RESUMEN
Chronic liver disease is a worldwide common pathology characterized by inflammatory and fibrotic processes that may lead to progressive evolution from chronic hepatitis to cirrhosis. Peripheral blood monocytes may play an important role in the pathogenesis and resolution of liver fibrosis. These cells may offer new approaches for better understanding the pathogenesisof liver fibrosis. This work defined the proportion of circulating classical monocyte subset with hematopoietic origin in peripheral blood to establish the possible potential role of this subset as non-invasive biomarker of liver fibrosis in patients with HCV related chronic liver disease. Forty patients with HCV induced chronic liver disease were classified according to the stage of liver fibrosis after METAVIR score into 4 groups, patients with stages F1, F2, F3 & F4 liver fibrosis (10 patients each) and 10 healthy subjects served as normal controls. Flowcytometric analysis for immunophenotypic characterization for identification of levels of circulating peripheral blood classical monocytes subset in different groups studied was carried out using monoclonal antibodies anti-CD45, anti-CD 14 and anti-CD 16. THE RESULTS: data demonstrated a significant down regulation (p< 0.01) in the proportion of classical monocytes subset (CD45+ve, CD 14+ve and CD 16-ve) in patients with chronic hepatitis C related liver disease compared to healthy subjects. Data also demonstrate that down regulation of the expression of classical monocyte subset paralleled the worsening severity of liver disease and the progression of liver fibrosis.
Asunto(s)
Regulación hacia Abajo , Hepatitis C/complicaciones , Cirrosis Hepática/etiología , Monocitos/citología , Animales , Anticuerpos Monoclonales , Biomarcadores , Estudios de Casos y Controles , Citometría de Flujo , Humanos , Antígenos Comunes de Leucocito/inmunología , Receptores de Lipopolisacáridos/metabolismo , Cirrosis Hepática/sangre , Ratones , Monocitos/inmunología , Receptores de IgG/metabolismoRESUMEN
Detection and follow up of fibrogenesis in chronic hepatitis C (CHC) is mandatory for early treatment and risk stratification. The current study included 120 patients with CHC, of whom 30 had liver cirrhosis (LC) and 30 had hepatocellular carcinoma (HCC). 15 wedge liver biopsies, taken during laparoscopic cholecystectomy, were included as normal controls. Cases were subjected to laboratory investigations, serologic markers for viral hepatitis and assessment of circulating levels of hyaluronic acid (HA) and platelet-derived growth factor (PDGF). Immunohistochemical expression of connective tissue growth factor (CTGF), PDGF and transforming growth factor-ß1 (TGF-ß1) was also carried out. A significant increase (p < 0.01) in serum HA was noticed in CHC, LC and HCC compared to controls. Although, a significant decrease in serum PDGF was detected in CHC and LC compared to controls, HCC values were comparable. A significant up-regulation of CTGF was detected in CHC, LC and HCC (p < 0.01) in contrast to its limited mild expression in normal livers. Intense PDGF positive staining was noticed in CHC, LC and HCC compared to scattered faint expression in controls. The significant expression and marked intensity of PDGF staining matched the progress to tumorigenesis. A positive TGF-ß1 immunostaining was also noticed in CHC, LC and HCC. An intense and extensive cytoplasmic expression of TGF-ß1 was encountered in patients with LC revealing that CTGF, PDGF and TGF-ß1 act synergistically in LC. Data revealed that HA and CTGF may be implicated as important diagnostic parameters for assessment of hepatic fibrosis and PDGF for monitoring malignant transformation in CHC.