Telaprevir‐based treatment effects on hepatitis C virus in liver and blood

Understanding hepatitis C virus (HCV) replication has been limited by access to serial samples of liver, the primary site of viral replication. Our understanding of how HCV replicates and develops drug‐resistant variants in the liver is limited. We studied 15 patients chronically infected with genotype 1 HCV treated with telaprevir (TVR)/pegylated‐interferon alpha/ribavirin. Hepatic fine needle aspiration was performed before treatment and at hour 10, days 4 and 15, and week 8 after initiation of antiviral therapy. We measured viral kinetics, resistance patterns, TVR concentrations, and host transcription profiles. All patients completed all protocol‐defined procedures that were generally well tolerated. First‐phase HCV decline (baseline/treatment day 4) was significantly slower in liver than in plasma (slope plasma: −0.29; liver, −0.009; P