CIRCULATING FIBROCYTES AS A POTENTIAL NON INVASIVE MARKER OF LIVER FIBROSIS IN PATIENTS WITH CHRONIC HEPATITIS C VIRUS INFECTION.

Background and Aims: Chronic hepatitis C virus (HCV) infection often leads to fibrosis and cirrhosis. Liver biopsy is currently the gold standard technique to quantitate liver fibrosis but it is an invasive procedure with even life-threatening complications. Direct and indirect markers of liver fibrosis have been studied although no accepted method is currently available to monitor disease progression. Peripheral blood fibrocytes are bone marrow-derived cells capable of producing extracellular matrix molecules, therefore considered to be potentially involved in fibrotic processes. The aim of the present study was to investigate whether the level of circulating fibrocytes is increased in patients with chronic hepatitis C as compared with healthy controls and whether it correlates with the histological stage of fibrosis. Methods: Between January 2006 and January 2007 we enrolled 70 patients affected with chronic HCV infection, without other known causes of liver disease, not on interferon or ribavirin. All patients underwent liver biopsy (Metavir score F0 to F4) and Fibroscan (liver stiffness measured in kilopascal units) for fibrosis measurement. Peripheral blood fibrocytes were measured on all patients by flow cytometry as positive for CD34, CD45 and collagen-I expression. Results: Patients with chronic hepatitis C had significantly higher levels of circulating fibrocytes as compared with healthy individuals (31.3% versus 17.59%, p = 0.04). Patients in the F0–F1 group had a percentage of circulating fibrocytes of 23.3±4 %, whereas the mean rate of circulating fibrocytes in the F2 and F3 group was 38.4±4 % and 44.8±2% respectively (p < 0.001 versus F0–F1). Patients in the F4 group had a mean rate of circulating fibrocytes of 50.6±2% (p < 0.001 versus the F0, F1, F2 stages). The percentage of circulating fibrocytes correlated positively with both the Metavir score and the liver stiffness. No correlation was found with serum ALT and HCV RNA levels. Conclusions: Peripheral blood fibrocytes are increased in patients with HCV infection and correlated with HCV-related liver fibrosis. Fibrocytes not only could be involved in the pathogenetic mechanisms of liver fibrosis but they also may act as a surrogate marker of liver fibrosis. Further studies are needed to thoroughly investigate their role in chronic HCV infection