Molecular diagnostics in the management of chronic hepatitis C: key considerations in the era of new antiviral therapies

Molecular tests that detect and/or quantify HCV RNA are important in the diagnosis and management of patients with chronic hepatitis C (CHC) undergoing anti-viral therapy. The primary goal of anti-HCV therapy is to achieve a sustained virologic response (SVR) defined as "undetectable" Hepatitis C Virus (HCV) RNA in the serum or plasma at 12 to 24 weeks following the end of treatment. HCV RNA viral load (VL) monitoring is used to guide treatment duration where decisions can be made on-therapy and to determine whether or not to stop therapy. In addition, clinicians determine treatment regimen and duration based on the HCV genotype (1-6) as well as the kinetics of HCV RNA levels. As direct acting antivirals (DAA) have revolutionized hepatitis C treatment, they have also lead to new HCV RNA VL result interpretations. Further, the clinical decisions were different for pegylated-interferon/ribavirin (PEGα/RBV)+ boceprevir or telaprevir-containing regimens approved in 2011 (e.g. one requiring an additional 4 week "lead-in" with PEGα/RBV), each having different HCV RNA values for futility rules, created complexity in clinical decisions. The future pegylated-interferon free DAA- regimens promise significantly improved cure rates along with fixed durations and simpler treatment rules. The intent of this article is to discuss the role of HCV RNA real-time PCR tests used in the management of CHC patients in the past and how this is likely to change in the era of interferon free DAA regimens.