Antiviral therapy: impact on HCV genetic diversity in Chronic Kidney Disease patients

Abstract

The therapy for patients with hepatitis C, for more than a decade, was based in the use of conventional interferon (IFN) or pegylated interferon (IFN-PEG) combined with ribavirin (RBV), administered for 24 or 48 weeks depending on the infecting genotype. Due to this, it is of extreme importance to recognize the mechanism behind the therapy, because even today its real functioning is unknown. Therefore, the insertion and/or exchange of nucleotides during the process of replication of HCV may have important implications in pathogenicity, persistence and resistance to antiviral agents. Another important point is the high prevalence and incidence of hepatitis C among patients affected by chronic kidney disease (CKD), with unfavorable effect on morbidity and mortality. The treatment of these patients pharmacokinetics, the predisposition to the toxicity and anemia induced by the use of the RBV. Considering these facts, the project aims to investigate the impact of antiviral therapy of ribavirin (monotherapy) and interferon combined with ribavirin in genetic diversity of the hepatitis C virus (HCV) in patients with chronic hepatitis C and chronic renal disease. After extraction, amplification by nested PCR and cloning of the product, the genetic information will be accessed by the technique of Sanger sequencing. The resulting sequences will be analyzed through techniques of bioinformatics to determine phylogenetic patterns before and after treatment with RBV or INF and RBV in hemodialysis patients. The project seeks better understand the incorporations of mutations during replication of the hepatitis C virus, specifically in the nucleotide sequence of the NS5B region of the genome of HCV, as well as the real role of the ribavirin in selection of viral populations. It is also expected that, broadening the knowledge about the mutations in the viral genome is possible the establishment of new ratings for the treatment of chronic renal patients. (AU)