Liver immune abnormalities persist after cure of Hepatitis C Virus by antiviral therapy

Direct-Acting Antiviral (DAA) drugs are highly effective in eliminating HCV in most chronically infected subjects, but it is unclear whether the multiple mechanisms employed by HCV to disable both innate and adaptive immunity cease to function as soon as HCV is eliminated. To test this, we evaluated the capacity of human liver tissue to respond to TLR3 and TLR4 ligands using non-infected liver tissue, tissue with active HCV infection, and tissue from which HCV had been eliminated by DAA. We found that DAA-treated, formerly HCV-infected liver tissue manifested ongoing abnormalities of innate immunity that mapped to liver non-parenchymal cells (NPC). Hepatic innate immunity was not suppressed but enhanced in HCV-infected tissue, and these abnormalities were not corrected in the successfully DAA-treated liver tissue. In conclusion, ongoing immune activation persists in formerly HCV-infected but now DAA-cured liver.