Intrahepatic cytokine profile in renal-transplant patients infected by hepatitis C virus.

In order to examine the immunopathogenesis of hepatitis C virus (HCV)-related liver injury in renal-transplant patients, intra-hepatic cytokine profiles were examined in 38 liver biopsies from 38 patients by measuring messenger RNA (mRNA) concentrations by a real-time PCR method of a Th1 cytokine (i.e., interferon (IFN)-gamma), a Th2 cytokines (i.e., interleukine (IL)-10), a proinflammatory cytokine (i.e., IL-8), and a potent fibrogenic factor (transforming growth factor [TGF]-beta). There was no significant difference in TGF-beta, IFN-gamma, IL-10, or IL-8 levels of expression according to liver-activity grade, liver-fibrosis stage, the concentration of HCV RNA at liver biopsies, or the HCV genotype. However, IFN-gamma/beta-actin mRNA concentration was higher than the IL-10/beta-actin mRNA concentration in patients with F3 Metavir score. Median IFN-gamma/beta-actin mRNA concentration tended to be higher in patients with A3 and A4 Metavir activity grades compared with those with A0 and A1 activity grades. There was a significant correlation between the duration of HCV infection and both TGF-beta/beta-actin (r(2)=0.19, P=0.04) and IL-8/beta-actin mRNA concentrations (r(2)=0.19, P=0.03). IFN-gamma/beta-actin mRNA concentration also increased according to the duration of HCV (r(2)=0.19, P=0.07). Finally, there was a significant correlation between the duration of HCV infection and liver fibrosis stage (r(2)=0.17, P=0.045). Intrahepatic Th1 cytokine profile seems to be predominant in patients with extensive fibrosis and activity scores, suggesting that it might be responsible for liver injury in renal transplant patients.