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The first protease inhibitor approved by the U.S. Food and Drug Administration (FDA). Ritonavir: Norvir: AbbVie: U.S. patent 5,541,206: March 1, 1996: AbbVie was part of Abbott Laboratories when patent was granted. As well as being a protease inhibitor in its own right, ritonavir inhibits the breakdown of other protease inhibitors.
In general, HCV genotype 1a is less resistant to mutation than genotype 1b. [18] For genotype 1b a single amino acid substitution (e.g. L31V) in the replicon had less than a 100 fold increase in resistance to the ledipasvir in Harvoni, while a two amino acid substitution had over a 1000 fold increase in resistance.
Worldwide the prevalence of hepatitis C virus infection in pregnant women and children has been estimated to be 1–8% and 0.05–5% respectively. [153] The vertical transmission rate has been estimated to be 3–5% and there is a high rate of spontaneous clearance (25–50%) in the children.
Over five direct and indirect mechanisms have been proposed for its mechanism of action. [43] The enzyme inosine triphosphate pyrophosphatase (ITPase) dephosphorylates ribavirin triphosphate in vitro to ribavirin monophosphate, and ITPase reduced enzymatic activity present in 30% of humans potentiates mutagenesis in hepatitis C virus.
A major risk for the development of HCC is persistent infection with HCV, and the highest risk for HCC development is associated with co-infection of HBV with HDV, HCV or HIV. [27] Risk factors that can lead to the development of HCC in those with chronic HCV include synchronous liver diseases, viral genotype, diabetes mellitus, and obesity.
The hepatitis C virus (HCV) [3] is a small (55–65 nm in size), enveloped, positive-sense single-stranded RNA virus of the family Flaviviridae. The hepatitis C virus is the cause of hepatitis C and some cancers such as liver cancer (hepatocellular carcinoma, abbreviated HCC) and lymphomas in humans. [4] [5]
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