Clinicopathological significance of serum fractalkine in primary biliary cirrhosis

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.