538 G-CSF is safe and improves adherence and SVR in HCV patients with genotype-1 who develop PEG-IFNa-2b related severe neutropenia. A multicenter study

POSTERSactivation of NF-~;B may be the overture to elevated expression of genes such as those encoding for the inducible isoform of the nitric oxide synthase (iNOS), which participates in the inflammatory responses, or for manganese superoxide dismutase (Mn-SOD), which exerts an important antioxidant function.Objective: This study is aimed to investigate, in patients with chronic HCV infection, possible alterations in NF-~;B activation and gene expression of the enzymes regulated by this nuclear factor iNOS and Mn-SOD, during the progression to more serious liver diseases as cirrhosis and hepatocarcinoma.Methods: Peripheral blood mononuclear cells were obtained of 15 controls without hepatopathy, 15 patients with chronic HCV infection, 15 HCV cirrhotic patients and 12 patients with HCV cirrhosis and hepatocarcinoma.Assessment of NF-~;B activation was studied in nuclear extracts from all groups by a radioactive electrophoretic mobility shift assay (EMSA).Analysis of iNOS and Mn-SOD mRNA expression was performed by quantitative real time RT-PCR.Results: Chronic hepatitis C virus infection induced a NF-~;B activation linked to increases in iNOS (+19%) and Mn-SOD (+22%) mRNA.No significant changes in NF-~;B activation or iNOS and Mn-SOD mRNA expression were observed in patients with compensated cirrhosis.NF-~;B activation was also detected in patients with hepatocarcinoma.This activation was correlated with increases in iNOS (+41%) and Mn-SOD (+15%) mRNA.Conclusions: Our results suggest that viral infection activates NF-~;B and up-regulates genes dependent of this nuclear factor.These modifications would act as defense mechanism against oxidative damage induced by HCV infection.The lack of alterations in cirrhotic group seems to support that NF-~;B activation might exert antiapoptotic and antifibrogenic effects, which may delay the development of cirrhosis.The changes observed in patients with hepatocarcinoma show that NF-~;B activation can play role during the pathogenesis of this tumour.