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Clinicopathological Significance of Serum Fractalkine in Primary Biliary Cirrhosis

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Abstract

Background

Primary biliary cirrhosis (PBC), characterized by cholangitis and loss of intrahepatic small bile ducts, predominantly affects middle-aged females. We have reported that fractalkine expression associated with chronic inflammation is observed in the damaged bile ducts and periductal vessels of PBC patients, which is closely associated with chronic cholangitis.

Aims

We investigated the association between serum fractalkine levels and clinicopathological findings in PBC patients.

Methods

Liver biopsy specimens before ursodeoxycholic acid treatment and serum samples at the time of liver biopsy and 1 and 2 years after treatment were obtained from 68 PBC patients (M/F = 14/54). Serum fractalkine levels were measured by enzyme-linked immunosorbent assay, and their association with clinicopathological findings (liver function data, autoantibodies, cholangitis activity, hepatitis activity, fibrosis, bile duct loss, and orcein-positive granules) was analyzed.

Results

Serum fractalkine levels were in the range of 0.1–33.2 ng/ml (average, 3.2 ng/ml). They were increased in PBC patients with high degrees of cholangitis activity, a mild degree of hepatitis activity, fibrosis, orcein-positive granules, and early stages. In cases with high serum fractalkine levels, those who exhibited good biochemical responses to treatment mostly showed improved serum fractalkine levels after treatment.

Conclusion

Serum fractalkine levels of PBC patients were high in cases with marked cholangitis activity at early stages. In addition, they closely correlated with the effect of therapy, indicating that fractalkine plays a role in the pathogenesis of initial cholangitis in early stage PBC and consequent chronic cholangitis. Thus, our results suggest that fractalkine is a good candidate for molecular-targeted treatment.

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Abbreviations

ADAM:

A disintegrin and metalloprotease

AMA:

Anti-mitochondrial antibody

CNSDC:

Chronic nonsuppurative destructive cholangitis

IBD:

Inflammatory bowel disease

PBC:

Primary biliary cirrhosis

RA:

Rheumatoid arthritis

TLR:

Toll-like receptor

UDCA:

Ursodeoxycholic acid

ULN:

Upper limit of normal

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Acknowledgments

This work was supported by grant No. 23590393 from the Ministry of Education, Culture, Sports, Science and Technology of Japan (K.H.) and by Health and Labour Sciences Research Grants for the Research on Measures for Intractable Diseases (Chief Tsubouchi, M.D.).

Conflict of interest

None.

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Authors and Affiliations

  1. Department of Human Pathology, Kanazawa University Graduate School of Medicine, Kanazawa, 920-8640, Japan

    Kenichi Harada, Yuko Kakuda & Yasuni Nakanuma

  2. Department of Hepatology, Clinical Research Center, National Hospital Organization (NHO), Nagasaki Medical Center, Nagasaki University Graduate School of Biomedical Sciences, Omura, Japan

    Minoru Nakamura

  3. Department of Medicine and Biosystemic Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

    Shinji Shimoda

Authors
  1. Kenichi Harada
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  2. Yuko Kakuda
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  3. Minoru Nakamura
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  4. Shinji Shimoda
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  5. Yasuni Nakanuma
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Corresponding author

Correspondence to Kenichi Harada.

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Harada, K., Kakuda, Y., Nakamura, M. et al. Clinicopathological Significance of Serum Fractalkine in Primary Biliary Cirrhosis. Dig Dis Sci 58, 3037–3043 (2013). https://doi.org/10.1007/s10620-013-2734-6

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  • DOI: https://doi.org/10.1007/s10620-013-2734-6

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