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- W2034896686 abstract "Hepatitis C virus (HCV) is a blood–borne pathogen that chronically infects approximately 130 million people worldwide and can lead to liver cirrhosis and hepatocellular carcinoma. HCV is divided in seven major genotypes, of which genotype 1 causes the majority of infections in the developed world. In contrast to several other chronic viral infections, e.g. human immunodeficiency virus (HIV) and hepatitis B virus (HBV), HCV can be eradicated in a subset of individuals who clear acute infection and in patients that achieve a sustained virologic response (SVR) after treatment. Cure of HCV decreases the risk of end-stage liver disease and/or hepatocellular carcinoma, even in patients who are cirrhotic. It is, therefore, generally recommended that chronically infected individuals undergo treatment if they are expected to tolerate the current medications. For more than a decade, treatment for all HCV genotypes has been based on a combination of interferon-a (IFNa) and ribavirin (RBV), with the main variables being duration of treatment, the formulation of IFNa, and the dosage of RBV. This combination has empirically proven efficacious but its mechanisms of action remain elusive. IFNa is believed to have both direct antiviral, as well as host immunostimulatory effects, and a wide array of mechanisms have been proposed for RBV, from increased viral mutagenesis to helper T cell modulation [6]. Even with optimal treatment duration, formulation and dosing, however, less than half of genotype 1/4 and approximately two thirds of genotype 2/3 infected patients achieve SVR [7]. Meanwhile, both drugs result in significant adverse events in the majority of patients, most notably cytopenias that frequently require growth factor administration, flu like symptoms, and neuropsychiatric side effects. It is for these reasons that new drugs are currently under development. HCV is a positive stranded RNA virus that encodes a single polyprotein, which is cleaved by host and viral proteases into its functional structural and non-structural (NS) subunits. Two of the viral gene products, namely the NS3-4A protease and NS5B polymerase, have proven attractive drug targets. Over the" @default.
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- W2034896686 date "2011-05-01" @default.
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- W2034896686 title "Evaluation of combination therapy against hepatitis C virus infection in human liver chimeric mice" @default.
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- W2034896686 doi "https://doi.org/10.1016/j.jhep.2010.09.034" @default.
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