Chronic hepatitis C (CHC) is an insidious liver disease that results from infection with the hepatitis C virus (HCV). It is estimated that ~150 million people or 3% of the population worldwide have been infected with HCV. Chronic infection can lead to liver fibrosis, cirrhosis, end-stage liver disease and hepatocellular carcinoma over the course of 15 to 30 years. Chronic hepatitis C is the leading cause for liver transplantation in the United States, Japan and in the European Union.
Recently, there have been significant breakthroughs identifying essential functions within the HCV replication cycle that have led to advances in drug discovery efforts. The first viral proteins to be clinically validated as therapeutic targets for Direct-acting Antiviral Agents (DAAs) were the NS3/4A protease and the NS5B polymerase. These targets are non-structural proteins with defined enzymatic functions that can be inhibited with small molecules. Similar to advancements against HIV, the recent development of protease and polymerase inhibitors brings hope for new treatment options for CHC.