Intrahepatic mRNA levels of interferon gamma and tumor necrosis factor alpha and response to antiviral treatment of chronic hepatitis C

Objectives: The impact of intrahepatic messenger RNA (mRNA) levels of inter feron gamma (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha) on the outcome of antiviral treatment of chronic hepatitis C was evaluated. Methods: Semiquantitative mRNA determination was performed on 36 pretreatme nt liver biopsies by reverse transcription/competitive polymerase chain rea ction. Results: Sustained response (normal aminotransferase levels and negative he patitis C virus [HCV] RNA for more than 6 months) was achieved in 13 patien ts, whereas 23 of 36 patients did not achieve sustained response (12 partia l responders, 11 complete nonresponders), In sustained responders, pretreat ment intrahepatic mRNA levels of IFN-gamma and TNF-alpha were lower than in nonsustained responders (IFN-gamma, 0.23 +/- 0.10 vs. 0.35 +/- 0.07, respe ctively; p = 0.024 and TNF-alpha, 1.2 +/- 0.7 vs. 2.3 +/- 1.4, respectively ; p = 0.009); similarly, HCV viral load was lower in sustained responders t han in nonresponders (663,424 +/- 756,389 copies/mL vs. 1,656,713 +/- 1,517 ,683 copies/mL, respectively; p = 0.037). In addition, TNF-alpha mRNA level s were correlated to HCV viral load and liver fibrosis scores. Conclusions: Higher intrahepatic mRNA levels of IFN-gamma and TNF-alpha. ma y reflect interferon resistance of HCV strains and may contribute to tissue damage in patients refractory to antiviral treatment.