Increased circulating and intrahepatic T-cell-specific chemokines in chronic hepatitis C: relationship with the type of virological response to peginterferon plus ribavirin combination therapy.

Abstract

To determine the serum and intrahepatic levels of T-helper-1-associated chemokines in patients with chronic hepatitis C before, during and after peginterferon plus ribavirin combination therapy and to search for correlations with baseline characteristics of hepatitis C virus-related chronic liver disease and type of therapeutic response. Serum chemokine levels were determined by enzyme-linked immunosorbent assays and intrahepatic chemokine messenger RNA and protein levels were tested by ribonuclease protection assay and immunohistochemistry. Serum and intrahepatic chemokine levels were elevated in all patients with chronic hepatitis C and showed a marked decrease in patients who obtained a virological response vs. non-responders. Increased serum interferon-gamma-inducible protein-10 levels at baseline in genotype 1-infected patients were significantly associated with greater degrees of intrahepatic inflammation and fibrosis (P = 0.0046 and P = 0.02, respectively) and with virological non-response (P = 0.01). In patients with genotype 1, basal serum interferon-gamma-inducible protein-10 levels greater than 299 pg/mL identified 80% of non-responders and lower than 299 pg/mL identified 63% of responders. Circulating and intrahepatic T-helper-1-associated chemokines are abnormally elevated in patients with chronic hepatitis C. Increased baseline serum interferon-gamma-inducible protein-10 levels in genotype 1-infected patients are associated with virological non-response to peginterferon plus ribavirin combination therapy.