title: Evidence of Active Pro-Fibrotic Response in Blood of Patients with Cirrhosis.
abstract: The role of systemic immunity in the pathogenesis of cirrhosis is not fully understood. Analysis of transcriptomic profiles in blood is an easy approach to obtain a wide picture of immune response at the systemic level. We studied gene expression profiles in blood from thirty cirrhotic patients and compared them against those of eight healthy volunteers. Most of our patients were male [n = 21, 70%] in their middle ages [57.4 ± 6.8 yr]. Alcohol abuse was the most frequent cause of cirrhosis (n = 22, 73%). Eleven patients had hepatocellular carcinoma (36.7%). Eight patients suffered from hepatitis C virus infection (26.7%). We found a signature constituted by 3402 genes which were differentially expressed in patients compared to controls (2802 over-expressed and 600 under-expressed). Evaluation of this signature evidenced the existence of an active pro-fibrotic transcriptomic program in the cirrhotic patients, involving the [extra-cellular matrix (ECM)-receptor interaction] & [TGF-beta signaling] pathways along with the [Cell adhesion molecules] pathway. This program coexists with alterations in pathways participating in [Glycine, serine and threonine metabolism], [Phenylalanine metabolism], [Tyrosine metabolism], [ABC transporters], [Purine metabolism], [Arachidonic acid metabolism]. In consequence, our results evidence the co-existence in blood of a genomic program mediating pro-fibrotic mechanisms and metabolic alterations in advanced cirrhosis. Monitoring expression levels of the genes involved in these programs could be of interest for predicting / monitoring cirrhosis evolution. These genes could constitute therapeutic targets in this disease.
authors: Unidad de Hepatología, Unidad de Trasplante Hepático. Hospital Universitario Río Hortega, Valladolid, Spain.
authors: Gloria
authors: G
authors: Sanchez-Antolín
authors: Unidad de Hepatología, Unidad de Trasplante Hepático. Hospital Universitario Río Hortega, Valladolid, Spain.
authors: Carolina
authors: C
authors: Almohalla-Alvarez
authors: Servicio de Análisis Clínicos, Hospital Clínico Universitario de Valladolid, Valladolid, Spain.
authors: Pilar
authors: P
authors: Bueno
authors: Investigación Médica en Infección e Inmunidad (IMI), Hospital Clínico Universitario de Valladolid-IECSCYL, Valladolid, Spain.
authors: Raquel
authors: R
authors: Almansa
authors: Investigación Médica en Infección e Inmunidad (IMI), Hospital Clínico Universitario de Valladolid-IECSCYL, Valladolid, Spain.
authors: Verónica
authors: V
authors: Iglesias
authors: Investigación Médica en Infección e Inmunidad (IMI), Hospital Clínico Universitario de Valladolid-IECSCYL, Valladolid, Spain.
authors: Lucia
authors: L
authors: Rico
authors: Investigación Médica en Infección e Inmunidad (IMI), Hospital Clínico Universitario de Valladolid-IECSCYL, Valladolid, Spain.
authors: Alicia
authors: A
authors: Ortega
authors: Escuela de Enfermería Universidad de Valladolid, Valladolid, Spain.
authors: Eva
authors: E
authors: Muñoz-Conejero
authors: Unidad de Hepatología, Unidad de Trasplante Hepático. Hospital Universitario Río Hortega, Valladolid, Spain.
authors: Felix
authors: F
authors: García-Pajares
authors: Investigación Médica en Infección e Inmunidad (IMI), Hospital Clínico Universitario de Valladolid-IECSCYL, Valladolid, Spain.
authors: Jesus F
authors: JF
authors: Bermejo-Martin
mesh_terms: D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007962:Leukocytes / Q000378:metabolism; D008103:Liver Cirrhosis / Q000097:blood* / Q000235:genetics* / Q000378:metabolism / Q000821:virology; D008297:Male; D055432:Metabolomics; D008875:Middle Aged