RESUMEN
Chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are among the most serious health conditions affecting about 600 million people worldwide leading to a number of severe liver diseases. Due to the lack of warning signs or mild symptoms during the early stage of the infection, a molecular signature associated with disease progression would be useful. Based on our recent paper where candidate biomarkers were determined through topological and modularity analysis of protein interaction networks (PINs), this study was focused on the evaluation of MIF, TNFRSF1A, FAS and TMSB4X as diagnostic biomarkers in chronic HBV and HCV infections. The aim was to establish a molecular profile, by combining those markers, that would discriminate the different stages during the progression of chronic hepatitis. One hundred and fifteen patients infected with HBV or HCV categorized into three groups: non-cirrhotic, cirrhotic and with HCC, and 20 healthy subjects were enrolled in this study. Serum levels of the aforementioned factors were measured by ELISA. TNFRSF1A serum levels appeared statistically significantly increased in all patient groups compared to control group with a p-value of <0.05. Furthermore, the combination of TNFRSF1A and TMSB4X serum levels successfully classified 63, 47% of patients indicating an association with HBV and HCV infections. Thus, variations of serum levels of TNFRSF1A and TMSB4X could be associated with the different stages of the disease and may be utilized for further research. On the other hand, we found no contribution of MIF and FAS serum levels for successful classification of patients.
Asunto(s)
Biomarcadores/sangre , Hepatitis B Crónica/sangre , Hepatitis B Crónica/virología , Hepatitis C Crónica/sangre , Hepatitis C Crónica/virología , Adulto , Anciano , Análisis de Varianza , Carcinoma Hepatocelular/sangre , Carcinoma Hepatocelular/etiología , Toma de Decisiones Clínicas , Sistemas de Apoyo a Decisiones Clínicas , Progresión de la Enfermedad , Femenino , Hepacivirus , Virus de la Hepatitis B , Hepatitis B Crónica/complicaciones , Hepatitis C Crónica/complicaciones , Humanos , Cirrosis Hepática/sangre , Cirrosis Hepática/etiología , Neoplasias Hepáticas/sangre , Neoplasias Hepáticas/etiología , Masculino , Persona de Mediana Edad , Adulto JovenAsunto(s)
Anticuerpos Monoclonales Humanizados/efectos adversos , Fármacos Dermatológicos/efectos adversos , Hepatitis B Crónica/etiología , Síndrome Inflamatorio de Reconstitución Inmune/inducido químicamente , Psoriasis/tratamiento farmacológico , Anticuerpos contra la Hepatitis B/sangre , Antígenos de Superficie de la Hepatitis B/sangre , Hepatitis B Crónica/inmunología , Humanos , Masculino , Persona de Mediana Edad , Recurrencia , UstekinumabRESUMEN
Low oxygen tension exerts a significant effect on the replication of several DNA and RNA viruses in cultured cells. In vitro propagation of hepatitis C virus (HCV) has thus far been studied under atmospheric oxygen levels despite the fact that the liver tissue microenvironment is hypoxic. In this study, we investigated the efficiency of HCV production in actively dividing or differentiating human hepatoma cells cultured under low or atmospheric oxygen tensions. By using both HCV replicons and infection-based assays, low oxygen was found to enhance HCV RNA replication whereas virus entry and RNA translation were not affected. Hypoxia signaling pathway-focused DNA microarray and real-time quantitative reverse transcription-PCR (qRT-PCR) analyses revealed an upregulation of genes related to hypoxic stress, glycolytic metabolism, cell growth, and proliferation when cells were kept under low (3% [vol/vol]) oxygen tension, likely reflecting cell adaptation to anaerobic conditions. Interestingly, hypoxia-mediated enhancement of HCV replication correlated directly with the increase in anaerobic glycolysis and creatine kinase B (CKB) activity that leads to elevated ATP production. Surprisingly, activation of hypoxia-inducible factor alpha (HIF-α) was not involved in the elevation of HCV replication. Instead, a number of oncogenes known to be associated with glycolysis were upregulated and evidence that these oncogenes contribute to hypoxia-mediated enhancement of HCV replication was obtained. Finally, in liver biopsy specimens of HCV-infected patients, the levels of hypoxia and anaerobic metabolism markers correlated with HCV RNA levels. These results provide new insights into the impact of oxygen tension on the intricate HCV-host cell interaction.