RESUMEN
BACKGROUND: Thrombocytopenia is a hallmark of advanced liver disease. Platelets, growth factors (GFs), and vascular integrity are closely linked factors in disease pathogenesis, and their relationship, particularly in early disease stages, is not entirely understood. The aim was to compare circulating platelets, growth factors, and vascular injury markers (VIMs) in hepatitis C-infected (HCV) patients with early fibrosis and cirrhosis. METHODS: Retrospective evaluation of serum GFs and VIMs by ELISA were evaluated from twenty-six HCV patients. Analytes from an earlier time-point were correlated with MELD at a later time-point. RESULTS: Platelets and GFs decreased, and VIMs increased with fibrosis. Platelets correlated positively with PDGF-AA, PDGF-BB, TGFB1, EGF, and P-selectin, and negatively with ICAM-3 and VCAM-1. P-selectin showed no correlations with VIMs but positively correlated with PDGF-AA, PDGF-BB, TGFB1, and EGF. Soluble VCAM-1 and ICAM-3 were linked to increasing fibrosis, liver enzymes, and synthetic dysfunction. Higher VCAM-1 and ICAM-3 and lower P-selectin at an earlier time-point were linked to higher MELD score at a later time-point. CONCLUSION: In chronic HCV, progressive decline in platelets and growth factors with fibrosis and their associations suggest that platelets are an important source of circulating GFs and influence GF decline with fibrosis. Enhanced markers of vascular injury in patients with early fibrosis suggest an earlier onset of endothelial dysfunction preceding cirrhosis. Associations of VIMs with platelets suggest a critical link between platelets and vascular homeostasis. Circulating markers of vascular injury may not only have prognostic importance but emphasize the role of vascular dysfunction in liver disease pathogenesis (NCT00001971).
Asunto(s)
Endotelio Vascular/fisiopatología , Hepatitis C Crónica/sangre , Cirrosis Hepática/sangre , Trombocitopenia/sangre , Adulto , Antígenos CD/sangre , Becaplermina/sangre , Biomarcadores , Moléculas de Adhesión Celular/sangre , Progresión de la Enfermedad , Enfermedad Hepática en Estado Terminal/sangre , Enfermedad Hepática en Estado Terminal/metabolismo , Factores de Crecimiento Endotelial/sangre , Endotelio Vascular/metabolismo , Ensayo de Inmunoadsorción Enzimática , Femenino , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/metabolismo , Homeostasis , Humanos , Cirrosis Hepática/etiología , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Selectina-P/sangre , Recuento de Plaquetas , Factor de Crecimiento Derivado de Plaquetas/metabolismo , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Trombocitopenia/etiología , Trombocitopenia/metabolismo , Factor de Crecimiento Transformador beta1/sangre , Molécula 1 de Adhesión Celular Vascular/sangreRESUMEN
Hepatitis C virus (HCV) infects 71 million individuals, and barriers to treatment remain. Bacterial translocation is a complication of chronic HCV infection, and this study evaluated circulating microbial components including lipopolysaccharide, peptidoglycan, and ß-D-glucan in addition to their pattern recognition receptors and degree of hepatic macrophage uptake. The findings suggest that regulation of serum peptidoglycan and ß-D-glucan differs from that of lipopolysaccharide. Additionally, macrophage activation in the liver may be better reflected by the degree of macrophage uptake than by circulating levels of microbial markers. These findings allow for a greater understanding of bacterial translocation and host immune activation during HCV infection.