenterology & Hepatology 17:8, 843-848
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   Michael P. Curry, John E. Hegarty. (2005) The gallbladder and biliary tract in cystic fibrosis. Current Gastroenterology Reports 7:2, 147-153
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   Andrew P. Feranchak. (2004) Hepatobiliary complications of cystic fibrosis. Current Gastroenterology Reports 6:3, 231-239
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   Michael R. Narkewicz. (2001) Markers of Cystic Fibrosis—Associated Liver Disease. Journal of Pediatric Gastroenterology and Nutrition 32:4, 421-422
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   Ronald J. Sokol, Peter R. Durie. (1999) Recommendations for Management of Liver and Biliary Tract Disease in Cystic Fibrosis. Journal of Pediatric Gastroenterology & Nutrition 28, S1-S13
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9. 9

   Salvatore Leonardi, Francesco Giambusso, Concetta Sciuto, Salvatore Castiglione, Nicolò Castiglione, Marin La Rosa. (1998) Are Serum Type III Procollagen and Prolyl Hydroxylase Useful as Noninvasive Markers of Liver Disease in Patients with Cystic Fibrosis?. Journal of Pediatric Gastroenterology & Nutrition 27:5, 603-605
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