Baseline Intrahepatic and Peripheral Innate Immune Responses are Associated with Hepatitis C Virus Eradication in Patients Receiving Direct Acting Antivirals

Hepatitis C virus (HCV) infection induces interferon stimulated genes (ISGs) and downstream innate immune responses. This study investigated whether baseline and on-treatment differences in these responses predict response versus virological breakthrough during therapy with direct acting antivirals (DAA). Microarray and nanostring analyses were performed on paired liver biopsies and analyzed using linear mixed models. As biomarkers for peripheral IFN responses, peripheral blood natural killer cells were assessed for pSTAT1 and TRAIL expression and for cytotoxicity. Thirteen HCV genotype 1b-infected patients who had previously failed a course of peginterferon/ribavirin were re-treated with asunaprevir/daclatasvir for 24 weeks. After pre-treatment biopsy, patients were randomized to undergo a second biopsy at week 2 or 4 on-therapy.