Background/aims: Upregulation of interleukin-8 by the hepatitis C virus non-structural-5A-protein leads to inhibition of the antiviral activity of interferon-alpha in vitro. The clinical significance of interleukin-8 levels for virologic response to interferon-alpha-based treatment in patients with chronic hepatitis C is unknown.
Methods: We investigated serum interleukin-8 in 59 healthy controls and 214 patients with chronic hepatitis C (genotype 1, n=152; genotype 2, 3, n=62) and different outcome to interferon-alpha-based therapy.
Results: In patients with chronic hepatitis C higher interleukin-8 levels were observed compared with healthy controls (P<0.0001). Hepatitis C genotype 1-infected patients with early and overall virologic response to interferon-alpha-based therapy showed lower interleukin-8 levels than non-responders (P=0.025 and P=0.035, respectively). In all patients, elevated interleukin-8 levels were associated with cirrhosis (genotype 1, P=0.0003; genotype 2, 3, P=0.009). Interleukin-8 levels in sustained virologic responders were still higher 24 weeks after the end-of-therapy compared with healthy controls (P<0.0001).
Conclusions: In genotype 1 infected patients, low pretreatment serum interleukin-8 is associated with virologic response to interferon-alpha-based therapy. Thus, the conclusion from in vitro studies that the upregulation of interleukin-8 by the hepatitis C virus contributes to the inhibition of the antiviral actions of interferon-alpha may also be applicable in vivo.