Elsevier

Journal of Hepatology

Volume 32, Issue 6, June 2000, Pages 911-920
Journal of Hepatology

Serum YKL-40 is increased in patients with hepatic fibrosis

https://doi.org/10.1016/S0168-8278(00)80095-1Get rights and content

Abstract

Background/Aims: YKL-40, a mammalian member of the chitinase family, is a lectin that binds heparin and chitin. The function of YKL-40 is unknown, but it may function in tissue remodelling. The aims of this study were to assess the level of circulating YKL-40 in patients with various kinds and degree of chronic liver disease and its possible relation to liver fibrosis.

Methods: Serum YKL-40 levels were determined byradioimmunoassay in 129 patients with suspected liver disease and related to histological findings and immunohistochemical staining of YKL-40 in a liver biopsy taken simultaneously with the blood sample.

Results: The median serum YKL-40 was highest in patients with alcoholic cirrhosis (532 μg/l), in particular in patients with additional alcoholic hepatitis (740 μg/l). Patients with alcoholic cirrhosis, post-hepatitic cirrhosis (425 μg/l) and non-cirrhotic fibrosis (330 μg/l) had significantly higher serum YKL-40 than normal subjects (102 μg/l), patients with fatty liver (195 μg/l) or patients with viral hepatitis without fibrosis (174 μg/l). Serum YKL-40 was significantly (p<0.001) related to the degree of liver fibrosis with the highest levels in patients with moderate (466 μg/l) to severe (676 μg/l) fibrosis. Serum YKL-40 was also increased (p=0.018) in patients with slight fibrosis (270 μg/l) compared to patients without fibrosis. Immunohistochemical analysis demonstrated positive staining for YKL-40 antigen in areas with fibrosis, particularly areas with active fibrogenesis. YKL-40 staining was never found in hepatocytes.

Conclusions: Our study indicates that the increased serum YKL-40 in patients with liver disease of various degree and aetiology seems to reflect fibrosis and fibrogenesis.

Section snippets

Patients

The study included 129 biopsies from consecutive patients (82 men and 47 women with a median age of 49 years (range 24–80 years)) referred to the Department of Gastroenterology between December 1992 and November 1994 with suspicion of liver disease. A blood sample and a liver biopsy were taken simultaneously from each patient. Diagnosis of the liver disease was based on histology and accepted biochemical and clinical criteria. Four subjects did not have any signs of liver disease or other

Results

The individual concentrations of serum YKL-40, PIIINP and hyaluronan in relation to the various liver diseases, determined by histopathological and clinical criteria, are illustrated in Fig. 1 (a, b and c) and the median levels are given in Table 2. The serum YKL-40 levels were highest in patients with alcoholic liver cirrhosis (median 532 μg/l and 5-fold increased compared with the median level of healthy age-matched controls), posthepatitic cirrhosis (425 μg/l) and noncirrhotic fibrosis (330

Discussion

Our present findings confirm that serum YKL-40 concentration is increased in patients with chronic liver disease. Most of the patients with alcoholic cirrhosis or posthepatitic cirrhosis had elevated serum YKL-40, and the highest levels were found in patients with alcoholic cirrhosis in combination with alcoholic hepatitis. These patients had a median level of serum YKL-40 which was 3-fold higher than the upper normal level, and many had more than 5-fold elevated serum YKL-40. Patients with

Acknowledgements

The expert technical assistance of Margit Bech and Vibeke Karlsen, Department of Pathology, Hvidovre Hospital, Denmark and Birgitte Olsen, Institute of Medical Anatomy Section A, The Panum Institute, University of Copenhagen, Denmark is gratefully acknowledged. We also appreciate helpful support from Hanne Hansen, Department of Clinical Physiology and Nuclear Medicine, Hvidovre Hospital, Denmark in the statistical calculations and the preparation of the figures, and from Lene Theil Skovgaard,

References (51)

  • T Roskams et al.

    Heparan sulfate proteoglycan expression in normal human liver

    Hepatology

    (1995)
  • DM Bissell et al.

    Connective tissue metabolism and hepatic fibrosis

  • SL Friedman

    The cellular basis of hepatic fibrosis. Mechanisms and treatment strategies

    N Engl J Med

    (1993)
  • AM Gressner

    Liver fibrosis: perspectives in pathobiochemical research and clinical outlook

    Eur J Clin Chem Clin Biochem

    (1991)
  • JS Johansen et al.

    A new biochemical marker for joint injury. Analysis of YKL-40 in serum and synovial fluid

    Br J Rheumatol

    (1993)
  • SW Krause et al.

    Differential screening identifies genetic markers of monocyte to macrophage maturation

    J Leukoc Biol

    (1996)
  • P Nyirkos et al.

    Human synovial cells secrete a 39 kDa protein similar to a bovine mammary protein expressed during the non-lactating period

    Biochem J

    (1990)
  • JS Johansen et al.

    Identification of proteins secreted by human osteoblastic cells in culture

    J Bone Miner Res

    (1992)
  • BW Morrison et al.

    neu and ras initiate murine mammary tumors that share genetic markers generally absent in c-myc and int-2-initiated tumors

    Oncogene

    (1994)
  • GH Renkema et al.

    Chitotriosidase, a chitinase, and the 39-kDa human cartilage glycoprotein, a chitin-binding lectin, are homologues of family 18 glycosyl hydrolases secreted by human macrophages

    Eur J Biochem

    (1998)
  • GFM Verheijden et al.

    Human cartilage glycoprotein-39 as a candidate autoantigen in rheumatoid arthritis

    Arthritis Rheum

    (1997)
  • B Volck et al.

    YKL-40, a mammalian member of the bacterial chitinase family, is a matrix protein of specific granules in human neutrophils

    Proc Assoc Am Assoc Physician

    (1998)
  • JS Johansen et al.

    Plasma YKL-40: a new potential marker of fibrosis in patients with alcoholic cirrhosis?

    Scand J Gastroenterol

    (1997)
  • G Menghini

    One-second biopsy of the liver - problems of its clinical application

    N Engl J Med

    (1970)
  • H Poulsen et al.

    Atlas of Liver Biopsies

    (1979)
  • Cited by (0)

    View full text