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Hepatitis C recurring after liver transplant may cause progressive liver dysfunction, and available treatment regimens are unsatisfactory. A better understanding of the mechanisms of action of drugs currently used to manage hepatitis C would be helpful.In a pilot, uncontrolled clinical trial, we treated 12 patients with post-liver transplantation hepatitis C with 1000–1200 mg qd of ribavirin, given as a monotherapy. We measured the transaminases levels, the liver disease grading and staging scores, the intrahepatic interferon-γ, tumor necrosis factor-α, interleukin (IL)-4 and IL-10 mRNA levels, the serum and liver hepatitis C virus (HCV) RNA titers, and the intrahepatic HCV envelope 2 protein staining score before and after 12 weeks of ribavirin monotherapy.Ribavirin induced a significant amelioration of the transaminases levels. This biochemical response was not associated with a distinct change in the intrahepatic T helper 1/T helper 2 cytokine mRNA profile. Furthermore, some histological parameters, such as the portal inflammation and the fibrosis scores, worsened significantly even in the short term. A slight, albeit not significant, decrease of serum HCV RNA level and intrahepatic HCV antigen staining score was observed. Intrahepatic genomic-strand (but not negative-strand) HCV RNA titer decreased significantly (P =0.024).Contrary to what is suggested by experimental data, administration of ribavirin alone to patients with recurrent hepatitis C after liver transplantation is not accompanied by a specific change of the intrahepatic interferon-γ, tumor necrosis factor-α, IL-4, or IL-10 mRNA transcription profile.