The effect of controlled therapy interruption in chronic HCV infection: Enhanced host immune response? A hypothesis

Abstract 

Background

We have hypothesized that prolonged viral suppression partially reverses immune tolerance in chronic hepatitis C virus infection. Brief periods of treatment interruption can then simulate ‘auto-vaccination’ and evoke powerful secondary host immune responses.

Objective

To determine the effect of controlled therapy interruption CTI on viral load in previous relapsers to interferon and ribavirin treatment.

Study design

Virus is maintained at undetectable levels for 2–8 weeks with pegylated interferon and ribavirin and then briefly interrupted, restarting as soon as viremia returns (cycle 1). It is suppressed for at least a further 4 weeks, then briefly interrupted again (cycle 2).

Results

Viremia relapsed within 2–4 weeks (time to relapse TTR) after the first treatment interruption in all four patients in cycle 1. TTR increased sevenfold with the second treatment interruption in patient 1 and was followed by sustained virological response with cycle 3. In patient 2, TTR increased threefold after cycle 2 and subsequent cycles. Serum ALT and bilirubin rose significantly with treatment interruption during cycles 2 and 3, returning to baseline with treatment resumption. Serum bilirubin rose to 12.3mg/dl when two doses of pegylated interferon were missed during cycle 4. In patients 3 and 4, TTR was unchanged after three consecutive cycles. However, VL has remained more than 1log below baseline for up to 18 months in both.

Conclusions

These observations suggest that CTI exerts significant control of chronic hepatitis C viremia.

Keywords: Hepatitis C virus, Immune response, Controlled therapy interruption, Interferon and ribavirin