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Background: Persistent hepatitis C virus (HCV) infection results from inefficient innate and adaptive immune responses and exhausted virus-specific T-cell responses. Host cytokines and innate immune responses play important roles in controlling HCV infection. Innate immune responses modulate adaptive immune responses. These responses have recently been shown to have roles in antiviral therapy for chronic HCV infection. My previous study has indicated that viral clearance early in the course of therapy is associated with the restoration of innate and adaptive immune responses, and thus has potential as a novel therapeutic strategy for chronic hepatitis C (CHC).

Methods: The efficacy and safety of induction therapy (IT) with natural (n)-interferon (IFN)-beta followed by pegylated-IFN-alpha and ribavirin (PR) alone (group A, n = 30) were compared with those of IT with a protease inhibitor (PI) (Simeprevir or Vaniprevir) plus PR (group B, n = 13) in patients with CHC with genotype 1b and high viral load.

Results: During IT with n-IFN-beta, the virologic response rates in group A and group B were 10% and 8% (p = 0.6792) at week 4; 30% and 16% (p = 0.6989) at week 12; and 47% and 20% (p = 0.0887) at week 24. During and after treatment with PR alone, or PI plus PR, the virologic response rates in groups A and B were 50% and 82% (p = 0.01535) at week 4: 53% and 91% (p = 0.006745) at week 8; 57% and 91% (p = 0.001126) at week 12; 57% and 100% (p = 0.001845) at the end of the treatment; and 57% and 80% (p = 0.005166) after treatment cessation.

Conclusion: IT with PI plus PR restored the innate immune response, was tolerated well, overcame virological breakthrough, enhanced early virologic responses, and resulted in a sustained virologic response in patients with intractable CHC. Thus, IT with PI plus PR is beneficial for patients with intractable CHC. Steps for augmenting immune responses must be identified.